Piper nigrum L. is an evergreen climbing vine, which belongs to the genus Piperia in the Piperaceae family. Piper nigrum L., which known as the “king of spices”, is used as both food and medicine. The main active substances in Piper nigrum L. are alkaloids mainly composed of amides, and essential oil, as well as phenolic compounds. In this paper, the chemical compositions, especially amide alkaloids, and their biological activities of Piper nigrum L. were summarized. These studies showed that Piper nigrum L., as a medicinal and food plant, had a wide range of biological activities and was deserved further research and in-depth utilization.

Glutathione peroxidase （GSH-Px） is a key selenoenzyme that protects the body from oxidative damage. A series of small molecular organic selenium compounds have been designed and synthesized as functional mimics of GPx, among which isoselenazolones are the most widely studied. Taking ebselen as a representative, the catalytic mechanism of isoselenazolones in mimicing GSH-Px activity in vivo, the therapeutic effects of isoselenazolones in stroke, sensorineurium deafness and tinnitus, treatmentresistant depression （TRD） and coronavirus disease 2019 （COVID-19）, and research on their chemical synthesis methods were summarized and discussed in this paper.

Objective To explore the effect of music therapy on children with autism spectrum disorder(ASD).Methods A systematic search was conducted in databases including CNKI,Wanfang data,VIP,PubMed,Elsevier Sci-ence Direct and Google Scholar for randomized controlled trials(RCT)on the effect of music therapy on children with ASD.The search period was from database inception to April,2024.The control group received non-music therapy interventions,including medication,educational therapy,cognitive-behavioral therapy,and structured treatment.The observation group received music therapy.Studies were systematically reviewed following the Co-chrane Handbook for Systematic Reviews,with two researchers independently screening literatures,extracting data,and assessing the risk of bias in the included studies.Statistic analysis was performed using Review Manag-er 5.4.Results Nine RCTs were included,involving 828 patients from France,China,Norway,Iran,the United States and Aus-tralia.The intervention types mainly included music therapy,parent-child cooperative music therapy,Orff music therapy,group music therapy,improvisational music therapy,Orff-Schulwerk-based music therapy,music inter-vention and family-centered music therapy.The overall outcomes(SMD=-0.30,95%CI-0.55 to-0.04,P=0.02),language function(MD=-2.09,95%CI-2.89 to-1.30,P<0.001)and physical behavior(SMD=-0.27,95%CI-0.53 to-0.01,P=0.040)improved better in the observation group.Conclusion Music therapy can improve the overall outcome of children with ASD,especially in language function and physical behavior.

Objective:To analyze the epidemic characteristics and trends of visceral leishmaniasis (VL) in Shaanxi Province, and provide a basis for formulating control strategies.Methods:The information on VL cases in Shaanxi Province from January 2012 to December 2024 were obtained from the Shaanxi Provincial Infectious Disease Reporting Management System, and demographic data were collected from the Shaanxi Statistical Yearbook. Descriptive epidemiological method was used to analyze the prevalence and the distribution by the three dimensions (time, region, and population). Joinpoint 4.9.1.0 software and Geoda 1.6 software were used for regression analysis and spatial clustering analysis, respectively. SuperMap 8C software was used for visualization.Results:From January 2012 to December 2024, a total of 304 cases of VL were reported in Shaanxi Province, with an annual incidence rate of 0.06/100 000. VL cases occurred in all months of the year in Shaanxi Province with no significant seasonality, yet the onset was predominantly concentrated from April to August(52.30%, 159/304). The majority of cases were male (61.51%, 187/304), aged 5 months to 4 years (17.11%, 52/304), and farmers (67.11%, 204/304). A total of 54 districts (counties, cities) of 10 cities in the province had reported cases, mainly concentrated in Weinan City (49.34%, 150/304). Joinpoint regression analysis revealed a significant overall upward trend in the VL incidence rate in Shaanxi Province from 2012 to 2024 [average annual percent change (AAPC) = 12.60%, 95% confidence interval ( CI): 6.01% - 19.62%, t = 3.95, P < 0.001]. The year 2020 was identified as a turning point in the trend. The incidence rate showed a rapid upward trend from 2012 to 2020 [annual percent change (APC) = 23.75%, 95% CI: 13.33% - 35.12%, t = 5.62, P < 0.001]. Global spatial autocorrelation analysis indicated significant positive spatial autocorrelation in VL incidence in 2012, 2014, 2015, 2018, and 2022 (Moran's I > 0, Z > 1.96, P < 0.05). Local spatial autocorrelation analysis identified 12 "high-high" clustering areas from 2012 to 2024, mainly located in Shangluo City in southern Shaanxi Province, and Weinan City and Yan'an City in northern Shaanxi Province. Conclusions:From 2012 to 2024, VL cases in Shaanxi Province are predominantly male farmers. The incidence of VL shows an overall upward trend, with significant spatial clustering. The prevention and control situation is severe. It is imperative to strengthen control measures, including vector disinfection and health education, to effectively control the spread and transmission of VL.

Objective:To investigate the effect of interaction between body mass index (BMI) and gender on the survival of advanced gastric cancer after immunotherapy.Methods:The retrospective cohort study was conducted. The clinicopathological data of 317 patients with advanced gastric cancer who were admitted to the Nanfang Hospital, Southern Medical University from November 2019 to October 2023 were collected. There were 205 males and 112 females, aged 56 (range, 21-79)years. All 317 patients were divided into three groups based on BMI of patients, including 58 cases with BMI <18.5 kg/m2 were classified as the low body mass group, 183 cases with BMI 18.5-24.0 kg/m2 were classified as the normal body mass group, and 76 cases with BMI >24.0 kg/m2 were classified as the overweight or obese group. Patients included in the study were treated with a programmed death-ligand 1 (PD-L1) based immunotherapy regimen for 3 cycles based on their specific conditions, and further decision was made whether to undergo radical surgery or continue comprehensive treatment after evaluating the efficacy. Observation indicators: (1) clinicopathological characteristics of patients; (2) follow-up and mortality status; (3) analysis of factors affecting survival of patients with advanced gastric cancer after immunotherapy. Comparison of measurement data with normal distribution among groups was conducted using the ANOVA. Comparison of measurement data with skewed distribution among groups was conducted using the Kruskal-Wallis H test. Comparison of count data among groups was conducted using the chi-square test. The Cox proportional hazard model was used for univariate and multivariate analyses. Nonlinear trend was analyzed using the restricted cubic spline (RCS) curve, and trend and correction graphs were created using the rcssci package (v1.0). Results:(1) Clinicopathological characteristics of patients. There was no significant difference in gender, age, Borrmann classification, Lauren classification, combined positive score of PD-L1, expression of human epidermal growth factor receptor 2, Epstein-Barr virus infection, carcino-embryonic antigen, CA19-9, CA72-4, alpha-fetoprotein, conversion surgery among the 3 groups of patients ( P>0.05), and there was a significant difference in mismatch repair combined with micro-satellite stability among the 3 groups of patients ( P<0.05). (2) Follow-up and mortality status. Of the 317 patients, 316 cases completed follow-up and 1 case in the overweight or obese group was lost to follow-up. The follow-up time of the 316 cases was 13.8(range, 0.9-48.2)months. During the follow-up, the number of death in the low body mass group, normal body mass group and overweight or obese group were 27, 70 and 31, respectively. (3) Analysis of factors affecting survival of patients with advanced gastric cancer after immunotherapy. Results of multivariate analysis showed that gender and BMI were independent factors affecting survival of patients with advanced gastric cancer after immunotherapy ( hazard ratio=0.066, 0.922, 95% confidence interval as 0.005-0.846, 0.855-0.994, P<0.05). Results of further analysis showed that the interaction between BMI and gender was an independent factor affecting survival of patients with advanced gastric cancer after immuno-therapy ( hazard ratio=1.152, 95% confidence interval as 1.024-1.296, P<0.05). Results of Cox regre-ssion analysis based on different gender showed that took patients of the normal body mass group as a reference, the male patients of the low body mass group had a significantly increased risk of death, showing a significant statistically difference ( hazard ratio=1.809, 95% confidence interval as 1.037-3.155, P<0.05). Results of RCS curve analysis showed that there was a non-linear correlation between BMI and survival of patients with advanced gastric cancer after immunotherapy ( P<0.05). Results of corrected RCS curve analysis using the rcssci package showed that there was a U-shaped relationship between BMI and survival of patients with advanced gastric cancer after immuno-therapy ( P<0.05), with the optimal cut-off value of BMI as 22.2 kg/m 2. Results of RCS curve analysis based on different gender showed that there was a U-shaped relationship between BMI and survival of male patients with advanced gastric cancer after immunotherapy ( P<0.05), with the optimal cut-off value of BMI as 22.7 kg/m 2. Conclusions:Gender, BMI and the interaction between BMI and gender are independent factors affecting survival of patients with advanced gastric cancer after immuno-therapy. There is a U-shaped relationship between BMI and survival of patients, with the optimal cut-off value of BMI as 22.2 kg/m 2, and there is a U-shaped relationship between BMI and survival of male patients, with the optimal cut-off value of BMI as 22.7 kg/m 2.

Objective To investigate the key targets and pathways of Juhongtai formula granules in improving acute lung injury(ALI).Methods Juhongtai formula granules and their drug-containing serum components were analyzed by UPLC-QTOF-MS/MS,and the active ingredients were screened based on the"Lipinski Rule of Five".The action targets of the above active ingredients were obtained through the TCMSP,Swiss Target Prediction and SuperPred databases,and the ALI-related targets were obtained from the GeneCards,OMIM,PharmGKB,CTD databases and GEO chip.The target protein-protein interaction network was constructed using the String database and Cytoscape to analyze the key targets.The DAVID database was used for GO functional annotation and KEGG pathway enrichment analysis,and the CB-dock2 platform was used for molecular docking verification.After one week of adaptive feeding,the experimental SD rats were randomly divided into the blank group,the model group,the positive control group,the negative control group and the Juhongtai formula granules group,with 6 rats in each group.The rat model of ALI was replicated by tracheal infusion of lipopolysaccharide.The pathological morphology of lung tissues in each group of rats was observed by HE staining,and the mRNA expressions of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),interleukin-1 β(IL-1β)and nitric oxide were detected by reverse transcription quantitative polymerase chain reaction(RT-qPCR).Results In total,44 components of the Juhongtai formula granules were identified,including 26 drug-containing serum components,and 21 key compounds were screened.A total of 22 intersection targets were obtained.The pathway enrichment results indicated the action of these targets on the advanced glycation end product receptor(AGE-RAGE)and TNF signaling pathways.The docking results showed that limonin,kaempferol and naringenin could be matched with prostaglandin peroxidase 2,nitric oxide synthase 2 and TNF.Animal experiments confirmed that the Juhongtai formula granules can alleviate inflammatory infiltration in lung tissue and reduce the expressions of TNF-α,IL6,IL-1β mRNA and nitric oxide.Conclusion Juhongtai formula granules can inhibit ALI-related inflammatory targets through the synergistic effects of multiple components such as limonin and kaempferol,regulate signaling pathways such as AGE-RAGE and TNF,reduce the production of inflammatory factors and nitric oxide,and improve ALI.

Objective To investigate the key targets and pathways of Juhongtai formula granules in improving acute lung injury(ALI).Methods Juhongtai formula granules and their drug-containing serum components were analyzed by UPLC-QTOF-MS/MS,and the active ingredients were screened based on the"Lipinski Rule of Five".The action targets of the above active ingredients were obtained through the TCMSP,Swiss Target Prediction and SuperPred databases,and the ALI-related targets were obtained from the GeneCards,OMIM,PharmGKB,CTD databases and GEO chip.The target protein-protein interaction network was constructed using the String database and Cytoscape to analyze the key targets.The DAVID database was used for GO functional annotation and KEGG pathway enrichment analysis,and the CB-dock2 platform was used for molecular docking verification.After one week of adaptive feeding,the experimental SD rats were randomly divided into the blank group,the model group,the positive control group,the negative control group and the Juhongtai formula granules group,with 6 rats in each group.The rat model of ALI was replicated by tracheal infusion of lipopolysaccharide.The pathological morphology of lung tissues in each group of rats was observed by HE staining,and the mRNA expressions of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),interleukin-1 β(IL-1β)and nitric oxide were detected by reverse transcription quantitative polymerase chain reaction(RT-qPCR).Results In total,44 components of the Juhongtai formula granules were identified,including 26 drug-containing serum components,and 21 key compounds were screened.A total of 22 intersection targets were obtained.The pathway enrichment results indicated the action of these targets on the advanced glycation end product receptor(AGE-RAGE)and TNF signaling pathways.The docking results showed that limonin,kaempferol and naringenin could be matched with prostaglandin peroxidase 2,nitric oxide synthase 2 and TNF.Animal experiments confirmed that the Juhongtai formula granules can alleviate inflammatory infiltration in lung tissue and reduce the expressions of TNF-α,IL6,IL-1β mRNA and nitric oxide.Conclusion Juhongtai formula granules can inhibit ALI-related inflammatory targets through the synergistic effects of multiple components such as limonin and kaempferol,regulate signaling pathways such as AGE-RAGE and TNF,reduce the production of inflammatory factors and nitric oxide,and improve ALI.

Critical care medicine(CCM)is a multifaceted discipline challenged by the inherent heterogeneity and complexity of critical illnesses.Establishing precise,standardized diagnostic and therapeutic systems has emerged as a crucial challenge requiring urgent resolution in this field.Surgical critical care,a pivotal branch of CCM,plays an indispensable role in managing patients with severe trauma,postoperative intra-abdominal infections,solid organ transplantation,and other life-threatening conditions.Evidence-based,etiology-guided therapy serves as the cornerstone of surgical critical care,where accurate identification and timely interventions constitute vital determinants for enhancing patient survival rates and improving prognoses.This article proposes an innovative diagnostic and therapeutic paradigm termed the urgency/physics-biology-chemistry(U/P-B-C)model.Built upon the established principle of urgent(urgency,U)life support in surgical critical care,this model emphasizes a novel conceptual framework centered on etiology-based(physics-biology-chemistry,P-B-C)diagnosis and treatment.Implementing the U/P-B-C innovative diagnostic and therapeutic model in surgical critical care facilitates precise identification of the fundamental pathological mechanisms underlying critical clinical conditions with complex and dynamic clinical environments,enables systematic clarification of clinical reasoning,and ultimately supports evidence-informed decision-making.Its core objectives encompass enhancing surgical intensivists' diagnostic-therapeutic capabilities and ensuring rigorous adherence to the principle of etiology-guided therapy,thereby providing both theoretical foundation and practical guidance for improving the success rate of patient resuscitation and optimizing prognosis in surgical critical care settings.

Objective To observe the changes in the serum level of tumor necrosis factor-α(TNF-α)during pegylated interferon-alpha(PEG-IFN-α)treatment in inactive HBsAg carriers(IHCs),to investigate the association between the dynamic changes of TNF-α and HBsAg clearance,and to assess the value of TNF-α as a potential biomarker for predicting the therapeutic efficacy of PEG-IFN-α.Methods A prospective study was conducted among 455 IHCs who attended our hospital from January 2018 to March 2023,and they were divided into treatment group and IHC control group.The 210 IHCs in the treatment group voluntarily received PEG-IFNα-2b treatment for 48 weeks,followed by follow-up for 24 weeks,and the 245 IHCs in the IHC control group were followed up for 72 weeks without treatment.The serum level of TNF-α was measured at baseline(week 0)and at weeks 12,24,48,and 72,and at week 72,the treatment group was further divided into HBsAg clearance group and non-clearance group.The serum level of TNF-α at different time points was compared between groups.The logistic regression analysis was used to assess the value of TNF-α in predicting HBsAg clearance.The t-test was used for comparison of normally distributed continuous data between two groups,and a one-way analysis of variance used for comparison between multiple groups;the repeated measures analysis of variance was used for comparison of normally distributed repeated measurement data within each group and between groups;the chi-square test or the Fisher's exact test was used for comparison of categorical data between groups.Univariate and multivariate logistic regression analyses were used to investigate the predictive factors for HBsAg clearance,and the receiver operating characteristic(ROC)curve was used to determine the cut-off value of TNF-α in predicting HBsAg clearance.Results At week 72,compared with the IHC control group,the treatment group had significantly higher HBsAg clearance rate(46.2%vs 1.2%,χ2=133.333,P<0.001)and seroconversion rate(34.8%vs 0.8%,χ2=94.650,P<0.001).The HBsAg clearance group and the non-clearance group had a significant increase in the serum level of TNF-α during treatment,which gradually returned to the baseline level after drug withdrawal(F=351.733 and 76.434,both P<0.001).Comparisons between groups showed that the HBsAg clearance group had the highest serum level of TNF-α at weeks 12,24,and 48,followed by the non-clearance group and the IHC control group(all P<0.001).The multivariate logistic regression analysis showed that baseline HBsAg level(odds ratio[OR]=0.329,95%confidence interval[CI]:0.189-0.571,P<0.001),baseline HBV DNA<20 IU/mL(OR=1.414,95%CI:1.057-1.787,P=0.045),ALT≥2×upper limit of normal at week 12(OR=1.127,95%CI:1.028-1.722,P=0.043),TNF-α level at week 12(OR=1.336,95%CI:1.018-1.754,P=0.037),and TNF-α level at week 24(OR=1.879,95%CI:1.477-2.391,P<0.001)were independent predictive factors for HBsAg clearance.The ROC analysis showed that TNF-α level at week 12 had an area under the ROC curve(AUC)of 0.846(95%CI:0.814-0.889)in predicting HBsAg clearance at week 72,with a sensitivity of 76.3%and a specificity of 81.0%,while TNF-α level at week 24 had an AUC of 0.912(95%CI:0.758-0.972),with a sensitivity of 81.4%and a specificity of 96.2%.Conclusion PEG-IFN-α can increase the serum level of TNF-α in IHCs,and the serum level of TNF-α at weeks 12 and 24 can effectively predict HBsAg clearance induced by PEG-IFN-α.

OBJECTIVE: To compare the effects of piriformis muscle release versus preservation in total hip arthroplasty (THA) via supercapsular percutaneously-assisted total hip (SuperPATH) approach on muscle injury. METHODS: Forty-nine patients undergoing initial THA via SuperPATH approach between June 2022 and June 2023 were randomly divided into two groups, with 24 patients in trial group and 25 patients in control group. The trial group received piriformis muscle release intraoperatively, whereas the control group underwent muscle preservation. There was no significant difference in baseline data such as gender, age, body mass index, disease type, American Society of Anesthesiologists (ASA) grading, and preoperative muscle infiltration, muscle atrophy, muscle injury serological indicators, Harris score, etc. ( P>0.05). The incision length, operation time, intraoperative blood loss, total blood loss, hospital stay, preoperative and postoperative 1-day muscle injury serological indicators [including creatine kinase (CK) and lactic dehydrogenase (LDH)], and incidence of complications between two groups were recorded. Harris score was used to evaluate the recovery of hip joint function. MRI was used to evaluate the extent of hip muscle injuries (gluteus minimus, gluteus medius, piriformis, obturator internus, quadratus femoris), including tendon integrity, degree of muscle fat infiltration, and degree of muscle atrophy preoperative and 1 year postoperatively. RESULTS: The operation time, intraoperative blood loss, and total blood loss in the trial group were significantly shorter than those in the control group ( P<0.05). There was no significant difference in the incision length and length of hospital stay between the two groups ( P>0.05). Both groups showed a significant increase in serum CK and LDH levels on postoperative day 1 compared to preoperative levels ( P<0.05), but there was no significant difference between the two groups ( P>0.05). All patients were followed up, the follow-up time for the trial group and the control group was (14.8±2.8) and (15.1±3.0) months, respectively, with no significant difference ( t=-0.400, P=0.691). Incisions healed by first intention in both groups, with 1 case in the trial group and 2 cases in the control group experiencing venous thrombosis in the calf muscle space. There was no complication such as deep vein thrombosis, pulmonary embolism, hip dislocation, prosthesis loosening, or periprosthetic infection in the lower limbs. There was no significant difference in the incidence of complications between the two groups ( P>0.05). At 1 year after operation, both groups of patients showed a significant increase in Harris scores compared to preoperative levels ( P<0.05), but there was no significant difference between the two groups ( P>0.05). Compared with preoperative results, both groups showed significant fat infiltration in the piriformis and obturator muscles at 1 year after operation ( P<0.05), while there was no significant fat infiltration in the gluteus minimus, gluteus medius, and quadratus femoris muscles ( P>0.05). At 1 year after operation, except for the higher incidence of piriformis muscle fat infiltration in the control group compared to the trial group ( P<0.05), there was no significant difference in the incidence of other muscle infiltrations between the two groups ( P>0.05). At 1 year after operation, both groups of piriformis and obturator muscles showed significant muscle atrophy compared to preoperative levels ( P<0.05). The gluteus minimus and gluteus medius showed mild atrophy compared to preoperative levels, while the maximum transverse diameter of the quadriceps muscle slightly increased, but the differences were not significant ( P>0.05). There was no significant difference in the maximum cross-sectional diameter or cross-sectional area changes of each muscle between the two groups ( P>0.05). At 1 year after operation, the continuity of the gluteus medius and quadratus femoris muscles in both groups was intact. Both groups had some patients with incomplete continuity of the piriformis muscle, obturator internus, and gluteus minimus, but the difference was not significant ( P>0.05). CONCLUSION The SuperPATH approach THA may cause injury to the piriformis, gluteus minimus, and obturator internus. The piriformis muscle release does not increase muscle injury, but it can shorten the operation time and reduce bleeding.
Humans ; Arthroplasty, Replacement, Hip/adverse effects* ; Male ; Female ; Muscle, Skeletal/surgery* ; Middle Aged ; Aged ; Postoperative Complications/epidemiology* ; Adult ; Operative Time ; Muscular Atrophy ; Creatine Kinase/blood* ; Length of Stay ; Treatment Outcome