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Objective. This study aims to observe the changes in pupil diameter (PD) after anesthesia with different doses of sufentanil with the ultrasound method and observe whether pupil contraction is correlated with hemodynamic changes and bispectral index (BIS) values. Methods. A total of 124 patients between the ages of 18–65 with ASA I–II undergoing general anesthesia for surgery were enrolled in the study. According to the sufentanil dose initially injected, they were randomly divided into groups P, S1, S2, and S3, with 31 cases in each group. Group P was injected with normal saline. Group S1 was injected with 0.2 μg/kg of sufentanil. Group S2 was injected with 0.4 μg/kg of sufentanil. Group S3 was injected with 0.6 μg/kg of sufentanil. Following propofol administration and eye closure, the pupil diameter (PD) of the patients in the four groups was observed and measured by ultrasound after the loss of consciousness (T1) and within 3 min after the sufentanil injection at an interval of 30 s (30 s (T2), 1 min (T3), 1 min 30 s (T4), 2 min (T5), 2 min 30 s (T6), and 3 min (T7)). PD, systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), and BIS values at T1–T7 were recorded. Results. The ultrasonic method was used to observe that different doses of sufentanil could make the patients’ pupils contract. During anesthesia induction, the changes in PD have a positive correlation with SBP, DBP, HR, and BIS values. Conclusion. Ultrasound can become a new noninvasive method to monitor pupil changes during general anesthesia, and ultrasonic observation of pupil changes has great potential for individualized analgesia management in the perioperative period.

Considering the protective ability of proteins and the potential toxicity of free Cu(II), it was proposed herein that the co-presence of protein could play an important role in suppressing the toxicity of free Cu(II) to the stability of bioactive quercetin if a flavonoid-protein-Cu(II) complex could be formed. In this study, the interaction between quercetin (a major flavonoid in the human diet) and bovine serum albumin (BSA) was investigated in the absence and presence of free Cu(II). The results demonstrated that both quercetin and free Cu(II) had a strong ability to quench the intrinsic fluorescence of BSA through a static procedure (i.e., formation of a BSA-monoligand complex). Site marker competitive experiments illustrated that the binding of both quercetin and Cu(II) to BSA mainly took place in subdomain IIA. The quenching process of free Cu(II) with BSA was easily affected by quercetin, and the increased binding capacity possibly resulted from the generation of a ternary quercetin-BSA-Cu(II) complex. The stability and free radical scavenging activity of bioactive quercetin during incubation was promoted in the BSA-diligand complex relative to a quercetin-Cu(II) complex. A quercetin-Cu(II) system could generate reactive oxygen species such as hydrogen peroxide (H

Lysine crotonylation (Kcr) is a newly identified protein translational modification and is involved in major biological processes including glycolysis, but its role in colorectal cancer (CRC) is unknown. Here, we found that the Kcr of α enolase (ENO1) was significantly elevated in human CRC tissues compared with the paratumoral tissues. CREB-binding protein (CBP) functioned as a crotonyltranferase of ENO1, and SIRT2 was involved in the decrotonylation of ENO1. Using quantitative mass spectrometry for crotonylomics analysis, we further found that K420 was the main Kcr site of ENO1 and ENO1 K420 Kcr promoted the growth, migration, and invasion of CRC cells in vitro by enhancing the activity of ENO1 and regulating the expression of tumor-associated genes. Our study reveals an important mechanism by which ENO1 regulates CRC through crotonylation.

NLRP3 inflammasome-dependent pyroptosis has been implicated in liver fibrosis progression. However, the definite intrahepatic cell types that undergo pyroptosis and the underlying mechanism as well as the clinical importance remain unclear. Here, augmented levels of pyroptosis-related indicators GSDMD, IL-1β, and IL-18 were verified in both liver fibrosis patients and CCl4-induced fibrotic mouse model. Confocal imaging of NLRP3 with albumin, F4/80 or α-SMA revealed that enhanced NLRP3 was mainly localized to kupffer cells (KCs), indicating that KCs are major cell types that undergo pyroptosis. Targeting pyroptosis by inhibitor MCC950 attenuated the severity and ameliorated liver function in fibrosis models. In addition, elevated S100A8 in liver fibrosis patients was correlated with pyroptosis-related indicators. S100A8 stimulated pyroptotic death of macrophages, which resulted in activation of human hepatic stellate cell line LX-2 cells and increased collagen deposition. Mechanistically, S100A8 activated TLR4/NF-κB signaling and upregulated its target genes NLRP3, pro-IL-1β, and pro-IL-18 expression, and induced reactive oxygen (ROS) abundance to activate NLRP3 inflammasome, finally leading to pyroptotic cell death in macrophages. More importantly, circulating GSDMD had the optimal predicting value for liver fibrosis progression. In conclusion, S100A8-mediated NLRP3 inflammasome-dependent pyroptosis by TLR4/NF-κB activation and ROS production in macrophages facilitates liver fibrosis progression. The identified GSDMD has the potential to be a biomarker for liver fibrosis evaluation.

Background: In the STEP trial (Strategy of Blood Pressure Intervention in older Hypertensive Patients), the risk of cardiovascular events is significantly lower in patients who received intensive systolic blood psressure (BP) treatment than in those who received standard treatment. This study compared the lifetime health benefits and medical costs of intensive BP treatment with those of standard BP treatment. Methods: A microsimulation model included 10 000 hypothetical samples of Chinese adults aged 60 to 80 years old with baseline systolic BP higher than 140 mm Hg. Primary outcome was the incremental cost-effectiveness ratio from a payer’s perspective. Secondary outcome was cardiovascular events, including acute coronary syndrome, stroke, acute decompensated heart failure, atrial fibrillation, and death from cardiovascular causes. Results: The model simulated that cardiovascular events occurred in 36.88% of the patients in the intensive treatment group, as compared to 41.28% of the patients in the standard treatment group over the lifetime horizon. The mean number of quality-adjusted life-years would be 0.16 higher in patients who received intensive treatment than in those who received standard treatment and would cost Chinese yuan 12 614 (International dollars 3018) more per quality-adjusted life-year gained. Most simulation results indicated that intensive treatment would be cost-effective (82%–95% below the willingness-to-pay threshold of Chinese yuan 72 000 [1× the gross domestic product per capita in China in 2020]). Sensitivity analyses showed that these conclusions were robust. Conclusions: In this study, intensive BP treatment prevented cardiovascular events among older patients with hypertension in China and was cost-effective in most scenarios. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03015311

The interactions between quercetin and bovine (or human) hemoglobin (Hb) were systematically investigated by fluorescence, UV-vis absorption spectroscopy, and molecular docking to demonstrate the structural mechanism by which quercetin affected the Hb redox state and stability. Quercetin could interact with the central cavity of the Hb molecule with one binding site to generate an Hb-quercetin complex, and the hydrophobic interaction played an important role in the formation of the complex. The binding constant for the Hb-quercetin complex at 298 K was observed to be 1.25 × 10

BACKGROUND Although gestation and childbirth are progressive physical processes for most pregnant women, there are both physical and great psychosocial challenges throughout the process, which increase the sensitivity and vulnerability of women. Even for women with low-risk pregnancies, it is common to experience degrees of fear, especially for primipara women when faced with childbirth. During their first pregnancy, women may have no relevant health knowledge or experience with delivery and have difficulty identifying prenatal depression and other existing mental health factors; a fear of childbirth (FOC) may engender adverse outcomes for mothers and babies. Social support is a very important influential factor for prenatal depression. METHODS This study adopted a descriptive cross-sectional design. The participant cohort involved 609 primipara women (≥18 years old) who had received routine prenatal care and visited a tertiary care hospital in Xi'an. The participants completed structured questionnaires, including the 10-item Edinburgh Postnatal Depression Scale (EPDS), 12-item Multidimensional Scale of Perceived Social Support (MSPSS), and 33-item Wijma Delivery Expectancy/Experience Questionnaire (W-DEQ), alongside contribution of information regarding their demographic characteristics. Descriptive and correlation analyses were adopted to verify the correlations among these variables. Multiple regression models were examined by the SPSS PROCESS procedure with bootstrapping to confirm the significance of the mediation effect. RESULTS The widespread prevalence of FOC in healthy pregnant women was 22.3% (WDEQ score ≥85). The mean scores of depression, social support, as well as FOC scores of participants were 9.50 (5.19), 70.91 (9.25), and 70.43 (20.88), respectively. Remarkable correlations were identified between pregnancy depressive symptoms, social support, and FOC. Results presented an indirect effect, indicating that the impacts of antenatal depression on FOC were mediated by social support. CONCLUSIONS Perceived social support played a mediating role between antenatal depression and FOC among healthy primipara women. Techniques and suggestions for boosting social support may be expected to have a positive impact on the depressive symptoms of pregnant women with FOC.

BACKGROUND: The coronavirus disease-2019 pandemic led to rapid expansion of telehealth services. This was speculated to improve healthcare access among underserved populations, including individuals unable to take time off work or arrange transportation. OBJECTIVE: We completed a quality improvement project to evaluate the feasibility of hybrid consultations that combined televisits and abbreviated in-person visits for neuromuscular referrals. METHODS: Using a censoring date of August 5, 2021, we reviewed all outpatient neuromuscular consultations from August 5, 2020 to February 5, 2021. For both hybrid and traditional in-person consultations, we reviewed no-show rates, completion rates of ordered diagnostic workup, and billing codes. For hybrid consultations only, we also reviewed intervals between initial televisit and subsequent examination and rates of video-enhanced versus audio-only televisits. RESULTS: During the study period, we completed 153 hybrid and 59 in-person new-patient consultations (no-show rates 9% and 27% respectively.) For hybrid consultations, 77% and 73% of laboratory and imaging studies were completed respectively, compared to 89% and 91% for in-person consultations. For hybrid visits, average RVUs (a marker for reimbursement) per consultation depended on whether audio-only televisits were billed as telephone calls or E/M visits per insurance payer rules, while video-enhanced televisits were uniformly billed as E/M visits. This resulted in average RVUs between 2.09 and 2.26, compared to 2.30 for in-person consultations. CONCLUSIONS: Telehealth-based hybrid neuromuscular consultations are feasible with minor caveats. However, the future of telehealth may be restricted by decreasing reimbursement rates particularly for audio-only televisits, limiting its potential to improve healthcare access.

p97/VCP, an evolutionarily concerned ATPase, partakes in multiple cellular proteostatic processes, including the endoplasmic reticulum (ER)-associated protein degradation (ERAD). Elevated expression of p97 is common in many cancers and is often associated with poor survival. Here we report that the levels of p97 positively correlated with the histological grade, tumor size, and lymph node metastasis in breast cancers. We further examined p97 expression in the stem-like cancer cells or cancer stem cells (CSCs), a cell population that purportedly underscores cancer initiation, therapeutic resistance, and recurrence. We found that p97 was consistently at a higher level in the CD44+/CD24−, ALDH+, or PKH26+ CSC populations than the respective non-CSC populations in human breast cancer tissues and cancer cell lines and p97 expression also positively correlated with that of SOX2, another CSC marker. To assess the role of p97 in breast cancers, cancer proliferation, mammosphere, and orthotopic growth were analyzed. Similarly as p97 depletion, two pharmacological inhibitors, which targets the ER-associated p97 or globally inhibits p97’s ATPase activity, markedly reduced cancer growth and the CSC population. Importantly, depletion or inhibition of p97 greatly suppressed the proliferation of the ALDH+ CSCs and the CSC-enriched mammospheres, while exhibiting much less or insignificant inhibitory effects on the non-CSC cancer cells. Comparable phenotypes produced by blocking ERAD suggest that ER proteostasis is essential for the CSC integrity. Loss of p97 gravely activated the unfolded protein response (UPR) and modulated the expression of multiple stemness and pluripotency regulators, including C/EBPδ, c-MYC, SOX2, and SKP2, which collectively contributed to the demise of CSCs. In summary, p97 controls the breast CSC integrity through multiple targets, many of which directly affect cancer stemness and are induced by UPR activation. Our findings highlight the importance of p97 and ER proteostasis in CSC biology and anticancer therapy.

Myeloperoxidase (MPO)-dependent hypochlorous acid (HOCl) generation plays crucial roles in diabetic vascular complications. As a natural polyphenol, quercetin has antioxidant properties in various diabetic models. Herein, we investigated the therapeutic mechanism for quercetin on MPO-mediated HOCl generation and endothelial dysfunction in diabetic vasculature. In vitro, the presence of MPO could amplify high glucose-induced endothelial dysfunction which was significantly inhibited by the NADPH oxidase inhibitor, HOCl or H2O2 scavengers, revealing the contribution of MPO/H2O2/HOCl to vascular endothelial injury. Furthermore, quercetin effectively inhibited MPO/high glucose-mediated HOCl generation and cytotoxicity to vascular endothelial cells. The inhibitive effect on MPO activity was related to the fact that quercetin reduced high glucose-induced H2O2 generation in endothelial cells and directly acted as a competitive substrate for MPO, thus limiting MPO/H2O2-dependent HOCl production. Moreover, quercetin could attenuate HOCl-caused endothelial dysfunction in endothelial cells and isolated aortas. In vivo, dietary quercetin significantly inhibited aortic endothelial dysfunction in diabetic mice, while this compound simultaneously suppressed vascular MPO expression and activity. Therefore, it was demonstrated herein that quercetin inhibited endothelial injury in diabetic vasculature via suppression of MPO/high glucose-dependent HOCl formation.

Objective To seek out the effect of curcumin on cholesterol efflux in THP-1 macrophages and clarify its specific mechanism. Methods THP-1 macrophages were cultured with curcumin at different concentrations, followed by detection of the toxicity of curcumin to cells utilizing CCK-8 assay. Following culturing with serum-free ox-LDL, THP-1 macrophages were transfected with mi-miR-125a-5p, or in-miR-125a-5p, or pcDNA3.1-SIRT6, or si-SIRT6 for 24 hr, prior to treatment with curcumin at different concentrations. Oil red O staining was applied to examine the formation rate of foam cells, the kits were used for measuring intracellular lipid content of THP-1 macrophages, and the fluorescence detection kit for observing the cholesterol efflux rate. The expressions of miR-125a-5p, SIRT6, and ABCA1 were assayed by qRT-PCR and Western blot. ELISA was adopted to assess the contents of TNF-α, IL-6, and MCP-1. The interaction between miR-125a-5p and SIRT6 was evaluated by dual-luciferase reporter gene assay. Results The optimal dosage of curcumin could reduce foam cell formation and intracellular lipid content, and promote cholesterol efflux in THP-1 macrophages. Meanwhile, curcumin markedly suppressed the expression of miR-125a-5p and upregulated the expression of SIRT6. MiR-125a-5p negatively targeted SIRT6. Overexpression of SIRT6 partially reversed the inhibition role of miR-125a-5p mimic in the biological function of curcumin. Silencing of SIRT6 could partially reverse the effect of the miR-125a-5p inhibitor on the biological function of curcumin. Conclusion urcumin could promote cholesterol efflux of THP-1 macrophages through miR-125a-5p/SIRT6 axis and regulate the expression of ABCA1.

To determine the distribution of two important virulence factors [lipooligosaccharide (LOS) and capsular polysaccharide (CPS)] inWhole-genome sequencing was carried out for 494Nine novel and 29 previously confirmed LOS classes were identified. LOS classes A, B, and C were the most common (48.2%, 238/494) among the 494 strains. Twenty-six capsular types were identified in 448 strains. HS2, HS4c, HS5/31, HS19, and HS8/17 were the most frequent CPS genotypes (58.7%, 263/448). Strains of 17 CPS genotypes (strain number5) had one or two prevalent LOS classes (Our results describe the genetic characteristics of the important virulence factors in

Organoid culture is an approach that allows three-dimensional growth for stem cells to self-organize and develop multicellular structures. Intestinal organoids have been widely used to study cellular or molecular processes in stem cell and cancer research. These cultures possess the ability to maintain cellular complexity as well as recapitulate many properties of the human intestinal epithelium, thereby providing an ideal in vitro model to investigate cellular and molecular signaling pathways. These include, but are not limited to, the mechanisms required for maintaining balanced populations of epithelial cells. Notch signaling is one of the major pathways of regulating stem cell functions in the gut, driving proliferation and controlling cell fate determination. Notch also plays an important role in regulating tumor progression and metastasis. Understanding how Notch pathway regulates epithelial regeneration and differentiation by using intestinal organoids is critical for studying both homeostasis and pathogenesis of intestinal stem cells that can lead to discoveries of new targets for drug development to treat intestinal diseases. In addition, use of patient-derived organoids can provide effective personalized medicine. This review summarizes the current literature regarding epithelial Notch pathways regulating intestinal homeostasis and regeneration, highlighting the use of organoid cultures and their potential therapeutic applications.

Background The number of cancer patients with diabetes mellitus (DM) is steadily rising. Little is known about the nutritional status of this population. This study characterized the nutritional status and survival of cancer patients with diabetes compared with those without diabetes. Methods A total of 8247 cancer patients were prospectively enrolled from 72 hospitals in China and followed until August 2019. A global estimation of the nutritional status was performed for each participant using standardized tools. The outcomes were cancer‐specific survival (CSS) and overall survival (OS). Results The incidence of diabetes was 7.6% in the whole population. In comparison with the non‐DM group, the DM group had greater body weight, but a similar fat‐free mass, a lower handgrip strength and a decreased Karnofsky performance score. A higher proportion of patients with diabetes were overweight/obese as indicated by BMI. The percentage of patients who were at risk of malnutrition (evaluated by PG‐SGA) was higher in the DM group (score ≥ 4, 56.7% vs 52.9%). Patients with DM showed a worse CSS (4‐year CSS, 62% vs 73%) and OS (4‐year OS 39% vs 52%). Diabetes was associated with an increased risk of both cancer‐specific (hazard ratio (HR) = 1.282, 95% confidence interval (CI) 1.070‐1.536) and overall (HR = 1.206, 95% CI 1.040‐1.399) mortality. Conclusions Cancer patients with diabetes had a larger body mass but lower muscle strength, poorer performance status and higher incidence of malnourishment. Diabetes was associated with compromised survival. Tailored nutritional intervention is necessary for this subpopulation of patients., In this large prospective cohort study, cancer patients with diabetes were found to have bigger body mass yet lower muscle strength, poorer performance status and higher incidence of malnourishment. Complication with diabetes independently predicted compromised survival among cancer patients.

BACKGROUND Currently, the prognostic stratification and therapeutic evaluation systems for multiple myeloma (MM) lack specific molecular indicators. OC-STAMP is a new gene and is also highly expressed in MM. METHODS A total of 160 MM patients have been investigated with both quantitative reverse transcription PCR (RT-qPCR), flow cytometry (FCM) and cytogenetic FISH on the same mononuclear cells isolated from bone marrow specimens. RESULTS We found that OC-STAMP mRNA levels were significantly higher in newly diagnosed cases of MM than in healthy donors (median, 0.52% vs. 0.02%, P

Background: Although the use of expanded-criteria donors (ECDs) alleviates the problem of organ shortage, it significantly increases the incidence of delayed graft function (DGF). DGF is a common complication after kidney transplantation; however, the effect of DGF on graft loss is uncertain based on the published literature. Hence, the aim of this study was to determine the relationship between DGF and allograft survival. Methods: We conducted a retrospective, multicenter, observation cohort study. A total of 284 deceased donors and 541 recipients between February 2012 and March 2017 were included. We used logistic regression analysis to verify the association between clinical parameters and DGF, and Cox proportional hazards models were applied to quantify the hazard ratios of DGF for kidney graft loss. Results: Among the 284 deceased donors, 65 (22.8%) donors were ECD. Of the 541 recipients, 107 (19.8%) recipients developed DGF, and this rate was higher with ECD kidneys than with standard-criteria donor (SCD) kidneys (29.2% vs. 17.1%; P = 0.003). The 5-year graft survival rate was not significantly different between SCD kidney recipients with and without DGF (95.8% vs. 95.4%; P= 0.580). However, there was a significant difference between ECD kidney recipients with and without DGF (71.4% vs. 97.6%; P = 0.001), and the adjusted hazard ratio (HR) for graft loss for recipients with DGF was 1.885 (95% confidence interval [CI] = 1.305–7.630; P = 0.024). Results showed that induction therapy with anti-thymocyte globulin was protective against DGF (odds ratio= 0.359; 95% CI= 0.197–0.652; P= 0.001) with all donor kidneys and a protective factor for graft survival (HR = 0.308; 95% CI = 0.130–0.728; P = 0.007) with ECD kidneys. Conclusion: DGF is an independent risk factor for graft survival in recipients with ECD kidneys, but not SCD kidneys. Key words: Chronic kidney disease; Delayed graft function; Expanded-criteria donors; Graft survival; Standard-criteria donors

Cigarette smoke is a common global environmental pollutant. Asthma, the most frequent allergic airway disease, is related to maternal exposure to cigarette smoke. Our previous studies demonstrated that prenatal exposure to nicotine (PNE), the major active product of smoking, impairs fetal thymopoiesis and CD4

Evidence suggests that there is a close association between myeloperoxidase (MPO) gene rs2333227 G>A polymorphism with Alzheimer’s disease (AD) susceptibility. We conducted a meta-analysis to explore the precise association between MPO rs2333227 G>A polymorphism and AD susceptibility. Online databases were searched and the relevant information was collected. Crudeodds ratios with 95% confidence intervals were calculated. Trial sequential analysis (TSA), heterogeneity analyses, accumulative analyses, sensitivity analyses, and publication biasestests were performed. Overall, nine publications (ten independent case-controls) were included in this meta-analysis, involving 3260 participants. Pooled results revealed no significant association between MPO rs2333227 G>A polymorphism and AD susceptibility was observed. TSA showed that the present meta-analysis remained inconclusive due to insufficient evidence. In summary, the current meta-analysis indicated that the MPO rs2333227 G>A polymorphism may not be acausalfactor in the development of AD.

Liver has numerous critical metabolic functions including lipid metabolism, which is usually dysregulated in obesity, the metabolic syndrome, and non-alcoholic fatty liver disease (NAFLD). Increasing evidence indicates bone morphogenetic proteins (BMPs) play an important role in adipogenesis and thermogenic balance in adipogenic progenitors and adipose tissue. However, the direct impact of BMPs on hepatic steatosis and possible association with NAFLD are poorly understood. Here, we found that BMP4 was up-regulated in oleic acid-induced steatosis and during the development of high fat diet (HFD)-induced NAFLD. Exogenous BMP4 reduced lipid accumulation and up-regulated the genes involved in lipid synthesis, storage and breakdown in hepatocytes. Exogenous BMP4 inhibited hepatic steatosis, reduced serum triglyceride levels and body weight, and alleviated progression of NAFLD in vivo. Mechanistically, BMP4 overexpression in hepatocytes down-regulated most components of the mTORC1 signaling axis. Collectively, these findings strongly suggest that BMP4 may play an essential role in regulating hepatic lipid metabolism and the molecular pathogenesis of NAFLD. Manipulating BMP4 and/or mTORC1 signaling axis may lead to the development of novel therapeutics for obesity, metabolic syndrome, and NAFLD.

Circular RNAs (circRNAs) have been established to be involved in numerous processes in the human genome, but their function in vascular aging remains largely unknown. In this study, we aimed to characterize and analyze the function of a circular intronic RNA, ciPVT1, in endothelial cell senescence. We observed significant downregulation of ciPVT1 in senescent endothelial cells. In proliferating endothelial cells, ciPVT1 knockdown induced a premature senescence‐like phenotype, inhibited proliferation, and led to an impairment in angiogenesis. An in vivo angiogenic plug assay revealed that ciPVT1 silencing significantly inhibited endothelial tube formation and decreased hemoglobin content. Conversely, overexpression of ciPVT1 in old endothelial cells delayed senescence, promoted proliferation, and increased angiogenic activity. Mechanistic studies revealed that ciPVT1 can sponge miR‐24‐3p to upregulate the expression of CDK4, resulting in enhanced Rb phosphorylation. Moreover, enforced expression of ciPVT1 reversed the senescence induction effect of miR‐24‐3p in endothelial cells. In summary, the present study reveals a pivotal role for ciPVT1 in regulating endothelial cell senescence and may have important implications in the search of strategies to counteract the development of age‐associated vascular pathologies., We characterized a novel circular intronic RNA ciPVT1, which originates from intron 4 of the PVT1 gene, was markedly reduced in senescent endothelial cells. Further functional and mechanistic investigations revealed that ciPVT1 may act as a competing endogenous RNA (ceRNA) to regulate CDK4 and its downstream gene by decoying miR‐24‐3p, thereby delaying endothelial cell senescence.

Background Published researches have suggested some associations between PPAR‐γ and ischemic stroke (IS) development. This meta‐analysis was conducted to evaluate the association between PPAR‐γ gene polymorphisms and IS risk. Materials and methods A systematic search was conducted in PubMed, Embase, Web of Science, China National Knowledge Infrastructure, and WanFang databases. The pooled association of odd ratios (ORs) and its 95% confidence interval (CI) was calculated to assess the IS risk of PPAR‐γ rs1801282 C/G and rs3856806 C/T polymorphisms. Furthermore, the heterogeneity test, cumulative analyses, sensitivity analyses, and publication bias were conducted. Result Sixteen publications with 3786 cases and 5343 controls were identified. Overall findings indicated that rs1801282 C/G polymorphism may be associated with an increased risk for IS (GG vs. CC: OR = 2.17 95%CI = 1.09–4.35, p = .03, I 2 = 0%; GG vs. CC+CG: OR = 2.15, 95%CI = 1.07–4.32, p = .03, I 2 = 0%). The similar results were also found in the subgroup analysis. In addition, no significant association was observed between rs3856806 C/T polymorphism and IS risk. Conclusion In conclusion, our study showed that PPAR‐γ rs1801282 C/G polymorphism probably plays an important role in IS occurrence. The result should be verified with more studies in the future., Ischemic strokes (IS) are one of the most common diseases resulting in disabilities and death among adults. Our meta‐analysis indicated that the individuals with G mutation of rs1801282 C/G polymorphism would face an increased risk of IS. But there was no significant association between rs3856806 C/T polymorphism and IS risk.

The endoplasmic reticulum unfolded protein response (UPR) is a conserved adaptive signaling in ER homeostasis and has emerged as critical in highly proliferating cells and potential treatment target for acute T-cell lymphoblastic leukemia (T-ALL).

Background Resistance to standard therapy is a major reason for the poor prognosis of pancreatic ductal adenocarcinoma (PDAC). Developing novel therapy to overcome PDAC drug-resistance is urgently needed. CRABP-II was highly expressed in all PDAC but not expressed in normal pancreatic tissues and chronic pancreatitis. CRABP-II was shown to promote PDAC migration and metastasis while its potential role in promoting PDAC drug-resistance was not known. Methods A paired cohort of human primary and relapsing PDAC tissues was assessed for CRABP-II expression by immunohistochemistry. CRISPR/cas9 gene editing was used to establish CRABP-II knockout cell lines and MTT assays were performed to assess gemcitabine sensitivity in vitro. Cleaved caspase-3/PARP blots and Annexin V staining were conducted to detect cell apoptosis. Gene expression microarray, Q-PCR, western blots, Co-IP and RNA-IP were used to study the molecular function of CRABP-II. Sucrose gradient ultracentrifugation was applied to isolate lipid rafts and LC–MS-MS was used to assess cholesterol content. Both subcutaneous CDX models and orthotopic PDX models were established to examine the efficacy of SNIPER-11 and the synergistic effect between SNIPER-11 and gemcitabine in vivo. Results A higher expression of CRABP-II was found in relapsing PDAC tissue and was associated with poor prognosis. Gemcitabine-resistant cell lines exhibited increased level of CRABP-II, while CRABP-II knockout resensitized PDAC cells to gemcitabine. Mechanistically, aberrant expression of CRABP-II increased the stability of SREBP-1c mRNA through cooperation with HuR and upregulated the downstream genes of SREBP-1c to favor cholesterol uptake and accumulation in lipid rafts. Increased lipid raft cholesterol accumulation facilitated ATK survival signaling and PDAC drug resistance. The small compound SNIPER-11 treatment effectively induced CRABP-II protein degradation, induced apoptosis, and suppressed tumor growth. Combination of SNIPER-11 and gemcitabine significantly reduced the lipid raft cholesterol content in CDX/PDX and profoundly inhibited tumor progression. Conclusions These findings identified CRABP-II as a novel regulator of cholesterol metabolism and suggested that CRABP-II is a selective target for overcoming PDAC drug resistance.

Purpose To investigate the frailty status in Chinese cancer patients through establishing a novel prediction algorithm. Methods The percentage of frailty in various age groups, locations, and tumor types in Chinese cancer patients was investigated. The prediction capacity of frailty on mortality of Chinese cancer patients was analysed by the frailty index composing of routine laboratory data (FI‐LAB) accessible from a blood test and calculated as the ratio of abnormal factors to 22 total variables. The establishment of a novel algorithm, MCP (mortality of cancer patients), to predict the 5‐year mortality in Chinese cancer patients was accomplished and the algorithm's prediction capacity was tested in the training and validation sets using receiver operating characteristic (ROC) analysis. Results We found that the risk of death in cancer patients can be successfully identified through FI‐LAB. The univariable and multivariable Cox regression were used to evaluate the effect of frailty on death. In the 5‐year follow‐up, 20.6% of the 2959 participants (age = 55.8 ± 11.7 years; 43.5% female) died, while the mean FI‐LAB score in baseline was 0.23 (standard deviation = 0.13; range = 0–0.73). Frailty (after adjusting for gender, age, and other confounders) directly correlated with an increased risk of death, hazard ratio of 12.67 (95% confidence interval [CI]: 7.19, 22.31), compared to those without frailty. In addition, the MCP algorithm (MCP) = 3.678 × FI‐LAB + 1.575 × sex + 1.779 × first tumor node metastasis staging, presented an area under the ROC (AUC) of 0.691 (95% CI: 0.656–0.726) and 0.648 (95% CI: 0.613–0.684) in the training and validation sets, respectively. Conclusion Frailty as defined by FI‐LAB was common and indicated a significant death risk in cancer patients. Our novel developed algorithm MCP had a passable prediction capacity on 5‐year MCP., To investigate the frailty status in Chinese cancer patients through establishing a novel prediction algorithm. Frailty as defined by FI‐LAB (frailty index composing of routine laboratory data) was common and indicated a significant death risk in cancer patients. Our novel developed algorithm mortality of cancer patients had a passable prediction capacity on 5‐year mortality of cancer patients.

Introduction/Aims The initial surge of the coronavirus disease‐2019 (COVID‐19) pandemic in early 2020 led to widespread cancellation of elective medical procedures in the United States, including nonurgent outpatient and inpatient electrodiagnostic (EDx) studies. As certain regions later showed a downtrend in daily new cases, EDx laboratories have reopened under the guidance of the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM). In our reopening experience guided by the AANEM, we measured relevant outcomes to determine further workflow adaptations. We aimed to detail our experience and share the lessons learned. Methods We reviewed the clinical volumes, billing data, diagnosis distributions, and rates of COVID‐19 exposure and transmission among patients and staff in our EDx laboratory during the first 6 months of reopening, starting on June 1, 2020. For context, we detailed the recent AANEM guidelines we adopted at our laboratory, supplemented by other consensus statements. Results We completed 816 outpatient studies from June 1 to December 1, 2020, reaching 97% of the total volume and 97% of total billing compared with the same time period in 2019. The average relative value units per study were similar. There were no major shifts in diagnosis distributions. We completed 10 of 12 requested inpatient studies during this period. There were no known COVID‐19 transmissions between patients and staff. Discussion Our experience suggests that it is possible to safely operate an EDx laboratory under the guidance of the AANEM and other experts, with clinical volume and billing rates comparable to pre‐pandemic baselines.

Small fiber neuropathy (SFN) is common, and can be associated with many medical conditions. The majority of the patients with SFN suffer from painful paresthesia which can negatively impact their quality of life. Skin biopsy with intraepidermal nerve fiber density evaluation is the gold standard diagnostic test. Autonomic function testing is useful when autonomic symptoms are present. Screening for associated conditions should be done in every patient, even when a known underlying associated condition is present, before the neuropathy evaluation. Etiology-specific treatment, lifestyle modification, and pain control are the key elements of SFN management. This article will review the clinical presentation, skin biopsy procedure, utility of diagnostic tests, associated conditions, management, and prognosis of SFN.

Background/objectives The assessment of nutritional status and the quality of life in patients with gastric cancer has become one of the important goals of current clinical treatment. The purpose of this study was to assess the nutritional status in hospitalized gastric cancer patients by using patient-generated subjective global assessment (PG-SGA) and to analyze the influence of nutritional status on the patients’ quality of life (QOL). Methods We reviewed the pathological diagnosis of gastric cancer for 2322 hospitalized patients using PG-SGA to assess their nutritional status and collected data on clinical symptoms, the anthropometric parameters (height, weight, body mass index (BMI), mid-arm circumference (MAC), triceps skin-fold thickness (TSF), and hand-grip strength (HGS). We also collected laboratory data (prealbumin, albumin, hemoglobin) within 48 h after the patient was admitted to the hospital. The 30-item European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30) was used for QOL assessment in all patients. Results By using PG-SGA, we found 80.4% of the patients were malnourished (score ≥ 4) and 45.1% of the patients required urgent nutritional support (score ≥ 9). In univariate analysis, old age (> 65 years, p

BACKGROUND In the pathogenesis and progression of prostate cancer, cell proliferation and cell migration results in tumor invasion and metastasis that is associated with patient morbidity and mortality. Rho-associated protein kinase (ROCK) has previously been shown to be upregulated in prostate cancer, but its biological role remains poorly understood. This study aimed to investigate the role of ROCK in the proliferation and migration of PC-3 and DU145 prostate cancer cells and to identify the possible targets involved by knockdown of ROCK1 and ROCK2 RNA expression. MATERIAL AND METHODS An RNA interference (RNAi) assay was performed to silence the expression of ROCK1 and ROCK2 in the PC-3 and DU145 human prostate cancer cell lines. Cells were also treated with a specific ROCK inhibitor, Y27632. A cell counting kit-8 (CCK-8) assay was used to determine the proliferation rate of prostate cancer cells, and cell migration and invasion assays were performed. Western blot and polymerase chain reaction were used to measure protein and RNA expression levels. RESULTS In PC-3 and DU145 prostate cancer cells, knockdown of ROCK1 and ROCK2 reduced cell migration and invasion. ROCK1 and ROCK2 regulated cell proliferation in PC-3 and DU145 prostate cancer cells. Protein levels of phosphorylated LIM kinase 1 (p-LIMK1) and matrix metalloproteinase-2 (MMP-2) were reduced in ROCK1 and ROCK2 siRNA transfected cells. CONCLUSIONS In PC-3 and DU145 human prostate cancer cells, ROCK promoted cell proliferation and migration by targeting LIMK1 and MMP-2.

Objective: To examine the cellular distribution and the expression of CD200 and its receptor 1 (CD200R1) in human deciduas in first-trimester pregnant women with spontaneous early abortion (SEA) an...

Background We examined changes in hepatitis B core-related antigen (HBcrAg) during the four sequential phases of chronic hepatitis B virus (HBV) infection: hepatitis B e antigen (HBeAg)-positive chronic infection (EPCI) and hepatitis (EPCH), followed by HBeAg-negative chronic infection (ENCI) and hepatitis (ENCH). We compared the performance of serum HBcrAg, hepatitis B surface antigen (HBsAg), and HBV DNA in predicting EPCH and ENCH. Methods We enrolled 492 consecutive patients: 49 with EPCI, 243 with EPCH, 101 with ENCI, and 99 with ENCH. HBcrAg was detected by chemiluminescent enzyme immunoassays. HBsAg and HBeAg were detected by chemiluminescent microparticle immunoassays. HBV DNA was detected by real-time PCR. Predictive performance of HBcrAg, HBsAg, and HBV DNA was evaluated using ROC curves. Results Areas under ROC curves (AUCs) of HBcrAg, HBsAg, and HBV DNA for predicting EPCH were 0.738, 0.812, and 0.717, respectively; optimal cutoffs were ≤1.43×10⁵ kU/mL, ≤1.89×10⁴ IU/mL, and ≤3.97×10⁷ IU/mL, with sensitivities and specificities of 66.3% and 77.6%, 65.0% and 93.9%, and 60.5% and 79.6%, respectively. AUCs of HBcrAg, HBsAg, and HBV DNA for predicting ENCH were 0.887, 0.581, and 0.978, respectively; optimal cutoffs were >26.8 kU/mL, >2.29×10² IU/mL, and >8.75×10³ IU/mL, with sensitivities and specificities of 72.7% and 95.1%, 86.9% and 39.6%, and 89.9% and 92.1%, respectively. Conclusions HBsAg and HBV DNA were the best predictors of EPCH and ENCH, respectively. HBcrAg is an important surrogate marker for predicting EPCH and ENCH.

Purpose To explore the effects of group singing therapy on depression symptoms and quality of life of patients with stable chronic obstructive pulmonary disease (COPD). Methods Patients with COPD were randomly allocated to intervention (n = 30) and control groups (n = 30). The intervention group received group singing therapy once a week for 24 sessions along with routine health education, whereas the control group only received the routine health education. All patients were administered the Hospital Anxiety and Depression Scale depression subscale (HADS-D) and the Clinical COPD Questionnaire (CCQ). Data were collected at baseline and at 1, 3, and 6 months. Results Fifty-six participants completed this trial. Significant between-group differences were observed with respect to the main effect of group and time as well as the effect of group × time interaction on HADS-D score. The HADS-D score was significantly improved 1, 3, 6 months after group singing therapy. The CCQ total scores were significantly different between the two groups with respect to the main effect of group and time and the group × time interaction effect. Significantly better CCQ was detected in the intervention group at 3 months and 6 months after intervention. Conclusions Group singing therapy reduces depressive symptoms and improves the quality of life of patients with stable COPD.

Astilbin (AST), a dihydro-flavonol glycoside, is a major bioactive ingredient in Astilbe thunbergii , Engelhardia roxburghiana , Smilax corbularia and Erythroxylum gonocladum , and has been shown to have anti-inflammatory, antioxidative and neuroprotective effects, suggesting potential therapeutic value in the treatment of Parkinson's disease (PD). We explored the neuroprotective effects of AST in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease mice. Mice were administered with MPTP (30 mg/kg, i.p) daily for 5 days, to establish a subacute Parkinson's disease model, followed by daily treatment with AST or saline for 7 days. Pole and traction tests showed that AST ameliorated the impaired motor functions in MPTP-induced Parkinson's disease mice. High performance liquid chromatography analysis revealed that AST treatment prevented MPTP-induced decreases in striatal dopamine levels. Immunofluorescence assays showed that AST reduced the loss of dopaminergic neurons and the activation of microglia and astrocytes in the substantia nigra. Western blot analyses revealed that AST suppressed α-synuclein overexpression and activated PI3K/Akt in the striatum following MPTP treatment. AST also prevented the MPTP-induced reduction in total superoxide dismutase and glutathione activity in the striatum. AST exerts neuroprotective effects on MPTP-induced PD mice by suppressing gliosis, α-synuclein overexpression and oxidative stress, suggesting that AST could serve as a therapeutic drug to ameliorate PD.

Due to the short length and differences in abundance of microRNAs, microRNA profile screening and quantification is challenging. In this study, we found that size selection magnetic beads could be employed to easily and efficiently remove long RNA transcripts. After removing the long transcripts, the remaining small RNAs could be concentrated and then reverse-transcribed using universal stem-loop primers (USLP), with six randomized nucleotides at the 3' end region. The efficiency of reverse transcription decreased when the number of randomized nucleotides was reduced. In addition, we found that touchdown qPCR improved microRNA profile detection, with lower CT values and better detection efficiency than the regular qPCR protocol, especially for those low-abundance microRNAs. Finally, we incorporated these observations to create a new protocol we named long transcripts minus touchdown qPCR (LTMT-qPCR). We performed a side-by-side comparison of LTMT with USLP and traditional stem-loop primer (TSLP) protocols. We found that LTMT has higher detection efficiency than USLP, especially for the detection of low-abundance microRNAs. Although LTMT was equivalent to TSLP in terms of microRNA profile detection, LTMT is more convenient, user-friendly, and cost-effective. Taken together, the present data indicate that LTMT is a simple, rapid, and user-friendly approach that has higher precision, accuracy, and sensitivity than the previously described methods, making it more suitable for microRNA profile screening and quantification.

Background Previous studies have shown that the brain‐derived neurotrophic factor (BDNF) rs6265 G > A polymorphism is closely related post‐traumatic stress disorder (PTSD) risk. However, the results were not consistent. We therefore conducted a meta‐analysis to explore the underlying relationships between BDNF rs6265 G > A polymorphism and PTSD risk. Materials and Methods Five online databases were searched, and all related studies were reviewed up to July 1, 2020. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were calculated to examine the statistical power of each genetic model. In addition, heterogeneity, sensitivity accumulative analysis, and publication bias were examined to check the statistical power. Result Overall, 16 publications involving 5,369 subjects were included in this systematic review and 11 case‐control studies were analyses in meta‐analysis. The pooled results indicated an increasing risk of A allele mutations with PTSD risk. Moreover, the sequential subgroup analysis also demonstrated some similar situations in Asian populations and other groups. Conclusion Current meta‐analysis suggests that the BDNF rs6265 G > A polymorphism might be involved in PTSD susceptibility., A meta‐analysis focused on the association between BDNF rs6265 G > A polymorphism and PTSD risk was conducted. 16 publications involving 5,369 subjects were included in this system review and 11 case‐controls were analyses in meta‐analysis. Current meta‐analysis suggests indicated that the BDNF rs6265 G > A polymorphism might be involved in PTSD susceptibility.

We previously demonstrated that apolipoprotein A-I (apoA-I), the major protein component of high-density lipoprotein (HDL), is an important target for myeloperoxidase (MPO)-catalyzed tyrosine chlorination in the circulation of subjects with cardiovascular diseases. Oxidation of apoA-I by MPO has been reported to deprive HDL of its protective properties. However, the potential effects of MPO-mediated site-specific tyrosine chlorination of apoA-I on dysfunctional HDL formation and atherosclerosis was unclear. Herein, Tyr192 in apoA-I was found to be the major chlorination site in both lesion and plasma HDL from humans with atherosclerosis, while MPO binding to apoA-I was demonstrated by immunoprecipitation studies in vivo. In vitro, MPO-mediated damage of lipid-free apoA-I impaired its ability to promote cellular cholesterol efflux by the ABCA1 pathway, whereas oxidation to lipid-associated apoA-I inhibited lecithin:cholesterol acyltransferase activation, two key steps in reverse cholesterol transport. Compared with native apoA-I, apoA-I containing a Tyr192 → Phe mutation was moderately resistant to oxidative inactivation by MPO. In high-fat-diet-fed apolipoprotein E-deficient mice, compared with native apoA-I, subcutaneous injection with oxidized apoA-I (MPO treated) failed to mediate the lipid content in aortic plaques while mutant apoA-I (Tyr192 → Phe) showed a slightly stronger ability to reduce the lipid content in vivo. Our observations suggest that oxidative damage of apoA-I and HDL involves MPO-dependent site-specific tyrosine chlorination, raising the feasibility of producing MPO-resistant forms of apoA-I that have stronger antiatherosclerotic activity in vivo.

Small fiber neuropathy is common and prevalent in the elderly. The disease can be associated with many medical conditions. It often has a negative impact on quality of life due to painful paresthesia, dizziness, and sedative side effects of pain medications. Skin biopsy is the gold standard diagnostic test. Screening for associated conditions is important, because etiology-specific treatment can slow down disease progression and ameliorate symptoms. Adequate pain control can be challenging due to safety and tolerability of pain medications in the elderly. Treatment should be individualized with the goals of controlling underlying causes, alleviating pain, and optimizing daily function.

To explore the synergistic immunomodulatory mechanism of interferon alpha-1b, interleukin-2 and thalidomide (ITI) regimen on patients with acute myeloid leukemia (AML).Sixty eight untreated de novo or relapsed or refractory or maintenance therapy patients with AML admitted in the Affiliated Cancer Hospital of Zhengzhou University and the other 11 medical units from March 2016 to May 2019 were treated with ITI regimen. Peripheral blood specimen per patient was collected into EDTA-K3 anticoagulation vacuum tube before the administration of ITI and 3 months after the treatment; peripheral blood lymphocyte subsets and perforin and Granzyme B expression were analyzed by using flow cytometry; the levels of VEGF, IFN-γ, TNF-α and IL-6 in the plasma were detected by using a cytometric bead array. Thirty-five healthy subjects from the hospital physical examination centre were selected as normal controls.The ratio of CD4The ITI regimen can raise the ratio of CD4干扰素α-1b、白介素-2联合沙利度胺方案治疗急性髓系白血病免疫调节作用的协同机制研究.探讨干扰素α-1b、白介素-2联合沙利度胺（简称"干白沙"方案）治疗急性髓系白血病（AML）的免疫调节的协同作用机制。.对2016年3月至2019年5月郑州大学附属肿瘤医院等11家医疗单位收治的初治或复发/难治性或行维持治疗的且自愿接受"干白沙"方案治疗的68例AML患者，采集患者用药前1天及规范用药3个月后的晨起空腹外周血标本，采用流式细胞术检测外周血淋巴细胞亚群及NK细胞颗粒酶B及穿孔素表达水平；微量样本多重定量技术（CBA）检测血浆中VEGF、IFN-γ、TNF-α、IL-6等4种细胞因子的表达水平。对照组为35例本院体检中心的健康体检者。.治疗前患者外周血CD4"干白沙"方案可提高外周血CD4

Since the initial emergence of coronavirus disease 2019 (COVID-19) in Wuhan, Hubei province, China, a rapid spread of the disease occurred around the world, rising to become an international global health concern at pandemic level. In the face of this medical challenge threatening humans, the development of rapid and accurate methods for early screening and diagnosis of COVID-19 became crucial to containing the emerging public health threat, and prevent further spread within the population. Despite the large number of COVID-19 confirmed cases in China, some problematic cases with inconsistent laboratory testing results, were reported. Specifically, a high false-negative rate of 41% on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection by real-time reverse transcription-polymerase chain reaction (qRT-PCR) assays was observed in China. Although serological testing has been applied worldwide as a complementary method to help identify SARS-CoV-2, several limitations on its use have been reported in China. Therefore, the use of both qRT-PCR and serological testing in the diagnosis of COVID-19 in China and elsewhere, presented considerable challenges, but when used in combination, can be valuable tools in the fight against COVID-19. In this review, we give an overview of the advantages and disadvantages of different molecular techniques for SARS-CoV-2 detection that are currently used in several labs, including qRT-PCR, gene sequencing, loop-mediated isothermal amplification (LAMP), nucleic acid mass spectrometry (MS), and gene editing technique based on clustered regularly interspaced short palindromic repeats (CRISPR/Cas13) system. Then we mainly review and analyze some causes of false-negative qRT-PCR results, and how to resolve some of the diagnostic dilemma.

Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) has been accepted as a rapid, accurate, and less labor-intensive method in the identification of microorganisms in clinical laboratories. However, there is limited data on systematic evaluation of its effectiveness in the identification of phylogenetically closely-related yeast species. In this study, we evaluated two commercially available MALDI-TOF systems, Autof MS 1000 and Vitek MS, for the identification of yeasts within closely-related species complexes. A total of 1,228 yeast isolates, representing 14 different species of five species complexes, including 479 of Candida parapsilosis complex, 323 of Candida albicans complex, 95 of Candida glabrata complex, 16 of Candida haemulonii complex (including two Candida auris), and 315 of Cryptococcus neoformans complex, collected under the National China Hospital Invasive Fungal Surveillance Net (CHIF-NET) program, were studied. Autof MS 1000 and Vitek MS systems correctly identified 99.2% and 89.2% of the isolates, with major error rate of 0.4% versus 1.6%, and minor error rate of 0.1% versus 3.5%, respectively. The proportion of isolates accurately identified by Autof MS 1000 and Vitek MS per each yeast complex, respectively, was as follows; C. albicans complex, 99.4% vs 96.3%; C. parapsilosis complex, 99.0% vs 79.1%; C glabrata complex, 98.9% vs 94.7%; C. haemulonii complex, 100% vs 93.8%; and C. neoformans, 99.4% vs 95.2%. Overall, Autof MS 1000 exhibited good capacity in yeast identification while Vitek MS had lower identification accuracy, especially in the identification of less common species within phylogenetically closely-related species complexes.

Background Interleukin-10 (IL-10) is an independent factor for predicting adverse outcomes in pediatric patients with hemophagocytic lymphohistiocytosis (HLH). However, little is known about its prognostic value in adult patients. Methods This single center retrospective study was conducted to explore the prognostic value of IL-10 in 101 adults newly diagnosed with HLH. The serum interleukin levels were quantitatively determined by chemiluminescence using cytokine profiling kits. Results Serum IL-10 levels were significantly increased in adult HLH patients. Elevated IL-10 levels was correlated with lower concentrations of hemoglobin (r = − 0.279, P = 0.005). IL-10 levels were significantly lower in patients with macrophage activation syndrome (MAS) than in those with infection-associated HLH (IAHS) and malignancy-associated HLH (MAHS) (P = 0.033, P = 0.012). Patients with MAS had relatively longer survival than those with IAHS and MAHS (P 9/L, lactate dehydrogenase ≥ 700 IU/L, albumin 1050 µg/L and IL-10 ≥ 129 pg/mL were poor prognostic factors for survival. However, multivariate analysis revealed that only high serum IL-10 levels (≥ 129 pg/mL) at diagnosis and high post-treatment ferritin levels (> 1050 µg/L) were independent risk factors for poor overall survival in adult HLH patients (HR: 4.087, 95% CI 2.064–8.090, P P Conclusions Our results suggest that higher serum IL-10 levels might be a prognostic marker in adult HLH patients.

Background A long-term of peritoneal dialysis (PD) using a hypertonic PD solution (PDS) leads to patient’s peritoneal membrane (PM) injury, resulting in ultrafiltration failure (UFF) and PD drop-out. Our previous study shows that PD effluent-derived mesenchymal stromal cells (pMSCs) prevent the PM injury in normal rats after repeated exposure of the peritoneal cavity to a PDS. This study was designed to compare the cytoprotection between pMSCs and umbilical cord-derived MSCs (UC-MSCs) in the treatment of both PM and kidney injury in uremic rats with chronic PD. Methods 5/6 nephrectomized (5/6Nx) Sprague Dawley rats were intraperitoneally (IP) injected Dianeal (4.25% dextrose, 10 mL/rat/day) and were treated with pMSCs or umbilical cord (UC)-MSCs (approximately 2 × 106/rat/week, IP). Ultrafiltration was determined by IP injection of 30 mL of Dianeal (4.25% dextrose) with 1.5-h dewell time, and kidney failure by serum creatinine (SCr) and blood urea nitrogen (BUN). The structure of the PM and kidneys was assessed using histology. Gene expression was examined using quantitative reverse transcription PCR, and protein levels using flow cytometric and Western blot analyses. Results We showed a slight difference in the morphology between pMSCs and UC-MSCs in plastic dishes, and significantly higher expression levels of stemness-related genes (NANOG, OCT4, SOX2, CCNA2, RAD21, and EXO1) and MSCs surface markers (CD29, CD44, CD90 and CD105) in UC-MSCs than those in pMSCs, but no difference in the differentiation to chondrocytes, osteocytes or adipocytes. pMSC treatment was more effective than UC-MSCs in the protection of the MP and remnant kidneys in 5/6Nx rats from PDS-induced injury, which was associated with higher resistance of pMSCs than UC-MSCs to uremic toxins in culture, and more reduction of peritoneal mesothelial cell death by the secretome from pMSCs than from UC-MSCs in response to PDS exposure. The secretome from both pMSCs and UC-MSCs similarly inactivated NOS2 in activated THP1 cells. Conclusions As compared to UC-MSCs, pMSCs may more potently prevent PDS-induced PM and remnant kidney injury in this uremic rat model of chronic PD, suggesting that autotransplantation of ex vivo-expanded pMSCs may become a promising therapy for UFF and deterioration of remnant kidney function in PD patients.

To observe the preventive effect of medicated plaster at Dazhui (GV 14) on preventing perioperative hypothermia in patients undergoing plasmakinetic resection of prostate (PKRP) and ureteroscopic laser lithotripsy.A total of 300 patients with ASA gradeⅠorⅡreceiving ureteroscopic laser lithotripsy or PKRP under total intravenous anesthesia (TIVA) were randomly divided into an observation group and a control group, 150 cases in each group. The patients in the control group received routine heat preservation measures, while on the basis of the control group, the patients in the observation group were treated with medicated plaster at Dazhui (GV 14) 30 min before operation. The temperature (ear temperature), mean arterial pressure (MAP), heart rate and blood oxygen saturation (SpOThe temperature at 5 and 10 min into operation as well as at the end of operation in the two groups was all lower than that before operation and at previous time point (The medicated plaster at Dazhui (GV 14) can effectively prevent perioperative hypothermia and improve comfort in patients undergoing PKRP and ureteroscopic laser lithotripsy.

Chronic kidney disease (CKD) affects more than 10% of the global population and is associated with significant morbidity and mortality. In most cases, this disease is developed silently, and it can progress to the end-stage renal failure. Therefore, early detection becomes critical for initiating effective interventions. Routine diagnosis of CKD requires both blood test and urinalyses in a clinical laboratory, which are time-consuming and have low sensitivity and specificity. Surface-enhanced Raman scattering (SERS) is an emerging method for rapidly assessing kidney function or injury. This study was designed to compare the differences between the SERS properties of the serum and urine for easy and simple detection of CKD. Enrolled for this study were 126 CKD patients (Stages 2–5) and 97 healthy individuals. SERS spectra of both the serum and urine samples were acquired using a Raman spectrometer (785 nm excitation). The correlation of chemical parameters of kidney function with the spectra was examined using prinicpal component analysis (PCA) combined with linear discriminant analysis (LDA) and partial least squares (PLS) analysis. Here, we showed that CKD was discriminated from non-CKD controls using PCA–LDA with a sensitivity of 74.6% and a specificity of 93.8% for the serum spectra, and 78.0% and 86.0 % for the urine spectra. The integration area under the receiver operating characteristic curve was 0.937 ± 0.015 ( p 2) of the serum spectra was 0.8540 for the serum urea ( p 2) of urine spectra was 0.7335 for the urine urea ( p

Objective We aim to explore the protective effect of bone marrow mesenchymal stem cells (BMSCs)-derived exosomal microRNA-221-3p (miR-221-3p) on ischemic stroke (IS) by targeting activating transcription factor 3 (ATF3). Methods The middle cerebral artery occlusion (MCAO) mice model and oxygen-glucose deprivation (OGD) neuron model were established. Extracellular vesicles were isolated from BMSCs (BMSC-EVs) and transfected with altered miR-221-3p or ATF3 to treat the MCAO mice and OGD-treated neurons. MiR-221-3p and ATF3 expression were determined, and the contents of inflammatory factors were detected. The pathological changes and apoptosis in mice brain tissues were observed. In cellular experiments, the viability and apoptosis of OGD-treated neurons were evaluated. Binding relationship between miR-221-3p and ATF3 was determined. Results MiR-221-3p was down-regulated and ATF3 was up-regulated in MCAO mice and OGD-treated neurons. BMSC-EVs and BMSC-EVs carrying up-regulated miR-221-3p attenuated inflammation, pathological changes and apoptosis in MCAO mice brain tissues, and also promoted viability and repressed apoptosis of OGD-treated neurons. ATF3 was verified as a target of miR-221-3p. Conclusion BMSC-EVs carrying miR-221-3p protect against IS by inhibiting ATF3. This study may be helpful for exploring therapeutic strategies of IS.

Background Prenatal whole-exome sequencing (WES) is becoming increasingly used when karyotype and microarray tests are not diagnostic of fetal malformations. Although the value of WES clearly emerges in terms of higher diagnostic rates, the limitations of prenatal phenotyping together with the counseling challenges for variants of uncertain significance and incidental results suggest that the routine application of prenatal WES is not yet easy. Methods Structurally abnormal fetuses with a mean gestational age of 24 weeks (range 13–38 weeks) were recruited from the Chong Qing Health Center for Women and Children. We performed a retrospective WES investigation in 85 fetuses, using DNA from amniotic fluid (66 samples, 77.6%), umbilical cord blood (10 samples, 11.8%), and fetal tissues (9 samples, 10.6%). Parental DNA was extracted from peripheral blood. Results Molecular diagnosis was obtained in 16 of the 85 fetuses (18.8%). According to the variant segregation mode and family history, 7 fetuses (43.75%) were affected by an autosomal dominant condition (6 variants were de novo and 1 variant was inherited from an unknowingly affected father), 7 fetuses (43.75%) had an autosomal recessive syndrome always associated with compound heterozygosity, and 2 fetuses (12.5%) had an X-linked condition (one mother was a carrier). In addition, the highest diagnostic rate was observed in fetuses with multisystem abnormalities (38.9%, 7/18). A variant of uncertain significance was detected in 16 samples (18.8%, 16/85). Conclusion Our study confirms that prenatal WES is an efficient tool for studying fetal abnormalities, although further improvements are needed to establish stronger fetal genotype-phenotype correlations.

To explore the association between two single nucleotide polymorphisms (SNPs), namely, rs4691383 and rs7667857, in the platelet-derived growth factor-C (PDGF-C) gene, the genotypes, environmental exposure factors, and nonsyndromic cleft lip with or without cleft palate (NSCL/P) in Western Chinese population.A total of 268 case-parent trios were selected, and two SNPs (rs4691383 andrs7667857) were genotyped by using polymerase chain reaction and restriction enzyme fragment length polymorphic method and direct sequencing method. Hardy-Weinberg equilibrium, linkage disequilibrium test, transmission disequilibrium test, and haplotype analysis were conducted to analyze the data. Meanwhile, the questionnaires on the epidemiology of cleft lip and palate filled by the included samples were collected, and the interaction between the genotypes of the two SNPs and environmental exposure factors was assessed by conditional logistic regression.The A allele at rs4691383 and the G allele at rs7667857 of PDGF-C gene were over-transmitted for NSCL/P (P0.05). No interaction effect was observed between the three environmental exposure factors (history of smoking/passive smoking, folic acid supplementation, and long-term inhalation of harmful environmental gases) and the PDGF-C genotypes among NSCL/P (P0.05).The rs4691383 and rs7667857 at PDGF-C gene are closely related to the occurrence of NSCL/P in Western Chinese population. However, the interaction between environmental exposure factors and PDGF-C genotypes is not obvious in the occurrence of NSCL/P.目的 探究中国西部汉族人群血小板源性生长因子C（PDGF-C）基因的靶向单核苷酸多态性（SNPs）位点rs4691383、rs7667857及其基因型以及环境暴露因素与非综合征型唇腭裂（NSCL/P）发生的相关性。方法 收集268个NSCL/P病例—父母核心三人家系，采用聚合酶链反应—限制性酶切片段长度多态法和直接测序法对2个靶向SNPs位点（rs4691383、rs7667857）进行基因分型，使用哈温平衡检验、连锁不平衡检验、传递不平衡检验、单倍型关联分析等方法进行统计学分析。同时收集纳入对象所填写的唇腭裂流行病学研究问卷，对PDGF-C基因和环境暴露因素之间是否存在交互作用进行条件Logistic回归分析。结果 PDGF-C基因rs4691383位点的A等位基因和rs7667857位点的G等位基因在NSCL/P发生中存在过度传递（P0.05）。孕妇吸烟/被动吸烟史、叶酸补充史、环境有害气体长期吸入史3个环境暴露因素与PDGF-C基因的SNPs位点基因型之间均不存在交互作用（P0.05）。结论 PDGF-C基因rs4691383位点和rs7667857位点多态性与中国西部汉族人群NSCL/P的发生具有相关性；但在NSCL/P的发生过程中环境暴露因素与PDGF-C基因的SNPs位点基因型之间的交互作用不明显。.