2022年 · 第135卷第06期

Upper abdominal magnetic resonance (MR) imaging is appropriate for body composition analysis.^[1]Especially for individuals with obesity, it is of great value to quantify the hepatic proton density fat fraction (PDFF) and the amount of abdominal adipose tissue during clinical evaluation and for research on obesity-related risks. Analytical results may be used to determine the optimal choice of surgical procedure and evaluate treatment outcomes. Multiple artificial intelligence (AI) algorithms and systems have been developed for the automated measurement of body composition. The basis of AI development and application is to have uniform standards for clinical data acquisition and management. The uneven quality of MR images is one of the major obstacles to AI system development and analytical results. A standardized process of MR scanning and clinical data management is urgently needed.

Since the diagnostic value of aldosterone to renin ratio (ARR) calculated by plasma renin concentration (PRC) or plasma renin activity (PRA) is still inconclusive, we conducted a meta-analysis by systematically reviewing relevant literature to explore the difference in the diagnostic efficacy of ARR calculated by PRC or PRA, so as to provide guidance for clinical diagnosis.

We searched PubMed, Embase, and Cochrane Library from the establishment of the database to March 2021. We included studies that report the true positive, false positive, true negative, and false negative values for the diagnosis of primary aldosteronism, and we excluded duplicate publications, research without full text, incomplete information, or inability to conduct data extraction, animal experiments, reviews, and systematic reviews. STATA 15.1 was used to analyze the data.

The pooled results showed that ARR (plasma aldosterone concentration [PAC]/PRC) had a sensitivity of 0.82 (95% confidence interval [CI]: 0.78-0.86), a specificity of 0.94 (95% CI: 0.92-0.95), a positive-likelihood ratio (LR) of 12.77 (95% CI: 7.04-23.73), a negative LR of 0.11 (95% CI: 0.07-0.17), and symmetric area under the curve (SAUC) of 0.982, respectively. Furthermore, the diagnostic odds ratio (DOR) of ARR (PAC/PRC) was 180.21. Additionally, the pooled results showed that ARR (PAC/PRA) had a sensitivity of 0.91 (95% CI: 0.86-0.95), a specificity of 0.91 (95% CI: 0.90-0.93), a positive LR of 7.30 (95% CI: 2.99-17.99), a negative LR of 0.10 (95% CI: 0.04-0.26), and SAUC of 0.976, respectively. The DOR of ARR (PAC/PRA) was 155.52. Additionally, we conducted a subgroup analysis for the different thresholds (<35 or ≥35) of PAC/PRC. The results showed that the DOR of the cut-off ≥35 groups was higher than the cut-off <35 groups (DOR = 340.15, 95% CI: 38.32-3019.66; DOR= 116.40, 95% CI = 23.28-581.92).

The research results suggest that the determination of ARR (PAC/PRC) and ARR (PAC/PRA) was all effective screening tools for PA. The diagnostic accuracy and diagnostic value of ARR (PAC/PRC) are higher than ARR (PAC/PRA). In addition, within a certain range, the higher the threshold, the better the diagnostic value.

Few studies have assessed the relationship between multimorbidity patterns and mortality risk in the Chinese population. We aimed to identify multimorbidity patterns and examined the associations of multimorbidity patterns and the number of chronic diseases with the risk of mortality among Chinese middle-aged and older adults.

We used data from the China Kadoorie Biobank and included 512,723 participants aged 30 to 79 years. Multimorbidity was defined as the presence of two or more of the 15 chronic diseases collected by self-report or physical examination at baseline. Multimorbidity patterns were identified using hierarchical cluster analysis. Cox regression was used to estimate the associations of multimorbidity patterns and the number of chronic diseases with all-cause and cause-specific mortality.

Overall, 15.8% of participants had multimorbidity. The prevalence of multimorbidity increased with age and was higher in urban than rural participants. Four multimorbidity patterns were identified, including cardiometabolic multimorbidity (diabetes, coronary heart disease, stroke, and hypertension), respiratory multimorbidity (tuberculosis, asthma, and chronic obstructive pulmonary disease), gastrointestinal and hepatorenal multimorbidity (gallstone disease, chronic kidney disease, cirrhosis, peptic ulcer, and cancer), and mental and arthritis multimorbidity (neurasthenia, psychiatric disorder, and rheumatoid arthritis). During a median of 10.8 years of follow-up, 49,371 deaths occurred. Compared with participants without multimorbidity, cardiometabolic multimorbidity (hazard ratios [HR] = 2.20, 95% confidence intervals [CI]: 2.14-2.26) and respiratory multimorbidity (HR= 2.13, 95% CI:1.97-2.31) demonstrated relatively higher risks of mortality, followed by gastrointestinal and hepatorenal multimorbidity (HR= 1.33, 95% CI:1.22-1.46). The mortality risk increased by 36% (HR= 1.36, 95% CI: 1.35-1.37) with every additional disease.

Cardiometabolic multimorbidity and respiratory multimorbidity posed the highest threat on mortality risk and deserved particular attention in Chinese adults.

Antiphospholipid syndrome (APS) is an autoimmune prothrombotic condition with significant morbidity. The objective of this study was to identify additional clinical and epidemiological risks of arterial thrombosis, venous thrombosis, and pregnancy morbidities in a large cohort of persistent antiphospholipid antibodies (aPLs)-positive carriers.

This was a cross-sectional cohort study of 453 consecutive patients with a documented positive aPL who attended Peking University People's Hospital. Among 453 patients screened, 297 patients had persistent positive aPL. We compared asymptomatic aPL carriers with thrombotic and obstetric APS patients. And the univariate analysis and multivariable logistic regression were used to evaluate the association between different risk factors and APS clinical manifestations. The levels of circulating markers of neutrophil extracellular traps (NETs) (cell-free DNA and citrullinated histone H3 [Cit-H3]) were assessed and compared among aPL-positive carriers with or without autoimmune disease and APS patients.

Additional risk factors associated with arterial thrombosis among aPL-positive carriers included: smoking (odds ratio [OR] = 6.137, 95% confidence interval [CI] = 2.408-15.637, P = 0.0001), hypertension (OR = 2.368, 95% CI = 1.249-4.491, P = 0.008), and the presence of underlying autoimmune disease (OR = 4.401, 95% CI = 2.387-8.113, P < 0.001). Additional risks associated with venous thrombosis among aPL carriers included: smoking (OR = 4.594, 95% CI = 1.681-12.553, P = 0.029) and the presence of underlying autoimmune disease (OR = 6.330, 95% CI = 3.355-11.940, P < 0.001). The presence of underlying autoimmune disease (OR = 3.301, 95% CI= 1.407-7.744, P = 0.006) is the additional risk, which demonstrated a significant association with APS pregnancy morbidity. Higher circulating levels of cell-free DNA and Cit-H3 were observed among APS patients and aPL patients with autoimmune diseases compared with those aPL carriers without underlying autoimmune diseases. Furthermore, control neutrophils that are conditioned with APS patients' sera have more pronounced NET release compared with those treated with aPL carriers' sera without underlying autoimmune diseases.

We identified several potential additional risk factors for APS clinical manifestations among a large cohort of Chinese aPL carriers. Our data may help physicians to risk stratify aPL-positive Asian patients.

Gestational diabetes mellitus (GDM) brings health issues for both mothers and offspring, and GDM prevention is as important as GDM management. It was shown that a history of GDM was significantly associated with a higher maternal risk for GDM recurrence. The incidence of GDM recurrence was unclear because of the incidence of second-child was low before 2016 in China. We aim to investigate the prevalence of GDM recurrence and its associated high-risk factors which may be useful for the prediction of GDM recurrence in China.

A retrospective study was conducted which enrolled participants who underwent regular prenatal examination and delivered twice in the same hospital of 18 research centers. All participants were enrolled from January 2018 to October 2018, where they delivered the second baby during this period. A total of 6204 women were enrolled in this study, and 1002 women with a history of GDM were analyzed further. All participants enrolled in the study had an oral glucose tolerance test (OGTT) result at 24 to 28 weeks and were diagnosed as GDM in the first pregnancy according to the OGTT value (when any one of the following values is met or exceeded to the 75-g OGTT: 0 h [fasting], ≥5.10 mmol/L; 1 h, ≥10.00 mmol/L; and 2 h, ≥8.50 mmol/L). The prevalence of GDM recurrence and development of type 2 diabetes mellitus were calculated, and its related risk factors were analyzed.

In 6204 participants, there are 1002 women (1002/6204, 16.15%) with a history of GDM and 5202 women (5202/6204, 83.85%) without a history of GDM. There are significant differences in age (32.43 ± 4.03 years vs. 33.00 ± 3.34 years vs. 32.19 ± 3.37 years, P < 0.001), pregnancy interval (4.06 ± 1.44 years vs. 3.52 ± 1.43 years vs. 3.38 ± 1.35 years, P = 0.004), prepregnancy body mass index (BMI) (27.40 ± 4.62 kg/m²vs. 23.50 ± 3.52 kg/m²vs. 22.55 ± 3.47 kg/m², P < 0.001), history of delivered macrosomia (22.7% vs. 11.0% vs. 6.2%, P < 0.001) among the development of diabetes mellitus (DM), recurrence of GDM, and normal women. Moreover, it seems so important in the degree of abnormal glucose metabolism in the first pregnancy to the recurrence of GDM and the development of DM. There are significant differences in OGTT levels of the first pregnancy such as area under the curve of OGTT value (18.31 ± 1.90 mmol/L vs. 16.27 ± 1.93 mmol/L vs. 15.55 ± 1.92 mmol/L, P < 0.001), OGTT fasting value (5.43 ± 0.48 mmol/L vs. 5.16 ± 0.49 mmol/L vs. 5.02 ± 0.47 mmol/L, P < 0.001), OGTT 1-hour value (10.93 ± 1.34 mmol/L vs. 9.69 ± 1.53 mmol/L vs. 9.15 ± 1.58 mmol/L, P < 0.001), OGTT 2-hour value (9.30 ± 1.66 mmol/L vs. 8.01 ± 1.32 mmol/L vs. 7.79 ± 1.38 mmol/L, P < 0.001), incidence of impaired fasting glucose (IFG) (fasting plasma glucose ≥5.6 mmol/L) (31.3% vs. 14.6% vs. 8.8%, P < 0.001), and incidence of two or more abnormal OGTT values (68.8% vs. 39.7% vs. 23.9%, P < 0.001) among the three groups. Using multivariate analysis, the factors, such as age (1.07 [1.02-1.12], P = 0.006), prepregnancy BMI (1.07 [1.02, 1.12], P = 0.003), and area under the curve of OGTT in the first pregnancy (1.14 [1.02, 1.26], P = 0.02), have an effect on maternal GDM recurrence; the factors, such as age (1.28 [1.01-1.61], P = 0.04), pre-pregnancy BMI (1.26 [1.04, 1.53], P = 0.02), and area under the curve of OGTT in the first pregnancy (1.65 [1.04, 2.62], P = 0.03), have an effect on maternal DM developed further.

The history of GDM was significantly associated with a higher maternal risk for GDM recurrence during follow-up after the first pregnancy. The associated risk factors for GDM recurrence or development of DM include age, high pre-pregnancy BMI, history of delivered macrosomia, the OGTT level in the first pregnancy, such as the high area under the curve of OGTT, IFG, and two or more abnormal OGTT values. To prevent GDM recurrence, women with a history of GDM should do the preconception counseling before preparing next pregnancy.

It is still unclear what the minimal infusion volume is to effectively predict fluid responsiveness. This study was designed to explore the minimal infusion volume to effectively predict fluid responsiveness in septic shock patients. Hemodynamic effects of fluid administration on arterial load were observed and added values of effective arterial elastance (Ea) in fluid resuscitation were assessed.

Intensive care unit septic shock patients with indwelling pulmonary artery catheter (PAC) received five sequential intravenous boluses of 100 mL 4% gelatin. Cardiac output (CO) was measured with PAC before and after each bolus. Fluid responsiveness was defined as an increase in CO >10% after 500 mL fluid infusion.

Forty-seven patients were included and 35 (74.5%) patients were fluid responders. CO increasing >5.2% after a 200 mL fluid challenge (FC) provided an improved detection of fluid responsiveness, with a specificity of 80.0% and a sensitivity of 91.7%. The area under the ROC curve (AUC) was 0.93 (95% CI: 0.84-1.00, P < 0.001). Fluid administration induced a decrease in Ea from 2.23 (1.46-2.78) mmHg/mL to 1.83 (1.34-2.44) mmHg/mL (P = 0.002), especially for fluid responders in whom arterial pressure did not increase. Notably, the baseline Ea was able to detect the fluid responsiveness with an AUC of 0.74 (95% CI: 0.59-0.86, P < 0.001), whereas Ea failed to predict the pressure response to FC with an AUC of 0.50 (95% CI: 0.33-0.67, P = 0.086).

In septic shock patients, a minimal volume of 200 mL 4% gelatin could reliably detect fluid responders. Fluid administration reduced Ea even when CO increased. The loss of arterial load might be the reason for patients who increased their CO without pressure responsiveness. Moreover, a high level of Ea before FC was able to predict fluid responsiveness rather than to detect the pressure responsiveness.

ClinicalTrials.gov, NCT04515511

At present, there is no consensus on the induction methods in term pregnancy with borderline oligohydramnios. This study aimed to compare the effectiveness and pregnancy outcomes of labor induction with dinoprostone or single-balloon catheter (SBC) in term nulliparous women with borderline oligohydramnios.

We conducted a retrospective cohort study from January 2016 to November 2018. During the study period, a total of 244 cases were enrolled. Of these, 103 cases were selected for induction using dinoprostone and 141 cases were selected for induction with SBC. The pregnancy outcomes between the two groups were compared. Primary outcomes were successful vaginal delivery rates. Secondary outcomes were maternal and neonatal adverse events. Multivariate logistic regression was used to assess the risk factors for vaginal delivery failure in the two groups.

The successful vaginal delivery rates were similar between the dinoprostone group and the SBC group (64.1% [66/103] vs. 59.6%, [84/141] P = 0.475), even after adjustment for potential confounding factors (adjusted odds ratio [aOR]: 1.07, 95% confidence interval [CI]: 0.57-2.00, P = 0.835). The incidence of intra-amniotic infection was lower in the dinoprostone group than in the SBC group (1.9% [2/103] vs. 7.8% [11/141], P < 0.001), but the presence of non-reassuring fetal heart rate was higher in the dinoprostone group than in the SBC group (12.6% [13/103] vs. 0.7%, [1/141] P < 0.001). Multivariate logistic regression showed that nuchal cord was a risk factor for vaginal delivery failure after induction with dinoprostone (aOR: 6.71, 95% CI: 1.96-22.95). There were three factors related to vaginal delivery failure after induction with SBC, namely gestational age (aOR: 1.51, 95% CI: 1.07-2.14), body mass index (BMI) >30 kg/m² (aOR: 2.98, 95% CI: 1.10-8.02), and fetal weight >3500 g (aOR: 2.49, 95% CI: 1.12-5.50).

Term nulliparous women with borderline oligohydramnios have similar successful vaginal delivery rates after induction with dinoprostone or SBC, with their advantages and disadvantages. In women with nuchal cord, the risk of vaginal delivery failure is increased if dinoprostone is used in the induction of labor. BMI >30 kg/m², large gestational age, and estimated fetal weight >3500 g are risk factors for vaginal delivery failure after induction with SBC.

Coronavirus disease 2019 (Covid-19) remains a serious health threat worldwide. We aimed to investigate whether low molecular weight heparin (LMWH) can promote organ function recovery in moderate Covid-19 pneumonia patients.

We initiated an LMWH protocol in Covid-19 patients with increased D-dimer, body mass index >30 kg/m² or a history of diabetes from January 18, 2020 at Shanghai Public Health Clinical Center. In this retrospective study, we assigned moderate Covid-19 pneumonia patients admitted between January 18th and April 18, 2020 receiving the LMWH protocol to the LMWH group. Moderate patients who met the inclusion criteria but did not receive LMWH protocol were included in the control group by 1:2 propensity score matching. General clinical information, indicators for renal function, arterial blood gas analyses, arterial blood lactic acid content (mmol/L), and coagulation indexes at 0 day, 3 days, 7 days, and 11 days after admission were recorded and compared between the two groups.

There were 41 patients in the LMWH group and 82 patients in the control group. General information in both groups were similar. Compared to the control group, the arterial blood lactic acid content (mmol/L) at day 11 (1.3 [1.1, 1.7] vs. 1.2 [0.9, 1.3], P = 0.016) was reduced in the LMWH group. The estimated glomerular filtration rate (eGFR) in the LMWH group was higher than that in the control group at day 7 (108.54 [89.11, 128.17] vs. 116.85 [103.39, 133.47], P= 0.039) and day 11 (113.74 [94.49, 126.34] vs. 128.31 [112.75, 144.12], P = 0.003). The serum creatinine levels (Scr) in the LMWH group were lower than that in the control group at day 7 (62.13 [51.47, 77.64] vs. 55.49 [49.50, 65.75], P= 0.038) and day 11 (63.35 [50.17, 75.73] vs. 51.62 [44.62, 61.24], P = 0.005).

LMWH treatment can reduce arterial blood lactic acid levels and improve eGFR in moderate Covid-19 pneumonia patients. Randomized controlled trials are warranted to further investigate this issue.

ChiCTR.org.cn, ChiCTR2000034796.

Breast cancer with low-positive human epidermal growth factor receptor 2 (HER2) expression has triggered further refinement of evaluation criteria for HER2 expression. We studied the clinicopathological features of early-stage breast cancer with low-positive HER2 expression in China and analyzed prognostic factors.

Clinical and pathological data and prognostic information of patients with early-stage breast cancer with low-positive HER2 expression treated by the member units of the Chinese Society of Breast Surgery and Chinese Society of Surgery of Chinese Medical Association, from January 2015 to December 2016 were collected. The prognostic factors of these patients were analyzed.

Twenty-nine hospitals provided valid cases. From 2015 to 2016, a total of 25,096 cases of early-stage breast cancer were treated, 7642 (30.5%) of which had low-positive HER2 expression and were included in the study. After ineligible cases were excluded, 6486 patients were included in the study. The median follow-up time was 57 months (4-76 months). The disease-free survival rate was 92.1% at 5 years, and the overall survival rate was 97.4% at 5 years. At the follow-up, 506 (7.8%) cases of metastasis and 167 (2.6%) deaths were noted. Multivariate Cox regression analysis showed that tumor stage, lymphvascular invasion, and the Ki67 index were related to recurrence and metastasis (P < 0.05). The recurrence risk prediction model was established using a machine learning model and showed that the area under the receiving operator characteristic curve was 0.815 (95% confidence interval: 0.750-0.880).

Early-stage breast cancer patients with low-positive HER2 expression account for 30.5% of all patients. Tumor stage, lymphvascular invasion, and the Ki67 index are factors affecting prognosis. The recurrence prediction model for breast cancer with low-positive HER2 expression based on a machine learning model had a good clinical reference value for predicting the recurrence risk at 5 years.

ChiCTR.org.cn, ChiCTR2100046766.

Tourette syndrome (TS) is a neuropsychiatric disorder with onset in childhood that warrants effective therapies. Gut microbiota can affect central physiology and function via the microbiota-gut-brain axis. Therefore, the gut microbiota plays an important role in some mental illnesses. A small clinical trial showed that fecal microbiota transplantation (FMT) may alleviate TS symptoms in children. Herein, FMT effects and mechanisms were explored in a TS mouse model.

TS mice model (TSMO) (n = 80) were established with 3,3^＇-iminodipropionitrile, and 80 mice were used as controls. Mice were grouped into eight groups and were subjected to FMT with feces from children or mice with or without TS, or were given probiotics. Fecal specimens were collected 3 weeks after FMT. 16S rRNA sequencing, behavioral observation, and serum serotonin (5-HT) assay were performed. Differences between groups were analyzed using Mann-Whitney U test and Kolmogorov-Smirnov (KS) tests.

A total of 18 discriminative microbial signatures (linear discriminant analysis score > 3) that varied significantly between TS and healthy mice (CONH) were identified. A significant increase in Turicibacteraceae and Ruminococcaceae in TSMO after FMT was observed (P < 0.05). Compared with non-transplanted TSMO, the symptoms of those transplanted with feces from CONH were alleviated (W = 336, P = 0.046). In the probiotic and FMT experiments, the serum 5-HT levels significantly increased in TSMO that received probiotics (KS = 1.423, P = 0.035) and in those transplanted with feces from CONH (W= 336.5, P = 0.046) compared with TSMO without transplantation.

This study suggests that FMT may ameliorate TS by promoting 5-HT secretion, and it provides new insights into the underlying mechanisms of FMT as a treatment for TS.

Circular RNAs (circRNAs) are considered to be important regulators in cancer biology. In this study, we focused on the effect of circRNA baculoviral inhibitor of apoptosis protein (IAP) repeat containing 6 (circBIRC6) on non-small cell lung cancer (NSCLC) progression.

The NSCLC and adjacent non-tumor tissues were collected at Shanghai Ninth People's Hospital. Quantitative real-time polymerase chain reaction was conducted for assessing the levels of circBIRC6, amyloid beta precursor protein binding protein 2 (APPBP2) messenger RNA (mRNA), baculoviral IAP repeat containing 6 mRNA (BIRC6), and microRNA-217 (miR-217). Western blot assay was adopted for measuring the protein levels of APPBP2, E-cadherin, N-cadherin, and vimentin. Colony formation assay, transwell assay, and flow cytometry analysis were utilized for evaluating cell colony formation, metastasis, and apoptosis. Dualluciferase reporter assay and RNA immunoprecipitation assay were carried out to determine the interaction between miR-217 and circBIRC6 and APPBP2 in NSCLC tissues. The murine xenograft model assay was used to investigate the function of circBIRC6 in tumor formation in vivo. Differences were analyzed via Student's t test or one-way analysis of variance. Pearson's correlation coefficient analysis was used to analyze linear correlation.

CircBIRC6 was overexpressed in NSCLC tissues and cells. Knockdown of circBIRC6 repressed the colony formation and metastasis and facilitated apoptosis of NSCLC cells in vitro and restrained tumorigenesis in vivo. Mechanically, circBIRC6 functioned as miR-217 sponge to promote APPBP2 expression in NSCLC cells. MiR-217 inhibition rescued circBIRC6 knockdown-mediated effects on NSCLC cell colony formation, metastasis, and apoptosis. Overexpression of miR-217 inhibited the malignant phenotypes of NSCLC cells, while the effects were abrogated by elevating APPBP2.

CircBIRC6 aggravated NSCLC cell progression by elevating APPBP2 via sponging miR-217, which might provide a fresh perspective on NSCLC therapy.

Many previous studies have confirmed the effectiveness and safety of peroral endoscopic myotomy (POEM) to treat achalasia. However, severe interlayer adhesions preclude the establishment of a submucosal tunnel and then result in aborted POEM procedures. To address this challenge, we introduced POEM with simultaneous submucosal and muscle dissection (POEM-SSMD) in 2014.^[1]During the short-term follow-up, the symptoms of the patient were significantly improved. Thus, for patients with esophageal interlayer adhesions, the relative indications of POEM may be extended. Nevertheless, only a few case reports using this technique with a shorter follow-up have been published to date. Hence, the present study aimed to further report the long-term outcomes of POEM-SSMD for achalasia with severe interlayer adhesions in a relatively larger population.

To the Editor:The mechanism of Lisfranc injury is complex and may cause different patterns of fractures or dislocation of the midfoot complex. Abduction force injury is a special injury pattern, which may cause the fracture or (and) dislocation of the lateral column of the Lisfranc joint, especially the cuboid.^[1,2,3]However, the anterolateral calcaneus is less commonly involved. Since the fragment of the calcaneocuboid (CC) joint facet is too uncon-spicuous to manifest on a plain X-ray, and surgeons always pay more attention to the Lisfranc joint, anterolateral calcaneal compression fracture and even Chopart joint injuries are often overlooked, which may lead to a delayed surgical management, chronic foot deformities, and functional disability.

To the Editor:The proprotein convertase subtilisin/kexin type 9 (PCSK9)-inhibitor, evolocumab, can bind with PCSK9 in plasma and reduce the degradation of the PCSK9-low density lipoprotein (LDL) receptor complex, thereby reducing LDL levels.^[1]In clinical practice, PCSK9 inhibitors can reduce low-density lipoprotein cholesterol (LDL-c) significantly and reduce triglycerides (TG) by about 8% to 17%.^[2]We used PCSK9 inhibitors to lower blood lipids in three patients with severe hypertriglyceridemia (HTG) and performed whole-exome sequencing (WES) to analyze the genes that may contribute to hyperlipidemia in detail. We have obtained patients' consent forms. We found that PCSK9 inhibitors significantly reduced blood lipid levels, regardless of the presence of HTG mutations. These results provide new evidence for the use of PCSK9 inhibitors in the treatment of patients with severe HTG.

To the Editor:Infertility is a public health concern in modern society. Oligoasthenospermia (OA) is one of the leading causes of male infertility that impacts about 5% of reproductive-aged couples worldwide. The etiology and pathogenesis of OA remain poorly understood. The characteristics of OA include a reduction in the total number (<33 × 10⁶per ejaculate or <12 × 10⁶/mL) or concentration of spermatozoa, and low or nil sperm motility (<32%).^[1]Traditional Chinese medicine (TCM) has a long history of treating male infertility by using drugs derived from natural sources, such as herbal or animal tissue-derived materials. Tortoise-shell glue (TSG), a classic TCM, is prominently used as a drug or supplement on multiple health conditions to replenish "Qi" , which is considered to be the energy source of the human body in the TCM theory. A mitochondrion, a cell's "powerhouse," is essential for cellular signaling and plays a role similar to that of "Qi" in TCM. The mid piece of sperm is packed with mitochondria; therefore, mitochondrial dysfunction may play a vital causative role in inadequate sperm mobility and male infertility.^[2]Mitochondria not only provide the spermatozoa the necessary energy for successful fertilization but are also closely associated with the viability of the spermatozoa via regulating the permeability by the mitochondrial permeability transition pore (mPTP),^[3]a transmembrane protein located in the inner membrane of mitochondria. Normally, it remains closed, but the opening of mPTP allows large molecules to pass through the mitochondrial membrane. Malfunction of mPTP leads to cell apoptosis, and in the case of OA, it results in a reduced sperm number and mobility.^[3]In the current study, we aimed to evaluate the therapeutic effects of TSG on spermatogenesis and reproductive hormones, and also investigate the potential protective effects of TSG on mitochondrial functions.

To the Editor:Autoimmune hepatitis (AIH) is a type of liver parenchymal inflammation mediated by the autoimmune response of liver cells. AIH was previously considered to be a chronic liver disease, but recent observers have confirmed that AIH patients can have acute onset or even liver failure (AIH-LF).^[1]The incidence of AIH-LF has also increased. Once LF occurs, the mortality rate within 90 days could reach >40%.^[2]Therefore, the occurrence of LF has a major impact on the prognosis of AIH. Although AIH-LF has a low incidence and a high mortality rate, some cases can still be cured by treatment. The clinical characteristics that may affect the prognosis of patients with AIH-LF are still unclear. To clarify the factors affecting the prognosis of AIH-LF, we compared the clinical characteristics of two groups of AIH-LF patients with different prognosis.

To the Editor:Primary vaginal carcinoma is a rare malignant disease, which represents only approximately 1% to 2% of female genital malignancies. Vaginal adenosis is defined by the presence of metaplastic cervical or endometrial epithelium within the vaginal wall, and is associated with a high risk of vaginal carcinoma. In women prenatally exposed to diethylstilboestrol (DES), vaginal adenosis may arise in up to 90%, and these are often associated with vaginal clear cell adenocarcinoma.^[1]DES is an orally active non-steroidal estrogen. The Food and Drug Administration began a clinical trial in 1943, and concluded that DES administration is beneficial for preventing premature deliveries and miscarriages.^[2]In addition to primary vaginal clear cell carcinoma (PVCCC), in-uterus exposure to DES can also lead to T-shaped uterus anomaly.^[3]In the Chinese population, PVCCC is an uncommon malignancy, and there are no reports on the relationship between PVCCC and DES exposure.^[4]Given the rarity of PVCCC, it is significant to analyze relevant cases, and provide some valuable information for future clinical and basic studies. Therefore, the present study described ten cases of PVCCC, and summarized the characteristics of the diagnosis, management, and prognosis of these patients.

To the Editor:China is the most populated country, and it is aging more quickly than almost any other country in the world. According to Worldometer,^[1]the population size of China, as of 2020, is around 1.4 billion, with the proportion of the 60-year olds and older being 17.30% in 2017 and expected to reach 35% in 2050. Older age tended to be closely correlated with multimorbidity. Ward and Schiller^[2]reported that 65% of men and 72% of women aged >65 years in the US had at least two chronic conditions in 2010. Accordingly, older adults living with multiple chronic conditions tend to be readmitted after discharge, further leading to increased expenditure and more utilization of medical resources. Many studies have reported higher read mission rates in elderly patients. However, previous studies have focused on investigating the factors that influence read mission for a single disease, rather than for the chronic comorbid conditions in the initial hospitalization and the changes in these conditions from initial hospitalization to read mission among the elderly in China. Furthermore, most studies have focused on Caucasian patients and have been conducted in the US. Little is known about Chinese patients due to the lack of large-scale data. Identifying the common chronic comorbid conditions and the changes in these conditions from initial hospitalization to read mission among older people is important as it will help in the understanding of the chronic conditions leading to avoidable read mission and facilitate the development of efficient intervention strategies for the reduction of read missions.

To the Editor:Corneal alkali burns (CABs) have been a difficult problem in clinical treatment for a long time. In severe cases, blindness occurs; hence, research on the repair mechanism underlying corneal injury is particularly important to identify potential therapeutic targets. Alkali-induced corneal injuries often trigger aggressive aseptic inflammatory responses, which are key to autoimmune responses.^[1]However, Nod-like receptor protein 3 (NLRP3) inflammasomes play an important role in aseptic inflammation.^[2]Under stimuli, such as infection or stress, the activated NLRP3 inflammasome not only processes procaspase-1 into mature caspase-1 but also further promotes the maturation and release of interleukin (IL)-1β and IL-18.^[3]Taurine (Tau) is widely distributed in ocular structures and is an immune regulator. Tau can maintain the stability of the corneal epithelium and improve the survival rate of corneal epithelial cells through antioxidant effects.^[4]The purpose of this study was to investigate the effect of Tau eye drops on CAB and elucidate the mechanism underlying corneal inflammatory responses.

To the Editor:According to guidelines from western countries as well as China, dietary patterns with low intake of cholesterol have been widely recommended for maintaining ideal lipid levels. As one of the major sources of both high-quality protein and dietary cholesterol, eggs have always been the focus in terms of diet. Although increased lipid levels induced by high egg intake have been revealed by randomized controlled trials (RCTs), they may not be sufficient to reflect the impacts of habitual egg intake due to high doses of egg intake of more than 7 eggs/week or even 14 eggs/week. Further, RCTs typically have shorter intervention periods of about 3 months, which may not observe a stable association due to homeostasis in cholesterol metabolism of human beings.^[1,2]Up to now, only three cohorts assessed the associations of egg intake with lipid levels or dyslipidemia, and the findings were still controversial. One recent cohort study has reported the non-significant association between higher egg intake (≥7vs.1 eggs/week) and lipid profiles. On the other hand, another cohort from Spain found that compared with < 1 egg/week, > 4 eggs/week had no significant influence on total cholesterol (TC) and triglyceride (TG), but significantly decreased high-density lipoprotein cholesterol (HDL-C) levels.^[4]However, none of these cohorts were from developing countries, and the association between moderate egg intake and lipid profiles has not been well illustrated. Egg consumption in China, a representative of developing countries, is relatively higher, and it may be possible to better explore the appropriate range of egg intake.

To the Editor:Augmented renal clearance (ARC) refers to an enhanced elimination of circulating solutes, including drugs, by the kidneys at a rate statistically higher than normal. On the first day of intensive care unit (ICU) admission, ARC occurrence may predict continued creatinine clearance (CrCl) elevation for 1 day to several weeks.^[1]ARC has a substantial adverse effect on renally cleared antibiotics' pharmacokinetics/pharmacodynamics. Treatment failure or worse outcomes are more frequent in ARC patients. Thus, a "one size fits all" approach to drug dosing in ARC patients is inappropriate; dosing requires adjustment for some variables.

To the Editor:Currently, from a pathological point of view, corneal collagen crosslinking (CXL) with riboflavin is the only new therapy for controlling keratoconus progression. Riboflavin, as a photosensitizer, can be activated after the ultraviolet radiation in the cornea and prevent it from damaging intraocular organizations. Therefore, the concentration of riboflavin in the corneal stroma must be maintained at a sufficient level during the treatment.^[1]Riboflavin, a type of water-soluble macromolecule, is resistant to permeating the corneal epithelial barrier. Thus, de-epithelial eye-dripping was adopted conventionally with complications such as inevitable pain, long recovery time, potential risk of infection, and so on; transepithelial corneal CXL is increasingly becoming a research hotspot. It is thus critically important to improve the transepithelial penetration of riboflavin. Although iontophoresis was reported, it had a slightly higher effect with no clear mechanism analysis.^[2,3,4]Corneal epithelium is lipophilic and hydrophobic, and hydrophilic drugs enter corneal stroma via intercellular pathways. In this study, permeability effects of riboflavin in different solvents into the cornea via iontophoresis were compared, and the changes of corneal epithelial cell layer organizations were analyzed to examine the solvent components that are most beneficial to iontophoresis and investigate the underlying mechanism of the penetration effect.

In the article "Impact of thymosin α1 as an immunomodulatory therapy on long-term survival of non-small cell lung cancer patients after R0 resection: a propensity score-matched analysis" which appeared in vol.134, issue 22, pages 2700-2709 of Chinese Medical Journal,^[1]the hazard ratio (HR) values inFigure 3Ashould be corrected as "HR (12-24 monthsvs. less than 12 months): 0.463 (95%CI: 0.341-0.683,P= 0.0001); HR (more than 24 monthsvs. less than 12 months): 0.284 (95%CI: 0.197-0.409,P< 0.0001); HR (12-24 monthsvs. more than 24 months): 1.632 (95%CI: 1.056-2.522,P= 0.0275)." The HR values inFigure 3Bshould be corrected as "HR (12-24 monthsvs. less than 12 months): 0.357 (95%CI: 0.216-0.588,P< 0.0001); HR (more than 24 monthsvs. less than 12 months): 0.171 (95% CI: 0.107-0.272,P< 0.0001); HR (12-24 monthsvs. more than 24 months): 2.090 (95%CI: 1.175-3.717,P= 0.0121)." The original results and conclusions are not affected.Figure 3is corrected as below.