2023年 · 第136卷第16期

Since the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in December 2019, the virus has overwhelmed the world’s health. Pregnant women as a vulnerable group, the broad implications of SARS-CoV-2 for obstetrical care and perinatal outcomes have raised concern and promoted the rapid development of research. Chinese clinicians and scientists working in obstetrics rapidly reported globally the clinical characteristics, pregnancy outcomes, and vertical transmission potential of SARS-CoV-2 infection in pregnancy on February 12, 2020^[1]and published clinical management consensus specific for SARS-CoV-2 infection in pregnancy at the earliest time,^[2]which were valuable for preventive and clinical practice in China and elsewhere in the early stages of the pandemic. With the passing of time and updating of information, developments have been achieved in our understanding of obstetric outcomes, vertical transmission, and therapeutics for the treatment and prevention of SARS-CoV-2 infection; furthermore, the progress shed light on the gaps in current knowledge for future work.

To improve the diagnosis and treatment of inflammatory breast cancer (IBC), the Chinese Society of Breast Surgery (CSBrS) of the Chinese Medical Association identified the key clinical issues for clinical practice guidelines through literature research and evaluated the relevant evidence with reference to the Grading of Recommendations Assessment, Development and Evaluation (GRADE).^[1]

Endometriosis, a heterogeneous, inflammatory, and estrogen-dependent gynecological disease defined by the presence and growth of endometrial tissues outside the lining of the uterus, affects approximately 5–10% of reproductive-age women, causing chronic pelvic pain and reduced fertility. Although the etiology of endometriosis is still elusive, emerging evidence supports the idea that immune dysregulation can promote the survival and growth of retrograde endometrial debris. Peritoneal macrophages and natural killer (NK) cells exhibit deficient cytotoxicity in the endometriotic microenvironment, leading to inefficient eradication of refluxed endometrial fragments. In addition, the imbalance of T-cell subtypes results in aberrant cytokine production and chronic inflammation, which contribute to endometriosis development. Although it remains uncertain whether immune dysregulation represents an initial cause or merely a secondary enhancer of endometriosis, therapies targeting altered immune pathways exhibit satisfactory effects in preventing disease onset and progression. Here, we summarize the phenotypic and functional alterations of immune cells in the endometriotic microenvironment, focusing on their interactions with microbiota and endocrine and nervous systems, and how these interactions contribute to the etiology and symptomology of endometriosis.

Esophageal cancer (EC) is one of the most common aggressive malignant tumors in the digestive system with a severe epidemiological situation and poor prognosis. The early diagnostic rate of EC is low, and most EC patients are diagnosed at an advanced stage. Multiple multimodality treatments have gradually evolved into the main treatment for advanced EC, including surgery, chemotherapy, radiotherapy, targeted therapy, and immunotherapy. And the emergence of targeted therapy and immunotherapy has greatly improved the survival of EC patients. This review highlights the latest advances in targeted therapy and immunotherapy for EC, discusses the efficacy and safety of relevant drugs, summarizes related important clinical trials, and tries to provide references for therapeutic strategy of EC.

The burden of chronic airway diseases, including chronic obstructive pulmonary disease (COPD), continues to increase, especially in low- and middle-income countries. Post-tuberculosis lung disease (PTLD) is characterized by chronic lung changes after the "cure" of pulmonary tuberculosis (TB), which may be associated with the pathogenesis of COPD. However, data on its prevalence, clinical manifestations, computed tomography features, patterns of lung function impairment, and influencing factors are limited. The pathogenic mechanisms underlying PTLD remain to be elucidated. This review summarizes the recent advances in PTLD and TB-associated COPD. Research is urgently needed both for the prevention and management of PTLD.

Severe liver disease (SLD), including cirrhosis and liver cancer, constitutes a major disease burden in China. We aimed to examine the association of genetic and healthy lifestyle factors with the incidence and prognosis of SLD.

The study population included 504,009 participants from the prospective China Kadoorie Biobank aged 30–79 years. The individuals were from 10 diverse areas in China without a history of cancer or liver disease at baseline. Cox regression was used to estimate adjusted hazard ratios (HRs) for incident SLD and death after SLD diagnosis associated with healthy lifestyle factors (smoking, alcohol, physical activity, and central adiposity). Additionally, the contribution of genetic risk for hepatitis B virus (HBV, assessed by genetic variants in major histocompatibility complex, class II, DP/DQ [HLA-DP/DQ] genes) was also estimated.

Compared with those with 0–1 healthy lifestyle factor, participants with 2, 3, and 4 factors had 12% (HR 0.88 [95% confidence interval [CI] 0.85, 0.92]), 26% (HR 0.74 [95%CI: 0.69, 0.79]), and 44% (HR 0.56 [95%CI: 0.48, 0.65]) lower risks of SLD, respectively. Inverse associations were observed among participants with both low and high genetic risks (HR per 1-point increase 0.83 [95% CI: 0.74, 0.94] and 0.91 [95% CI: 0.82, 1.02], respectively; P_interaction = 0.51), although with a non-significant trend among those with a high genetic risk. Inverse associations were also observed between healthy lifestyle factors and liver biomarkers regardless of the genetic risk. Despite the limited power, healthy lifestyle factors were associated with a lower risk of death after incident SLD among participants with a low genetic risk (HR 0.59 [95%CI: 0.37, 0.96]).

Lifestyle modification may be beneficial in terms of lowering the risk of SLD regardless of the genetic risk. Moreover, it is also important for improving the prognosis of SLD in individuals with a low genetic risk. Future studies are warranted to examine the impact of healthy lifestyles on SLD prognosis, particularly among individuals with a high genetic risk.

Lung cancer prevails and induces high mortality around the world. This study provided real-world information on the evolution of clinicopathological profiles and survival outcomes of lung cancer, and provided survival information within stage I subtypes.

Patients pathologically confirmed with lung cancer between January 2009 and December 2018 were identified with complete clinicopathological information, molecular testing results, and follow-up data. Shifts in clinical characteristics were evaluated using χ² tests. Overall survival (OS) was calculated through the Kaplan–Meier method.

A total of 26,226 eligible lung cancer patients were included, among whom 62.55% were male and 52.89% were smokers. Non-smokers and elderly patients took increasingly larger proportions in the whole patient population. The proportion of adenocarcinoma increased from 51.63% to 71.80%, while that of squamous carcinoma decreased from 28.43% to 17.60%. Gene mutations including EGFR (52.14%), KRAS (12.14%), and ALK (8.12%) were observed. Female, younger, non-smoking, adenocarcinoma patients and those with mutated EGFR had better survival prognoses. Importantly, this study validated that early detection of early-stage lung cancer patients had contributed to pronounced survival benefits during the decade. Patients with stage I lung cancer, accounted for an increasingly considerable proportion, increasing from 15.28% to 40.25%, coinciding with the surgery rate increasing from 38.14% to 54.25%. Overall, period survival analyses found that 42.69% of patients survived 5 years, and stage I patients had a 5-year OS of 84.20%. Compared with that in 2009–2013, the prognosis of stage I patients in 2014–2018 was dramatically better, with 5-year OS increasing from 73.26% to 87.68%. Regarding the specific survival benefits among stage I patients, the 5-year survival rates were 95.28%, 93.25%, 82.08%, and 74.50% for stage IA1, IA2, IA3, and IB, respectively, far more promising than previous reports.

Crucial clinical and pathological changes have been observed in the past decade. Notably, the increased incidence of stage I lung cancer coincided with an improved prognosis, indicating actual benefits of early detection and management of lung cancer.

Previous research demonstrated that a homozygous mutation of g.136372044G>A (S12N) in caspase recruitment domain family member 9 (CARD9) is critical for producing Aspergillus fumigatus-induced (Af-induced) T helper 2 (T_H2) - mediated responses in allergic bronchopulmonary aspergillosis (ABPA). However, it remains unclear whether the CARD9^S12N mutation, especially the heterozygous occurrence, predisposes the host to ABPA.

A total of 61 ABPA patients and 264 controls (including 156 healthy controls and 108 asthma patients) were recruited for sequencing the CARD9 locus to clarify whether patients with this heterozygous single-nucleotide polymorphisms are predisposed to the development of ABPA. A series of in vivo and in vitro experiments, such as quantitative real-time polymerase chain reaction, flow cytometry, and RNA isolation and quantification, were used to illuminate the involved mechanism of the disease.

The presence of the p.S12N mutation was associated with a significant risk of ABPA in ABPA patients when compared with healthy controls and asthma patients, regardless of Aspergillus sensitivity. Relative to healthy controls without relevant allergies, the mutation of p.S12N was associated with a significant risk of ABPA (OR: 2.69 and 4.17 for GA and AA genotypes, P = 0.003 and 0.029, respectively). Compared with patients with asthma, ABPA patients had a significantly higher heterozygous mutation (GA genotype), indicating that p.S12N might be a significant ABPA-susceptibility locus (aspergillus sensitized asthma: OR: 3.02, P = 0.009; aspergillus unsensitized asthma: OR: 2.94, P = 0.005). The mutant allele was preferentially expressed in ABPA patients with heterozygous CARD9^S12N, which contributes to its functional alterations to facilitate Af-induced T_H2-mediated ABPA development. In terms of mechanism, Card9 wild-type (Card9^WT) expression levels decreased significantly due to Af-induced decay of its messenger RNA compared to the heterozygous Card9^S12N. In addition, ABPA patients with heterozygous CARD9^S12N had increased Af-induced interleukin-5 production.

Our study provides the genetic evidence showing that the heterozygous mutation of CARD9^S12N, followed by allele expression imbalance of CARD9^S12N, facilitates the development of ABPA.

Plasminogen activator inhibitor-1 (PAI-1) plays an important role in the pathophysiology of sepsis, but the exact mechanism remains debatable. In this study, we investigated the associations among the serum levels of PAI-1, the incidence of 4G/5G promoter PAI-1 gene polymorphisms, immunological indicators, and clinical outcomes in septic patients.

A total of 181 patients aged 18-80 years with sepsis between November 2016 and August 2018 in the intensive care unit in the Xinhua Hospital were recruited in this retrospective study, with 28-day mortality as the primary outcome. The initial serum level of PAI-1 and the presence of rs1799768 single nucleotide polymorphisms (SNPs) were examined. Univariate logistic regression and multivariate analyses were performed to determine the factors associated with different genotypes of PAI-1, serum level of PAI-1, and 28-day mortality.

The logistic analysis suggested that a high serum level of PAI-1 was associated with the rs1799768 SNP of PAI-1 (4G/4G and 4G/5G) (Odds ratio [OR]: 2.49; 95% confidence interval [CI]: 1.09, 5.68). Furthermore, a high serum level of PAI-1 strongly influenced 28-day mortality (OR 3.36; 95% CI 1.51, 7.49). The expression and activation of neutrophils (OR 0.96; 95% CI 0.93, 0.99), as well as the changes in the expression patterns of cytokines and chemokine-associated neutrophils (OR: 1.00; 95% CI: 1.00, 1.00), were both regulated by the genotype of PAI-1.

Genetic polymorphisms of PAI-1 can influence the serum levels of PAI-1, which might contribute to mortality by affecting neutrophil activity. Thus, patients with severe sepsis might clinically benefit from enhanced neutrophil clearance and the resolution of inflammation via the regulation of PAI-1 expression and activity.

Management of gastric leak after sleeve gastrectomy (SG) is challenging due to its unpredictable outcomes. We aimed to summarize the characteristics of SG leaks and analyze interventions and corresponding outcomes in a real-world setting.

To retrospectively review of 15,721 SG procedures from 2010 to 2020 based on a national registry. A cumulative sum analysis was used to identify a fitting curve of gastric leak rate. The Kaplan–Meier method and log-rank tests were performed to calculate and compare the probabilities of relevant outcomes. The logistic regression analysis was conducted to determine the predictors of acute leaks.

A total of 78 cases of SG leaks were collected with an incidence of 0.5% (78/15,721) from this registry (6 patients who had the primary SG in non-participating centers). After accumulating 260 cases in a bariatric surgery center, the leak rate decreased to a stably low value of under 1.17%. The significant differences presented in sex, waist circumference, and the proportion of hypoproteinemia and type 2 diabetes at baseline between patients with SG leak and the whole registry population (P = 0.005, = 0.026, <0.001, and = 0.001, respectively). Moreover, 83.1% (59/71) of the leakage was near the esophagogastric junction region. Leakage healed in 64 (88.9%, 64/72) patients. The median healing time of acute and non-acute leaks was 5.93 months and 8.12 months, respectively. Acute leak (38/72, 52.8%) was the predominant type with a cumulative reoperation rate >50%, whereas the cumulative healing probability in the patients who required surgical treatment was significantly lower than those requring non-surgical treatment (P = 0.013). Precise dissection in the His angle area was independently associated with a lower acute leak rate, whereas preservation ≥2 cm distance from the His angle area was an independent risk factor.

Male sex, elevated waist circumference, hypoproteinaemia, and type 2 diabetes are risk factors of gastric leaks after SG. Optimizing surgical techniques, including precise dissection of His angle area and preservation of smaller gastric fundus, should be suggested to prevent acute leaks.

Cancer stem-like cells (CSCs) are a small subset of cells in tumors that exhibit self-renewal and differentiation properties. CSCs play a vital role in tumor formation, progression, relapse, and therapeutic resistance. B7-H3, an immunoregulatory protein, has many protumor functions. However, little is known about the mechanism underlying the role of B7-H3 in regulating gastric cancer (GC) stemness. Our study aimed to explore the impacts of B7-H3 on GC stemness and its underlying mechanism.

GC stemness influenced by B7-H3 was detected both in vitro and in vivo. The expression of stemness-related markers was examined by reverse transcription quantitative polymerase chain reaction, Western blotting, and flow cytometry. Sphere formation assay was used to detect the sphere-forming ability. The underlying regulatory mechanism of B7-H3 on the stemness of GC was investigated by mass spectrometry and subsequent validation experiments. The signaling pathway (Protein kinase B [Akt]/Nuclear factor erythroid 2-related factor 2 [Nrf2] pathway) of B7-H3 on the regulation of glutathione (GSH) metabolism was examined by Western blotting assay. Multi-color immunohistochemistry (mIHC) was used to detect the expression of B7-H3, cluster of differentiation 44 (CD44), and Nrf2 on human GC tissues. Student’s t-test was used to compare the difference between two groups. Pearson correlation analysis was used to analyze the relationship between two molecules. The Kaplan–Meier method was used for survival analysis.

B7-H3 knockdown suppressed the stemness of GC cells both in vitro and in vivo. Mass spectrometric analysis showed the downregulation of GSH metabolism in short hairpin B7-H3 GC cells, which was further confirmed by the experimental results. Meanwhile, stemness characteristics in B7-H3 overexpressing cells were suppressed after the inhibition of GSH metabolism. Furthermore, Western blotting suggested that B7-H3-induced activation of GSH metabolism occurred through the AKT/Nrf2 pathway, and inhibition of AKT signaling pathway could suppress not only GSH metabolism but also GC stemness. mIHC showed that B7-H3 was highly expressed in GC tissues and was positively correlated with the expression of CD44 and Nrf2. Importantly, GC patients with high expression of B7-H3, CD44, and Nrf2 had worse prognosis (P = 0.02).

B7-H3 has a regulatory effect on GC stemness and the regulatory effect is achieved through the AKT/Nrf2/GSH pathway. Inhibiting B7-H3 expression may be a new therapeutic strategy against GC.

To the Editor: In neurosurgery, intraoperative fluid administration is essential in maintaining appropriate systemic and cerebral perfusion pressure, oxygenation, and metabolism. Meningioma resection can involve massive intraoperative blood loss due to an abundant blood supply in structures. Moreover, the routine use of mannitol during meningioma resection may affect hemodynamic stability. Fluid overload is correlated to neurological, pulmonary, or gastrointestinal (GI) edema, which has unfavorable outcomes.^[1]Thus, neurosurgeries, particularly meningioma resection, require individualized fluid therapy to achieve a balance between inadequate fluid and fluid overload.

To the Editor: Type 2 diabetes (T2D) is one of the most common and fastest growing non-communicable diseases worldwide. Sex hormone-binding globulin (SHBG) is a circulating homodimeric glycoprotein that can bind androgens and estrogens with high affinity in blood and regulate their bioavailability.^[1]Emerging evidence has shown that low levels of SHBG are associated with T2D.^[2]Genetic factors are important factors that affect the development of T2D. However, the combined effect of SHBG and genetic factors on T2D risk is largely unknown. In the current study, we analyzed data from the Survey on Prevalence in East China for Metabolic Diseases and Risk Factors (SPECT-China) to evaluate whether SHBG levels could interact with genetic predisposition to increase the T2D risk in men and postmenopausal women and examined the joint association of SHBG and genetic predisposition with T2D.

To the Editor: The overall prevalence of asthma among Chinese adults (aged ≥20 years) was 4.2%, representing 45.7 million people.^[1]With high disease burden of asthma in China, it needs to better understand the status of asthma treatment in China from physicians’ and patients’ perspectives. The 2021 Global Initiative of Asthma (GINA) report developed two Treatment Tracks based on the choice of relievers.^[2]For patients with moderate asthma (Steps 3 and 4), the recommended regimen is low- or medium-dose inhaled corticosteroid (ICS)/formoterol as daily maintenance therapy with additional low-dose ICS/formoterol as needed (known as maintenance and reliever therapy [MART]) in Track 1, or medium- or high-dose ICS/long-acting β2-agonist (LABA) as daily maintenance therapy with additional short-acting β2-agonist (SABA) as needed in Track 2.

To the Editor: Psoriatic arthritis (PsA) is a type of arthritic condition that occurs in patients with psoriasis. Early identification of patients at risk and the knowledge of risk factors is crucial for dermatologists. The Chinese Psoriasis Standardized Diagnosis and Treatment Center (CPSDTC) registry database is a prospective, multicenter cohort study launched by the Peking University First Hospital in July 2020 to gather clinical information on Chinese patients with psoriasis. Our study aimed to report the clinical features of Chinese psoriatic patients using the Psoriasis Epidemiology Screening Tool (PEST) for the early referral of arthritis.

To the Editor:Gastric cancer (GC) is the sixth most common type of cancer and the third most common cause of cancer-related deaths worldwide.^[1]Due to the lack of typical clinical symptoms in the early stage of GC, most patients have advanced-stage disease at the time of initial treatment and have a poor prognosis. The rate of radical resection is low. Even after radical resection, recurrence or death occurs in 50% to 90% of patients, and the 5-year overall survival (OS) rate is less than 30%.^[2]Therefore, various multimodal strategies, which would presumably reduce the risk of cancer recurrence and improve survival, are being explored to eliminate any residual tumors and micro-metastases. Neoadjuvant chemotherapy (NAC) followed by surgery is recommended as the standard of care for patients with localized resectable GC, based on significantly improved OS rates in patients observed in randomized controlled trials.^[2]

To the Editor: Cancer has been recognized as an independent predisposing factor of venous thromboembolism (VTE), including pulmonary embolism (PE) and deep vein thrombosis (DVT). Patients with cancer have a sevenfold increased risk of VTE compared with those without cancer.^[1]Evidence from autopsy in cancer patients showed that PE is an important disease complication in patients with cancer.^[2]Optimal management of PE patients with cancer has become a major concern that challenges clinicians in daily clinical practice. Understanding the risk factors of all-cause death in PE patients with cancer in the real world may enable optimal management and improve their survival. Therefore, this study was performed to characterize cancer-associated PE and evaluate the clinical predictors of in-hospital death based on the data of PE patient population in China.

To the Editor: Invasive ventilation is a necessary form of respiratory support in the intensive care unit. Noninvasive ventilation (NIV) is frequently used as a sequential respiratory support following extubation in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) to prevent the recurrence of respiratory failure, avoid reintubation, and improve the prognosis.^[1]However, some patients may have a poor tolerance to NIV, and possibly leading to the development of face pressure ulcers and dys-expectoration. A high-flow nasal cannula (HFNC) delivers a heated and humidified air/oxygen mixture at high flow through a nasal cannula. In recent years, HFNC has been widely used in respiratory support in children and adults and accepted as a sequential therapy in patients after extubation. Studies have shown that HFNC is not inferior to NIV in hypoxemic respiratory failure, especially in some specific conditions.^[2,3]These conditions include patients at high risk of respiratory failure after extubation, postextubation application for acute respiratory failure, and prevention of invasive mechanical ventilation in patients with acute hypoxemic respiratory failure. Nevertheless, several confounding mediators such as hypercapnia or dys-expectoration, were not taken into account in above trials. In our clinical work, we have observed that the effect of HFNC seemed to be not inferior or even superior to NIV after extubation, particularly in AECOPD patients with hypercapnia and dys-expectoration. Thus, this retrospective analysis was conducted to determine whether hypercapnic patients with AECOPD can benefit from sequential HFNC therapy after extubation.

To the Editor: For recipients with relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL), allogeneic hematopoietic stem cell transplantation (allo-HSCT) often fails to provide them with a satisfactory prognosis. The chimeric antigen receptor T (CAR-T) cells are proven to be safe and effective for these patients.^[1]But there are few published studies assessing the advantages of CAR-T compared to traditional chemotherapy as a bridging treatment followed by HSCT. Consequently, we conducted this study to confirm whether children and young adult R/R B-ALL patients with CAR-T therapy could expect a better post-HSCT prognosis, compared to R/R patients only receiving traditional chemotherapy before transplantation.

To the Editor: Non-alcoholic fatty liver disease (NAFLD) includes a spectrum of diseases: simple steatosis, non-alcoholic steatohepatitis (NASH), and the related fibrosis and cirrhosis.^[1]The treatment of NAFLD should aim to reverse or prevent liver fibrosis, which is associated with liver-specific morbidity or mortality, rather than just to reduce circulating liver enzyme activities and improve NASH.