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The high incidence of chronic postsurgical pain (CPSP) has been a major issue after breast cancer surgery (BCS). The impact of regional anesthesia (RA) techniques on CPSP remains conflicting. In this propensity score-matched cohort study, we aimed to investigate the effect of preoperative single-shot erector spinae plane block (ESPB) adding to general anesthesia (GA) on the incidence of CPSP at 1 year following BCS. Data of adult female patients who underwent unilateral BCS between October 2019 and June 2020 were retrospectively collected. Patients were grouped to ESPB combined with GA (ESPB + GA) and GA alone, respectively. All patients were prospectively followed up at 1 year after surgery. CPSP and neuropathic pain (NP) were measured using the brief pain inventory–short form (BPI-SF) and ID Pain scale. Eleven confounding factors were managed by propensity score matching (PSM) to achieve between-group balance. The primary outcome was the incidence of CPSP at 1 year after BCS. The secondary outcomes include proportion of NP, severity, and interference of CPSP at 1 year after surgery, acute postoperative pain, postoperative nausea and vomiting (PONV), hospital length of stay (LOS), and adverse events. After PSM, data for 194 patients were available for analysis (97 in each group). No significant difference in the incidence of CPSP (P = 1.000) nor percentage of patients with NP (P = 0.442) was found between the two groups. Both matched groups had similar intensity of CPSP (P = 0.547) measured by BPI-SF as well as the rates of moderate to severe CPSP (P = 1.000). A significant decrease in acute pain scores (P = 0.043) and rates of rescue analgesics demand (P = 0.042) were observed in the ESPB + GA group compared to the GA group. Multivariate logistic regression on the total study cohort showed that axillary lymph node dissection (ALND) (OR 3.541, 95% CI: 1.273–9.851, P = 0.015), radiotherapy (OR 1.918, 95% CI: 1.067–3.448, P = 0.029) and acute postoperative pain within 24 h (OR 2.109, 95% CI: 1.097–4.056, P = 0.036) were independent risk factors for the development of CPSP. We found that preoperative single-shot ESPB was not associated with reduced incidence of CPSP at 1 year after BCS. ALND, radiotherapy, and acute postoperative pain within 24 h were independent risk factors for the development of CPSP after BCS. The study was registered in the Chinese Clinical Trial Registry (ID: ChiCTR2000038464, date of registration: September 23, 2020).

Background This study aims to describe the association between sharp score and clinical indexes, bone metabolism indexes, Disease Activity Score (DAS28) and sociodemographic factors in rheumatoid arthritis (RA). Methods Data were collected from the HIS (hospital information system), a national inpatient database in China, with information on the patients hospitalized during the period from 2012 to 2019. The association between sharp score and effective factors were identified using multinomial logistic regression and association rule mining (ARM). Results Three thousand eight hundred and forty patients were included: 82.66% males, 17.34% females, mean (SD) age 56.95 (12.68) years and symptom duration 3.45 (1.09) years. Spearman correlation analysis and Association rules analysis showed that there were significant positive correlations between sharp score and effective factors. Logistic regression analysis presented that erythrocyte sedimentation rate (ESR), high-sensitivity C-reactive protein (CRP), rheumatoid factor (RF) were risk factors of sharp score. In the analysis of individual outcomes, sex, age, symptom duration, DSA28 score, RF, ever drinker, and radiographic grading of hands were influence factors of sharp score. Conclusion Sharp score should be taken into consideration in formulating treatment strategies in RA.

Patients with primary Sjögren's syndrome (pSS) reportedly believe that their symptoms worsen on extreme weather days due to variations in environmental conditions. However, few studies have assessed the acute effects of environmental exposure on the onset of pSS. This study aimed to evaluate the exposure-response relationship between extreme environmental conditions and pSS outpatient visits.We obtained data on pSS outpatient visits from two provincial general hospitals in Hefei, China, during 2014-2019. A distributed lag non-linear model was used to estimate the exposure-lag-response relationship between environmental variables and pSS.We detected significant and non-linear associations between extreme environments and pSS. The estimated relative risk (RR) for a lag of 3 days was 1.11 (95% CI: 1.03 to 1.19) for extreme cold and for a lag of 21 days was 1.07 (95% CI: 1.01 to 1.12) for extreme dampness. Long sunshine duration was positively correlated with pSS (lag 11, 1.05, 95% CI: 1.01 to 1.08). Moreover, female patients were more susceptible to these effects. Patients older than 65 years old were more vulnerable to frigid environments (lag 3, RR = 1.30, 95% CI: 1.09 to 1.54), while younger patients were more vulnerable to extreme dampness (lag 21, RR = 1.10, 95% CI: 1.03 to 1.16). Extreme cold and high humidity were negatively correlated with the same-day outpatient visits.Our findings suggest a potential relationship between exposure to extreme environmental conditions and increased risk of pSS outpatient visits. We therefore suggest that policymakers and doctors aim to further our understanding of environmental effects on pSS and adopt adequate measures to alleviate pSS symptoms. Key Points • Extreme cold, extreme dampness, and long sunshine duration increased the risk of pSS outpatient visits, especially for females. • Young pSS patients are more susceptible to a rise in humidity. • Elderly pSS patients are more sensitive to extreme cold weather.

Dexmedetomidine had sedative and analgesic effects and did not produce significant respiratory depression at therapeutic doses. To compare the sedative and analgesic effects and safety of dexmedetomidine combined with remifentanil or sufentanil in patients undergoing liposuction. A total of 100 subjects were randomized 1:1 to two groups: Group R and Group S. First, patients were administered midazolam 0.02 mg·kg−1. Anesthesia was induced with an intravenous infusion of dexmedetomidine 1 µg kg−1 (15 min) and remifentanil 0.1 µg kg−1 min−1 (Group R) or sufentanil 0.1 µg kg−1h−1 (Group S). Anesthesia was maintained with an intravenous infusion of dexmedetomidine 1.0 µg kg−1h−1, midazolam 0.015 mg kg−1h−1, remifentanil 0.1 µg kg−1min−1 (Group R), or sufentanil 0.1 µg kg−1h−1 (Group S). Hemodynamic and respiratory changes, modified OAA/S score and BIS values, postoperative Visual Analogue Scale pain scores, satisfaction of the patient and surgical team with the procedure, and adverse events and recovery time were recorded. Group R received significantly less midazolam and midazolam per hour compared to Group S (Group R vs. Group S: 3.4 ± 1.7 mg vs. 5.1 ± 2.0 mg, P

Esophageal cancer is a malignant tumor with a five-year survival rate of less than 20%. Early diagnosis and exploration of esophageal cancer pathogenesis are of great significance for the treatment and prognosis of esophageal cancer. Long non-coding RNA (lncRNA) plays a vital role in the occurrence and development of different types of tumors. However, the role of exosome LncRNA in esophageal squamous cell carcinoma (ESCC) is rarely reported. In this study, we detected high expression of lncRNA LINC01711 in ESCC tissues and was associated with poor prognosis. Silencing LINC01711 can inhibit the proliferation, migration, invasion, and growth of ESCC cell lines, and induce apoptosis. Linc01711 was identified as a competitive endogenous RNA that suppressed miR-326, and up-regulated the expression of fascin actin-bundling protein 1 (FSCN1). Besides, in vivo experiments showed that the administration of exosome-derived LINC01711 (LINC01711-Exo) promoted the growth of tumors in nude mice. In general, exosomal LINC01711 promoted the proliferation, migration, and invasion of esophageal cancer cells by up-regulating FSCN1 and down-regulating miR-326, thus improved the occurrence and development of ESCC.

Background Patients with ankylosing spondylitis (AS) have reported that their pain becomes worse when the local weather changes. However, there is limited evidence verifying the short-term associations between meteorological factors and outpatient visits for patients with AS. Therefore, this study evaluates this possible association. Methods Meteorological data and data on daily AS outpatient visits to a general hospital in Hefei, China, from 2014 to 2019 were collected and analysed. Distributed lag nonlinear models and Poisson regression models were employed to determine the association between weather conditions and outpatient visits; the results were also stratified by gender and age. Results High relative humidity is significantly associated with all patient visits in lag 1 (RR = 1.113, 95% CI 1.021 to 1.213) and lag 7 days (RR = 1.115, 95% CI 1.014 to 1.227). A low relative risk to the nadir is observed in lag 4 days (RR = 0.920, 95% CI 0.862 to 0.983). Male and young patients ( Conclusions Our findings suggest a potential relationship between exposure to weather conditions and increased risk of AS outpatient visits. These results can aid hospitals in preparing for and managing hospital visits by AS patients when the local weather conditions change.

Desmoplasia in the extracellular matrix (ECM) is one of the hallmarks of pancreatic cancer (PC), a virtually incurable disease. Decorin, a classical small leucine-rich proteoglycan found in the ECM, was upregulated in PC tissue samples according to the data of TCGA. However, decorin plays a protective role in the ECM. So it is necessary to study the roles of decorin in the progression of PC. A significantly upregulated expression of decorin was observed in the PC tissue samples compared with the normal tissues. However, there was no considerable difference in the level of expression of decorin during different pathological stages, which was supported by the immunoblot analysis. Western blot showed a higher expression of decorin A in the para-carcinoma tissue than in the cancerous tissue but the expression of decorin B, C, and D was elevated in the cancerous tissue. The results of the MTT and scratch wound healing assays revealed an elevated proliferation ability and migration rate in decorin B-overexpressing cells but were inhibited in the decorin A-overexpressing cells. Overexpression of decorin A significantly elevated the expression of the apoptosis-related genes and Decorin B-overexpression elevated proliferation-related genes. All the results showed that decorin B played important roles in the promoting of PC.

AIM: To evaluate the effect of vitrectomy combined with scleral shortening for eyes with myopic macular retinoschisis. METHODS: Thirty-seven patients with myopic macular retinoschisis who underwent pars plana vitrectomy (PPV) combined with scleral shortening were reviewed. Axial length (AL), the height of macular retinoschisis, the height of retinal detachment if existed, the diameter of macular hole if existed and best corrected visual acuity (BCVA) were obtained. The preoperative and postoperative parameters were compared. RESULTS: At postoperative 24mo, the mean AL and height of macular retinoschisis were reduced significantly by 0.79 mm and 256.51 μm (t=8.064, P

Background: Salt-inducible kinases (SIKs) belonging to an AMP-activated kinase (AMPK) family, have functions in tumourgeniesis and metastasis in many solid tumours. However, the role of SIKs in breast cancer is not clear. In this study we aimed to determine the function of SIKs (SIK1, SIK2 and SIK3) in human breast cancer. Method: A cohort of breast cancer tissues (n=102) were analysed using qPCR to determine changes in SIK expression (SIK1, SIK2, SIK3 and housekeeping GAPDH ) between cancer and normal tissues and different aetiologies of cancer. In addition, a breast disease spectrum array (TMA) was probed for SIK expression at the protein level. SIK1, 2 and 3 were knocked down using shRNA in the human breast cancer cell lines MCF-7 and MDA-MB-231 and changes in cell behaviour were assessed using a number of cell function assays.Results: At the messenger level, expression of SIK2 was lower in breast cancer than normal tissue (p=0.0179), while expression of SIK1 and SIK3 had no significant difference between breast cancer and normal tissue. SIK3 expression was associated with ER status in the cohort (p=0.02). The level of SIK2 expression was significantly different in Stage I and Stage III. While SIK3 expression was significantly higher in ER positive breast cancer than ER negative breast cancer. Further analysis using Kaplan-Meier survival was performed for SIKs expression in an online database (http://kmplot.com/analysis/index.php?p=background) which showed that that an increased expression of SIKs was associated with good prognosis in the breast cancer cohort (p Citation Format: Ling Xin, Chang Liu, Yinhua Liu, Robert E. Mansel, Eleri Davies, Wen G. Jiang, Tracey A. Martin. Salt-inducible kinases suppress tumour function and regulate drug resistance in breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS4-41.

Xin Zhou,1 Shou-Gen Cao,1 Xiao-Jie Tan,1 Xiao-Dong Liu,1 Ze-Qun Li,1 Ling-Xin Kong,2 Yu-Long Tian,1 Dan Liu,1 Shuai Shen,1 Yu-Qi Sun,1 Hai-Tao Jiang,1 Yan-Bing Zhou1 1Department of Gastrointestinal Surgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, People’s Republic of China; 2Department of Rehabilitation, The Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, People’s Republic of ChinaCorrespondence: Yan-Bing ZhouDepartment of Gastrointestinal Surgery, The Affiliated Hospital of Qingdao University, No. 16 Jiangsu Road, Shinan District, Qingdao City, Shandong Province, People’s Republic of ChinaTel +86-13708971773Email zhouyanbing999@aliyun.comPurpose: Transcutaneous electrical acupoint stimulation (TEAS) is an innovative choice for postoperative pain management. However, the safety and effectiveness of this traditional Chinese medicine (TCM) therapy for patients who underwent gastrectomy is largely unknown. So, the purpose of this study is to evaluate the safety and effectiveness of TEAS for patients who underwent gastrectomy.Patients and Methods: We recruited 96 patients with gastric cancer from May 2019 to November 2019; 82 patients were enrolled, and 81 patients completed. Patients were randomly assigned to TEAS group (TG) received TEAS on postoperative day (POD) 1– 3 or control group (CG) at a 1:1 ratio. The primary outcomes were pain score and consumption of analgesics. The secondary were the time of first postoperative flatus and defecation, frequency of postoperative nausea, vomiting, distention, diarrhea, comfort of semi-fluid diet, Clavien-Dindo grade (C-D grade) and length of postoperative day. We performed hematological analysis to explore the possible mechanisms.Results: Overall, 81 patients were enrolled included in the analysis. Compared with CG, pain scores in TG were lower on POD 1– 5 (average: 2.55± 0.21 vs 3.10± 0.42, P< 0.001), and the use rate of opioids was lower (43.9 vs 75.0, P=0.004); time of first postoperative flatus (55.63± 16.74 vs 72.60± 20.92, P< 0.001) and defecation (72.20± 16.24 vs 95.78± 17.75, P< 0.001) were shorter; the frequency of nausea were fewer (1.88± 1.09 vs 2.58± 0.77, P=0.029) and patients were more comfortable with semi-fluid diet (7.63± 0.63 vs 6.93± 0.69, P< 0.001); among the hematologic results, β-endorphin (β-End), interleukin-2 (IL-2), motilin (MTL) on POD 3, POD 5 were lower, 5-hydroxytryptamine (5-HT), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) were higher. And no adverse event was reported.Conclusion: TEAS can relieve postoperative pain and promote the recovery of gastrointestinal function. Consequently, it can be an adjunctive therapy to enhance postoperative recovery for patients after gastrectomy.Keywords: stomach neoplasms, acupuncture therapy, enhanced recovery after surgery, pain management, gastrointestinal function

To evaluate changes in the sleep patterns of patients undergoing general anesthesia for maxillofacial plastic surgery. A total of 200 consecutive craniofacial plastic surgery patients were enrolled in this study. Sixteen patients who did not stay in the craniofacial ward on the night before surgery were excluded, providing a final total of 184 patients. PSQI was used to evaluate sleep quality 1 month before surgery (baseline) and on the night before surgery. According to the baseline sleep quality score, patients were assigned to the sleep disorder group (SD group, n = 51, 27.7%; PSQI score > 5) or non-sleep disorder group (NSD group, n = 133, 72.3%; PSQI score ≤ 5). The PSQI score on the night before the operation was compared with the baseline score. Amongst the total sample size, the incidence of disturbed sleep on the night before surgery was significantly higher than baseline (PSQI score > 5: 89,48.4% vs.51,27.7%, respectively, P = 0.037). In the NSD group, the PSQI score the night before surgery was significantly increased compared with the baseline score (5.6 ± 3.2 vs. 2.4 ± 1.4, respectively, P

Long noncoding RNAs (lncRNAs) are >200‐bp molecules that do not generally code for proteins. Human lncRNAs have well‐characterized roles in gene expression regulation, particularly with regard to protein‐coding genes, and their dysregulation has been linked to disease. Here, we set out to investigate changes in the expression of lncRNAs related to apoptosis and autophagy in the peripheral blood mononuclear cells (PBMCs) of rheumatoid arthritis (RA). In addition, we aimed to correlate lncRNA expression profiles with clinical indexes and self‐perception of patients (SPP). To this end, we employed RNA sequencing of lncRNAs in PBMCs from three patients with RA and three healthy controls. We used bioinformatics to screen several dysregulated lncRNAs related to apoptosis and autophagy. To validate key lncRNA candidates, we performed quantitative reverse transcriptase–PCR on 20 patients with RA and 20 healthy controls. We found the expression of seven lncRNAs (MAPKAPK5‐AS1, ENST00000619282, C5orf17, LINC01189, LINC01006, DSCR9 and MIR22HG) was significantly altered in PBMCs of patients with RA. Receiver operating characteristic curve analysis suggested that MIR22HG [area under the curve (AUC) = 0.846, P = 0.000], DSCR9 (AUC = 0.783, P = 0.005), LINC01189 (AUC = 0.677, P = 0.034), MAPKAPK5‐AS1 (AUC = 0.644, P = 0.025) and ENST00000619282 (AUC = 0.636, P = 0.043) are potential biomarkers of RA. Spearman's correlation analysis revealed selected lncRNAs correlated with clinical indexes and SPP. Therefore, we highlight that some lncRNAs related to apoptosis and autophagy may serve as potential biomarkers for diagnosis and monitoring of RA progression, which also correlate with several clinical indexes and SPP., We investigated changes in the expression of lncRNAs related to apoptosis and autophagy in the peripheral blood mononuclear cells (PBMCs) of rheumatoid arthritis (RA). Expression of seven lncRNAs (MAPKAPK5‐AS1, ENST00000619282, C5orf17, LINC01189, LINC01006, DSCR9, and MIR22HG) was significantly altered in PBMCs of RA patients. Squares, triangles, and circles represent lncRNAs, miRNAs, and mRNAs, respectively. Red nodes: upregulation; blue nodes: downregulation.

Objective To investigate the clinicopathological characteristics and prognostic factors of early-stage breast cancer patients with indications for breast cancer susceptibility genes 1/2 (BRCA1/2) genetic testing in China. Methods Based on the indication criteria for BRCA genetic testing specified in the National Comprehensive Cancer Network (NCCN) clinical practice guidelines in oncology, genetic/familial high-risk assessment: Breast and ovarian (Version 2. 2019), a retrospective analysis was performed on patients with early-stage invasive breast cancer treated at Breast Disease Center, Peking University First Hospital between January 2008 and December 2016. Clinicopathological characteristics of all patients were analyzed, and prognoses were calculated using the Kaplan-Meier method and a Cox proportionate hazards model. Results A total of 906 early-stage breast cancer patients who had indications for BRCA genetic testing and had complete clinicopathological data and follow-up information were included in the study group, accounting for 34.7% of all breast cancer patients treated in Breast Disease Center, Peking University First Hospital during the study period. Compared with breast cancer patients without indications for BRCA genetic testing, the overall survival (OS) and disease-free survival (DFS) of patients with indications were not significantly different. In the study group, patients with premenopausal status, high T stage, lymph node positive, estrogen receptor (ER) negative, Ki-67>20% and presence of a vascular tumor thrombus had worse prognosis. There were more family histories of gastrointestinal cancer in patients with related indications than in patients without such indications. Conclusions Single-center data showed that more than 30% of patients with early-stage breast cancer had indications for BRCA genetic testing. There was no prognostic difference in patients with or without indications for BRCA genetic testing. Premenopausal status, high T stage, lymph node positive, ER negative, Ki-67>20%, and presence of a vascular tumor thrombus were associated with poor prognosis.

WHAT IS KNOWN AND OBJECTIVE Prior to nasotracheal intubation (NTI), topical nasal vasoconstrictors are used to prevent NTI-related epistaxis (NTIRE). Since we learned that there is no significant increase in NTIRE among hypertensive patients undergoing NTI with adequate lubrication but without vasoconstrictors, we initiated this randomized controlled study to assess the necessity of vasoconstrictor use in reducing NTIRE. METHODS Patients with the American Society of Anesthesiologists Physical Status Classification 1 and normal coagulation function, planned to undergo maxillofacial surgery with NTI were enrolled. Patients were randomly (1:1) assigned to each of the treatment groups: nasal treatment using pure oxybuprocaine gel with adequate lubrication (group G) or 1% ephedrine in addition to oxybuprocaine gel with adequate lubrication (group EG). In addition, the incidence and severity of NTIRE and intubation adjustments were studied. RESULTS A total of 844 patients, 429 and 415 (groups G and EG, respectively), were included in the analysis. No significant differences were observed in the NTIRE incidence rates in groups G (28%) and EG (27%; p = 0.75, relative risk [RR] = 0.95, 95% confidence interval [CI] 0.70-1.29). No significant differences in the NTIRE incidence rates between the two nostrils were observed in both groups (group G: left, 27.9% vs. right, 28% [p = 0.98, RR = 1.01, 95% CI 0.67-1.51]; group EG: left, 25.8% vs. right, 27.9% [p = 0.63, RR = 1.12, 95% CI 0.72-1.73]. No significant difference was observed in the severity of NTIRE (p = 0.74). In case of difficult advancement of the endotracheal tube, NTIRE incidence was 71% vs. 12% with smooth intubation (p

Background and ObjectiveGut microbiota dysbiosis following stroke affects the recovery of neurological function. Administration of prebiotics to counteract post-stroke dysbiosis may be a potential therapeutic strategy to improve neurological function. We aim to observe the effect of lactulose on neurological function outcomes, gut microbiota composition, and plasma metabolites in mice after stroke.MethodsMale C57BL/6 mice (20–25 g) were randomly divided into three groups: healthy control, photothrombotic stroke + triple-distilled water, and photothrombotic stroke + lactulose. After 14 consecutive days of lactulose administration, feces, plasma, and organs were collected. 16S rDNA sequencing, plasma untargeted metabolomics, qPCR, flow cytometry and Elisa were performed.ResultsLactulose supplementation significantly improved the functional outcome of stroke, downregulated inflammatory reaction, and increased anti-inflammatory factors in both the brain and gut. In addition, lactulose supplementation repaired intestinal barrier injury, improved gut microbiota dysbiosis, and partially amended metabolic disorder after stroke.ConclusionLactulose promotes functional outcomes after stroke in mice, which may be attributable to repressing harmful bacteria, and metabolic disorder, repairing gut barrier disruption, and reducing inflammatory reactions after stroke.

This study was designed to explore the sulfation patterns of chondroitin sulfate (CS)/dermatan sulfate (DS), and keratan sulfate (KS) and the expression of carbohydrate sulfotransferases (CHSTs) in 26 pancreatic tumor and normal tissues. CS/DS and KS profiles were simultaneously determined. Pancreatic tumor tissues exhibited increased ΔDi-0S, ΔDi-4S, and ΔDi-6S levels, with absolute ΔDi-4S content being highest, followed by ΔDi-6S. However, as for the contents of KS-6S and KS-6S,6'S, there were no significant regular change. The expression levels of CHST1 and CHST4 were 37 and 15 times higher than those in normal tissues. PCA and OPLS-DA revealed that ΔDi-4S and ΔDi-6S levels could be reliably used to differentiate between healthy and cancerous tissues. The up-regulation of CHST3, CHST12, CHST13, and CHST15 was directly correlated with C-4 and C-6 sulfation. These data provide a foundation for future studies of the role of ΔDi-4S and ΔDi-6S in the progression of pancreatic cancer.

A glycoside hydrolase family 57 protein, designated APU_Aquae, from hyperthermophilic bacterium Aquifex aeolicus was expressed in Escherichia coli. APU_Aquae was biochemically defined as a novel bifunctional amylopullulanase, which exhibited efficient activity towards rice starches. It is extremely thermostable with half-life of 7 h at 100 °C. Therefore, APU_Aquae was used to simplify the process of enzymatic debranching treatment in resistant starch type III (RS3) preparation from rice starches. Starch pregelatinization and enzymatic hydrolysis were combined into one step. It took only 7 h, which was much shorter than that of other enzymatic treatments. RS3 content of treated rice starches was 40.5 ± 0.7%. APU_Aquae treatment resulted in more medium branch chains B1 with degree of polymerization (DP) values 13–24, which might be one main reason to promote the RS3 formation. This study provides the new design for the industrial RS3 production.

Coronavirus disease 2019 (COVID-19) is associated with high morbidity and mortality worldwide in both the general population and kidney transplant recipients. Acute kidney injury is a known complication of COVID-19 and appears to most commonly manifest as acute tubular injury on renal biopsy. Coagulopathy associated with COVID-19 is a known but poorly understood complication that has been reported to cause thrombotic microangiopathy on rare occasions in native kidneys of patients with COVID-19. Here, we report the first case of biopsy-proven thrombotic microangiopathy in a kidney transplant recipient with COVID-19 who developed acute pancreatitis and clinical features of microangiopathic hemolytic anemia. The patient recovered with supportive care alone., Highlights • Kidney transplant recipients with coronavirus disease 2019 (COVID-19) demonstrate higher mortality rates compared to the general population and frequent allograft dysfunction. • COVID-19 can cause a wide spectrum of extrapulmonary involvement, including coagulopathy, gastrointestinal symptoms, and acute kidney injury. • When diagnosing and treating kidney transplant recipients with acute allograft dysfunction in the setting of COVID-19, thrombotic microangiopathy should be considered.

Objective To identify a new genetic cause in patients segregating distal hereditary motor neuropathy (dHMN) with an autosomal recessive pattern. Methods Whole‐exome sequencing was conducted in two siblings and was combined with segregation analysis. Additionally, 83 unrelated dHMN patients with unknown genetic cause were screened. RNA analysis was performed using blood lymphocytes and HEK293 cells transfected with mutant plasmids. Immunohistochemistry and Western blot analysis was applied to the nerve tissue. The enzymatic activities of mutant proteins were measured in the cultured cells to verify the pathogenicity of variants. Results The clinical features of the patients showed late‐onset phenotype of distal motor neuropathy without sensory involvement. We identified that compound heterozygous variants of c.1342C>T and c.2071_2072delGCinsTT in the membrane metalloendopeptidase (MME) gene co‐segregated with the phenotype in a dHMN family. In an additional group of 83 patients with dHMN, compound heterozygous variants of c.1416+2T>C and c.2027C>T in MME were identified in one patient. The splice site variant c.1416+2T>C results in skipping of exon 13. The stop variant c.1342C>T induces mRNA degradation via nonsense‐mediated mRNA decay. Transcript levels of MME in the lymphocytes showed no significant differences between the patients and controls. We also identified that MME variants were associated with mild decrease in protein expression in the sural nerve and significant impairments of enzymatic activity. Interpretation Variants in the MME gene were associated with not only a Charcot‐Marie‐Tooth neuropathy phenotype but also with an autosomal‐recessive dHMN phenotype. Loss of function may play a role in the pathogenesis of dHMN.

Neutral lipid storage disease with myopathy (NLSDM) is a triglyceride metabolic disorder caused by defects of adipose triglyceride lipases (ATGL). The coexistence of lipid vacuoles and rimmed vacuoles in the myofibers is a characteristic pathological change in some NLSDM cases. However, it has not been explored whether autophagic abnormalities exist in the NLSDM myofibers with rimmed vacuole. Herein, we report that 5 patients with NLSDM initially presented with muscle weakness in the right arm related to long-term physical efforts, then developed muscle weakness of other limbs. Pathogenic mutations in the PNPLA2 gene were identified in all patients. Myopathological analysis showed a coexistence of massive lipid vacuoles and rimmed vacuoles, which was not associated with the age of onset or mutation sites, but closely related to the severity of muscle degeneration. The rimmed vacuoles showed strong immunopositivity to autophagic markers, but were negative to apoptotic markers. Significant immunoreactivity of p62 was observed in the rimmed vacuoles, while the lysosomal marker LAMP1 was severely decreased. Our study expanded the clinical and genetic spectrum of NLSDM. Loss of ATGL activity in muscle fibers with rimmed vacuoles induced a marked increase in autophagic formation, but lowered down the turnover of autolysosomes due to malfunction of lysosomes.

Background IgG4-related disease (IgG4-RD) often affects multiple organs and tissues, especially the kidneys, and is characterized by interstitial nephritis, obstructive nephropathy, and in rare cases glomerulopathy (including membranous nephropathy). Case presentation In this article, we report a patient with nephrotic syndrome as the only initial manifestation. Membranous nephropathy was confirmed by renal biopsy, but without any renal interstitial lesions. The nephrotic syndrome completely resolved after treatment with immunosuppressants but recurred after drug withdrawal, which was accompanied by acute kidney injury. Ultimately, IgG4-related interstitial nephritis with membranous nephropathy was confirmed by a second renal biopsy. After routine administration of steroids and cyclophosphamide, renal function returned to normal after 2 months, and nephrotic syndrome was ameliorated after 5 months. Conclusion Special attention should be paid to this rare condition in the clinical setting. In patients with membranous nephropathy (MN) that is accompanied by multi-system damage, impaired renal function, elevated IgG4 levels (absolute or relative value), negative PLA2R, and/or renal interstitial plasma cell infiltration, the possibility of IgG4-related kidney disease (IgG4-RKD) should be carefully assessed.

Background Mutations in the SYNJ1 gene have been associated with early-onset of atypical Parkinson's disease or severe neurodegeneration with intractable seizures. Due to the rarity of the disease, there were limitations in the quality of available treatment options for SYNJ1-related diseases. Methods Two affected siblings from a non-consanguineous family were evaluated through a set of clinical and laboratory tests. The genetic screening was performed through exome next generation sequencing. SYNJ1 mutant transcripts were purified and cloned into the vectors for Sanger sequence of single-stranded DNA. Relative level of the SYNJ1 transcript was measured by quantitative PCR. Results The clinical features were characterized by a triad of symptomatic progression including diplopia, dystonia, and Parkinsonism. The dystonic symptoms were outstanding in the siblings, which preceded the Parkinsonism symptoms and became the main symptoms. Clonazepam resolved the clinical symptoms, especially the severe trunk dystonia and dystonic postures of limbs. Compound heterozygous variants (c.2579-2A > G; p.A860Gfs*5 and c.3845C > A; p.P1282L) were identified in the SYNJ1 gene co-segregating in this family. The proline residue is highly conserved across species and predicted to be damaging by several in silico tools. The splice site variant caused a skip of exon 20 and a significant reduction of the SYNJ1 transcript expression. Conclusions Our study expanded the clinical and genetic spectrums of the SYNJ1-related diseases. Although our study was a preliminary observation, it indicated that clonazepam could improve the dystonic symptoms caused by mutations in the SYNJ1 gene.

The present work was tested the anti-proliferation activity of Rhus typhina fruits extract (RTFE) in HEK293 and HT-29 cells, and studied their underlying mechanisms through the analysis of oxidative stress and apoptosis-related genes expressions by flow cytometer and RT-qPCR. In addition, the bioactive constituents were identified from RTFE by chromatography and NMR analysis. Among the various type of the fractions from the RTFE, the ethyl acetate fraction (EAF) was showed the potent anti proliferation effect in HT-29 cells. Thus EAF was selected for the further extensive analysis. Cytotoxcity and RT-qPCR results revealed that the treatment of EAF significantly inhibit the growth of the HT-29 cells by the up regulating of Bax and down regulation of Bcl-2, Survivn, AIF and SOD-2 gene expressions in time and dose dependent manner. Followed by sub G1 accumulation and the G0/G1 phase arrest, ROS production, and mitochondrial transmembrane potential (ΔΨm). Finally, the active anti-proliferations agents such as luteolin and luteolin-7-O-glucuronide were identified from EAF by NMR. This work suggests that EAF could be a functional food to treat the chronic diseases.

BACKGROUND We provide detailed analysis and outcomes in patients post-kidney transplant (KT) developing ascites, which has never been categorically reported. METHODS Ascites was identified by ICD9/10 codes and detailed chart review in patients post-KT from 01/2004-06/2019. The incidence of patient death and graft loss were determined per 100-person-years, and the incidence rate ratio was obtained. RESULTS Of 3329 patients receiving KT, 83 (2.5%) patients had new-onset ascites, of whom 58% were male, 21% blacks, and 29% whites. Seventy-five percentage were on hemodialysis. Patients were maintained primarily on tacrolimus and mycophenolate for immunosuppression. Only 14% of patients with ascites had the appropriate diagnostic workup. There was a trend toward an increased mortality in patients with ascites (incidence rate ratio, IRR [95% CI]: 1.8 [0.92, 3.19], p = .06), and a significantly higher incidence of graft loss (IRR: 5.62 [3.97, 7.76], p

Many studies have verified the safety of combined radiotherapy and immune checkpoint blockades (ICBs) without the specific radiation dose or sequencing of combination. We aimed to evaluate the expression and response of PD-1, TIM-3, LAG-3 after neoadjuvant radiotherapy (NRT) and explore the possibility and optimal schedule of combining immunotherapy with radiotherapy in treating rectal cancer. Immunohistochemistry was performed to detect the expression of PD-1, TIM-3, LAG-3, CD8, and CD3. These molecules' expression was detected on the specimens of 76 rectal cancer patients following NRT and 13 of these patients before NRT. The expression of ICBs was assessed by the percentage of positive cells. The levels of PD-1 and immune cells (ICs) LAG-3 in rectal cancer increased after NRT (0% vs. 3%, p=0.043 and 5% vs. 45%, p=0.039, respectively). However, TIM-3 in ICs and tumor cells (TCs) were both decreased (80% vs. 50%, p=0.011, 90% vs. 0%, p=0.000, respectively). The LAG-3 expression was higher in patients treated with short-course RT than long-course RT (22.5% vs. 8.0%, p=0.0440 in ICs; 0% vs. 70%, p0.001 in TCs). On the contrary, CD8 was higher after long-course RT (15% vs. 8%, p=0.0146). Interestingly, the level of ICs TIM-3 was low ineight weeks after long-course RT (p=0.045). The expressions of PD-1, ICs TIM-3, ICs LAG-3, CD3, and CD8 were associated with the disease-free survival (DFS) in univariate analysis (p=0.036, 0.008, 0.018, 0.025, and 0.004, respectively). Adjusted by the relevant variables, PD-1 (HR 0.274; 95% CI 0.089-0.840; p=0.024) and ICs TIM-3 (HR 0.425; 95% CI 0.203-0.890; p=0.023) were independent prognostic factors of DFS in rectal cancer patients following NRT. In conclusion, we have identified that PD-1 and ICs LAG-3 presented a trend towards increased expression after NRT, supporting the ICBs and NRT combination as a potential treatment option for local advanced rectal cancer patients. The radiotherapeutic mode and timing of the treatment might significantly affect the expression of ICBs, which indicated that the sequencing and time window of ICBs immunotherapy utility might deserve a high value.

The present study aimed to investigate the differential expression of long non-coding RNAs (lncRNAs) in rheumatoid arthritis (RA). High-throughput gene sequencing technology was used to detect the expression of lncRNA and mRNA in three patients with RA (RA group) and normal controls (NC group). A Bioinformatics analysis was used to assess the effects of differentially expressed mRNAs on signaling pathways and biological functions. The selected dysregulated lncRNAs were verified by reverse transcription-quantitative (RT-q)PCR in the peripheral blood mononuclear cells (PBMCs) of patients with RA and age- and sex-matched controls. A correlation analysis was used to analyze the relationship between lncRNAs and clinical indexes. From the lncRNA sequencing data, significantly differentially expressed lncRNAs between the RA and NC groups were identified by a fold change ≥2 and P

Peroxiredoxin 6 (PRDX6) is one antioxidant enzyme which could control the levels of reactive oxygen species and to avoid oxidative damage of sperm. In this study, we aimed to investigate the position change of PRDX6 in human sperm under oxidative stress during cryopreservation. Semen samples were obtained from 98 healthy donors and 27 asthenozoospermic donors. The plasma membrane protein and cytoplasmic protein of sperm samples were extracted and analyzed after cryopreservation. Western blot and immunofluorescence were used to measure the expressions of PRDX6. Liquid chromatography mass spectrometric (LC-MS/MS) analysis was performed to confirm the component of sperm membrane complex. Western blot showed that the detection rate of PRDX6 in plasma membranes with low sperm motility (≤20%) was significantly higher than that with high sperm motility (≥40%). Western blot and Immunofluorescence revealed that cryopreservation and thawing induced the position change of the PRDX6 from cytoplasm to sperm membrane. LC-MS/MS analysis showed that PRDX6, ADP/ATP translocase 4 (ANT4) and glyceraldehyde-3-phosphte dehydrogenase (GAPDHS) were present in the components of membrane complex after cryopreservation. The present study indicated that the presence of PRDX6 in sperm plasma membrane was related to sperm motility. GAPDHS and ANT4 may be involved the position change of the PRDX6 from cytoplasm to sperm membrane under oxidative stress during cryopreservation.

Background The vast majority of polyomavirus nephropathy (PVN) is due to BK virus, but rare cases result from JC virus reactivation. To date, only a handful of biopsy-proven JC-PVN cases have been reported. Here, we describe the clinical and pathologic findings in 7 patients with biopsy-proven JC-PVN. Methods Search of the pathology archives at 2 institutions found 7 cases of JC-PVN. Clinical data were extracted from the electronic medical records, and the biopsies were reviewed. Results Four cases were diagnosed at 6 y posttransplant or later. The remaining 3 cases presented within approximately 2 y posttransplant, of which 2 showed subclinical JC-PVN on surveillance biopsy. Two early presenting patients were treated for acute rejection just before acquiring JC-PVN. Late presenting patients had higher chronicity, which correlated to worse outcome. All but 1 biopsy showed nonspecific inflammation within areas of interstitial fibrosis without significant inflammation in unscarred cortex. The earliest presenting patient was the exception and showed active inflammation with tubulitis. Viral cytopathic changes were detected in all cases with moderate or high-histologic viral load (pvl), showing preference for the distal tubules and medulla. The 2 cases with low pvl did not demonstrate cytopathic changes but were SV40 positive. Conclusions JC-PVN can be insidious in presentation, which may cause delayed or missed diagnosis. Unlike BK-PVN, which typically occurs early in the posttransplant period, JC-PVN can occur both early and late following transplant. Overreliance on negative plasma and urine BK viral loads to exclude PVN can be a pitfall.

Background: The most severe effects of rheumatoid arthritis (RA) are loss of physical function, which may have a significant impact on self-perception of patient (SPP). However, the inherent relationship between SPP and the key proteins is not clear. The aim of this study was to get an insight into SPP of RA in connection with the the apoptosis-related proteins. Methods: We set out to investigate changes of the apoptosis-related proteins expression in the peripheral blood mononuclear cells (PBMCs) of RA. Additionally, we aimed to correlate the apoptosis-related proteins expression profiles with SPP and clinical indexes. To this end, we employed antibody microarrays of the the apoptosis-related proteins in PBMCs from four RA patients and seven healthy controls. We used bioinformatics to screen several the apoptosis-related proteins. To validate key protein candidates, we performed Enzyme linked immunosorbent assay (ELISA) on 30 RA patients and 30 healthy controls. Results: We found the expression of ten the apoptosis-related proteins (caspase3, CD40, SMAC, HSP27, HTRA, IGFBP-1, IGFBP-6, sTNF-R1, sTNF-R2, TRAILR-3) were significantly altered in PBMCs of RA patients. Receiver operating characteristic (ROC) curve analysis suggested that these ten the apoptosis-related proteins are potential biomarkers of RA. Spearman Correlation analysis and Logistic-regression analysis revealed that the 10 selected the apoptosis-related proteins correlated with SPP and clinical indexes. Conclusion: Therefore, we highlight some the apoptosis-related proteins may serve as potential biomarkers in prediction of SPP for RA patients, although the underlying mechanisms need to be further explored.

Objective. To analyse the clinical features of diabetic peripheral neuropathy (DPN) and employ data mining technology to explore the rules of Chinese herbal medicine (CHM) therapy. Methods. The clinical data of 216 patients with DPN and qi-yin deficiency syndrome were obtained, and the clinical features of the patients were assessed by cluster analysis. Relevant information was entered into the clinical diagnosis and treatment collection system, and data mining techniques were used to analyse the drug frequency, core CHM, CHM pair, and so on. Results. In this study, glycated haemoglobin (HbA1c) and homocysteine (HCY) were closely related to the pathogenesis of DPN. Overall, 162 patients had typical DPN syndrome characteristics, and we analysed 216 prescriptions, including 182 CHM. The frequencies of prescription of Astragalus membranaceus, Ligusticum wallichii, Poria cocos, and Radix Rehmanniae were greater than 45%. A Bayesian network analysis diagram showed that the 9 most common core CHM included Astragalus membranaceus, Ligusticum wallichii, Poria cocos, atractylodes rhizome, and Salvia miltiorrhiza Bge. According to the association rules of CHM, Radix Ophiopogon is used for Codonopsis pilosula; Astragalus membranaceus and atractylodes rhizome for Rehmannia are also frequently used. Astragalus membranaceus and Cinnamomi Ramulus or Ligusticum wallichii and Moutan bark were highly related to a decreased Michigan Diabetic Neuropathy Score. Conclusion. HbA1c and HCY are related risk factors for DPN. Numbness is a typical syndrome characteristic. Astragalus membranaceus is a monarch CHM and is used most frequently.

Kaposi sarcoma (KS) is a vascular neoplasm caused by human herpesvirus-8 (HHV-8) infection. KS is most often seen in individuals with acquired immunodeficiency syndrome but can occur in patients who are on immunosuppressive therapy. While the skin and oral mucosa are the typical sites for KS, lesions of the tonsil are quite rare with only a few reported cases. Here, we present a case of tonsillar KS occurring in a renal transplant patient. He presented with dysphagia, odynophagia, and weight loss. Oral examination revealed tonsillar hypertrophy with purple discoloration. Imaging revealed diffuse enlargement of Waldeyer's ring with enlarged right cervical lymph nodes, worrisome for post-transplant lymphoproliferative disorder. Microscopic examination of the tonsillectomy specimen showed a vascular proliferation positive for HHV-8, consistent with KS. The patient was subsequently treated with immunosuppression reduction and the addition of sirolimus, which resulted in complete resolution of oropharyngeal and cervical lesions.

Rheumatoid arthritis (RA) is a chronic autoimmune disorder that is diagnosed mainly on the basis of patient signs, symptoms, and laboratory indices. However, the exact causes of RA are unclear. Moreover, there is a lack of any method of dynamically evaluating the efficacy of the medication administered to treat RA. Here, we applied a random walk model to reveal the compatibility among the various constituents of traditional Chinese medicine and evaluate their therapeutic efficacy against RA. Drugs commonly used to treat RA were investigated using cluster analysis. The association rule analysis was applied to identify compatibilities among the constituents. A random walk model was developed to evaluate drug efficacy based on an in-house database comprising the clinical records of 9,408 RA patients. Frequently administered medicines were combined into three correlated sets. The evaluation based on the random walk method showed that the drug combination improved ESR, CRP, C3, C4, and IgA more effectively than any single drug. The present study demonstrated that the TCM constituents complement each other and various combinations of them produce different therapeutic effects on RA treatment.

To explore the prescription patterns of different dosage forms of Chinese herbal medicines (CHMs) for the treatment of rheumatoid arthritis (RA) and their effects on immune-inflammatory indices. Clinical data were collected from patients with RA in 4 hospitals (3 Class A comprehensive hospitals and 1 Class B comprehensive hospital) in Anhui Province, China, from August 2012 to June 2018 via the electronic medical record gathering system. Following extraction of prescription information, each prescribed herb was quantified and standardized according to the knowledge base to establish a database of RA treatment formulae. The medical records were divided into the granules group and decoction pieces group. Core herbs and their combination patterns were obtained from the two groups of cases using Liquorice software. Changes in immune-inflammatory and hepatic and renal function indices were compared between the two groups using SPSS 23.0 software. The Aprior module of SPSS Clementine 11.1 software was applied to analyse the correlation between CHMs and improvement in indices. Finally, the ORACLE 10 g tool was used to evaluate the random walk model of the immune-inflammatory indices between the two groups. (1) We retrospectively analysed 35,898 prescriptions for 6,829 patients with RA who received CHM treatment. There were 3,816 patients in the granules group and 3,013 in the decoction pieces group. (2) The core herbs were Pi (Spleen)-strengthening and dampness-resolving drugs, blood-activating and stasis-resolving drugs, wind/dampness-dispelling drugs and heat-clearing and detoxifying drugs. (3) Both dosage forms could improve immune-inflammatory indices in RA patients, with similar efficacy and no influence on hepatic or renal function. (4) Herba Siegesbeckiae and Oldenlandia had a stronger association with immune-inflammatory indices in the two groups. (5) The immune-inflammatory indices showed obvious improvement after treatment with granules and decoction pieces of CHMs, and there were long range correlations between the comprehensive evaluation indices and interventions. The principal CHM treatment methods for RA in four hospitals in Anhui Province are strengthening Pi and resolving dampness, activating blood and resolving stasis, dispelling wind/dampness and clearing heat. Granules and decoction pieces of CHMs have similar efficacy in improving immune-inflammatory indices in RA patients and could be used as treatment options for RA.