Volume 135 · Issue 14 · 2022

嵌合抗原受体T细胞（CAR-T）疗法大大提高了复发/难治性恶性血液病患者的疾病缓解率和长期生存率。^[1,2,3]目前，市场上有几种商业化的CAR-T产品，并进行了大量的CAR-T临床试验。应关注CAR-T疗法的安全性。CAR-T疗法的主要不良反应是细胞因子释放综合征（CRS）和免疫效应细胞相关神经毒性综合征（ICANS）。^[4]此外，CAR-T治疗相关凝血病(CARAC)也很突出[补充表1，http://links.lww.com/CM9/B173]。在血液系统恶性肿瘤患者中，包括B细胞急性淋巴细胞白血病（B-ALL）、非霍奇金淋巴瘤和多发性骨髓瘤（MM），超过一半的患者在接受CAR-T治疗后出现血小板减少或至少出现一项凝血参数异常。大约19.6%的凝血病患者经历了具有临床意义的出血，14%至50%的凝血病患者进一步发展为弥散性血管内凝血（DIC）；6.7%~42.9%的DIC患者死亡。目前国际上对CAR-T治疗相关不良事件的分级标准和治疗指南仅关注CRS和ICANS，而CARAC尚未进行系统总结。为了规范CARAC的管理，促进CAR-T疗法的安全应用，血栓与止血组和生物治疗委员会的专家基于全球临床经验和研究进展制定了本共识（详细信息见补充文件，http://links.lww.com/CM9/B173）。

The increasing burden of non-alcoholic fatty liver disease (NAFLD) worldwide imposes an emerging public health issue. We perform the current study to estimate the global prevalence, incidence, disease progression, and clinical outcomes of NAFLD.

A systematic search was conducted in Medline, Embase, Web of Science, Google Scholar, and Cochrane CENTRAL that screened articles in English language published from January 2000 to December 2021. NAFLD prevalence, incidence, rate of disease progression, and outcomes were calculated with the DerSimonian-Laird random effects model with arcsine transformation.

Our search identified 59,156 records, of which 578 studies fulfilled our inclusion criteria. The overall prevalence of NAFLD was 29.38% (95% confidence interval [CI] 28.09–30.69) regardless of the diagnostic techniques. Looking at the group in which the diagnosis was made by ultrasound exclusively, the pooled prevalence was 30.49% (95% CI 29.55–31.43). NAFLD has become more prevalent during the year 2011–2021 (31.63%, 95% CI 30.23–33.04) compared with year 2000–2010 (27.94%, 95% CI 26.23–29.69). The pooled estimation of non-alcoholic steatohepatitis prevalence was 8.26% (95% CI 1.13–21.01), 46.49% (95% CI 35.93–57.20), and 46.72% (95% CI 37.57–55.98) in general population, NAFLD patients, and severe/morbidly obese patients, respectively. Based on a total of 110,142 newly developed NAFLD patients, the pooled incident rate was estimated as 46.24 cases per 1000 person-years (95% CI 43.21–49.30). In patients with NAFLD, the incident rate of hepatocellular carcinoma was 1.46 (95% CI 0.90–2.03) cases per 1000 person-years. The overall pooled estimate of NAFLD related mortality was 23.91 (95% CI 13.55–37.18) death per 1000 person-years.

The prevalence of NAFLD is increasing globally. It is contributing to poor clinical outcomes including hepatocellular carcinoma and death. Rising awareness and urgent actions are warranted to control the NAFLD pandemic across the globe.

PROSPERO, No. CRD42020171104.

肠道微生物群衍生的代谢物影响宿主生理学和病理学，其中短链脂肪酸（SCFAs）是肠道微生物群衍生的代谢物的主要类别。^[1]SCFAs是含有1至6个碳原子的脂肪酸，包括乙酸盐、丙酸盐、丁酸盐和戊酸盐，它们提供身体每日总能量的6%至10%和结肠上皮所需能量的60%至70%。^[2]厌氧菌主要产生SCFAs^[1]在肠道里。一旦产生，SCFAs主要在结肠中吸收（90%-95%），到达循环，并在远端器官和组织中发挥作用。^[2]

白癜风是一种自身免疫性皮肤病，其特征在于皮肤的白色斑块失去功能性表皮黑素细胞。皮肤进行性色素脱失严重损害患者的生活质量。80%以上的白癜风患者有双侧对称的色素脱失模式，属于非节段性白癜风。然而，很少有研究揭示了协调白癜风患者皮肤免疫细胞模式活动的细胞和分子机制。了解是什么协调了皮肤免疫细胞的活动对于确定疾病的治疗靶点至关重要。

Gallbladder and biliary tract cancer (GBTC) has greatly damaged the health of patients and is accompanied by a dismal prognosis. The worldwide distribution of GBTC shows extensive variance and the updated data in China is lacking. This study was to determine the current status, trends, and predictions in the burden of GBTC over the past 30 years in China.

This was a descriptive, epidemiological, secondary analysis of the Global Burden of Disease, Injuries, and Risk Factor Study 2019 data. Data including incidence, prevalence, mortality, and disability-adjusted life years (DALYs) of GBTC in China by year, age, and sex were assessed. Joinpoint regression analysis was conducted to evaluate trends of disease burden due to GBTC from 1990 to 2019. Nordpred age-period-cohort analysis was applied for the projection of mortality and incidence due to GBTC from 2019 to 2044.

Nationally, there were 38,634 (95% uncertainty interval [UI]: 27,350–46,512) new cases and 47,278 (95% UI: 32,889–57,229) patients due to GBTC, causing 34,462 (95% UI: 25,220–41,231) deaths, and 763,584 (95% UI: 566,755–920,493) DALYs in 2019. Both cases and rates of burden owing to GBTC were heavier among males and at old age. From 1990 to 2019, the age-standardized rates of incidence, prevalence, mortality, and DALYs of GBTC generally increased from 1990 to 2019, with average annual percentage change at 0.8% (95% confidential interval [CI]: 0.6–1.0%), 1.3% (95% CI: 1.1–1.5%), 0.4% (95% CI: 0.2–0.6%), and 0.2% (95% CI: 0.1–0.4%), respectively. Even though the age-standardized incidence rate and age-standardized mortality rate in both sexes were predicted to decline gradually from 2019 to 2044, the number of new cases and deaths were expected to grow steadily.

GBTC is becoming a major health burden in China, particularly among males and older individuals. Given the aging population and increasing burden, effective strategies and measurements are urged to prevent or reduce the number of new cases and deaths of GBTC.

High-dose dual therapy (HDDT) with proton pump inhibitors (PPIs) and amoxicillin has attracted widespread attention due to its favorable efficacy in eradicating Helicobacter pylori (H. pylori). This study aimed to compare the efficacy and safety of high-dose PPI–amoxicillin dual therapy and bismuth-containing quadruple therapy for H. pylori rescue treatment.

This was a prospective, randomized, multicenter, non-inferiority trial. Patients recruited from eight centers who had failed previous treatment were randomly (1:1) allocated to two eradication groups: HDDT (esomeprazole 40 mg and amoxicillin 1000 mg three times daily; the HDDT group) and bismuth-containing quadruple therapy (esomeprazole 40 mg, bismuth potassium citrate 220 mg, and furazolidone 100 mg twice daily, combined with tetracycline 500 mg three times daily; the tetracycline, furazolidone, esomeprazole, and bismuth [TFEB] group) for 14 days. The primary endpoint was the H. pylori eradication rate. The secondary endpoints were adverse effects, symptom improvement rates, and patient compliance.

A total of 658 patients who met the criteria were enrolled in this study. The HDDT group achieved eradication rates of 75.4% (248/329), 81.0% (248/306), and 81.3% (248/305) asdetermined by the intention-to-treat (ITT), modified intention-to-treat (MITT), and per-protocol (PP) analyses, respectively. The eradication rates were similar to those in the TFEB group: 78.1% (257/329), 84.2% (257/305), and 85.1% (257/302). The lower 95% confidence interval boundary (–9.19% in the ITT analysis, –9.21% in the MITT analysis, and –9.73% in the PP analysis) was greater than the predefined non-inferiority margin of –10%, establishing a non-inferiority of the HDDT group vs. the TFEB group. The incidence of adverse events in the HDDT group was significantly lower than that in the TFEB group (11.1% vs. 26.8%, P < 0.001). Symptom improvement rates and patients’ compliance were similar between the two groups.

Fourteen-day HDDT is non-inferior to bismuth-containing quadruple therapy, with fewer adverse effects and good treatment compliance, suggesting HDDT as an alternative for H. pylori rescue treatment in the local region.

Clinicaltrials.gov, NCT04678492.

As a non-invasive and effective diagnostic method for small intestinal bacterial overgrowth (SIBO), wild-use of breath test (BT) has demonstrated a high comorbidity rate in patients with diarrhea-predominant irritable bowel syndrome (IBS-D) and SIBO. Patients overlapping with SIBO respond better to rifaximin therapy than those with IBS-D only. Gut microbiota plays a critical role in both of these two diseases. We aimed to determine the microbial difference between IBS-D overlapping with/without SIBO, and to study the underlying mechanism of its sensitivity to rifaximin.

Patients with IBS-D were categorized as BT-negative (IBSN) and BT-positive (IBSP). Healthy volunteers (BT-negative) were enrolled as healthy control. The patients were clinically evaluated before and after rifaximin treatment (0.4 g bid, 4 weeks). Blood, intestine, and stool samples were collected for cytokine assessment and gut microbial analyses.

Clinical complaints and microbial abundance were significantly higher in IBSP than in IBSN. In contrast, severe systemic inflammation and more active bacterial invasion function that were associated with enrichment of opportunistic pathogens were seen in IBSN. The symptoms of IBSP patients were relieved in different degrees after therapy, but the symptoms of IBSN rarely changed. We also found that the presence of IBSN-enriched genera (Enterobacter and Enterococcus) are unaffected by rifaximin therapy.

IBS-D patients overlapping with SIBO showed noticeably different fecal microbial composition and function compared with IBS-D only. The better response to rifaximin in those comorbid patients might associate with their different gut microbiota, which suggests that BT is necessary before IBS-D diagnosis and use of rifaximin.

Chinese Clinical Trial Registry, ChiCTR1800017911.

The hepatitis B virus X (HBx) protein plays a critical role in the initiation and progression of hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC). In the early stage of the disease, HBx facilitates tumor onset by inactivating the tumor suppressor p53. The p53-encoding gene, however, is frequently mutated or deleted as the cancer progresses to the late stage and, under such circumstance, the p53 homolog TAp63 can harness HCC growth by transactivating several important p53-target genes.

To determine whether HBx regulates TAp63, we performed co-immunoprecipitation assay, real-time quantitative polymerase chain reaction, immunoblotting, and flow cytometry analysis in p53-null cancer cell lines, Hep3B and H1299.

HBx interacts with the transactivation domain of TAp63, as HBx was co-immunoprecipitated with TAp63 but not with ΔNp63. The interaction between HBx and TAp63 abolished transcriptional activity of TAp63, as evidenced by the reduction of the levels of its target genes p21 and PUMA, consequently leading to restricted apoptosis and augmented proliferation of HCC cells.

HBV induces progression of HCC that harbors defective p53 by inhibiting the tumor suppressor TAp63.

This study aimed to reveal the treatment patterns and clinical outcomes of diverse palbociclib-based regimens in Han patients with estrogen receptor-positive (ER+) metastatic breast cancer in routine clinical practice.

The clinical data of patients with ER+ metastatic breast cancer treated with palbociclib were collected from the National Cancer Center database. The efficacy profile of palbociclib in this Han population was evaluated, especially for various combination regimens. The efficacy of palbociclib-based therapy in patients with prior everolimus treatment was also assessed.

A total of 186 patients from 89 cities in 18 provinces in China were enrolled. The median progression-free survival (PFS) was similar among different palbociclib-combined groups (P = 0.566): 10.0 months (95% confidence interval [CI] 3.8–16.1) in the +exemestane group, 9.7 months (95% CI 6.3–13.1) in the +letrozole group, 7.8 months (95% CI 5.5–10.2) in the +fulvestrant group, 7.2 months (95% CI 3.2–11.3) in the +toremifene group, and 6.1 months (95% CI 1.2–11.0) in the +anastrozole group. Thirty-four patients (18.3%) had received everolimus for their metastatic disease before the prescription of palbociclib. The disease control rate was significantly lower in patients who had received previous everolimus than in the everolimus-naïve group (50.0% vs. 82.2%, P < 0.001). Patients pre-treated with everolimus had significantly worse PFS than those in the everolimus-naïve group (3.4 months vs. 8.8 months, P = 0.001). After propensity score matching, patients pre-treated with everolimus had similar PFS (4.4 months, 95% CI 0.5–8.2) compared with everolimus-naïve patients (6.1 months, 95% CI 4.7–7.5, P = 0.439).

Various palbociclib-based regimens have promising efficacy in ER+ metastatic breast cancer in real-world settings, even in patients who had been pre-treated with everolimus.

Joint dislocations significantly impact public health. However, a comprehensive study on the incidence, distribution, and risk factors for joint dislocations in China is lacking. We conducted the China National Joint Dislocation Study, which is a part of the China National Fracture Study conducted to obtain the national incidence and risk factors for traumatic fractures, and to investigate the incidence and risk factors for joint dislocations.

For this national retrospective epidemiological study, 512,187 participants were recruited using stratified random sampling and probability-proportional-to-size method from January 19 to May 16, 2015. Participants who sustained joint dislocations of the trunk, arms, or legs (skull, sternum, and ribs being excluded) in 2014 were personally interviewed to obtain data on age, educational background, ethnic origin, occupation, geographic region, and urbanization degree. The joint-dislocation incidence was calculated based on age, sex, body site, and demographic factors. The risk factors for different groups were examined using multiple logistic regression.

One hundred and nineteen participants sustained 121 joint dislocations in 2014. The population-weighted incidence rate of joint dislocations of the trunk, arms, or legs was 0.22 (95% confidence interval [CI]: 0.16, 0.27) per 1000 population in 2014 (men, 0.27 [0.20, 0.34]; women, 0.16 [0.10, 0.23]). For all ages, previous dislocation history (male: OR 42.33, 95% confidence interval [CI]: 12.03–148.90; female: OR 54.43, 95% CI: 17.37–170.50) and alcohol consumption (male: OR 3.50, 95% CI: 1.49–8.22; female: OR 2.65, 95% CI: 1.08–6.50) were risk factors for joint dislocation. Sleeping less than 7 h/day was a risk factor for men. Compared with children, women aged ≥15 years (female 15–64 years: OR 0.16, 95% CI: 0.04–0.61; female ≥65 years: OR 0.06, 95% CI: 0.01–0.41) were less likely to sustain joint dislocations. Women with more than three children were at higher dislocation risk than women without children (OR 6.92, 95% CI: 1.18–40.78).

The up-to-date data on joint dislocation incidence, distribution, and risk factors can be used as a reference for national healthcare, prevention, and management in China. Specific strategies for decreasing alcohol consumption and encouraging adequate sleeping hours should be developed to prevent or reduce dislocation incidents.

Chinese Clinical Trial Registry, ChiCTR-EPR-15005878.

胃食管反流病（GERD）是由于食管功能障碍导致胃和十二指肠内容物反流到食管中，从而导致一系列症状。^[1]东亚GERD的发病率为2.5%至7.8%。^[2]食管裂孔疝（HH）是指胃的上部通过食管裂孔突出到胸部。HH与GERD密切相关，可在GERD的发展和发病率增加中发挥作用。^[3]GERD和HH患者的手术治疗包括HH修复和Nissen、Toupet或Dor胃底折叠术（DF）。然而，术后并发症与胃底折叠术有关，包括吞咽困难和腹胀，这降低了胃底折叠术的益处。

2020年，首仿注射用异硫蓝产品（通告编号：2020 LP00901，批号：118210301，5 mL：50 mg，广东和铂药业股份有限公司）获得中国国家药品监督管理局批准。该多中心、单臂、III期、开放性临床验证试验由中国乳腺外科学会组织，旨在评估该国产仿制药异硫蓝注射液用于中国早期乳腺癌（BC）患者前哨淋巴结活检（SLNB）的疗效和安全性。

致编辑：2019冠状病毒病（COVID-19），由严重急性呼吸综合征冠状病毒2（新型冠状病毒）引起，是全球范围内威胁人类健康和生存的严重公共卫生危机。^[1]据报道，新型冠状病毒感染患者的C反应蛋白、乳酸脱氢酶、D-二聚体、血浆细胞因子、血小板和白细胞等实验室特征异常。^[2,3]为了增强针对新型冠状病毒病的保护性免疫应答，疫苗已经在几个国家迅速开发并施用于健康个体或患有各种疾病的患者。^[4,5]然而，尽管接种了疫苗，一些健康个体仍然感染了新型冠状病毒病毒。新冠肺炎疫苗接种患者的临床和实验室指标的变化仍然未知。在本研究中，我们报告了疫苗接种对新冠肺炎患者的影响。

致编辑：银屑病是一种慢性免疫相关的炎症性皮肤病。银屑病的临床严重程度差异很大，复发频繁。^[1]已经进行了许多尝试来鉴定银屑病的生物标志物；然而，目前尚无特异性标志物可以准确监测疾病严重程度和治疗疗效。环状RNA（circRNAs）是一类新的内源性非编码RNA，其高度稳定且对RNase R具有抗性，因为它们可以在没有5的情况下形成共价闭环^′上限和3^′尾巴。^[2]据报道，circRNAs可以存在于体液中，如血清和血浆，并且可以作为几种疾病的诊断和预后的分子生物标志物。^[3]在这项研究中，我们检测了circRNAs的改变，并研究了hsa_circ_0056856作为银屑病患者和健康对照（HCs）血清样本中疾病严重程度的生物标志物的潜在价值。

致编辑：帕金森病（PD）是第二常见的神经退行性疾病，睡眠障碍是主要的致残性非运动症状。^[1]过度日间嗜睡（EDS）被定义为在清醒时间不适当和不希望的嗜睡，这可能发生在诸如说话或驾驶等活动中。在PD患者中，EDS增加了事故风险，并导致生活质量差。^[2]