ObjectiveTo explore the effects of Kaixuan Jiedu core prescription （KXJD） on sphingolipid metabolism in the mouse model of imiquimod-induced psoriasis-like skin lesions. MethodsThirty-seven male C57BL/6J mice were randomly assigned into five groups： healthy control （n=11）， model （n=11）， methotrexate （MTX， n=5）， low-dose （15.21 g·kg^-1） KXJD （n=5）， and high-dose （30.42 g·kg^-1） KXJD （n=5）. Psoriasis-like skin lesions were induced in mice with 62.5 mg 5% imiquimod cream applied on the back. The KXJD groups and MTX group were treated with 0.2 mL corresponding decoction and MTX， respectively， by gavage daily， while the other groups were given an equal volume of normal saline by the same way. After 5 days of treatment， back skin lesions were collected. Firstly， healthy control and model mice were selected for tandem mass tag （TMT） quantitative proteomics （control vs model=3 vs 3） and targeted lipid metabolomics （control vs model=11 vs 11）. Then， the binding degree between core components and target proteins was predicted via network pharmacology and molecular docking. Finally， an animal experiment was performed to decipher the specific regulation mechanism of KXJD on sphingolipid metabolism. Immunohistochemistry was employed to determine the expression level of sphingosine-1-phosphate （S1P）， and Western blot was employed to determine the expression levels of sphingosine kinase 2 （SPHK2） and monocyte chemotactic protein-1 （MCP-1）. ResultsTMT proteomics and targeted lipid metabolomics suggested that sphingolipid metabolism was active in the psoriatic skin， and key proteases ［serine palmitoyltransferase， long chain base subunit 2 （SPTLC2）， SPHK2， delta（4）-desaturase sphingolipid 1 （Degs1）， and ceramide synthase 4 （CerS4）］ and 8 sphingolipid metabolites （including ceramides， sphingol， sphingomyelin， and glycosphingolipid） expressed abnormally （P<0.05） compared with those in the healthy skin. The molecular docking results indicated that the binding energy between the active components （quercetin， kaempferol， and luteolin） in KXJD and key proteins involved in sphingolipid metabolism was less than-8 kal·mol^-1. Further experimental verification showed elevated expression levels of SPHK2， S1P， and MCP-1 in psoriatic skin compared with healthy skin （P<0.05）， and KXJD down-regulated the expression levels of SPHK2， S1P， and MCP-1 compared with the model group （P<0.05）. ConclusionThis study indicates that there is an imbalance in sphingolipid metabolism in psoriatic skin lesions. KXJD may reduce psoriasis-like lesions in mice by regulating sphingolipid metabolism via the SPHK2/S1P/MCP-1 pathway.

ObjectiveTo explore the effects of Kaixuan Jiedu core prescription （KXJD） on sphingolipid metabolism in the mouse model of imiquimod-induced psoriasis-like skin lesions. MethodsThirty-seven male C57BL/6J mice were randomly assigned into five groups： healthy control （n=11）， model （n=11）， methotrexate （MTX， n=5）， low-dose （15.21 g·kg^-1） KXJD （n=5）， and high-dose （30.42 g·kg^-1） KXJD （n=5）. Psoriasis-like skin lesions were induced in mice with 62.5 mg 5% imiquimod cream applied on the back. The KXJD groups and MTX group were treated with 0.2 mL corresponding decoction and MTX， respectively， by gavage daily， while the other groups were given an equal volume of normal saline by the same way. After 5 days of treatment， back skin lesions were collected. Firstly， healthy control and model mice were selected for tandem mass tag （TMT） quantitative proteomics （control vs model=3 vs 3） and targeted lipid metabolomics （control vs model=11 vs 11）. Then， the binding degree between core components and target proteins was predicted via network pharmacology and molecular docking. Finally， an animal experiment was performed to decipher the specific regulation mechanism of KXJD on sphingolipid metabolism. Immunohistochemistry was employed to determine the expression level of sphingosine-1-phosphate （S1P）， and Western blot was employed to determine the expression levels of sphingosine kinase 2 （SPHK2） and monocyte chemotactic protein-1 （MCP-1）. ResultsTMT proteomics and targeted lipid metabolomics suggested that sphingolipid metabolism was active in the psoriatic skin， and key proteases ［serine palmitoyltransferase， long chain base subunit 2 （SPTLC2）， SPHK2， delta（4）-desaturase sphingolipid 1 （Degs1）， and ceramide synthase 4 （CerS4）］ and 8 sphingolipid metabolites （including ceramides， sphingol， sphingomyelin， and glycosphingolipid） expressed abnormally （P<0.05） compared with those in the healthy skin. The molecular docking results indicated that the binding energy between the active components （quercetin， kaempferol， and luteolin） in KXJD and key proteins involved in sphingolipid metabolism was less than-8 kal·mol^-1. Further experimental verification showed elevated expression levels of SPHK2， S1P， and MCP-1 in psoriatic skin compared with healthy skin （P<0.05）， and KXJD down-regulated the expression levels of SPHK2， S1P， and MCP-1 compared with the model group （P<0.05）. ConclusionThis study indicates that there is an imbalance in sphingolipid metabolism in psoriatic skin lesions. KXJD may reduce psoriasis-like lesions in mice by regulating sphingolipid metabolism via the SPHK2/S1P/MCP-1 pathway.

The sterile electrode acupuncture needle for single use is an innovative product that combines traditional acupuncture with modern electronic technology, and it has obtained Class Ⅱ medical device registration certificate. This acupuncture device consists of a needle body and a handle. The diameter of the needle body ranges from 0.16 mm to 0.55 mm, and the length from 7 mm to 150 mm. The spiral spray technology is adopted to modify the micron-level insulating coat on stainless steel needle body. The needle holder is connected to the electroacupuncture device (conductive), the micro-film insulated needle body (non-conductive) and the membrane-free needle tip (conductive) can provide a precise electrical stimulation for different tissue layers of acupoints (such as deep nerves and fascia). The intradermal stimulation test, cytotoxicity test and hypersensitivity reaction test have showed a favorable biocompatibility, laying a solid and reliable safety for clinical application. This acupuncture device is suitable for the in-depth invasive stimulation at the sites of human body surface in combination with electroacupuncture equipment in medical institutions.
Humans ; Needles ; Acupuncture Therapy/instrumentation* ; Electrodes ; Equipment Design ; Electroacupuncture/instrumentation* ; Acupuncture Points ; Animals

Recently, male reproductive health has attracted extensive attention, with the adverse effects of circadian disruption on male fertility gradually gaining recognition. However, the mechanism by which circadian disruption leads to damage to male reproductive system remains unclear. In this review, we first summarized the dual regulatory roles of circadian clock genes on the male reproductive system: (1) circadian regulation of testosterone synthesis via the hypothalamic-pituitary-testicular (HPT) and hypothalamic-pituitary-adrenal (HPA) axes; (2) non-circadian regulation of spermatogenesis. Next, we further listed the possible mechanisms by which circadian disruption impairs male fertility, including interference with the oscillatory function of the reproductive system, i.e., synchronization of the HPT axis, crosstalk between the HPT axis and the HPA axis, as well as direct damage to germ cells by disturbing the non-oscillatory function of the reproductive system. Future research using spatiotemporal omics, epigenomic assays, and neural circuit mapping in studying the male reproductive system may provide new clues to systematically unravel the mechanisms by which circadian disruption affects male reproductive system through circadian clock genes.
Male ; Humans ; Animals ; Circadian Clocks/physiology* ; Hypothalamo-Hypophyseal System/physiology* ; Circadian Rhythm/genetics* ; Spermatogenesis/physiology* ; Pituitary-Adrenal System/physiology* ; Testis/physiology* ; Testosterone/biosynthesis* ; CLOCK Proteins ; Infertility, Male/physiopathology*

To investigate the impact of preoperative serum follicle-stimulating hormone (FSH) levels on the probability of testicular sperm retrieval, we conducted a study of nonobstructive azoospermic (NOA) men with different testicular volumes (TVs) who underwent microdissection testicular sperm extraction (micro-TESE). A total of 177 NOA patients undergoing micro-TESE for the first time from April 2019 to November 2022 in Shenzhen Zhongshan Obstetrics and Gynecology Hospital (formerly Shenzhen Zhongshan Urology Hospital, Shenzhen, China) were retrospectively reviewed. The subjects were divided into four groups based on average TV quartiles. Serum hormone levels in each TV group were compared between positive and negative sperm retrieval subgroups. Overall sperm retrieval rate was 57.6%. FSH levels (median [interquartile range]) were higher in the positive sperm retrieval subgroup compared with the negative outcome subgroup when average TV was <5 ml (first quartile [Q1: TV <3 ml]: 43.32 [17.92] IU l -1 vs 32.95 [18.56] IU l -1 , P = 0.048; second quartile [Q2: 3 ml ≤ TV <5 ml]: 31.31 [15.37] IU l -1 vs 25.59 [18.40] IU l -1 , P = 0.042). Elevated serum FSH levels were associated with successful micro-TESE sperm retrieval in NOA men whose average TVs were <5 ml (adjusted odds ratio [OR]: 1.06 per unit increase; 95% confidence interval [CI]: 1.01-1.11; P = 0.011). In men with TVs ≥5 ml, larger TVs were associated with lower odds of sperm retrieval (adjusted OR: 0.84 per 1 ml increase; 95% CI: 0.71-0.98; P = 0.029). In conclusion, elevated serum FSH levels were associated with positive sperm retrieval in micro-TESE in NOA men with TVs <5 ml. In men with TV ≥5 ml, increases in average TVs were associated with lower odds of sperm retrieval.
Humans ; Male ; Azoospermia/surgery* ; Sperm Retrieval/statistics & numerical data* ; Adult ; Follicle Stimulating Hormone/blood* ; Retrospective Studies ; Testis/pathology* ; Microdissection ; Organ Size

Addressing the enduring challenge of evaluating traditional Chinese medicines (TCMs), the integrated evidence chain-based effectiveness evaluation of TCMs (Eff-iEC) has emerged. This paper explored its capacity through a demonstration study that evaluated the effectiveness evidence of six commonly used anti-hepatic fibrosis Chinese patent medicines (CPMs), including Biejiajian Pill (BP), Dahuang Zhechong Pill (DZP), Biejia Ruangan Compound (BRC), Fuzheng Huayu Capsule (FHC), Anluo Huaxian Pill (AHP), and Heluo Shugan Capsule (HSC), using both Eff-iEC and the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system. The recognition of these CPMs within the TCM academic community was also assessed through their inclusion in relevant medical documents. Results showed that the evidence of BRC and FHC received higher assessments in both Eff-iEC and GRADE system, while the assessments for others varied. Analysis of community recognition revealed that Eff-iEC more accurately reflects the clinical value of these CPMs, exhibiting superior evaluative capabilities. By breaking through the conventional pattern of TCMs effectiveness evaluation, Eff-iEC offers a novel epistemology that better aligns with the clinical realities and reasoning of TCMs, providing a coherent methodology for clinical decision-making, new drug evaluations, and health policy formulation.

(±)-Talapyrones A-F (1-6), six pairs of dimeric polyketide enantiomers featuring unusual 6/6/6 and 6/6/6/5 ring systems, were isolated from the fungus Talaromyces adpressus. Their structures were determined by spectroscopic analysis and HR-ESI-MS data, and their absolute configurations were elucidated using a modified Mosher's method and electronic circular dichroism (ECD) calculations. (±)-Talapyrones A-F (1-6) possess a 6/6/6 tricyclic skeleton, presumably formed through a Michael addition reaction between one molecule of α-pyrone derivative and one molecule of C₈ poly-β-keto chain. In addition, compounds 2/3 and 4/5 are two pairs of C-18 epimers, respectively. Putative biosynthetic pathways of 1-6 were discussed.
Polyketides/isolation & purification* ; Talaromyces/chemistry* ; Stereoisomerism ; Molecular Structure ; Circular Dichroism ; Pyrones/chemistry*

Objective To extract and summarize the clinical registration information of periodontitis registered in the US ClinicalTrials.gov and Chinese Clinical Trial Registry(ChiCTR),and further analyze the registration characteristics of periodontitis clinical trials.Methods The ClinicalTrials.gov and ChiCTR data-bases were searched and compiled for periodontitis clinical registration information from 2000 to December 26,2024,including registration number,country/region of registration,annual number of registered projects,sample size,study type and design,study phase,and trial progress status.Results As of December 26,2024,a total of 520 242 registered clinical trials were retrieved from the ClinicalTrials.gov registry platform,of which 1 542(0.30%)were related to periodontitis.There were 189(12.26%)studies on periodontitis-related pro-jects in Turkey,while a total of 37(2.4%)projects were initiated by researchers in China,which ranked ninth.The Chinese Clinical Trial Register(ChiCTR)had 92 954 registered projects,of which 165 were on pe-riodontitis,and most of them were conducted by well-known affiliated hospitals and stomatology hospitals.The number of registrations in the ClinicalTrials.gov database increased year by year and reached a peak in 2022(146 registrations).Trial designs were focused on interventional and observational studies.ClinicalTri-als.gov study phases were focused on phases 2 and 4,while ChiCTR was clustered at phase 0(pre-registra-tion).Conclusion The number of clinical registrations for periodontitis in China's database is relatively low,and despite a steady upward trend,there is still a gap compared with other countries internationally.Future re-search should focus on how to encourage more oral health related research institutions to register on the plat-form and how to increase the sample size.

Objective To analyze the risk factors,traditional Chinese medicine(TCM)syndromes,and pathogen distribution in patients with bronchiectasis(BE)complicated with type 2 diabetes mellitus(T2DM).Methods From June 2022 to June 2024,a total of 299 patients with acute exacerbation of BE admitted to Guangdong Integrated Chinese and Western Medicine Hospital Affiliated to Guangzhou University of Chinese Medicine were selected.Based on the presence of T2DM,the patients were divided into the BE-T2DM group(74 cases)and the BE-only group(225 cases).Clinical data of the patients were collected,and univariate analysis and multivariate logistic regression models were used to identify risk factors for BE complicated with T2DM.TCM syndromes and pathogen distribution were statistically analyzed.Results(1)Univariate analysis showed that there were statistically significant differences between the two groups in gender,age,body mass index(BMI),hypertension,coronary atherosclerotic heart disease(shortened to coronary heart disease),atherosclerosis,the ratio of forced expiratory volume in one second to forced vital capacity(FEV1/FVC),white blood cell count(WBC),neutrophil count analysis for the risk factors showed that gender,BMI,hypertension,and FEV1/FVC were the independent risk factors for BE complicated with T2DM.(2)In terms of the distribution of TCM syndromes,both groups were mainly characterized by phlegm-heat accumulating in the lung syndrome and phlegm-damp obstructing the lung syndrome,and BE-T2DM group had a higher proportion of phlegm-heat accumulating in the lung syndrome.(3)For the infection of pathogens,BE-T2DM group had a higher infection rate of Haemophilus influenzae,Acinetobacter baumannii,and Klebsiella pneumoniae,while the BE-only group was predominantly infected with Pseudomonas aeruginosa;BE-T2DM group had a significantly higher rate of viral infections,mainly infected with influenza A virus,rhinovirus,and SARS-CoV-2;BE-T2DM group also suffered from fungal infections,usually infected with Candida albicans.Conclusion For BE patients complicated with T2DM,the independent risk factors are gender,BMI,hypertension,and FEV1/FVC;the common TCM syndromes are phlegm-heat accumulating in the lung and phlegm-damp obstructing the lung;pathogen infections are mainly caused by Gram-negative bacteria,viruses,and fungi.

Objective This study aims to investigate the effects of transcatheter arterial chemoembolization(TACE)using EqualSpheres,CalliSpheres,and Lipiodol loaded with idarubicin on VX2 liver cancer in rabbits.Methods Twelve New Zealand white rabbits were randomly assigned to three groups:EqualSpheres group,CalliSpheres group,and Lipiodol group(n=4 per group).The VX2 liver cancer animal model was successfully established through ultrasound-guided percutaneous puncture.EqualSpheres,CalliSpheres,and Lipiodol were employed as embolization agents loaded with idarubicin for the embolization procedure.Peripheral blood samples were collected at intervals of 5 minutes,0.5,1,4,12 and 24 hours following embolization and were centrifuged to obtain serum.At 24 hours post-TACE treatment,the rabbits in both the experimental and control groups were euthanized,and both liver cancer tissues and normal liver tissues were collected.UPLC-MS/MS was used to measure the drug concentration of idarubicin in peripheral blood and tissue samples,and Graphpad software was used to construct drug concentration-time curves in peripheral blood.The pharmacokinetic curves were constructed to evaluate the dynamic in vivo distribution characteristics.Results The average drug concentration in the EqualSpheres group(920.06 ng/mL)was significantly higher than that in both the CalliSpheres group(79.47 ng/mL)and the Lipiodol group(118.71 ng/mL).However,the average drug concentration in normal liver tissue of all the three groups was lower,and the difference was not statistically significant.The peripheral blood drug concentration of the three groups decreased at 5 minutes post-TACE and increased over the next 24 hours.The average blood concentration curve of EqualSpheres group increased more steadily compared to the CalliSpheres group and the Lipiodol group.The Cmax of the Lipiodol group was reached at 0.5 hours,measuring 11.54 ng/mL.Both the CalliSpheres group and the EqualSpheres group achieved their Cmax at 5 minutes,with values of 7.82 and 8.36 ng/mL,respectively.Conclusion EqualSpheres loaded with idarubicin achieve a high drug concentration at the tumor site while maintaining a low concentration in peripheral blood over 24 hours.This study demonstrates the stable drug release capability of idarubicin-loaded EqualSpheres.