2022年 · 第135卷第07期

Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by thrombotic or obstetric events caused by persistent antiphospholipid antibodies (aPLs), namely lupus anticoagulant, anticardiolipin antibodies, or anti-β2 glycoprotein I (anti-β2GPI) antibodies.^[1]The main target antigen in APS is β2GPI, through which aPL binds to the cell membrane and subsequently activates membrane receptors and down-stream signal transducers. This may activate natural killer (NK) cells, leading to obstetric complications.

Vitiligo is a prevailing disfiguring skin disorder characterized by the selective absence of functional melanocytes, affecting 0.5% to 1% of the global population.^[1]Several hypotheses have been proposed for its pathogenesis, including autoimmunity, oxidative stress, genetic and environmental factors, and metabolic abnormalities.^[2]No individual factor can completely explain the complex progression of this disease. Most of the human genome encodes RNAs that are not translated into proteins, termed noncoding RNAs (ncRNAs).^[3]Accumulating studies have demonstrated that ncRNAs act as regulators of vitiligo. We summarize the regulation of ncRNAs in the pathogenesis of vitiligo, especially microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs, to pave the way to develop more effective diagnostic and therapeutic approaches for vitiligo [Figure 1].

Postsurgical stricture is the most common cause of esophageal stenosis in children after congenital esophageal atresia repair,^[1,2]followed by congenital esophageal stenosis and chemical corrosion burns.^[3]Endoscopic or radiologic balloon dilation is the standard method for treatment of esophageal stenosis, but in some complicated cases with severe hyperplasia and severe restenosis and even occlusion, the effect of endoscopic treatment is limited. In 1993, Bulyninet al^[4]reported, for the first time, the successful use of magnetic recanalization technology to treat refractory esophageal stenosis in children and pioneered the history of magnetic surgery to treat pediatric esophageal diseases. This technology makes full use of magnetic devices and forces which can effectively remove the scar tissue in the anastomotic region without damaging the muscle layer of the digestive tract wall^[5]and obtain the ideal therapeutic effect after surgery. In the past decade, magnetic recanalization technology has been further developed for the treatment of esophageal stenosis in children,^{[6,7,8,9,10,11,12,13,14,15]}which is superior to endoscopic dilatation and other methods, providing a new tool for the treatment of recalcitrant esophageal stenosis in children.

The new emerging avian influenza A H7N9 virus, causing severe human infection with a mortality rate of around 41%. This study aims to provide a novel treatment option for the prevention and control of H7N9.

H7 hemagglutinin (HA)-specific B cells were isolated from peripheral blood plasma cells of the patients previously infected by H7N9 in Jiangsu Province, China. The human monoclonal antibodies (mAbs) were generated by amplification and cloning of these HA-specific B cells. First, all human mAbs were screened for binding activity by enzyme-linked immunosorbent assay. Then, those mAbs, exhibiting potent affinity to recognize H7 HAs were further evaluated by hemagglutination-inhibiting (HAI) and microneutralization in vitro assays. Finally, the lead mAb candidate was selected and tested against the lethal challenge of the H7N9 virus using murine models.

The mAb 6-137 was able to recognize a panel of H7 HAs with high affinity but not HA of other subtypes, including H1N1 and H3N2. The mAb 6-137 can efficiently inhibit the HA activity in the inactivated H7N9 virus and neutralize 100 tissue culture infectious dose 50 (TCID₅₀) of H7N9 virus (influenza A/Nanjing/1/2013) in vitro, with neutralizing activity as low as 78 ng/mL. In addition, the mAb 6-137 protected the mice against the lethal challenge of H7N9 prophylactically and therapeutically.

The mAb 6-137 could be an effective antibody as a prophylactic or therapeutic biological treatment for the H7N9 exposure or infection.

The first-line treatment for lung cancer is surgical resection, and one-lung ventilation (OLV) is the most basic anesthetic management method in lung surgery. During OLV, inflammatory cytokines are released in response to the lung tissue damage and promote local and contralateral lung damage through the systemic circulation. We designed a randomized, prospective study to evaluate the effect of the urinary trypsin inhibitor (UTI) ulinastatin on the inflammatory response after video-assisted thoracic lobectomy in patients with lung cancer.

Adult patients aged 19 to 70 years, who were scheduled for video-assisted thoracic lobectomy surgery to treat lung cancer between May 2020 and August 2020, were enrolled in this randomized, prospective study. UTI (300,000 units) mixed with 100 mL of normal saline in the ulinastatin group and 100 mL of normal saline in the control group was administered over 1 h after inducing anesthesia.

The baseline (T0) interferon-γ (IFN-γ)/interleukin-4 (IL-4) ratio was not different between the groups (6941.3 ± 2778.7 vs. 6954.3 ± 2752.4 pg/mL, respectively; P > 0.05). The IFN-γ/IL-4 ratio was significantly higher in ulinastatin group at 30 min after entering the recovery room than control group (20,148.2 ± 5054.3 vs. 6674.0 ± 2963.6, respectively; adjusted P < 0.017). Conclusion: Administering UTI attenuated the anti-inflammatory response, in terms of INF-γ expression and the IFN-γ/IL-4 ratio, after video-assisted thoracic surgery in lung cancer patients.

Clinical Research Information Service of Korea National Institute of Health (CRIS), KCT0005533.

Family clustering of esophageal cancer (EC) has been found in high-risk areas of China. However, the relationships between cancer family history and esophageal cancer and precancerous lesions (ECPL) have not been comprehensively reported in recent years. This study aimed to provide evidence for identification of high-risk populations.

This study was conducted in five high-risk areas in China from 2017 to 2019, based on the National Cohort of Esophageal Cancer. The permanent residents aged 40 to 69 years were examined by endoscopy, and pathological examination was performed for suspicious lesions. Information on demographic characteristics, environmental factors, and cancer family history was collected. Unconditional logistic regression was applied to evaluate odds ratios between family history related factors and ECPL.

Among 33,008 participants, 6143 (18.61%) reported positive family history of EC. The proportion of positive family history varied significantly among high-risk areas. After adjusting for risk factors, participants with a family history of positive cancer, gastric and esophageal cancer or EC had 1.49-fold (95% confidence interval [CI]: 1.36-1.62), 1.52-fold (95% CI: 1.38-1.67), or 1.66-fold (95% CI: 1.50-1.84) higher risks of ECPL, respectively. Participants with single or multiple first-degree relatives (FDR) of positive EC history had 1.65-fold (95% CI: 1.47-1.84) or 1.93-fold (95% CI: 1.46-2.54) higher risks of ECPL. Participants with FDRs who developed EC before 35, 45, and 50 years of age had 4.05-fold (95% CI: 1.30-12.65), 2.11-fold (95% CI: 1.37-3.25), and 1.91-fold (95% CI: 1.44-2.54) higher risks of ECPL, respectively.

Participants with positive family history of EC had significantly higher risk of ECPL. This risk increased with the number of EC positive FDRs and EC family history of early onset. Distinctive genetic risk factors of the population in high-risk areas of China require further investigation.

ChiCTR-EOC-17010553.

Till date, the optimal treatment strategy for delivering adjuvant androgen deprivation therapy (ADT) in localized and locally advanced prostate cancer (PCa), as a lower stage in PCa progression compared with metastatic PCa, is still unclear. This study compares the efficacy of castration alone with complete androgen blockade (CAB) as adjuvant ADT in patients with localized and locally advanced PCa undergoing radical prostatectomy (RP).

Patients diagnosed with PCa, without lymph node or distant metastasis, who received RP in West China Hospital between January 2009 and April 2019, were enrolled in this study. We performed survival, multivariable Cox proportional hazard regression, and subgroup analyses.

A total of 262 patients were enrolled, including 107 patients who received castration alone and 155 patients who received CAB. The survival analysis revealed that there was no significant difference between the two groups (hazard ratios [HR]=1.07, 95% confidence intervals [95% CI]=0.60-1.90, P=0.8195). Moreover, the multivariable Cox model provided similarly negative results before and after adjustment for potential covariant. Similarly, there was no significant difference in the clinical recurrence between the two groups in both non-adjusted and adjusted models. Furthermore, our subgroup analysis showed that CAB achieved better biochemical recurrence (BCR) outcomes than medical castration alone as adjuvant ADT for locally advanced PCa (P for interaction=0.0247, HR=0.37, 95% CI=0.14-1.00, P=0.0497).

Combined androgen blockade achieved better BCR outcomes compared with medical castration alone as adjuvant ADT for locally advanced PCa without lymph node metastasis.

Keloids are benign fibrous growths that are caused by excessive tissue build-up. Severe keloids exert more significant effects on patients’ quality of life than do mild keloids. We aimed to identify factors associated with the progression from mild keloids to severe keloids, as distinct from those associated with the formation of keloids.

In this retrospective case-control study, 251 patients diagnosed with keloids at West China Hospital between November 2018 and April 2021 were grouped according to the severity of lesions (mild [n = 162] or severe [n = 89]). We collected their basic characteristics, living habits, incomes, comorbidities, and keloid characteristics from Electronic Medical Records in the hospital and the patients’ interviews. Conditional multivariable regression was performed to identify the independent risk factors for the progression of keloids.

Eighty-nine patients (35.5%) were classified as having severe keloids. We found the distribution of severe keloids varied with sex, age, excessive scrubbing of keloids, family income, the comorbidity of rheumatism, disease duration, characteristics of the location, location in sites of high-stretch tension, the severity and frequency of pain, the severity of pruritus, and infection. Multivariable analysis revealed significant associations between severe keloids and infection (odds ratio [OR], 3.55; P = 0.005), excessive scrubbing of keloids (OR, 8.65; P = 0.001), low or middle family income (OR, 13.44; P = 0.021), comorbidity of rheumatism (OR, 18.97; P = 0.021), multiple keloids located at multiple sites (OR, 3.18; P = 0.033), and disease duration >15 years (OR, 2.98; P = 0.046).

Doctors should implement more active and thorough measures to minimize the progression of mild keloids in patients who have any of the following risk factors: infection, excessive scrubbing of keloids, low or middle family income, comorbidity of rheumatism, multiple keloids located at multiple sites, and disease duration >15 years.

Pulmonary microvascular endothelial cells (PMVECs) were not complex, and the endothelial barrier was destroyed in the pathogenesis progress of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). Previous studies have demonstrated that hepatocyte growth factor (HGF), which was secreted by bone marrow mesenchymal stem cells, could decrease endothelial apoptosis. We investigated whether mTOR/STAT3 signaling acted in HGF protective effects against oxidative stress and mitochondria-dependent apoptosis in lipopolysaccharide (LPS)-induced endothelial barrier dysfunction and ALI mice.

In our current study, we introduced LPS-induced PMEVCs with HGF treatment. To investigate the effects of mammalian target of rapamycin (mTOR)/signal transducer and activator of transcription 3 (STAT3) pathway in endothelial oxidative stress and mitochondria-dependent apoptosis, mTOR inhibitor rapamycin and STAT3 inhibitor S3I-201 were, respectively, used to inhibit mTOR/STAT3 signaling. Moreover, lentivirus vector-mediated mTORC1 (Raptor) and mTORC2 (Rictor) gene knockdown modifications were introduced to evaluate mTORC1 and mTORC1 pathways. Calcium measurement, reactive oxygen species (ROS) production, mitochondrial membrane potential and protein, cell proliferation, apoptosis, and endothelial junction protein were detected to evaluate HGF effects. Moreover, we used the ALI mouse model to observe the mitochondria pathological changes with an electron microscope in vivo.

Our study demonstrated that HGF protected the endothelium via the suppression of ROS production and intracellular calcium uptake, which lead to increased mitochondrial membrane potential (JC-1 and mitochondria tracker green detection) and specific proteins (complex I), raised anti-apoptosis Messenger Ribonucleic Acid level (B-cell lymphoma 2 and Bcl-xL), and increased endothelial junction proteins (VE-cadherin and occludin). Reversely, mTOR inhibitor rapamycin and STAT3 inhibitor S3I-201 could raise oxidative stress and mitochondria-dependent apoptosis even with HGF treatment in LPS-induced endothelial cells. Similarly, mTORC1 as well as mTORC2 have the same protective effects in mitochondria damage and apoptosis. In in vivo experiments of ALI mouse, HGF also increased mitochondria structural integrity via the mTOR/STAT3 pathway.

In all, these reveal that mTOR/STAT3 signaling mediates the HGF suppression effects to oxidative level, mitochondria-dependent apoptosis, and endothelial junction protein in ARDS, contributing to the pulmonary endothelial survival and barrier integrity.

Breast cancer (BC) is among the commonly diagnosed malignancies, which displaced lung cancer to become the most leading diagnosed cancer worldwide in 2020.^[1]Approximately 15% to 20% of BC patients are positive for the human epidermal growth factor receptor 2 gene (Her-2) and exhibits a high degree of malignancy. However, the definition ofHer-2positivity remains controversial and fluctuating. The reasons for the uncertainty include different technical issues and laboratory experience, different accuracy of testing and cut-off point determination, tumor heterogeneity, preliminary clinical data and differential interpretation among pathologists.^[2]To makeHer-2assessment better suitable for selecting patients for anti-Her-2receptor treatment, the American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) proposed recommendations to improve the analytic validity of Her-2 for the first time in 2007 and updated these in 2013 and 2018.^[3]For clinicians, it was important to reveal the relationship amongHer-2status, anti-Her-2therapy and prognosis and to further focus on the exact group of patients who would benefit from anti-Her-2therapy.

Post-intubation or post-tracheostomy tracheal stenosis is the most common cause of acquired benign airway stenosis. Incidence of post-intubation tracheal stenosis (PITS) is decreasing due to the widespread use of the high-volume low-pressure cuff, and awareness of the need to monitor the cuff pressure. Nevertheless, post-tracheostomy tracheal stenosis (PTTS) incidence is still very high and seriously affects the patients’ quality of life. PTTS is often caused by damage to the airway cartilage, regional ischemic necrosis, tracheotomy site infection, and friction between the distal tracheotomy tube and the tracheal wall. Previous studies have reported that surgical resection and reconstruction is the best choice for PTTS management; however, the advent of endoscopic technology has made it a suitable alternative for surgical management, especially for patients with long destroyed tracheal segments or those with severe comorbidities.^[1]

To the Editor:Invasive pulmonary mucormycosis (IPM) is a rare but life-threatening opportunistic fungal disease with a high mortality rate of 40% to 80%.^[1]Although IPM accounts for approximately 9.2% of all mucormycosis cases, it has the highest mortality rate (66.6%). A definitive diagnosis of IPM depends on the histopathological findings, regardless of culture results of the respiratory tract specimens or lung tissues.

To the Editor:Hypertension is a well-known cardiovascular disease in which the kidney is an important target due to its role in the regulation of fluid, electrolyte balance, and blood pressure.^[1]Glomerulosclerosis, renal tubule interstitial fibrosis, and proteinuria are the main pathological characteristics of hypertensive kidney injury.^[2]

To the Editor:Acute fatty liver of pregnancy (AFLP) is an uncommon but potentially fatal disease unique to pregnancy that typically occurs in the third trimester and is one of the leading causes of maternal mortality in critically ill patients.^[1]The Swansea diagnostic criteria have been widely used in the diagnosis of AFLP worldwide since their proposal. The Swansea criteria include clinical symptoms and laboratory tests, imaging, and pathological examination results. Some studies have shown that the Swansea criteria score is a potential clinical tool for evaluating disease severity.^[2]The clinical symptoms lack specificity, and a pathological examination cannot be performed in most patients; therefore, the most important criteria are based on the laboratory examination results. In these criteria, the laboratory examination results mainly reflect dysfunction in the following: liver (total bilirubin >14 μmol/L, aspartate aminotransaminase [AST] or alanine aminotransferase [ALT] >42 U/L, coagulopathy [prothrombin time >14 s or activated partial thromboplastin time >34 s], low blood glucose <4 mmol/L, elevated blood ammonia >47 μmol/L), kidney (serum creatinine >150 μmol/L), and blood (leukocyte count >11 × 10⁹/L). If the damage to a patient organ is aggravated, the Swansea criteria score will increase. However, it is unclear whether the Swansea criteria score could be useful for assessing maternal and fetal complications in patients with AFLP.

To the Editor:Acute lobar nephronia (ALN), also known as acute focal bacterial nephritis, is a severe form of upper urinary tract infection (UTI) that is characterized by the presence of an inflammatory mass lesion in the kidney without abscess formation. It is considered to be the midpoint between acute pyelonephritis and renal abscess.^[1]ALN was first described in 1979 as a radiologic diagnosis in ten adults and two children.^[2]

To the Editor:Minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) are common histological subtypes of nephrotic syndrome in adults and children.^[1,2]Corticosteroids are the first-line treatment, whereas some patients present with steroid-dependent nephrotic syndrome. Repeated treatment with steroids is required, accompanied by serious adverse effects related to prednisone monotherapy in the long term.^[3]Leflunomide is a competitive and reversible inhibitor of dihydroorotate dehydrogenase that inhibits protein tyrosine kinases in proliferating T cells and B cells and has anti-inflammatory and antiproliferative effects.^[4]We previously reported that leflunomide therapy reduced the rate of relapse and the amount of prednisone to maintain remission in 16 adult patients with MCD and steroid-dependent or steroid-resistant nephrotic syndrome.^[5]We performed a retrospective study to investigate the efficacy and safety of leflunomide in steroid-dependent MCD and FSGS.

To the Editor:Group BStreptococcus(GBS) colonizes the vagina and rectum of 7-30% of pregnant women and contributes to materno-neonatal invasive infections. To date, the pathogenesis of clinical GBS strains has remained elusive.

To the Editor: The "eighteen antagonistic medicaments," an indispensable component of Oriental Pharmacology, states that sargassum and licorice should not be administered simultaneously.^[1]Researchers have reported that co-administration of licorice and sargassum exerted toxic effects on the heart, liver, and kidney of rats.^[2,3]However, the classic recipe "Hai-Zao-Yu-Hu-Tang," (containing licorice and sargassum) is currently used, though the safety profile of this medication has not been clearly defined. Therefore, a toxicological study of the combination of sargassum and licorice is necessary to determine its safety profile. In this study, a sub-acute toxicity test was used to evaluate toxicity. The main active components of licorice were liquirtin, isoliquiritin, liquiritigenin, isoliquiritigenin, and glycyrrhizic acid (GL). GL may be converted into glycyrrhetinic acid (GA)in vivo. Research has shown that the plasma concentrations of GA in rats are elevated after the oral administration of laminaria-licorice extractvs.licorice extract alone.^[4]In this study, we developed an ultra-performance liquid chromatography coupled with triple-quadrupole mass spectrometry (UPLC-TQ/MS) method for the simultaneous determination of the six main components of licorice in rat plasma.

To the Editor:Bullous pemphigoid (BP) is a chronic autoimmune blistering disease characterized by the association with autoantibodies to two hemidesmosomal proteins (BP180 and BP230) interfering with the adhesion of basal epidermal keratinocytes. The global incidence of BP is 2.5 to 75 cases/million per year.^[1]Genetic, environmental, and stochastic factors contribute to the susceptibility to BP. We performed a retrospective study on BP in Northeast China to evaluate its clinical characteristics. The data of BP patients from Shenyang Seventh People’s Hospital between January 2015 and January 2020 were analyzed, including 464 BP patients from Northeast China. All patients met the BP diagnostic standard. This study was approved by the Institutional Review Board of Shenyang Seventh People’s Hospital (No. 2015-WQ-01).

To the Editor:Parkinson disease (PD) is the second most common neurodegenerative disorder associated with significant disability and negative impact on quality of life (QoL), affecting 2% to 3% of the population ≥65 years of age.^[1]Although the disorder is defined by motor features including asymmetric tremor, bradykinesia, and rigidity, various non-motor features are typically seen, including cognitive impairment, depression, sensory symptoms, autonomic dysfunction, and sleep disturbances. Due to the complexity, PD is challenging to treat. There are currently no effective treatments to prevent or halt the progression of PD.

To the Editor:Bladder cancer is the most common malignant tumor of the urinary system in the Asian population. In China, it is reported 80,000 new cases each year with an increasing incidence every year. Among these cases, 75% are of non-muscle invasive bladder cancer (NMIBC). In muscular invasive bladder cancer (MIBC) and NMIBC patients, radical cystectomy is considered as a primary approach of treatment due to the higher risk of tumor progression. Furthermore, cystoscopy and traditional transurethral resection are the main approaches for diagnosing and staging of bladder cancer. However, these approaches are relatively risky because of their complications and high peri-operative mortality.^[1]Moreover, the most critical limitation of cystoscopy is its inefficient ability to differentiate between malignant tumors and healthy urothelium considering the multifocal aspect of the disease and inconspicuous but significant lesions (such as carcinomain situ).