酒精使用障碍（AUD）是一种非常常见、难治的医学疾病。AUD的症状是由以伏隔核(NAc)为中心的几个神经回路的功能障碍引起的。病例报告和动物研究表明，伏隔核深部脑刺激（NAc-DBS）治疗可能是严重AUD的一种有效的减害治疗方法。6例严重难治性AUD患者接受了NAc-DBS，安全性指标和临床结果被记录下来。在基线和6个月时，使用正电子发射断层扫描（FDG-PET）测量NAc中的葡萄糖代谢。功能磁共振成像（fMRI）用于表征术后NAc与大脑其余部分的功能连接变化，以及NAc和背侧纹状体对酒精视觉线索的反应性。该研究已在ClinicalTrials.gov（NCT03660124）注册。所有患者的渴望程度都有所降低。12个月时饮酒量、酒精相关的强迫行为和焦虑明显减少。抑郁无明显变化。FDG-PET分析显示，6个月后NAc代谢减少，这与强迫性饮酒行为的改善相关。临床改善与NAc和视觉联合皮层之间的功能连接减少相关。主动深部脑刺激（DBS）与被动观看含酒精图片时背侧纹状体的激活减少有关。NAc-DBS在严重的难治性AUD患者中是可行和安全的。它与食欲和成瘾行为的减少有关。这一过程的潜在机制是下调NAc，破坏其与视觉联合皮质的功能连接，以及干扰线索诱发的背侧纹状体反应性。

Background::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.Methods::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.Results::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). Conclusion::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.Trial registration::ClinicalTrials.gov, NCT04515511

目的:探究我国2016至2020年整形美容器械注册临床研究的特征和发展趋势。方法:通过ClinicalTrials.gov和中国临床试验注册中心数据库检索2016至2020年在我国开展的已注册整形美容器械临床研究，提取适应证、器械类型、申办方类型和研究设计特征等数据进行描述性统计分析。结果:2016至2020年共有118项已注册的整形美容器械临床研究纳入分析，其中100项(84.7%)研究由医疗机构发起，其余由医疗器械企业发起。研究数量从2016年的12项增加到了2020年的42项，各年增长率平均值约为39.6%。其中适应证为皮肤缺陷类研究项目90项(76.3%)，颌面部缺陷研究21项(17.8%)，毛发缺陷研究5项(4.2%)，乳房美学缺陷研究2项(1.7%)。皮肤缺陷类研究数量最多的适应证为瘢痕、痤疮、鼻唇沟皱纹和葡萄酒色斑。在器械类型上，涉及光电器械73项(61.9%)，手术类器械20项(16.9%)，注射类器械19项(16.1%)；在各类光电器械中，激光治疗设备是研究的热点。共有11项采用激光治疗设备进行瘢痕治疗的临床研究，其中6项研究采用平行对照研究设计，其余研究采用自身对照；样本量范围为15~110例。结论:我国整形美容器械注册临床研究数量近年来持续增加，皮肤类相关适应证和光电类器械是目前该领域的研究热点。

Background::Although overnight fasting is recommended prior to endoscopic retrograde cholangiopancreatography (ERCP), the benefits and safety of high-carbohydrate fluid diet (CFD) intake 2 h before ERCP remain unclear. This study aimed to analyze whether high-CFD intake 2 h before ERCP can be safe and accelerate patients’ recovery.Methods::This prospective, multicenter, randomized controlled trial involved 15 tertiary ERCP centers. A total of 1330 patients were randomized into CFD group ( n = 665) and fasting group ( n = 665). The CFD group received 400 mL of maltodextrin orally 2 h before ERCP, while the control group abstained from food/water overnight (>6 h) before ERCP. All ERCP procedures were performed using deep sedation with intravenous propofol. The investigators were blinded but not the patients. The primary outcomes included postoperative fatigue and abdominal pain score, and the secondary outcomes included complications and changes in metabolic indicators. The outcomes were analyzed according to a modified intention-to-treat principle. Results::The post-ERCP fatigue scores were significantly lower at 4 h (4.1 ± 2.6 vs. 4.8 ± 2.8, t = 4.23, P <0.001) and 20 h (2.4 ± 2.1 vs. 3.4 ± 2.4, t= 7.94, P <0.001) in the CFD group, with least-squares mean differences of 0.48 (95% confidence interval [CI]: 0.26–0.71, P <0.001) and 0.76 (95% CI: 0.57–0.95, P <0.001), respectively. The 4-h pain scores (2.1 ± 1.7 vs. 2.2 ± 1.7, t = 2.60, P = 0.009, with a least-squares mean difference of 0.21 [95% CI: 0.05–0.37]) and positive urine ketone levels (7.7% [39/509] vs. 15.4% [82/533], χ2 = 15.13, P <0.001) were lower in the CFD group. The CFD group had significantly less cholangitis (2.1% [13/634] vs. 4.0% [26/658], χ2 = 3.99, P = 0.046) but not pancreatitis (5.5% [35/634] vs. 6.5% [43/658], χ2 = 0.59, P = 0.444). Subgroup analysis revealed that CFD reduced the incidence of complications in patients with native papilla (odds ratio [OR]: 0.61, 95% CI: 0.39–0.95, P = 0.028) in the multivariable models. Conclusion::Ingesting 400 mL of CFD 2 h before ERCP is safe, with a reduction in post-ERCP fatigue, abdominal pain, and cholangitis during recovery.Trail Registration::ClinicalTrials.gov, No. NCT03075280.

目的:了解由中国研究者发起的抗结核药物临床试验时空分布、总体特点及其实施现状，剖析存在的问题并给出建议。方法:利用ClinicalTrials.gov和中国临床试验注册中心数据库检索建库至2022年6月30日关于已注册中国研究者发起的抗结核药物相关临床试验，根据注册时间、注册机构类别及其所在地区、研究类型、研究对象、研究状态、治疗干预等维度分层分析。结果:ClinicalTrials.gov和中国临床试验注册中心已注册的由中国研究者发起的抗结核药物临床试验分别有30项和59项，注册数量波动式上升，并呈现东高、中低、西居中的地区分布特征。60.67%（54/89）的临床试验在结核病定点医疗机构注册，评估单一或抗结核药物组合的临床试验为主，其余为在此基础上增加了对症治疗、宿主导向免疫治疗和中医辨证施治的研究。处于尚未纳入、纳入进行中、纳入完成并继续实施、研究完成和状态未知的项目数量分别为30项、26项、2项、22项和9项。结论:近5年中国主持的抗结核药物临床试验迎来注册研究的高峰，然而临床试验全周期、全流程信息的注册完整性不足。亟需增加注册规范相关培训，加大临床试验注册全周期结果的公布，从而践行临床试验注册的宗旨。

Background::Although the treatment of peripheral T-cell lymphoma (PTCL) has undergone advancements during the past several years, the response rate and long-term effects with respect to patients with PTCL remain unsatisfactory—particularly for relapsed or refractory (R/R) patients. This phase II trial was designed to explore the efficacy and safety of an all-oral regimen of chidamide plus prednisone, cyclophosphamide, and thalidomide (CPCT) for R/R PTCL patients who could not tolerate the standard chemotherapy for a variety of reasons.Methods::We conducted a multicenter phase II clinical trial in which we combined chidamide (30 mg twice weekly) with prednisone (20 mg daily after breakfast), cyclophosphamide (50 mg daily after lunch), and thalidomide (100 mg daily at bedtime) (the CPCT regimen) for a total of fewer than 12 cycles as an induction-combined treatment period, and then applied chidamide as single-drug maintenance. Forty-five patients were ultimately enrolled from August 2016 to April 2021 with respect to Chinese patients at nine centers. Our primary objective was to assess the overall response rate (ORR) after the treatment with CPCT.Results::Of the 45 enrolled patients, the optimal ORR and complete response (CR)/CR unconfirmed (CRu) were 71.1% (32/45) and 28.9% (13/45), respectively, and after a median follow-up period of 56 months, the median progression-free survival (PFS) and overall survival (OS) were 8.5 months and 17.2 months, respectively. The five-year PFS and OS rates were 21.2% (95% confidence interval [CI], 7.9-34.5%) and 43.8% (95% CI, 28.3-59.3%), respectively. The most common adverse event was neutropenia (20/45, 44.4%), but we observed no treatment-related death.Conclusion::The all-oral CPCT regimen was an effective and safe regimen for R/R PTCL patients who could not tolerate standard chemotherapy for various reasons.Trial Registration::ClinicalTrials.gov, NCT02879526.

Background::Albuvirtide is a once-weekly injectable human immunodeficiency virus (HIV)-1 fusion inhibitor. We present interim data for a phase 3 trial assessing the safety and efficacy of albuvirtide plus lopinavir-ritonavir in HIV-1-infected adults already treated with antiretroviral drugs.Methods::We carried out a 48-week, randomized, controlled, open-label non-inferiority trial at 12 sites in China. Adults on the World Health Organization (WHO)-recommended first-line treatment for >6 months with a plasma viral load >1000 copies/mL were enrolled and randomly assigned (1:1) to receive albuvirtide (once weekly) plus ritonavir-boosted lopinavir (ABT group) or the WHO-recommended second-line treatment (NRTI group). The primary endpoint was the proportion of patients with a plasma viral load below 50 copies/mL at 48 weeks. Non-inferiority was prespecified with a margin of 12%.Results::At the time of analysis, week 24 data were available for 83 and 92 patients, and week 48 data were available for 46 and 50 patients in the albuvirtide and NRTI groups, respectively. At 48 weeks, 80.4% of patients in the ABT group and 66.0% of those in the NRTI group had HIV-1 RNA levels below 50 copies/mL, meeting the criteria for non-inferiority. For the per-protocol population, the superiority of albuvirtide over NRTI was demonstrated. The frequency of grade 3 to 4 adverse events was similar in the two groups; the most common adverse events were diarrhea, upper respiratory tract infections, and grade 3 to 4 increases in triglyceride concentration. Renal function was significantly more impaired at 12 weeks in the patients of the NRTI group who received tenofovir disoproxil fumarate than in those of the ABT group.Conclusions::The TALENT study is the first phase 3 trial of an injectable long-acting HIV drug. This interim analysis indicates that once-weekly albuvirtide in combination with ritonavir-boosted lopinavir is well tolerated and non-inferior to the WHO-recommended second-line regimen in patients with first-line treatment failure.Trial registration::ClinicalTrials.gov Identifier: NCT02369965; https://www.clinicaltrials.gov.

目的:分析中国临床试验注册中心(ChiCTR)数据库与美国ClinicalTrials.gov数据库中关于中国急性胰腺炎临床研究的注册情况。方法:检索ChiCTR与ClinicalTrials.gov数据库，搜集、整理并分析关于注册的中国急性胰腺炎临床研究情况，检索时限为建库至2020年12月31日。通过人为分组，比较不同注册年份(2007-2014年组和2015-2020年组)及不同经费来源(自筹、企业资助、公共经费)的临床研究特征。结果:共获得157项注册的中国急性胰腺炎相关临床研究，其中ChiCTR数据库99项，ClinicalTrials.gov数据库58项。注册研究的地区分布排名前3位的依次是四川省(28.0%)、上海市(14.6%)、江苏省(12.1%)，共占注册试验总数量的54.7%。157项中干预性研究91项，观察性研究41项，其他类型25项。研究设计使用盲法34项(21.6%)，随机平行对照研究84项(53.5%)。Ⅳ期研究30项(19.1%)，Ⅱ、Ⅲ期研究7项(4.4%)。2007-2014年组注册试验倾向于采用随机平行对照试验设计(68.3%比45.4%， P＝0.005)和随机化分组(76.7%比47.4%， P＝0.001)，2015-2020年组倾向于较大样本量(72.6%比47.4%， P＝0.002)和有数据管理委员会(53.6%比25.0%， P＝0.001)，两组间差异均有统计学意义。ChiCTR数据库92项的经费来源分别为自筹48项、企业资助5项、公共经费38项、其他1项，自筹和公共经费来源占86.9%。 结论:中国急性胰腺炎注册临床研究数量整体随时间呈上升趋势，研究的经费来源以自筹和公共财政为主，目前Ⅱ、Ⅲ期临床试验较为缺乏。

目的:通过评估超声监测胃残余量的应用效果，为指导重症患者肠内营养方案提供证据。方法:系统检索CNKI、中国生物医学文献数据库、万方、维普、中国临床试验注册中心、PubMed、Embase、Cochrane Library、ClinicalTrials.gov等数据库，收集超声监测胃残余量在重症患者肠内营养中应用的RCT，检索时限为建库至2019年12月31日。由2名研究者独立检索文献、筛选文献、提取资料、评价质量，采用RevMan 5.3软件进行Meta分析。结果:共纳入10篇文献，共897例患者。与注射器回抽法相比，超声监测胃残余量可以降低反流/呕吐发生率（ RR=0.53，95% CI为0.38~0.75）、误吸发生率（ RR=0.48，95% CI为0.30~0.77），提高白蛋白水平（ MD=1.53，95% CI为0.71~2.35），减少护士操作时间（ MD=-5.62，95% CI为-7.59~-3.65），合并效应量有统计学意义（ P<0.05）；但不改变腹泻发生率（ RR=0.77，95% CI为0.53~1.11）与住院病死率（ RR=0.73，95% CI为0.41~1.28），合并效应量无统计学意义（ P>0.05）。 结论:超声监测胃残余量在重症患者肠内营养中应用可能有助于减少并发症的发生，改善患者的营养状况。

Background::Asymptomatic or symptomatic infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can be followed by reinfection. The protection conferred by prior infection among coronavirus disease 2019 (COVID-19) patients is unclear. We assessed the incidence of SARS-CoV-2 reinfection and the protection effect of previous infection against reinfection.Methods::We searched PubMed, EMBASE, Cochrane, Scopus, Web of Science, and ClinicalTrials.gov for publications up until the end date of May 1, 2021. The reinfection rate of recovered patients and the protection against reinfection were analyzed using meta-analysis.Results::Overall, 19 studies of 1096 reinfection patients were included. The pooled reinfection rate was 0.65% (95% confidence interval [CI] 0.39-0.98%). The symptomatic reinfection rate was a bit lower (0.37% [95% CI 0.11-0.78%], I2 = 99%). The reinfection rate was much higher in high-risk populations (1.59% [95% CI 0.30-3.88%], I2= 90%). The protection against reinfection and symptomatic reinfection was similar (87.02% [95% CI 83.22-89.96%] and 87.17% [95% CI 83.09-90.26%], respectively). Conclusions::The rate of reinfection with SARS-CoV-2 is relatively low. The protection against SARS-CoV-2 after natural infection is comparable to that estimated for vaccine efficacy. These data may help guide public health measures and vaccination strategies in response to the COVID-19 pandemic. High-quality clinical studies are needed to establish the relevant risk factors in recovered patients.