Objective To summarize the characteristics of chemotherapy-induced peripheral neuropathy(CIPN)in children with acute B-lymphoblast leukemia(B-ALL)and to identify the influencing factors and prognosis of CIPN.Methods The clinical data of 60 children with B-ALL admitted to the 29th Ward of the Department of Hematology and Oncology,Children's Hospital Affiliated to Soochow University from June 2020 to December 2023 who received chemotherapy and had finished chemotherapy for 6 months were retrospectively reviewed.Results There were 37 cases of B-ALL combined with CIPN;the incidence of CIPN was 61.7% .Increasing age of onset was a risk factor for CIPN in children[OR=1.209,95% CI(1.023-1.428),P=0.026]with the highest incidence of sensory nerve dysfunction(78.4% ).Electromyography indicated that B-ALL combined with CIPN was multiple peripheral neurogenic lesions with certain reversibility.In the induction stage of chemotherapy,13 cases(35.1% )showed CIPN,accounting for the highest proportion.The CIPN improvement rate 6 months after chemotherapy was 67.6%,the age of onset[OR=2.418,95% CI(0.212-2.106),P=0.018]and the severity of CIPN[OR=203.394,95% CI(2.29-18 065.04). P=0.02]were risk factors for poor prognosis of children with CIPN.The older the age of onset was,the higher the severity of CIPN and worse prognosis were found.Conclusions Children with B-ALL complicated with CIPN are reversible multiple peripheral nerve lesions,and the occurrence and outcome of CIPN is potentially related to individual differences of children.

Objective To analyze the genetic subtypes of human immunodeficiency virus (HIV) and the prevalence of pretreatment drug resistance in the newly reported HIV-infected men in Guangxi. Methods The stratified random sampling method was employed to select the newly reported HIV-infected men aged≥50 years old in 14 cities of Guangxi from January to June in 2020.The pol gene of HIV-1 was amplified by nested reverse transcription polymerase chain reaction and then sequenced.The mutation sites associated with drug resistance and the degree of drug resistance were then analyzed. Results A total of 615 HIV-infected men were included in the study.The genetic subtypes of CRF01_AE,CRF07_BC,and CRF08_BC accounted for 57.4% (353/615),17.1% (105/615),and 22.4% (138/615),respectively.The mutations associated with the resistance to nucleoside reverse transcriptase inhibitors (NRTI),non-nucleoside reverse transcriptase inhibitors (NNRTI),and protease inhibitors occurred in 8 (1.3%),18 (2.9%),and 0 patients,respectively.M184V (0.7%) and K103N (1.8%) were the mutations with the highest occurrence rates for the resistance to NRTIs and NNRTIs,respectively.Twenty-two (3.6%) patients were resistant to at least one type of inhibitors.Specifically,4 (0.7%),14 (2.3%),4 (0.7%),and 0 patients were resistant to NRTIs,NNRTIs,both NRTIs and NNRTIs,and protease inhibitors,respectively.The pretreatment resistance to NNRTIs had much higher frequency than that to NRTIs (2.9% vs.1.3%;χ²=3.929,P=0.047).The prevalence of pretreatment resistance to lamivudine,zidovudine,tenofovir,abacavir,rilpivirine,efavirenz,nevirapine,and lopinavir/ritonavir was 0.8%, 0.3%, 0.7%, 1.0%, 1.3%, 2.8%, 2.9%, and 0, respectively. Conclusions CRF01_AE,CRF07_BC,and CRF08_BC are the three major strains of HIV-infected men≥50 years old newly reported in Guangxi,2020,and the pretreatment drug resistance demonstrates low prevalence.
Male ; Humans ; Middle Aged ; Reverse Transcriptase Inhibitors/therapeutic use* ; HIV Infections/drug therapy* ; Drug Resistance, Viral/genetics* ; China/epidemiology* ; Mutation ; HIV-1/genetics* ; Protease Inhibitors/therapeutic use* ; Genotype

OBJECTIVE: To investigate whether astragalus polysaccharides (APS) combined with berberine (BBR) can reduce high-fat diet (HFD)-induced obesity in mice. METHODS: Except for normal mice, 32 HFD-induced obese mice were randomized into HFD, APS (1,000 mg/kg APS), BBR (200 mg/kg BBR), and APS plus BBR (1,000 mg/kg APS plus 200 mg/kg BBR) groups, respectively. After 6-week treatment (once daily by gavage), the obesity phenotype and pharmacodynamic effects were evaluated by histopathological examination of epididymal fat, liver, and colon using hematoxylin-eosin staining and serum biochemical analyses by an automated chemistry analyzer. The feces were collected at the 12 th week, and taxonomic and functional profiles of gut microbiota were analyzed by 16S ribosomal ribonucleic acid (16S rRNA) sequencing. RESULTS: Compared with HFD group, the average body weight of APS plus BBR group was decreased (P<0.01), accompanied with the reduced fat accumulation, enhanced colonic integrity, insulin sensitivity and glucose homeostasis (P<0.05 or P<0.01). Importantly, APS combined with BBR treatment was more effective than APS or BBR alone in improving HFD-induced insulin resistance (P<0.05 or P<0.01). 16S rRNA sequence-based analysis of fecal samples demonstrated that APS combined with BBR treatment exhibited a better impact on HFD-induced gut microbiota dysbiosis, exclusively via the enriched abundances of Bacteroides, which corresponded to the large increase of predicted bacterial genes involved in carbohydrate metabolism. CONCLUSION APS combined with BBR may synergistically reduce obesity and modulate the gut microbiota in HFD-fed mice.
Mice ; Animals ; Diet, High-Fat ; Berberine/therapeutic use* ; Mice, Obese ; RNA, Ribosomal, 16S/genetics* ; Gastrointestinal Microbiome ; Obesity/drug therapy* ; Insulin Resistance ; Mice, Inbred C57BL

Objectives: To investigated the safety and efficacy of treating patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) and elevated levels of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) with levosimendan within 24 hours of first medical contact (FMC). Methods: This multicenter, open-label, block-randomized controlled trial (NCT03189901) investigated the safety and efficacy of levosimendan as an early management strategy of acute heart failure (EMS-AHF) for patients with NSTEMI and high NT-proBNP levels. This study included 255 patients with NSTEMI and elevated NT-proBNP levels, including 142 males and 113 females with a median age of 65 (58-70) years, and were admitted in the emergency or outpatient departments at 14 medical centers in China between October 2017 and October 2021. The patients were randomly divided into a levosimendan group (n=129) and a control group (n=126). The primary outcome measure was NT-proBNP levels on day 3 of treatment and changes in the NT-proBNP levels from baseline on day 5 after randomization. The secondary outcome measures included the proportion of patients with more than 30% reduction in NT-proBNP levels from baseline, major adverse cardiovascular events (MACE) during hospitalization and at 6 months after hospitalization, safety during the treatment, and health economics indices. The measurement data parameters between groups were compared using the t-test or the non-parametric test. The count data parameters were compared between groups using the χ² test. Results: On day 3, the NT-proBNP levels in the levosimendan group were lower than the control group but were statistically insignificant [866 (455, 1 960) vs. 1 118 (459, 2 417) ng/L, Z=-1.25,P=0.21]. However, on day 5, changes in the NT-proBNP levels from baseline in the levosimendan group were significantly higher than the control group [67.6% (33.8%,82.5%)vs.54.8% (7.3%,77.9%), Z=-2.14, P=0.03]. There were no significant differences in the proportion of patients with more than 30% reduction in the NT-proBNP levels on day 5 between the levosimendan and the control groups [77.5% (100/129) vs. 69.0% (87/126), χ²=2.34, P=0.13]. Furthermore, incidences of MACE did not show any significant differences between the two groups during hospitalization [4.7% (6/129) vs. 7.1% (9/126), χ²=0.72, P=0.40] and at 6 months [14.7% (19/129) vs. 12.7% (16/126), χ²=0.22, P=0.64]. Four cardiac deaths were reported in the control group during hospitalization [0 (0/129) vs. 3.2% (4/126), P=0.06]. However, 6-month survival rates were comparable between the two groups (log-rank test, P=0.18). Moreover, adverse events or serious adverse events such as shock, ventricular fibrillation, and ventricular tachycardia were not reported in both the groups during levosimendan treatment (days 0-1). The total cost of hospitalization [34 591.00(15 527.46,59 324.80) vs. 37 144.65(16 066.90,63 919.00)yuan, Z=-0.26, P=0.80] and the total length of hospitalization [9 (8, 12) vs. 10 (7, 13) days, Z=0.72, P=0.72] were lower for patients in the levosimendan group compared to those in the control group, but did not show statistically significant differences. Conclusions: Early administration of levosimendan reduced NT-proBNP levels in NSTEMI patients with elevated NT-proBNP and did not increase the total cost and length of hospitalization, but did not significantly improve MACE during hospitalization or at 6 months.
Male ; Female ; Humans ; Aged ; Natriuretic Peptide, Brain ; Simendan/therapeutic use* ; Non-ST Elevated Myocardial Infarction ; Heart Failure/drug therapy* ; Peptide Fragments ; Arrhythmias, Cardiac ; Biomarkers ; Prognosis

Diosgenin, a steroidal sapogenin, obtained from Trigonella foenum-graecum, Dioscorea, and Rhizoma polgonati, has shown high potential and interest in the treatment of various cancers such as oral squamous cell carcinoma, laryngeal cancer, esophageal cancer, liver cancer, gastric cancer, lung cancer, cervical cancer, prostate cancer, glioma, and leukemia. This article aims to provide an overview of the in vivo, in vitro, and clinical studies reporting the diosgenin's anticancer effects. Preclinical studies have shown promising effects of diosgenin on inhibiting tumor cell proliferation and growth, promoting apoptosis, inducing differentiation and autophagy, inhibiting tumor cell metastasis and invasion, blocking cell cycle, regulating immunity and improving gut microbiome. Clinical investigations have revealed clinical dosage and safety property of diosgenin. Furthermore, in order to improve the biological activity and bioavailability of diosgenin, this review focuses on the development of diosgenin nano drug carriers, combined drugs and the diosgenin derivatives. However, further designed trials are needed to unravel the diosgenin's deficiencies in clinical application.
Male ; Humans ; Carcinoma, Squamous Cell/drug therapy* ; Diosgenin/metabolism* ; Mouth Neoplasms/drug therapy* ; Apoptosis ; Prostatic Neoplasms/drug therapy*

Biliary tract cancer has insidious onset and high degree of malignancy, and radical resection is often impossible when it is diagnosed.Conversion therapy can achieve tumor downgrading, so that patients who were initially unresectable have a chance to achieve R0 resection.However, due to the high heterogeneity and complex immune microenvironment of biliary tract cancer, conversion therapy is still in the stage of active exploration.As a new type of conversion therapy, combination of targeted therapy and immunotherapy is of great significance to effectively improve the efficiency of conversion therapy.Further exploration of combination mechanism and improvement of immune microenvironment are expected to become the future direction of combination of targeted therapy and immunotherapy.
Antineoplastic Combined Chemotherapy Protocols ; Biliary Tract Neoplasms/surgery* ; Combined Modality Therapy ; Gastrectomy ; Humans ; Immunotherapy ; Tumor Microenvironment

With reference to the production process documented in Chinese Pharmacopoeia, this paper prepared the calibrator samples of Xiaochaihu Granules from multiple batches and established a method for fingerprint analysis and content determination that could be used to evaluate Xiaochaihu Granules available in market. Multiple batches of Chinese herbal pieces contained in Xiaochaihu Granules were collected for preparing the calibrator samples according to the process in Chinese Pharmacopoeia. Following the establishment of fingerprints for calibrator samples by UHPLC, the method for determining the contents of saikosaponin B2, saikosaponin B1, baicalin, wogonoside, baicalein, liquiritin, glycyrrhizin G2 and glycyrrhizic acid in Xiaochaihu Granules was established. The experimental results showed that the fingerprints of calibrator samples had 26 common peaks, covering the chemical compounds of main herbs Bupleuri Radix, Scutellariae Radix, Changii Radix, Glycyrrhizae Radix et Rhizoma, and Rhizoma Zingiberis Recens. The similarity of fingerprints for 47 batches of Xiaochaihu Granules from 31 companies with the calibrator sample fingerprint ranged from 0.74 to 0.99, indicating good applicability of the established fingerprint. The contents of main components baicalin, saikosaponin B2, and glycyrrhizic acid in Xiaochaihu Granules were within the ranges of 22.917-49.108 mg per bag(RSD 19%), 0.28-2.19 mg per bag(RSD 62%), and 0.897-6.541 mg per bag(RSD 41%), respectively. The quality difference in saikosaponin B2, and glycyrrhizic acid among different manufacturers was significant. The fingerprint analysis and content determination method for calibrator samples of Xiaochaihu Granules prepared according to the production process in Chinese Pharmacopoeia has been proved suitable for evaluating the quality of Xiaochaihu Granules from different manufacturers. Saikosaponin B2, glycyrrhizic acid, and liquiritin should be added as content control indicators for Xiaochaihu Granules, aiming to further improve the product quality.
Chromatography, High Pressure Liquid/methods* ; Drugs, Chinese Herbal/chemistry* ; Glycyrrhizic Acid/analysis* ; Rhizome/chemistry* ; Scutellaria baicalensis

Objective: To analyze HIV transmission hotspots and characteristics of cross-regional transmission in Guangxi Zhuang autonomous region (Guangxi) based on the molecular network analysis, and provide evidence for optimization of precise AIDS prevention and control strategies. Methods: A total of 5 996 HIV pol sequences sampled from Guangxi between 1997 and 2020 were analyzed together with 165 534 published HIV pol sequences sampled from other regions. HIV-TRACE was used to construct molecular network in a pairwise genetic distance threshold of 0.5%. Results: The proportion of HIV sequences entering the molecular network of HIV transmission hotspots in Guangxi was 31.5% (1 886/5 996). In the molecular network of HIV cross-regional transmission, the links within Guangxi accounted for 51.6% (2 613/5 062), the links between Guangxi and other provinces in China accounted for 48.0% (2 430/5 062), and the links between Guangxi and other countries accounted for 0.4% (19/5 062). The main regions which had cross-regional linked with Guangxi were Guangdong (49.5%, 1 212/2 449), Beijing (17.5%, 430/2 449), Shanghai (6.9%, 168/2 449), Sichuan (5.7%, 140/2 449), Yunnan (4.2%, 102/2 449), Shaanxi (3.8%, 93/2 449), Zhejiang (2.8%, 69/2 449), Hainan (2.0%, 49/2 449), Anhui (1.5%, 37/2 449), Jiangsu (1.3%, 33/2 449), and other regions (each one <1.0%), respectively. The risk factors of entering the molecular network of HIV transmission hotspots in Guangxi included being aged ≥50 years (compared with being aged 25-49 years, aOR=1.68,95%CI:1.46-1.95), males (compared with females, aOR=1.21,95%CI:1.05-1.40), being single (compared with being married, aOR=1.18,95%CI:1.00-1.39), having education level of high school or above (compared with having education level of junior high school or below, aOR=1.21,95%CI:1.04-1.42), acquired HIV through homosexual intercourse (compared with acquired with HIV through heterosexual intercourse, aOR=1.77, 95%CI:1.48-2.12). The risk factors of cross-regional transmission included males (compared with females, aOR=1.74,95%CI:1.13-2.75), having education level of high school or above (compared with having education level of junior high school or below, aOR=1.96,95%CI:1.43-2.69), being freelancer/unemployed/retired (compared with being farmers, aOR=1.50,95%CI:1.07-2.11), acquired HIV through homosexual intercourse (compared with acquired with HIV through heterosexual intercourse, aOR=3.28,95%CI:2.30-4.72). Conclusion: There are HIV transmission hotspots in Guangxi. Guangxi and other provinces in China form a complex cross-regional transmission network. Future studies should carry out social network surveys in high-risk populations inferred from the molecular network analysis for the timely identification of hidden transmission chains and reduction of the second-generation transmission of HIV.
Acquired Immunodeficiency Syndrome ; China/epidemiology* ; Disease Hotspot ; Female ; HIV Infections/epidemiology* ; Heterosexuality ; Humans ; Male

"Xiang thinking" is the main thinking mode in traditional Chinese medicine(TCM) with both philosophical and scientific connotations, and has an important influence on the emergence and development of TCM. This study systematically expounded the philosophical connotation and characteristics of "Xiang thinking", and its application in the construction of TCM theory, clinical syndrome differentiation and treatment, the formation of medicinal properties, and interpretation of efficacy of Chinese medicine. "Xiang thinking" in TCM develops and changes continuously with practical application, and its historical evolution can be summarized into three stages, i.e., "Ying Xiang(corresponding to Xiang)" "Fa Xiang(following Xiang)", and "Bian Xiang(differentiating Xiang)". The understanding of Xiang is based on the means and methods of human observation of things and the backgrounds of the philosophy, science, and development. The result of comparison depends on the depth and breadth of Xiang. In the real world, Xiang is showing new construction characteristics with multiple dimensions and levels. Therefore, this study proposed the thinking of "Bian Xiang", which is expected to provide a thinking approach that can realize the transformation from "Xiang thinking" to scientific research for the exploration and innovative research on life origin in the field of contemporary and TCM.
Humans ; Medicine, Chinese Traditional ; Drugs, Chinese Herbal

Recent population studies have significantly advanced our understanding of how age shapes the gut microbiota.However,the actual role of age could be inevitably confounded due to the complex and variable environmental factors in human populations.A well-controlled envi-ronment is thus necessary to reduce undesirable confounding effects,and recapitulate age-dependent changes in the gut microbiota of healthy primates.Herein we performed 16S rRNA gene sequenc-ing,characterized the age-associated gut microbial profiles from infant to elderly crab-eating maca-ques reared in captivity,and systemically revealed the lifelong dynamic changes of the primate gut microbiota.While the most significant age-associated taxa were mainly found as commensals such as Faecalibacterium,the abundance of a group of suspicious pathogens such as Helicobacter was exclusively increased in infants,underlining their potential role in host development.Importantly,topology analysis indicated that the network connectivity of gut microbiota was even more age-dependent than taxonomic diversity,and its tremendous decline with age could probably be linked to healthy aging.Moreover,we identified key driver microbes responsible for such age-dependent network changes,which were further linked to altered metabolic functions of lipids,carbohydrates,and amino acids,as well as phenotypes in the microbial community.The current study thus demon-strates the lifelong age-dependent changes and their driver microbes in the primate gut microbiota,and provides new insights into their roles in the development and healthy aging of their hosts.