Objective This study aimed to investigate the potential relationship between urinary metals copper (Cu), arsenic (As), strontium (Sr), barium (Ba), iron (Fe), lead (Pb) and manganese (Mn) and grip strength. Methods We used linear regression models, quantile g-computation and Bayesian kernel machine regression (BKMR) to assess the relationship between metals and grip strength.Results In the multimetal linear regression, Cu (β=-2.119), As (β=-1.318), Sr (β=-2.480), Ba (β=0.781), Fe (β= 1.130) and Mn (β=-0.404) were significantly correlated with grip strength (P < 0.05). The results of the quantile g-computation showed that the risk of occurrence of grip strength reduction was -1.007 (95％ confidence interval:-1.362, -0.652; P < 0.001) when each quartile of the mixture of the seven metals was increased. Bayesian kernel function regression model analysis showed that mixtures of the seven metals had a negative overall effect on grip strength, with Cu, As and Sr being negatively associated with grip strength levels. In the total population, potential interactions were observed between As and Mn and between Cu and Mn (Pinteractions of 0.003 and 0.018, respectively).Conclusion In summary, this study suggests that combined exposure to metal mixtures is negatively associated with grip strength. Cu, Sr and As were negatively correlated with grip strength levels, and there were potential interactions between As and Mn and between Cu and Mn.

Objective:To discuss the effect of cold exposure on nociception in the rats and its regulatory mechanism on transient receptor potential(TRP)ion channels in the sensory neurons,and to provide the basis for clarifying the biological mechanism of cold-sensitive pain.Methods:Sixteen female SD rats were divided into control group(n=8)and cold group(n=8).The rats in control group were exposed to the environment of(24±2)℃,and the rats in cold group were exposed to low temperature(4 ℃±1 ℃)in an artificial intelligence climate chamber for 4 h daily,for one week.Von Frey filaments were used to detect the mechanical withdrawal threshold(MWT)of the rats in two groups;immunofluorescence staining was used to observe the expression levels of TRPA1,TRPM8,TRPV1,and TRPV4 in dorsal root ganglion(DRG)tissue of the rats in two groups,the expression levels of calcitonin gene-related peptide(CGRP)and substance P(SP)in DRG tissue of the rats in two groups,and the expression levels of TRPA1,TRPM8,TRPV1,and TRPV4 in synovial tissue of the rats in two groups.Results:Compared with control group,the MWT of the rats in cold group was significantly decreased(P＜0.05),the expression levels of TRPA1 and TRPM8 in DRG tissue were significantly increased(P＜0.05),the expression level of TRPV1 was significantly decreased(P＜0.05),there was no significant difference in the expression level of TRPV4(P＞0.05),and the expression levels of CGRP and SP were significantly increased(P＜0.05).Compared with control group,the expression level of TRPA1 in synovial tissue of the rats in cold group was significantly increased(P＜0.05),while the expression levels of TRPM8,TRPV1,and TRPV4 were significantly decreased(P＜0.05).Conclusion:Short-term cold exposure can induce the hyperalgesia of the rats,and its mechanism may be associated with the changes in the expression of TRP ion channels in DRG and synovial tissues.TRPA1 sensory neurons play an important role in local joint cold pain.

Objective To observe the clinical effect of Dongjing Tiaoshen Comprehensive Therapy combined with computerized cognitive behavioral therapy for insomnia(CCBT-I)in the treatment of chronic insomnia patients with liver depression and spleen deficiency syndrome.Methods A total of 60 patients with chronic insomnia of liver depression and spleen deficiency type were randomly divided into observation group and control group,30 cases in each group.Both groups of patients were treated with CCBT-I as the basic treatment,the observation group was additionally treated with Dongjing Tiaoshen Comprehensive Therapy,i.e.,mind-regulating acupuncture therapy combined with regular aerobic exercises and Dantian Qigong exercises,and the control group was additionally treated with cranial electrotherapy stimulation.The course of treatment for the two groups covered 4 weeks.The changes of Pittsburgh Sleep Quality Index(PSQI)score,Self-rating Anxiety Scale(SAS)score and Self-rating Depression Scale(SDS)score in the two groups were observed before and after treatment,and the clinical efficacy of the two groups was evaluated after treatment.Results(1)After 4 weeks of treatment,the total effective rate of the observation group was 86.67%(26/30),and that of the control group was 70.00%(21/30).The intergroup comparison(tested by rank sum test)showed that the curative effect of the observation group was significantly superior to that of the control group,and the difference was statistically significant(P＜0.05).(2)After treatment,the PSQI scores of the two groups were significantly lower than those before treatment(P＜0.05),and the decrease of PSQI scores in the observation group was significantly superior to that in the control group,the difference being statistically significant(P＜0.05).(3)After treatment,the SAS and SDS scores of the two groups were significantly lower than those before treatment(P＜0.05),and the decrease of SAS and SDS scores in the observation group tended to be superior to that in the control group,but there was no significant difference between the two groups(P＞0.05).Conclusion For the treatment of chronic insomnia of liver depression and spleen deficiency type,the combination of Dongjing Tiaoshen Comprehensive Therapy with CCBT-I can significantly improve the sleep quality,relieve anxiety and depression,and improve the quality of life of the patients,which exerts significant efficacy.

Objective To observe the pharmacokinetic effect of amoxicillin and clavulanate potassium tablets on amoxicillin in Chinese healthy subjects under fasting and high fat and high calorie diet.Methods 71 healthy subjects were given a single dose of amoxicillin potassium clavulanate tablets(0.375 g)on fasting or high fat diet,and venous blood samples were collected at different time points.The concentrations of amoxicillin in human plasma were determined by HPLC-MS/MS method,and the pharmacokinetic parameters were calculated by non-atrioventricular model using PhoenixWinNonlin 8.0 software.Results The main pharmacokinetic parameters of amoxicillin potassium clavulanate tablets after fasting and high fat diet were(5 105.00±1 444.00),(4 593.00±1 327.00)ng·mL-1,and postprandial-fasting ratio 89.40％,90％confidence interval(79.55％-100.19％);t1/2 were(1.52±0.16),(1.39±0.22)h;AUC0-t were(12 969.00±1 841.00),(11 577.00±1 663.00)ng·mL-1·h,and postdietary/fasting ratio 89.20％,90％confidence interval(83.92％-94.28％);AUC0-∞ were(13 024.00±1 846.00),(11 532.00±1 545.00)ng·mL-1·h,and postprandial-fasting ratio 88.60％,90％confidence interval(83.48％-93.50％).The median Tmax(range)were 1.63(0.75,3.00)and 2.50(0.75,6.00)h,respectively,and the Tmax of postprandial medication was delayed(P＜0.01).Conclusion Compared with fasting condition,amoxicillin Tmax was significantly delayed after high fat diet,while Cmax,AUC0-t and AUC0-∞ were not significantly changed,indicating that food could delay the absorption of amoxicillin,but did not affect the degree of absorption.

Objective:Based on the forgetting curve principle to construct a model for the popularization of cardiopulmonary resuscitation among college students and validate its effectiveness, providing reference for the promotion of cardiopulmonary resuscitation.Methods:A randomized controlled trial was conducted. In October 2021, a multistage random sampling method was used to select 262 freshmen and sophomores from the School of Mathematics and Physics at Leshan Normal University as the control group, and 262 freshmen and sophomores from the School of Electronic Information and Artificial Intelligence as the experimental group.The control group received conventional training, while the experimental group, in addition to conventional training, received cardiopulmonary resuscitation retraining based on the Ebbinghaus forgetting curve at three time intervals: within 1 week, within 1 month, and within 1 to 6 months after training. The retraining included online self-learning, on-site observation reinforcement, and social practice sublimation. The cardiopulmonary resuscitation knowledge awareness rate and cardiopulmonary resuscitation skill assessment of the two groups were compared before training, immediately after training, and 6 months after training.Results:The final number of participants was 256 in the control group (126 males and 130 females) and 224 in the experimental group (110 males and 114 females). There were no statistically significant differences in cardiopulmonary resuscitation knowledge awareness rate and cardiopulmonary resuscitation skill scores between the two groups before and immediately after training (both P>0.05). Immediately after training, the average cardiopulmonary resuscitation knowledge awareness rate in the experimental and control groups were 91% (1 626/1 792) and 88% (1 806/2 048), respectively, which were significantly higher than the pre-training rates of 55% (989/1 792) and 55% (1 129/2 048) ( χ2=8.46, 7.30, both P<0.01). The cardiopulmonary resuscitation skill scores were (42.00 ± 3.55) and (41.68 ± 3.40), respectively, higher than the pre-training scores of (15.41 ± 4.85) and (15.92 ± 4.66) ( t=84.47, 45.56, both P<0.05). Six months after training, the awareness rates of determination of consciousness and cardiac arrest judgment, cardiopulmonary resuscitation steps, chest compression location, frequency, depth, and the ratio of chest compressions to artificial ventilation in the experimental group in college students were 90% (201/224), 93% (208/224), 92% (206/224), 93% (208/224), 89% (200/224), and 94% (210/224), respectively, higher than those in the control group, which were 62% (158/256), 71% (182/256), 77% (198/256), 73% (186/256), 70% (178/256), and 69% (176/256) ( χ2 values were 4.21-7.03, all P<0.01). The cardiopulmonary resuscitation skill score in the experimental group was (49.77 ± 3.68), higher than the control group′s (34.95 ± 4.79) ( t=38.25, P<0.01). The proportion of students confident in using cardiopulmonary resuscitation to save others was 92% (206/224) in the experimental group, higher than 58% (148/256) in the control group ( χ2=7.68, P<0.01). Six months after training, the cardiopulmonary resuscitation skill score in the experimental group was (49.77 ± 3.68), higher than the immediate post-training score of (42.00 ± 3.55), whereas the control group's cardiopulmonary resuscitation skill score was (34.95 ± 4.79), lower than the immediate post-training score of (41.68 ± 3.40) ( t=22.74, 18.33, both P<0.01). Conclusions:The cardiopulmonary resuscitation popularization model for college students based on the forgetting curve is conducive to mastering cardiopulmonary resuscitation knowledge and skills among trained college students, enhancing their confidence in using cardiopulmonary resuscitation techniques to rescue others. Moreover, it helps save the human, financial, and material resources required for cardiopulmonary resuscitation training to a certain extent and is worthy of promotion.

Objective:To conduct a nationwide physician survey to better understand clinicians’ disease awareness, treatment patterns, and experience of Waldenstr?m macroglobulinemia (WM) in China.Methods:This cross-sectional study was conducted from February 2022 to July 2022 by recruiting clinicians with WM treatment experience from hematology, hematology-oncology, and oncology departments throughout China. Quantitative surveys were designed based on the qualitative interviews.Results:The study included 415 clinicians from 219 hospitals spread across thirty-three cities and twenty-two provinces. As for diagnosis, the laboratory tests prescribed by physicians for suspected WM patients were relatively consistent (92% -99% recommendation for laboratory, 79% -95% recommendation for pathology, 96% recommendation for gene testing, and 63% -83% recommendation for imaging examination). However, from a physician's perspective, there was 22% misdiagnosis occurred in clinical practice. The rate of misdiagnosis was higher in lower-level hospitals than in tertiary grade A hospitals (29% vs 21%, P<0.001). The main reasons for misdiagnosis were that WM was easily confused with other diseases, and physicians lacked the necessary knowledge to make an accurate diagnosis. In terms of gene testing in clinical practice, 96% of participating physicians believed that WM patients would require gene testing for MYD88 and CXCR4 mutations because the results of gene testing would aid in confirming diagnosis and treatment options. In terms of treatment, 55% of physicians thought that the most important goal was to achieve remission, while 54% and 51% of physicians wanted to improve laboratory and/or examination results and extend overall survival time, respectively. Among patients with treatment indications, physicians estimated that approximately 21% of them refused to receive treatment, mainly owing to a lack of affordable care and disease awareness. When selecting the most appropriate treatment regimens, physicians would consider patient affordability (63% ), comorbidity (61% ), and risk level (54% ). Regimens containing Bruton tyrosine kinase inhibitor (BTKi) were most widely recommended for both treatment-na?ve and relapsed/refractory patients (94% for all patients, 95% for treatment-na?ve patients, and 75% for relapsed/refractory patients), and most physicians recommended Ibrutinib (84% ). For those patients who received treatment, physicians reported that approximately 23% of patients did not comply with the treatment regimen due to a lack of affordability and disease awareness. Furthermore, 66% of physicians believe that in the future, increasing disease awareness and improving diagnosis rates is critical. Conclusions:This study is the first national physician survey of WM conducted in China. It systematically describes the issues that exist in WM diagnosis and treatment in China, such as a high rate of misdiagnosis, limited access to gene testing and new drugs, and poor patient adherence to treatment. Chinese doctors believe that improving doctors’ and patients’ understanding of WM is one of the most urgent issues that must be addressed right now.

The purpose of this study was to investigate the regulatory effects of biofilm associated non-coding small RNA(sRNA)00085 on the survival and environmental fitness of Listeria monocytogenes.Homologous recombination technology was used to construct a deletion mutant strain(△sRNA 00085)and a complementary strain(C △sRNA 00085)of the sRNA00085 target gene.The differences in biological characteristics were compared among the standard strain,△sRNA 00085,and C△sRNA 00085.The deletion of sRNA00085 led to a significant decrease in biofilm formation capacity and sensitivity to several antibiotics,including penicillin,piperacillin,doxycycline,tetracycline,vancomycin,and cotrimoxazole.However,only the minimum inhibitory concentration(MIC)of tetracycline exhibited a significant decrease in △sRNA00085.Meanwhile,the decreased biofilm formation and antibiotic resistance of the sRNA00085 mutant were restored in the C△sRNA00085 strain.Furthermore,we investigated the transcription levels of tetracycline resistance-related genes in L.monocytogenes.Down-regu-lated transcription of the tetS gene but no significant difference in transcription of the tetA gene were observed in △sRNA 00085 compared with the standard strain and C△sRNA00085.Moreover,the elimination of sRNA00085 did not affect bacterial growth ability or sensitivity to disinfectants.These findings highlight that sRNA00085 plays an important role in the environ-mental adaptability of L.monocytogenes by affecting bacterial biofilm formation and resistance.

Purpose: Pancreatic cancer (PC) is a common malignant tumor of the digestive system, and its 5-year survival rate is only 4%. N6-methyladenosine (m6A) RNA methylation is the most common post-transcriptional modification and dynamically regulates cancer development, while its role in PC treatment remains unclear. Materials and Methods: We treated PC cells with gemcitabine and quantified the overall m6A level with m6A methylation quantification. Real-time quantitative reverse transcription polymerase chain reaction and Western blot analyses were used to detect expression changes of m6A regulators. We verified the m6A modification on the target genes through m6A-immunoprecipitation (IP), and further in vivo experiments and immunofluorescence (IF) assays were applied to verify regulation of gemcitabine on Wilms’ tumor 1–associated protein (WTAP) and MYC. Results: Gemcitabine inhibited the proliferation and migration of PC cells and reduced the overall level of m6A modification. Additionally, the expression of the “writer” WTAP was significantly downregulated after gemcitabine treatment. We knocked down WTAP in cells and found target gene MYC expression was significantly downregulated, m6A-IP also confirmed the m6A modification on MYC. Our experiments showed that m6A-MYC may be recognized by the “reader” IGF2BP1. In vivo experiments revealed gemcitabine inhibited the tumorigenic ability of PC cells. IF analysis also showed that gemcitabine inhibited the expression of WTAP and MYC, which displayed a significant trend of co-expression. Conclusion Our study confirmed that gemcitabine interferes with WTAP protein expression in PC, reduces m6A modification on MYC and RNA stability, thereby inhibiting the downstream pathway of MYC, and inhibits the progression of PC.

OBJECTIVE: This study aimed to explore the association between humidity exposure and the risk of cardiovascular disease (CVD), utilizing follow-up data and relative humidity (RH) metric assessments. METHODS: We extracted the baseline data from the China Hypertension Survey (CHS) of 24,510 enrolled participants aged ≥ 35 years without a history of CVD between 2012 and 2015 and followed them up from 2018 to 2019. The National Meteorological Information Center (NMIC) of the China Meteorological Administration (CMA) provided the quality-controlled relative humidity (RH) datasets. Cox proportional hazards models were used to estimate hazard ratios ( HRs) for CVD in relation to RH. RESULTS: During the follow-up period (2018-2019), 973 patients with CVD were identified. The HR of CVD risk was 1.17 (95% CI: 1.04-1.31) per 10% increase in summer mean RH. Compared with participants in the 3 ^rd quintile group, those in the 1 ^st and 5 ^th quintiles of RH had a higher risk of CVD. For summer mean RH, the HRs (95% CIs) for the 1 ^st and 5 ^th quintiles were 1.34 (1.04-1.71) and 1.44 (1.14-1.83), respectively. The relationship ("U" shape) between summer mean RH and the risk of CVD was nonlinear. Stratified analyses indicated that the risk of CVD was substantially influenced by the summer mean RH in female, older individuals, and those in southern China. CONCLUSION Unsuitable (too high or low) humidity environments affect the risk of CVD. Our study highlights those future policies for adapting to climate change should consider the humidity-CVD relationship.
Humans ; Humidity/adverse effects* ; Cardiovascular Diseases/etiology* ; Female ; Male ; Middle Aged ; Prospective Studies ; China/epidemiology* ; Adult ; Aged ; Risk Factors ; Proportional Hazards Models ; Seasons

OBJECTIVE: To explore whether casticin (CAS) suppresses stemness in cancer stem-like cells (CSLCs) obtained from human cervical cancer (CCSLCs) and the underlying mechanism. METHODS: Spheres from HeLa and CaSki cells were used as CCSLCs. DNA methyltransferase 1 (DNMT1) activity and mRNA levels, self-renewal capability (Nanog and Sox2), and cancer stem cell markers (CD133 and CD44), were detected by a colorimetric DNMT activity/inhibition assay kit, quantitative real-time reverse transcription-polymerase chain reaction, sphere and colony formation assays, and immunoblot, respectively. Knockdown and overexpression of DNMT1 by transfection with shRNA and cDNA, respectively, were performed to explore the mechanism for action of CAS (0, 10, 30, and 100 nmol/L). RESULTS: DNMT1 activity was increased in CCSLCs compared with HeLa and CaSki cells (P<0.05). In addition, HeLa-derived CCSLCs transfected with DNMT1 shRNA showed reduced sphere and colony formation abilities, and lower CD133, CD44, Nanog and Sox2 protein expressions (P<0.05). Conversely, overexpression of DNMT1 in HeLa cells exhibited the oppositive effects. Furthermore, CAS significantly reduced DNMT1 activity and transcription levels as well as stemness in HeLa-derived CCSLCs (P<0.05). Interestingly, DNMT1 knockdown enhanced the inhibitory effect of CAS on stemness. As expected, DNMT1 overexpression reversed the inhibitory effect of CAS on stemness in HeLa cells. CONCLUSION CAS effectively inhibits stemness in CCSLCs through suppression of DNMT1 activation, suggesting that CAS acts as a promising preventive and therapeutic candidate in cervical cancer.
Female ; Humans ; Cell Line, Tumor ; HeLa Cells ; Neoplastic Stem Cells/metabolism* ; RNA, Small Interfering/metabolism* ; Uterine Cervical Neoplasms/metabolism*