ObjectiveTo systematically compare the differential regulation of the maternal-fetal interface cell lineages and communication networks in the CBA/J×DBA/2 mouse model of recurrent pregnancy loss （RPL） by the two classic therapeutic methods-tonifying the kidney to stabilize the fetus and invigorating the spleen to stabilize the fetus （Shoutai Wan， Juyuan Jian）-of traditional Chinese medicine （TCM） at the single-cell resolution and clarify their modern scientific connotations. MethodsFemale non-pregnant CBA/J mice were caged with male BALB/c （blank group） and DBA/2 （modeling group） mice separately. Pregnant mice in the modeling group were randomly grouped as follows： high/low-dose Shoutai Wan， high/low-dose Juyuan Jian， model （RPL）， and positive control （dydrogesterone）， with 10 mice in each group. Starting from the day after the detection of the vaginal plug， mice were administrated with drugs or an equal volume of normal saline by gavage for 10 consecutive days. After the intervention， the following indicators were measured. ① Macroscopic evaluation： general conditions， uterine wet weight， embryo loss rate， four coagulation parameters ［prothrombin time （PT）， activated partial thromboplastin time （APTT）， fibrinogen （FIB）， and thrombin time （TT）］， and peripheral blood estradiol （E₂） and progesterone （Pg） levels. The decidua with embryos was stained with hematoxylin-eosin （HE） and evaluated by transmission electron microscopy （TEM）. The expression of B-cell lymphoma-2 （Bcl-2）， vascular endothelial growth factor （VEGF）， angiotensin Ⅱ （AngⅡ）， matrix metalloproteinase-2 （MMP-2）， interleukin-6 （IL-6）， leukemia inhibitory factor （LIF）， CXC chemokine ligand 12 （CXCL12）， and microtubule-associated protein 1 light chain 3 homolog （LC3）Ⅰ/Ⅱ was quantified by Western blot. ② Mechanism analysis at the single-cell level： The decidua with embryos from the blank， model， high-dose Shoutai Wan， and high-dose Juyuan Jian groups （6 mice per group， with 3 single-cell samples per group， totaling 24 mice） were analyzed by the BD Rhapsody™ platform， and the whole-cell atlas was drawn by uniform manifold approximation and projection （UMAP） dimensionality reduction clustering combined with the single-cell mouse cell atlas （scMCA）. The differentially expressed genes （DEGs） and cell interaction networks were analyzed via Gene Ontology （GO）， Kyoto Encyclopedia of Genes and Genomes （KEGG）， and CellChat， and the protein-protein interaction （PPI） map of subtype cells was constructed. The CytoTRACE pseudo-temporal analysis was performed to explore the developmental trajectories of core immune cells （natural killer cells， NK cells） from maternal and fetal sources. Results① Pathological and Western blot results indicated that compared with the blank group， the RPL group showed an increase in the embryo loss rate （P<0.01）， down-regulated expression of Bcl-2， LIF， MMP-2， and Vegf in the decidua with embryos （P<0.05）， up-regulated protein levels of CXCL-12， AngⅡ， and IL-6 （P<0.05）， blocked angiogenesis， apoptosis-inflammation imbalance， and coagulation dysfunction. Both prescriptions dose-dependently reduced the abortion rate and restored the angiogenesis-inflammation balance， and Shoutai pill showed superior performance in restoring the E₂ level to the Pg level （P<0.05）. ② Single-cell transcriptome analysis indicated that compared with the blank group， the RPL group showed differences in multiple key cell populations such as decidual cells， trophoblast cells， endothelial cells， erythroblasts， NK cells， and macrophages at the maternal-fetal interface. Immunity and angiogenesis were the key links in RPL. Compared with the RPL group， high-dose Shoutai Wan reversed the changes of NK cells in the embryonic layer （upregulating the mRNA levels of 17 genes and downregulating the mRNA levels of 29 genes） and macrophages （upregulating the mRNA levels of 117 genes and downregulating the mRNA levels of 53 genes） through the regulation of gene expression. High-dose Shoutai pill regulated the immune cells to affect unfolded proteins， cell adhesion， and programmed cell death， thereby promoting decidualization and angiogenesis and modulating embryo-membrane development. High-dose Juyuan Jian regulated the key subgroups of NK cells （up-regulating the mRNA levels of 9 genes and down-regulating the mRNA levels of 17 genes） and macrophages （up-regulating the mRNA levels of 110 genes and down-regulating the mRNA levels of 81 genes）， which affected decidual inflammation and apoptosis and intervened in glycolysis. ③ The pseudo-temporal analysis and communication network indicated that the communication frequency of the RPL group decreased. High-dose Shoutai Wan restored maternal-fetal tolerance through pathways such as NKG2D， CDH5， GDF， and FASLG. High-dose Juyuan Jian enhanced the IL-6/LIFR/JAK/signal transducer and activator of transcription 3 （STAT3） and desmosome/SEMA6/tumor necrosis factor-like weak inducer of apoptosis （TWEAK） signaling to improve endometrial receptivity. The RPL group showed an increased proportion of toxic dNK7， a decreased proportion of reparative dNK4， and blocked embryo fNK1. High-dose Shoutai Wan down-regulated dNK7 and up-regulated dNK4. High-dose Juyuan Jian inhibited the terminal differentiation of dNK7 and up-regulated LILRB1， thus restoring the balance of cytotoxicity and repair. ConclusionBoth the kidney-tonifying and spleen-invigorating methods are effective in treating RPL. NK and macrophages are the key immune cells in the interaction between the embryo and the membrane. The kidney-tonifying method （Shoutai Wan） has an advantage in regulating the phenotypes of unfolded protein， cell adhesion， and programmed cell death， and shows expression characteristics closer to the physiological state in the regulation of NKG2D and CDH5 signals. The spleen-invigorating method （Juyuan Jian） has an advantage in regulating epithelial-mesenchymal transition （EMT）， angiogenesis， and glycolysis and shows higher communication intensity in the IL-6 and LIFR pathways.

The incidence of papillary thyroid microcarcinoma (PTMC) is steadily rising. Although conventional thyroid surgery techniques are well-established, they present challenges such as functional impairment and overtreatment. Cellular-level fluorescence-guided imaging technology (EndoSCell^®) enables precise intraoperative tumor localization and real-time identification of neurovascular structures via high-resolution imaging and targeted labeling. This technology significantly improves surgical precision, reduces the incidence of postoperative complications including recurrent laryngeal nerve injury and hypoparathyroidism, and strengthens standards for functional preservation. This article aimed to systematically explore recent advances in the application of EndoSCell^® for PTMC management, analyze its influence on the innovation of surgical approaches and the enhancement of functional preservation criteria, and discuss future directions, thereby providing a theoretical basis for clinical practice.

Objective To establish and verify a double-antibody sandwich ELISA method for detecting the content of varicellazoster virus(VZV) glycoprotein E(VZV-gE) antigen in recombinant zoster virus-like particle(VLP) vaccine, so as to provide key technical support for the optimization of production process and the establishment of quality standards.MethodsMultiple anti-VZV-gE monoclonal antibodies were screened by epitope binning analysis to select capture antibody and detection antibody, and the working concentrations of which were determined by chessboard titration. A double-antibody sandwich ELISA was established to detect the VZV-gE antigen content in the drug substance and drug product of the recombinant zoster VLP vaccine. The linear range, specificity, dilution linearity, accuracy, precision and limit of quantitation(LOQ) of the method were investigated. In addition, the VZV-gE antigen content in multiple batches of drug substance and drug product of vaccine was detected using the established method to investigate the consistency of VZV-gE antigen content.ResultsA double-antibody sandwich ELISA for detecting VZV-gE antigen content in the recombinant zoster VLP vaccine was successfully established using ab272686 monoclonal antibody as capture antibody and VZV-M545 monoclonal antibody as detection antibody. This method could specifically identify VZV-gE antigen and had stability-indicating characteristics. The curve of VZV-gEM reference standard fitted well with A_(450)in the range of 0. 781-100 ng/mL, with R~2= 1. The dilution linearity ranges for detecting drug substance and lyophilized drug product were 4 100-262 400 and 200-12 800, respectively.The recovery rates of accuracy verification were all within the range of 80%-120%. Both the coefficients of variation(CVs)in intra-and inter-assay precision verification were less than 20%, while the LOQs for detecting VZV-gE antigen in the drug substance and lyophilized drug product were both 2 ng/mL. The detection results of VZV-gE antigen content in four batches of drug substance and lyophilized drug product met the expectations and showed good consistency.ConclusionThe established double-antibody sandwich ELISA has good specificity, accuracy, precision and linearity, which is suitable for the detection of VZV-gE antigen content in the recombinant zoster VLP vaccine.

Objective: To investigate the associations between childhood obesity and performance of six minute walk test (6MWT), providing evidence for exercise tolerance assessment and exercise intervention strategies for children and adolescents. Methods: From March 2021 to December 2023, a cohort study was conducted among students recruited from a primary and secondary school in Chongqing, a total of 709 valid samples were included. The 6MWT was used to assess exercise tolerance, with vital signs measured before and after the test. Anthropometric indicators, including height, weight, and waist circumference, were measured using standardized procedures. Generalized additive models (GAM) and restricted cubic spline (RCS) regression were employed to analyze the nonlinear relationships between obesity related indicators and six minute walk distance (6MWD). Results: The mean 6MWD of participants was (602.59±70.73)m. GAM showed that after adjusting for confounding factors, body mass index (BMI) and weight had non linear relationships with 6MWD [effective degrees of freedom were 1.55 and 7.13 respectively], and overweight/obesity was associated with a decrease in 6MWD ( β =-18.65) (all P <0.01). Further RCS regression analysis showed that both BMI and weight showed an "inverted U shaped" non linear relationship with 6MWD in the overall population and sex stratified subgroups; the 6MWD of females was lower than that of males, and it showed a significant downward trend with the increase of BMI or weight (all P <0.05). Conclusion Body weight and BMI in children and adolescents have an important impact on 6MWD, and obesity in children and adolescents is markedly associated with decline in exercise tolerance.

At present， the systematic excavation of the clinical experience and academic thought of the Sichuan school of Chinese medicine vis-à-vis its dominant disease entities remains fragmentary， and replicable paradigms are scarce. Confronted with empirical fragmentation， data heterogeneity and decision-making subjectivity， the standardised distillation， inheritance and clinical translation of these distinctive experiences has become a critical bottleneck constraining the development of the Sichuan school. The integration of artificial-intelligence technologies in data processing， pattern recognition and intelligent decision-making has rendered deep mining of traditional Chinese medicine（TCM） clinical knowledge and patterns imperative. Constructing an intelligent modern TCM diagnostic-therapeutic-evaluative system is now the obligatory route for inheritance and innovation in Chinese medicine， and simultaneously provides a technological breakthrough for intelligent decision paradigms in the dominant diseases of the Sichuan school. Accordingly， this study adopts the regional academic school as its point of entry， focuses on the dominant diseases of the Sichuan school， and proposes an innovative pathway of "four-dimensional data-multi-modal fusion-multi-agent decision-making". Specifically， four data dimensions are defined and instantiated： （Ⅰ） knowledge from classical medical literature and historical case records. （Ⅱ） objective four-diagnosis phenotypic data. （Ⅲ） master physicians' prescribing regularities. （Ⅳ） characteristic mechanisms of renowned formulae. Leveraging multi-modal data fusion and generative artificial intelligence， the entire causal chain of Famous Physicians and Renowned Formulas is explicated to reconstruct the diagnostic-therapeutic cognitive logic of the regional school. Finally， a multi-agent collective-decision model is established and refined for the dominant diseases of the Sichuan school， capable of generating precise， individualised treatment regimens and thereby advancing an intelligent diagnostic-therapeutic paradigm that delivers more efficient and accurate clinical decision support.

ObjectiveThis paper aims to conduct the feature analysis and correlation analysis on the ocular collateral features and differential metabolites in patients with chronic hepatitis B （CHB） complicated by glucose metabolism disorder （GMD），particularly those with the damp-heat syndrome type，by integrating shadowless scleral imaging and metabolomics technologies. MethodsA total of 313 patients were recruited from the Hepatology and Endocrinology Outpatient Departments of Public Health Clinical Center of Chengdu according to the inclusion/exclusion criteria，and they were divided into a CHB group and a CHB complicated by GMD groups （damp-heat syndrome group and non-damp-heat syndrome group）. All patients underwent high-definition ocular image acquisition and feature extraction using an intelligent analysis system for shadowless scleral imaging to analyze the differences in the counting of morphological feature scores of ocular collaterals among groups. By using a digital sampling method，24 patients from each group were randomly selected，along with 20 healthy volunteers，for untargeted metabolomic analysis of peripheral serum. Differential metabolites were identified，statistically analyzed，and subjected to potential biomarker analysis and pathway enrichment. Spearman method was performed to conduct the correlation analysis on the differential ocular collateral features and differential metabolites，followed by correlation network construction. ResultsCompared with those in the CHB group，patients with CHB complicated by GMD showed significant changes in ocular collateral feature scores such as "hillock"，"blood vessels"，and "pale dusky coloration" （P<0.05）. In comparison with those in the healthy group，metabolites including N-acetylglucosamine，acetylhomoserine，and myo-inositol （AUC>0.7） were identified as potential biomarkers for the disease. Compared with those in the CHB complicated by GMD group with non-damp-heat syndrome，patients with damp-heat syndrome exhibited significant changes in feature scores of "plaques"，"yellow coloration"，"spleen"，and "gallbladder" （P<0.05）. In comparison with those in the healthy group，metabolites such as O²′-4a-cyclic tetrahydrobiopterin，theobromine，xanthurenic acid，and L-glutamic acid 5-phosphate （AUC>0.7） were identified as potential biomarkers for the damp-heat syndrome type. The Spearman correlation analysis reveals weak to moderate linear correlations between the differential scleral collateral features and metabolites. By constructing a "disease-syndrome" network of ocular diagnosis and metabolites，"xanthurenic acid-gallbladder" and "theobromine-plaque/yellow coloration" were identified as specific molecular-phenotypic correlated biomarker clusters for CHB complicated by GMD with dampness-heat syndrome. ConclusionPatients with CHB complicated by GMD demonstrate differential ocular diagnostic features and serum metabolites corresponding to disease states and dampness-heat syndrome. These objective biomarkers can guide both clinical syndrome differentiation and medication. The macro-micro integration based on ocular feature clusters and potential metabolic biomarkers offers an innovative approach to a combined traditional Chinese and Western medicine diagnosis and treatment model for this disease.

Background: s/Aims: Sarcomatoid hepatocellular carcinoma (HCC) is a rare histological subtype of HCC characterized by extremely poor prognosis; however, its molecular characterization has not been elucidated. Methods: In this study, we conducted an integrated multiomics study of whole-exome sequencing, RNA-seq, spatial transcriptome, and immunohistochemical analyses of 28 paired sarcomatoid tumor components and conventional HCC components from 10 patients with sarcomatoid HCC, in order to identify frequently altered genes, infer the tumor subclonal architectures, track the genomic evolution, and delineate the transcriptional characteristics of sarcomatoid HCCs. Results: Our results showed that the sarcomatoid HCCs had poor prognosis. The sarcomatoid tumor components and the conventional HCC components were derived from common ancestors, mostly accessing similar mutational processes. Clonal phylogenies demonstrated branched tumor evolution during sarcomatoid HCC development and progression. TP53 mutation commonly occurred at tumor initiation, whereas ARID2 mutation often occurred later. Transcriptome analyses revealed the epithelial–mesenchymal transition (EMT) and hypoxic phenotype in sarcomatoid tumor components, which were confirmed by immunohistochemical staining. Moreover, we identified ARID2 mutations in 70% (7/10) of patients with sarcomatoid HCC but only 1–5% of patients with non-sarcomatoid HCC. Biofunctional investigations revealed that inactivating mutation of ARID2 contributes to HCC growth and metastasis and induces EMT in a hypoxic microenvironment. Conclusions We offer a comprehensive description of the molecular basis for sarcomatoid HCC, and identify genomic alteration (ARID2 mutation) together with the tumor microenvironment (hypoxic microenvironment), that may contribute to the formation of the sarcomatoid tumor component through EMT, leading to sarcomatoid HCC development and progression.

OBJECTIVE: The analgesic effect of acupuncture has been widely accepted. Nevertheless, the mechanism behind its analgesic effect remains elusive, thus impeding the progress of research geared toward enhancing the analgesic effect of acupuncture. This paper investigated the role of acupuncture needle surface textures on acupuncture's analgesic effect by creating four experimental acupuncture needles with different patterns of surface augmentation. METHODS: Four types of acupuncture needles with different surface textures (the lined needle, circle needle, sandpaper needle, and threaded needle) were designed. Additionally, the force/torque measurement system used a robot arm and mechanical sensor to measure the force on the needle during insertion and manipulation. To perform acupuncture analgesia experiments, four experimental acupuncture needles and a normal needle were inserted into the Zusanli (ST36) acupoint of rats with inflammatory pain. By comparing the force and torque and the analgesic efficacy of the different acupuncture needles, these experiments tested the role of acupuncture needle body texture on acupuncture analgesia. RESULTS: The analgesic effects of different acupuncture needle body textures varied. Specifically, the force required to penetrate the skin with the lined needle was not greater than that for the normal needle; however, the needle with inscribed circles and the sandpaper-roughened needle both required greater force for insertion. Additionally, the torque of the lined needle reached 2 × 10^-4 N·m under twisting manipulation, which was four times greater the torque of a normal needle (5 × 10^-5 N·m). Furthermore, the lined needle improved pain threshold and mast cell degranulation rate compared to the normal needle. CONCLUSION Optimizing the texture of acupuncture needles can enhance acupuncture analgesia. The texture of our experimental acupuncture needles had a significant impact on the force needed to penetrate the skin and the torque needed to manipulate the needle; it was also linked to variable analgesic effects. This study provides a theoretical basis for enhancing the analgesic efficacy of acupuncture through the modification of needles and promoting the development of acupuncture therapy. Please cite this article as: Sun MZ, Wang X, Li YC, Liu YH, Yu Y, Ren LJ, Gu W, Yao W. Effects of acupuncture needle modification on acupuncture analgesia. J Integr Med. 2025; 23(1): 66-78.
Needles ; Acupuncture Analgesia/methods* ; Animals ; Rats ; Male ; Acupuncture Points ; Rats, Sprague-Dawley

OBJECTIVE: To assess relationships between cold spells and genitourinary hospitalization risk. METHODS: Hospitalization records for genitourinary system diseases (GUDs) from 16 districts in Beijing (2013-2018) were analyzed. Cold spells were defined based on varying intensity thresholds. A two-stage analytical method was employed: first, generalized linear models assessed district-specific associations between cold spells and hospitalizations; second, random-effects meta-analysis aggregated the district-level results. Subgroup analyses were performed by admission type (emergency vs. outpatient), age, and sex. RESULTS: A total of 271,579 GUD-related hospitalizations were recorded. Cold spells (p1day2，daily mean temperature below the 1 ^st percentiles of the daily mean temperature distribution from January 1, 2013, to December 31, 2018, lasting for two or more consecutive days) were linked to a significant rise in hospitalization risks: 1.43 (95% CI: 1.32-1.56) for all GUDs, 1.35 (95% CI: 1.23-1.49) for urinary system diseases, and 1.46 (95% CI: 1.28-1.67) for renal failure, when compared to non-cold spell days. Emergency admissions showed higher risk increases than outpatient admissions. CONCLUSION Extreme cold spells significantly elevate hospitalization risks for GUDs. This highlights the urgent need for targeted public health interventions to mitigate cold-related health impacts, especially for vulnerable populations.
Humans ; Hospitalization/statistics & numerical data* ; Male ; Female ; Cold Temperature/adverse effects* ; Infant ; Child, Preschool ; Middle Aged ; Adult ; Child ; Aged ; Adolescent ; Young Adult ; Beijing/epidemiology* ; Female Urogenital Diseases/etiology* ; Male Urogenital Diseases/etiology* ; Infant, Newborn ; Risk Factors

Objective To investigate the value of repeat renal biopsy in the treatment and prognosis of nephrotic syndrome(NS)and acute kidney injury(AKI)following immunosuppressive therapy in patients with lupus nephritis(LN). Methods A retrospective analysis was conducted for the clinicopathological data and follow-up records of LN patients undergoing repeat renal biopsy at Peking Union Medical College Hospital from January 1,2009 to December 31,2021. Results A total of 76 patients(55 females,72.4%)were included in this study,with the mean age at the first biopsy being(29.0±10.4)years,the median inter-biopsy interval of 4.0(2.0,7.0) years,and the median total follow-up duration of 7.5(5.0,13.8)years.Pathological transformation occurred in 46(60.5%)patients,and 2 patients had comorbid diabetic nephropathy.At repeat renal biopsy,50(65.8%) patients presented NS.These patients demonstrated lower estimated glomerular filtration rate(eGFR)(P<0.001),higher chronicity index(CI)(P=0.029),and higher complement C3(P<0.001)and C4(P<0.001)levels than those with NS at the first renal biopsy(n=50).Among the 28(36.8%) patients with AKI at repeat renal biopsy,8(28.6%)experienced acute exacerbation of chronic renal insufficiency.These patients exhibited higher serum creatinine level(P=0.002),C4 level(P=0.033),CI(P=0.042),and prevalence of thrombotic microangiopathy(P=0.046)than the patients showing AKI at the first renal biopsy(n=16),while the activity index(AI)showed no significant difference(P=0.051).Over 50% of NS and AKI patients underwent treatment modifications post-repeat renal biopsy,with clinical remission rates comparable to those after the first renal biopsy(both P>0.05).Elevated CI(≥5,P=0.001)and serum creatinine(≥140 μmol/L,P<0.001)at repeat renal biopsy were identified as independent risk factors for poor prognosis.The patients with AKI at repeat renal biopsy had higher incidence of endpoint events than the non-AKI patients(P=0.015).Neither AKI at the first renal biopsy nor NS at both biopsies had significant associations with prognosis. Conclusions Repeat renal biopsy reveals not only sustained high disease activity but also accelerates chronic progression in LN patients,which underscore its critical role in guiding the therapy for severe LN post-immunosuppression.AKI,CI≥5,and serum creatinine ≥140 μmol/L at repeat renal biopsy are strongly associated with poor prognosis.
Humans ; Lupus Nephritis/drug therapy* ; Female ; Retrospective Studies ; Adult ; Male ; Prognosis ; Biopsy ; Kidney/pathology* ; Acute Kidney Injury/pathology* ; Nephrotic Syndrome/pathology* ; Glomerular Filtration Rate ; Young Adult ; Immunosuppressive Agents/therapeutic use* ; Middle Aged