Volume 135 · Issue 02 · 2022

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.

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.

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).

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.

Physical therapy is regarded as an essential aspect in achieving optimal outcomes following total knee arthroplasty (TKA). The coronavirus disease 2019 (COVID-19) pandemic has made face-to-face rehabilitation inaccessible. Virtual reality (VR) is increasingly regarded as a potentially effective option for offering health care interventions. This systematic review and meta-analysis investigate VR-based rehabilitation’s effectiveness on outcomes following TKA.

From inception to May 22, 2021, PubMed/Medline, Embase, Web of Science, the Cochrane Central Register of Controlled Trials, Scopus, PsycINFO, Physiotherapy Evidence Database, China National Knowledge Infrastructure, and Wanfang were comprehensively searched to identify randomized controlled trials (RCTs) evaluating the effect of VR-based rehabilitation on patients following TKA according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement and the Cochrane Handbook for Systematic Reviews of Interventions.

Eight studies were included in the systematic review, and seven studies were included in the meta-analysis. VR-based rehabilitation significantly improved visual analog scale (VAS) scores within 1 month (standardized mean difference [SMD]: -0.44; 95% confidence interval [CI]: -0.79 to -0.08, P = 0.02), the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) within 1 month (SMD: -0.71; 95% CI: -1.03 to -0.40, P < 0.01), and the Hospital for Special Surgery Knee Score (HSS) within 1 month and between 2 months and 3 months (MD: 7.62; 95% CI: 5.77 to 9.47, P < 0.01; MD: 10.15; 95% CI: 8.03 to 12.27, P < 0.01; respectively) following TKA compared to conventional rehabilitation. No significant difference was found in terms of the Timed Up and Go (TUG) test.

VR-based rehabilitation improved pain and function but not postural control following TKA compared to conventional rehabilitation. More high-quality RCTs are needed to prove the advantage of VR-based rehabilitation. As the COVID-19 pandemic continues, it is necessary to promote this rehabilitation model.

Postoperative chylous ascites is an infrequent condition after colorectal surgery and is easily treatable. However, its effect on the long-term oncological prognosis is not well established. This study aimed to investigate the short-term and long-term impact of chylous ascites treated with neoadjuvant therapy followed by rectal cancer surgery and to evaluate the incidence of chylous ascites after different surgical approaches.

A total of 898 locally advanced rectal cancer patients treated with neoadjuvant chemoradiotherapy followed by surgery between January 2010 and December 2018 were included. The clinicopathological data and outcomes of the patients with chylous ascites were compared with those of the patients without chylous ascites. The primary endpoint was recurrence-free survival (RFS). To balance baseline confounders between groups, propensity score matching (PSM) was performed for each patient with a logistic regression model.

Chylous ascites was detected in 3.8% (34/898) of the patients. The incidence of chylous ascites was highest after robotic surgery (6.9%, 6/86), followed by laparoscopic surgery (4.2%, 26/618) and open surgery (1.0%, 2/192, P = 0.021). The patients with chylous ascites had a significantly higher number of lymph nodes harvested (15.6 vs. 12.8, P = 0.009) and a 3-day longer postoperative hospital stay (P = 0.017). The 5-year RFS rate was 64.5% in the chylous ascites group, which was significantly lower than the rate in the no chylous ascites group (79.9%; P = 0.007). The results remained unchanged after PSM was performed. The chylous ascites group showed a nonsignificant trend towards a higher peritoneal metastasis risk (5.9% vs. 1.6%, P = 0.120). Univariate analysis and multivariate analysis confirmed chylous ascites (hazard ratio= 3.038, P < 0.001) as an independent negative prognostic factor for RFS.

Considering the higher incidence of chylous ascites after laparoscopic and robotic surgery and its adverse prognosis, we recommend sufficient coagulation of the lymphatic tissue near the vessel origins, especially during minimally invasive surgery.

Acute kidney injury (AKI) is a common and serious complication following lung transplantation (LTx), and it is associated with high mortality and morbidity. This study assessed the incidence of AKI after LTx and analyzed the associated perioperative factors and clinical outcomes.

This retrospective study included all adult LTx recipients at the China-Japan Friendship Hospital in Beijing between March 2017 and December 2019. The outcomes were AKI incidence, risk factors, mortality, and kidney recovery. Multivariate analysis was performed to identify independent risk factors. Survival analysis was presented using the Kaplan-Meier curves.

AKI occurred in 137 of the 191 patients (71.7%), with transient AKI in 43 (22.5%) and persistent AKI in 94 (49.2%). AKI stage 1 occurred in 27/191 (14.1%), stage 2 in 46/191 (24.1%), and stage 3 in 64/191 (33.5%) of the AKI patients. Renal replacement therapy (RRT) was administered to 35/191 (18.3%) of the patients. Male sex, older age, mechanical ventilation (MV), severe hypotension, septic shock, multiple organ dysfunction (MODS), prolonged extracorporeal membrane oxygenation (ECMO), reintubation, and nephrotoxic agents were associated with AKI (P < 0.050). Persistent AKI was independently associated with preoperative pulmonary hypertension, severe hypotension, post-operative MODS, and nephrotoxic agents. Severe hypotension, septic shock, MODS, reintubation, prolonged MV, and ECMO during or after LTx were related to severe AKI (stage 3) (P < 0.050). Patients with persistent and severe AKI had a significantly longer duration of MV, longer duration in the intensive care unit (ICU), worse downstream kidney function, and reduced survival (P < 0.050).

AKI is common after LTx, but the pathogenic mechanism of AKI is complicated, and prerenal causes are important. Persistent and severe AKI were associated with poor short- and long-term kidney function and reduced survival in LTx patients.

Delayed graft function (DGF) is the main cause of renal function failure after kidney transplantation. This study aims at investigating the value of hypothermic machine perfusion (HMP) parameters combined with perfusate biomarkers on predicting DGF and the time of renal function recovery after deceased donor (DD) kidney transplantation.

HMP parameters, perfusate biomarkers and baseline characteristics of 113 DD kidney transplantations from January 1, 2019 to August 31, 2019 in the First Affiliated Hospital of Xi’an Jiaotong University were retrospectively analyzed using univariate and multivariate logistic regression analysis.

In this study, the DGF incidence was 17.7% (20/113); The multivariate logistic regression results showed that terminal resistance (OR: 1.879, 95% CI 1.145-3.56) and glutathione S-transferase (GST)(OR = 1.62, 95% CI 1.23-2.46) were risk factors for DGF; The Cox model analysis indicated that terminal resistance was an independent hazard factor for renal function recovery time (HR = 0.823, 95% CI 0.735-0.981). The model combining terminal resistance and GST (AUC = 0.888, 95% CI: 0.842-0.933) significantly improved the DGF predictability compared with the use of terminal resistance (AUC = 0.756, 95% CI 0.693-0.818) or GST alone (AUC = 0.729, 95% CI 0.591-0.806).

According to the factors analyzed in this study, the combination of HMP parameters and perfusate biomarkers displays a potent DGF predictive value.

In-hospital mortality in patients with coronavirus disease 2019 (COVID-19) is high. Simple prognostic indices are needed to identify patients at high-risk of COVID-19 health outcomes. We aimed to determine the usefulness of the CONtrolling NUTritional status (CONUT) index as a potential prognostic indicator of mortality in COVID-19 patients upon hospital admission.

Our study design is of a retrospective observational study in a large cohort of COVID-19 patients. In addition to descriptive statistics, a Kaplan-Meier mortality analysis and a Cox regression were performed, as well as receiver operating curve (ROC).

From February 5, 2020 to January 21, 2021, there was a total of 2969 admissions for COVID-19 at our hospital, corresponding to 2844 patients. Overall, baseline (within 4 days of admission) CONUT index could be scored for 1627 (57.2%) patients. Patients’ age was 67.3 ± 16.5 years and 44.9% were women. The CONUT severity distribution was: 194 (11.9%) normal (0-1); 769 (47.2%) light (2-4); 585 (35.9%) moderate (5-8); and 79 (4.9%) severe (9-12). Mortality of 30 days after admission was 3.1% in patients with normal risk CONUT, 9.0% light, 22.7% moderate, and 40.5% in those with severe CONUT (P < 0.05). An increased risk of death associated with a greater baseline CONUT stage was sustained in a multivariable Cox regression model (P < 0.05). An increasing baseline CONUT stage was associated with a longer duration of admission, a greater requirement for the use of non-invasive and invasive mechanical ventilation, and other clinical outcomes (all P < 0.05). The ROC of CONUT for mortality had an area under the curve (AUC) and 95% confidence interval of 0.711 (0.676-0746).

The CONUT index upon admission is potentially a reliable and independent prognostic indicator of mortality and length of hospitalization in COVID-19 patients.

Despite improvements in disease diagnosis, treatment, and prognosis, breast cancer is still a leading cause of cancer death for women. Compelling evidence suggests that targeting cancer stem cells (CSCs) have a crucial impact on overcoming the current shortcomings of chemotherapy and radiotherapy. In the present study, we aimed to study the effects of T cells and a critical anti-tumor cytokine, interferon-gamma (IFN-γ), on breast cancer stem cells.

BALB/c mice and BALB/c nude mice were subcutaneously injected with 4T1 tumor cells. Tumor growth and pulmonary metastasis were assessed. ALDEFLOUR^TM assays were performed to identify aldehyde dehydrogenase^bright (ALDH^br) tumor cells. ALDH^br cells as well as T cells from tumor-bearing BALB/c mice were analyzed using flow cytometry. The effects of CD8⁺ T cells on ALDH^br tumor cells were assessed in vitro and in vivo. The expression profiles of ALDH^br and ALDH^dim 4T1 tumor cells were determined. The levels of plasma IFN-γ were measured by enzyme-linked immunosorbent assay, and their associations with the percentages of ALDH^br tumor cells were evaluated. The effects of IFN-γ on ALDH expression and the malignancy of 4T1 tumor cells were analyzed in vitro.

There were fewer metastatic nodules in tumor-bearing BALB/c mice than those in tumor-bearing BALB/c nude mice (25.40 vs. 54.67, P < 0.050). CD8⁺ T cells decreased the percentages of ALDH^br 4T1 tumor cells in vitro (control vs. effector to target ratio of 1:1, 10.15% vs. 5.76%, P < 0.050) and in vivo (control vs. CD8⁺ T cell depletion, 10.15% vs. 21.75%, P < 0.001). The functions of upregulated genes in ALDH^br 4T1 tumor cells were enriched in the pathway of response to IFN-γ. The levels of plasma IFN-γ decreased gradually in tumor-bearing BALB/c mice, while the percentages of ALDH^br tumor cells in primary tumors increased. IFN-γ at a concentration of 26.68 ng/mL decreased the percentages of ALDH^br 4T1 tumor cells (22.88% vs. 9.88%, P < 0.050) and the protein levels of aldehyde dehydrogenase 1 family member A1 in 4T1 tumor cells (0.86 vs. 0.49, P < 0.050) and inhibited the abilities of sphere formation (sphere diameter <200 μm, 159.50 vs. 72.0; ≥200 μm, 127.0 vs. 59.0; both P < 0.050) and invasion (89.67 vs. 67.67, P < 0.001) of 4T1 tumor cells.

CD8⁺ T cells and IFN-γ decreased CSC numbers in a 4T1 mouse model of breast cancer. The application of IFN-γ may be a potential strategy for reducing CSCs in breast cancer.

Microglia plays an indispensable role in the pathological process of sleep deprivation (SD). Here, the potential role of microglial CX3C-chemokine receptor 1 (CX3CR1) in modulating the cognition decline during SD was evaluated in terms of microglial neuroinflammation and synaptic pruning. In this study, we aimed to investigat whether the interference in the microglial function by the CX3CR1 knockout affects the CNS’s response to SD.

Middle-aged wild-type (WT) C57BL/6 and CX3CR1^-/- mice were either subjected to SD or allowed normal sleep (S) for 8 h to mimic the pathophysiological changes of middle-aged people after staying up all night. After which, behavioral and histological tests were used to explore their different changes.

CX3CR1 deficiency prevented SD-induced cognitive impairments, unlike WT groups. Compared with the CX3CR1^-/- S group, the CX3CR1^-/- SD mice reported a markedly decreased microglia and cellular oncogene fos density in the dentate gyrus (DG), decreased expression of pro-inflammatory cytokines, and decreased microglial phagocytosis-related factors, whereas increased levels of anti-inflammatory cytokines in the hippocampus and a significant increase in the density of spines of the DG were also noted.

These findings suggest that CX3CR1 deficiency leads to different cerebral behaviors and responses to SD. The inflammation-attenuating activity and the related modification of synaptic pruning are possible mechanism candidates, which indicate CX3CR1 as a candidate therapeutic target for the prevention of the sleep loss-induced cognitive impairments.

具有自身免疫性特征的间质性肺炎（IPAF）一词基于临床、血清学和形态学领域（特异性胸部影像学特征、组织病理学特征或多室受累，包括非特异性间质性肺炎[NSIP]、机化性肺炎、NSIP伴机化性肺炎重叠和淋巴样间质性肺炎）的组合，旨在描述具有间质性肺病（ILD）和指示结缔组织病（CTD）的临床特征但不符合既定CTD分类标准的患者。^[1]然而，胸部高分辨率计算机断层扫描（HRCT）中常见的间质性肺炎（UIP）模式不包括在IPAF形态学域中，因此具有UIP和自身抗体阳性但没有IPAF临床域中七种症状之一的患者被排除在IPAF之外，并可能被认为患有“特发性肺纤维化（IPF）”。^[1]目前缺乏长期随访研究，特别是很少有研究描述抗体阳性伴或不伴肺外综合征的IPF患者的临床特征和放射学表现。由于自身抗体存在于约22%的IPF患者中，^[2]自身抗体阳性有临床意义吗？或者自身抗体阳性或阴性的IPF患者是否具有相似的疾病行为或生存结局？有必要在有或没有抗体的IPF患者中进行长期随访研究。我们在中国的ILD中心进行了这项为期9年的回顾性研究，以比较有或无自身抗体的IPF患者的临床特征、放射学表现和长期无移植生存率。

过敏性鼻炎（AR）是一种昂贵且高度流行的慢性疾病。^[1]更严重的是，许多AR患者还患有过敏性哮喘（AA）。AR的存在是AA发展的危险因素。^[2]此外，AA仍然是所有年龄段死亡的重要原因。^[3]因此，预测和预防AA可以减少意外死亡、严重的健康危害和社会巨大的经济负担。

动脉瘤性蛛网膜下腔出血（aSAH）是一种典型的神经外科急症。患者的预后与初始疾病的严重程度和术后并发症有关，尤其是迟发性脑缺血（DCI）。DCI发生在高达30%的蛛网膜下腔出血（SAH）患者中，通常发生在出血后2周，是aSAH死亡和残疾的主要原因之一。目前，普遍认为DCI主要与脑血管痉挛（CVS）有关。然而，在积极的抗CVS治疗后，仍有一部分患者发生DCI，这表明CVS并不是DCI的全部原因。^[1]

甲状腺乳头状癌（PTC）是甲状腺癌中最常见的类型（占80%以上）。^[1]尽管PTC是一种分化良好的内分泌肿瘤，但不幸的是，某些PTC表现出恶性特征，如侵袭性和转移性；这些特征导致5年生存率低。^[1]然而，甲状腺外转移的基本分子机制仍不清楚。

冠状病毒疾病2019（新冠肺炎）是一种由新发现的冠状病毒引起的传染病，已迅速传播到世界大部分地区，并导致全球疫情。然而，很少有信息可用于描述新冠肺炎疫情免疫缺陷人群的特征，尤其是关注作为该人群典型代表的肾移植后患者的信息。了解该人群的易感性、临床特征、治疗策略和预后对于大流行中免疫缺陷患者的管理具有重要意义。

前交叉韧带（ACL）撕裂是运动医学门诊患者的常见病。为了恢复ACL损伤膝关节的静态和动态稳定性以及运动学，股骨和胫骨隧道的准确位置在ACL重建中起着重要作用，尤其是股骨隧道。^[1]一些研究试图通过在整个股骨足迹的中心重建ACL来最大化前内侧(AM)和后外侧(PL)束的功能结果^[2,3];然而，手术后不稳定持续存在。因此，各种研究得出结论，单束和双束技术在ACL重建中可以产生相似的疗效。^[4]

致编辑：由于血小板抗原，特别是血型抗原（如ABO抗原）、人白细胞抗原（HLA）、人血小板抗原（HPA）、CD36（血小板糖蛋白IV）具有免疫原性，可通过输血、妊娠、药物等免疫因素产生相应的同种抗体，患者血小板抗原和抗体的免疫反应会导致各种类型的同种免疫性血小板减少症，包括免疫性血小板输血难治性、输血后紫癜、胎儿/新生儿同种免疫性血小板减少症。^[1,2,3,4]血小板输注是治疗同种免疫性血小板减少症的有效方法。抗原阴性血小板（缺乏某些不与同种抗体反应的抗原的血小板体内）是避免相关同种免疫反应和获得血小板输注满意治疗结局的关键。^[1]为此，建立一个具有合适数量已知血小板抗原或抗原基因型且符合当地人群血小板免疫血液学特征的供者的完整血小板供者数据库（PDD），是同种免疫性血小板减少症患者快速找到抗原匹配的血小板供者的有效途径。

致编辑：噬血细胞性淋巴组织细胞增多症（HLH）是一种严重甚至致命的炎症。恶性HLH（M-HLH）是继发性HLH（sHLH）最常见的类型之一，尤其是在成人中。HLH可以作为恶性疾病的初始表现（此处称为“恶性肿瘤触发的HLH”）或在化疗引起的医源性免疫抑制的情况下发生（“化疗期间的HLH”或Ch-HLH）。^[1]在大多数情况下，化疗期间的HLH与由于化疗诱导的免疫抑制而发生的触发感染有关。^[2]细菌、真菌和病毒都可能导致这种情况。如先前报道的，M-HLH和Ch-HLH患者的生存率非常差，中位总生存率为0.9至1.2年，6个月生存率分别为67%和63%。^[3]对于Ch-HLH的治疗尚未达成共识，其范围从推迟后续化疗阻滞到基于依托泊苷的积极HLH导向治疗。^[1]JAK1/2（Janus激酶1/2）抑制剂ruxolitinib通过抑制JAK-信号转导和转录激活因子（STAT）途径抑制炎症因子风暴，在治疗HLH中表现出潜在的有效性，其有效性已在HLH小鼠模型和一些临床病例中得到证实。^[4]在此，我们报告了一例在急性髓细胞白血病（AML）治疗过程中使用ruxolitinib治疗EB病毒（EBV）相关HLH的罕见病例。

致编辑：皮质醇与止血密切相关。^[1]在肾上腺功能亢进，即库欣综合征（CS）患者中，活化部分凝血活酶时间（APTT）减少，凝血因子水平升高，血栓形成风险增加已被反复报道。^[1,2]然而，没有研究报道肾上腺功能减退患者的止血状况，肾上腺功能减退常见于垂体疾病患者。

致编辑：昼夜节律的改变似乎是帕金森病（PD）睡眠障碍、抑郁和其他非运动症状的偶然原因。^[1,2]通过恢复昼夜节律，强光疗法（BLT）可能是PD的一种潜在的新治疗选择。然而，没有研究最终证明BLT对PD非运动症状的影响。

致编辑：肾病综合征（NS）是一种常见的临床综合征，以大量蛋白尿和低白蛋白血症为特征，但从未在藏族人群中进行过研究。这是一项针对2009年至2016年在四川大学华西医院接受肾活检的藏族患者的单中心、回顾性研究。纳入了所有14岁以上的患者。排除标准为病理材料不足、移植肾活检和妊娠。根据世界卫生组织标准和组织学肾小球疾病分类方案定义肾脏病理特征。定量和定性数据分别表示为平均值±标准偏差和百分比。学生的t检验或Mann-Whitney检验分别用于比较参数或非参数连续变量。χ²和Fisher精确检验用于比较定性变量。所有统计数据均通过SPSS 23.0软件（SPSS Inc.，芝加哥，伊利诺伊州，美国）进行分析；P<0.05被认为具有统计学意义。

致编辑：衰老会引起人体代谢能力的变化^[1]而代谢综合征是2型糖尿病（T2DM）的重要病因之一。近年来，T2DM已成为人类十大杀手之一。^[2]≥25%的65岁以上人群报告了T2DM。^[3]肝脏是最重要的代谢中心，其代谢紊乱与T2DM有关。^[4]然而，关于老年T2DM患者肝脏代谢紊乱的研究有限。因此，有必要结合现代组学方法对这些患者的肝脏代谢进行分析。在这项研究中，我们整合了代谢组学和转录组学分析，分析了T2DM衰老小鼠肝脏中发生变化的特定代谢物和基因，为老年T2DM患者的治疗提供了理论依据。

致编辑：多发性骨髓瘤（MM）目前被认为是一种无法治愈的肿瘤和全身性疾病，一线治疗在MM患者中起着至关重要的作用，因为大多数患者在一线治疗后不能存活。^[1]来那度胺是治疗MM的一线药物，以胶囊形式销售，商品名为Revlimid^®这对于MM发病率的增加有很大的需求。此外，来那度胺在中国MM患者中的药代动力学（PK）数据很少或没有，大多数来那度胺PK试验是在年轻健康志愿者中进行的。本研究旨在比较重庆LUMMY制药有限公司（中国重庆）生产的仿制来那度胺10 mg胶囊（批号1308010）与Revlimid的PKs和生物等效性®来那度胺原药10mg胶囊(批号A0263BA)，由Celgene International Sarl(Boudry，Switzerland)制造；在中国MM患者中进行了比较，为患者提供品牌来那度胺的经济替代品。