OBJECTIVE: To observe the effects of antagonistic needling therapy on lower limb spasticity and the muscle morphology of the tibialis anterior and gastrocnemius in patients with stroke. METHODS: A total of 100 patients with post-stroke lower limb spasticity were randomly divided into an antagonistic needling group (50 cases, 1 case dropped out) and a routine acupuncture group (50 cases, 1 case dropped out). Both groups received basic treatment and rehabilitation training. The routine acupuncture group was treated with scalp acupuncture at anterior oblique line of vertex-temporal and vertex lateral line 1, combined with body acupuncture at Jianyu (LI15), Hegu (LI4), Zusanli (ST36), Taichong (LR3), etc. on the affected side, with Quchi (LI11) and Hegu (LI4), Zusanli (ST36) and Fenglong (ST40), Yanglingquan (GB34) and Taichong (LR3) connected to an electroacupuncture device, using disperse wave at 2 Hz of frequency. The antagonistic needling group used the same scalp and upper limb acupoints as the routine acupuncture group, with additional antagonistic needling on the lower limb at Yanglingquan (GB34), Qiuxu (GB40), Jiexi (ST41), and Xuanzhong (GB39) on the affected side, with Quchi (LI11) and Hegu (LI4), Yanglingquan (GB34) and Qiuxu (GB40), Jiexi (ST41), and Xuanzhong (GB39) connected to an electroacupuncture device, using disperse wave at 2 Hz of frequency. Both groups received treatment once daily for 6 consecutive days per course, with a total of 4 courses. The modified Ashworth scale (MAS), Holden functional ambulation classification (FAC), lower limb Fugl-Meyer assessment (FMA), composite spasticity scale (CSS), and musculoskeletal ultrasound parameters (thickness and fiber length of the tibialis anterior and gastrocnemius, and pennation angle of the gastrocnemius on both sides) were evaluated before and after treatment. Clinical efficacy was compared between the two groups. RESULTS: Compared before treatment, the MAS grades and CSS scores were decreased in both groups after treatment (P<0.01), with greater reductions in the antagonistic needling group (P<0.05, P<0.01). FAC grades and FMA scores were increased in both groups after treatment (P<0.01, P<0.05), with greater improvements in the antagonistic needling group (P<0.05). The muscle thickness, fiber length of the tibialis anterior, the muscle thickness, fiber length and pennation angle of the gastrocnemius on the affected side were improved in both groups after treatment (P<0.01), with greater improvements in the antagonistic needling group (P<0.01, P<0.05). On the unaffected side, these parameters were also increased after treatment in both groups (P<0.01, P<0.05), but the antagonistic needling group showed smaller increases than the routine acupuncture group (P<0.01, P<0.05). The total effective rate in the antagonistic needling group was 91.8% (45/49), higher than 81.6% (40/49) in the routine acupuncture group (P<0.05). CONCLUSION Antagonistic needling could effectively reduce spasticity, improve motor function, and enhance muscle structure in patients with post-stroke lower limb spasticity.
Humans ; Male ; Female ; Acupuncture Therapy ; Middle Aged ; Muscle Spasticity/pathology* ; Aged ; Stroke/physiopathology* ; Lower Extremity/physiopathology* ; Acupuncture Points ; Adult ; Muscle, Skeletal/pathology* ; Treatment Outcome

BACKGROUND: Temozolomide (TMZ) resistance is a significant challenge in treating glioblastoma (GBM). Collagen remodeling has been shown to be a critical factor for therapy resistance in other cancers. This study aimed to investigate the mechanism of TMZ chemoresistance by GBM cells reprogramming collagens. METHODS: Key extracellular matrix components, including collagens, were examined in paired primary and recurrent GBM samples as well as in TMZ-treated spontaneous and grafted GBM murine models. Human GBM cell lines (U251, TS667) and mouse primary GBM cells were used for in vitro studies. RNA-sequencing analysis, chromatin immunoprecipitation, immunoprecipitation-mass spectrometry, and co-immunoprecipitation assays were conducted to explore the mechanisms involved in collagen accumulation. A series of in vitro and in vivo experiments were designed to assess the role of the collagen regulators prolyl 4-hydroxylase subunit alpha 1 (P4HA1) and yes-associated protein (YAP) in sensitizing GBM cells to TMZ. RESULTS: This study revealed that TMZ exposure significantly elevated collagen type I (COL I) expression in both GBM patients and murine models. Collagen accumulation sustained GBM cell survival under TMZ-induced stress, contributing to enhanced TMZ resistance. Mechanistically, P4HA1 directly binded to and hydroxylated YAP, preventing ubiquitination-mediated YAP degradation. Stabilized YAP robustly drove collagen type I alpha 1 ( COL1A1) transcription, leading to increased collagen deposition. Disruption of the P4HA1-YAP axis effectively reduced COL I deposition, sensitized GBM cells to TMZ, and significantly improved mouse survival. CONCLUSION P4HA1 maintained YAP-mediated COL1A1 transcription, leading to collagen accumulation and promoting chemoresistance in GBM.
Temozolomide ; Humans ; Glioblastoma/drug therapy* ; Animals ; Mice ; Cell Line, Tumor ; Drug Resistance, Neoplasm/genetics* ; YAP-Signaling Proteins ; Hydroxylation ; Dacarbazine/pharmacology* ; Adaptor Proteins, Signal Transducing/metabolism* ; Transcription Factors/metabolism* ; Collagen/biosynthesis* ; Collagen Type I/metabolism* ; Prolyl Hydroxylases/metabolism* ; Antineoplastic Agents, Alkylating/therapeutic use*

This study investigated the effects of Rehmanniae Radix Praeparata on striatal neuronal apoptosis in rats with attention deficit hyperactivity disorder(ADHD) based on the B-cell lymphoma-2(Bcl-2)/Bcl-2-associated X protein(Bax)/caspase-3 signaling pathway. Twenty-four 3-week-old male spontaneously hypertensive rats(SHR) were randomly divided into a model group, a methylphenidate group(2 mg·kg~(-1)·d~(-1)), and a Rehmanniae Radix Praeparata group(2.4 mg·kg~(-1)·d~(-1)). Age-matched male Wistar Kyoto(WKY) rats were used as the normal control group, with 8 rats in each group. The rats were administered by gavage for 28 days. Body weight and food intake were recorded for each group. The open field test and elevated plus maze test were used to assess hyperactivity and impulsive behaviors. Nissl staining was used to detect changes in striatal neurons and Nissl bodies. Terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL) fluorescence staining was used to detect striatal cell apoptosis. Western blot was employed to detect the expression levels of Bcl-2, Bax, and caspase-3 proteins in the striatum. The results showed that compared with the model group, Rehmanniae Radix Praeparata significantly reduced the total movement distance, average movement speed, and central area residence time in the open field test, and significantly reduced the ratio of open arm entries, open arm stay time, and head dipping in the elevated plus maze test. Furthermore, it increased the number of Nissl bodies in striatal neurons, significantly downregulated the apoptosis index, significantly increased Bcl-2 protein expression and the Bcl-2/Bax ratio, and reduced Bax and caspase-3 protein expression. In conclusion, Rehmanniae Radix Praeparata can reduce hyperactivity and impulsive behaviors in ADHD rats. Its mechanism may be related to the regulation of the Bcl-2/Bax/caspase-3 signaling pathway in the striatum, enhancing the anti-apoptotic capacity of striatal neurons.
Animals ; Male ; Apoptosis/drug effects* ; Rats ; Drugs, Chinese Herbal/administration & dosage* ; Caspase 3/genetics* ; Proto-Oncogene Proteins c-bcl-2/genetics* ; bcl-2-Associated X Protein/genetics* ; Rehmannia/chemistry* ; Attention Deficit Disorder with Hyperactivity/physiopathology* ; Signal Transduction/drug effects* ; Neurons/cytology* ; Rats, Inbred SHR ; Rats, Inbred WKY ; Humans ; Corpus Striatum/cytology* ; Plant Extracts

OBJECTIVE: To explore the association between acupuncture during controlled ovarian hyperstimulation (COH) and the live birth rate (LBR) using different propensity score methods. METHODS: In this retrospective cohort study, eligible women who underwent a COH were divided into acupuncture and non-acupuncture groups. The primary outcome was LBR, as determined by propensity score matching (PSM). LBR was defined as the delivery of one or more living infants that reached a gestational age over 28 weeks after embryo transfer. The propensity score model encompassed 16 confounding variables. To validate the results, sensitivity analyses were conducted using three additional propensity score methods: propensity score adjustment, inverse probability weighting (IPW), and IPW with a "doubly robust" estimator. RESULTS: The primary cohort encompassed 9751 patients (1830 [18.76%] in the acupuncture group and 7921 [81.23%] in the non-acupuncture group). Following 1:1 PSM, a higher LBR was found in the acupuncture cohort (41.4% [755/1824] vs 36.4% [664/1824], with an odds ratio of 1.23 [95% confidence interval, 1.08-1.41]). Three additional propensity score methods produced essentially similar results. The risk of serious adverse events did not significantly differ between the two groups. CONCLUSION This retrospective study revealed an association between acupuncture and an increased LBR among patients undergoing COH, and that acupuncture is a safe and valuable treatment option. Please cite this article as: Zheng XY, Jiang ZY, Li YT, Li CL, Zhu H, Yu Z, Yu SY, Yang LL, Tang SY, Lü XY, Liang FR, Yang J. Association between acupuncture and live birth rates after fresh embryo transfer: A cohort study based on different propensity score methods. J Integr Med. 2025; 23(5):528-536.
Humans ; Female ; Propensity Score ; Embryo Transfer ; Adult ; Acupuncture Therapy ; Retrospective Studies ; Pregnancy ; Live Birth ; Birth Rate ; Cohort Studies

OBJECTIVE: To explore the key target molecules and potential mechanisms of oridonin against non-small cell lung cancer (NSCLC). METHODS: The target molecules of oridonin were retrieved from SEA, STITCH, SuperPred and TargetPred databases; target genes associated with the treatment of NSCLC were retrieved from GeneCards, DisGeNET and TTD databases. Then, the overlapping target molecules between the drug and the disease were identified. The protein-protein interaction (PPI) was constructed using the STRING database according to overlapping targets, and Cytoscape was used to screen for key targets. Molecular docking verification were performed using AutoDockTools and PyMOL software. Using the DAVID database, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were conducted. The impact of oridonin on the proliferation and apoptosis of NSCLC cells was assessed using cell counting kit-8, cell proliferation EdU image kit, and Annexin V-FITC/PI apoptosis kit respectively. Moreover, real-time quantitative PCR and Western blot were used to verify the potential mechanisms. RESULTS: Fifty-six target molecules and 12 key target molecules of oridonin involved in NSCLC treatment were identified, including tumor protein 53 (TP53), Caspase-3, signal transducer and activator of transcription 3 (STAT3), mitogen-activated protein kinase kinase 8 (MAPK8), and mammalian target of rapamycin (mTOR). Molecular docking showed that oridonin and its key target molecules bind spontaneously. GO and KEGG enrichment analyses revealed cancer, apoptosis, phosphoinositide-3 kinase/protein kinase B (PI3K/Akt), and other signaling pathways. In vitro experiments showed that oridonin inhibited the proliferation, induced apoptosis, downregulated the expression of Bcl-2 and Akt, and upregulated the expression of Caspase-3. CONCLUSION Oridonin can act on multiple targets and pathways to exert its inhibitory effects on NSCLC, and its mechanism may be related to upregulating the expression of Caspase-3 and downregulating the expressions of Akt and Bcl-2.
Diterpenes, Kaurane/chemistry* ; Carcinoma, Non-Small-Cell Lung/pathology* ; Humans ; Network Pharmacology ; Lung Neoplasms/pathology* ; Cell Proliferation/drug effects* ; Apoptosis/drug effects* ; Molecular Docking Simulation ; Protein Interaction Maps/drug effects* ; Cell Line, Tumor ; Signal Transduction/drug effects* ; Gene Expression Regulation, Neoplastic/drug effects* ; Reproducibility of Results ; Gene Ontology

ObjectiveThis study leverages structural data from antigen-antibody complexes of the influenza A virus neuraminidase (NA) protein to investigate the spatial recognition relationship between the antigenic epitopes and antibody paratopes. MethodsStructural data on NA protein antigen-antibody complexes were comprehensively collected from the SAbDab database, and processed to obtain the amino acid sequences and spatial distribution information on antigenic epitopes and corresponding antibody paratopes. Statistical analysis was conducted on the antibody sequences, frequency of use of genes, amino acid preferences, and the lengths of complementarity determining regions (CDR). Epitope hotspots for antibody binding were analyzed, and the spatial structural similarity of antibody paratopes was calculated and subjected to clustering, which allowed for a comprehensively exploration of the spatial recognition relationship between antigenic epitopes and antibodies. The specificity of antibodies targeting different antigenic epitope clusters was further validated through bio-layer interferometry (BLI) experiments. ResultsThe collected data revealed that the antigen-antibody complex structure data of influenza A virus NA protein in SAbDab database were mainly from H3N2, H7N9 and H1N1 subtypes. The hotspot regions of antigen epitopes were primarily located around the catalytic active site. The antibodies used for structural analysis were primarily derived from human and murine sources. Among murine antibodies, the most frequently used V-J gene combination was IGHV1-12*01/IGHJ2*01, while for human antibodies, the most common combination was IGHV1-69*01/IGHJ6*01. There were significant differences in the lengths and usage preferences of heavy chain CDR amino acids between antibodies that bind within the catalytic active site and those that bind to regions outside the catalytic active site. The results revealed that structurally similar antibodies could recognize the same epitopes, indicating a specific spatial recognition between antibody and antigen epitopes. Structural overlap in the binding regions was observed for antibodies with similar paratope structures, and the competitive binding of these antibodies to the epitope was confirmed through BLI experiments. ConclusionThe antigen epitopes of NA protein mainly ditributed around the catalytic active site and its surrounding loops. Spatial complementarity and electrostatic interactions play crucial roles in the recognition and binding of antibodies to antigenic epitopes in the catalytic region. There existed a spatial recognition relationship between antigens and antibodies that was independent of the uniqueness of antibody sequences, which means that antibodies with different sequences could potentially form similar local spatial structures and recognize the same epitopes.

Objective To analyze the effect of the activation rate of peripheral blood monocytes on the recovery of patients after liver transplantation and to initially explore the possible influencing factors for differences in monocyte activation rates. Methods A total of 139 patients who underwent orthotopic liver transplantation from September 2020 to June 2023 at Department of Liver Surgery and Transplantation of Zhongshan Hospital, Fudan University were selected. The proportion of CD14^＋HLA-DR^＋ monocytes in peripheral blood was defined as the monocyte activation rate. The difference in monocyte activation rates between postoperative day 7 (POD7) and postoperative day 1 (POD1) was calculated as Δ, and patients were divided into Δ＞0 group (n＝73) and Δ＜0 group (n＝66). The two groups were compared in terms of complete blood count, liver and kidney function, coagulation indicators, infection indicators, ICU length of stay, total length of hospitalization, and 90-day mortality. Changes in the proportions of different monocytes subsets (Mo0, Mo1, Mo2, and Mo3) and HLA-DR expression in peripheral blood on POD1 and POD7 were detected using flow cytometry. Results The ICU length of stay in the Δ＜0 group was significantly longer than that in the Δ＞0 group (18[12, 26] days vs 14[10, 20.5] days, P＝0.018). On POD1, the proportion of Mo0 in the Δ＞0 group was significantly lower than that in the Δ＜0 group (P＜0.05); on POD7, the proportion of Mo0 in the Δ＞0 group was significantly lower than that in the Δ＜0 group (P＜0.001), while the proportions of Mo1, Mo2, and Mo3 were significantly higher than those in the Δ＜0 group (P＜0.001). Compared to POD1, the HLA-DR expression level of Mo0 in peripheral blood of patients with liver transplantation significantly decreased on POD7 (P＜0.01), while there was no significant difference in HLA-DR expression levels of Mo1, Mo2, and Mo3. Conclusions Increased proportion of Mo0 (CD14^lowCD16⁻HLA-DR^low) among peripheral blood monocyte subsets may be one of the influencing factors for the differences in monocyte activation rates in patients with liver transplantation. The difference in monocyte activation rate can serve as a new clinical indicator for assessing changes in the immune status and postoperative recovery of patients with liver transplantation.

Objective:To evaluate the service capability and operational efficiency of surgical departments in a hospital using data analysis models such as entropy weight TOPSIS and Boston matrix analysis, for references for optimizing medical resource allocation, promoting refined management and sustainable development of the hospital.Methods:The operational data of 24 surgical departments (A~X) in a tertiary public hospital in 2023 from its information system were extracted. The number of doctors, actual number of open beds, and average length of stay etc., were served as evaluation indicators. The TOPSIS and rank sum ratio methods were used to evaluate the medical service capabilities, the data envelopment analysis (DEA) was used to analyze operational efficiency, and Boston matrix analysis was used for departmental classification.Results:In terms of medical service capabilities, the top 5 departments were F, S, K, D, and C ( Ci>0.41), all of which were in the excellent category; The bottom three departments were L, N, and G ( Ci<0.04), all of which were in the poor range. From the perspective of operational efficiency, 8 departments had achieved strong DEA effectiveness, while the remaining 16 departments were non DEA effective, resulting in resource redundancy or insufficient output. According to the Boston Matrix analysis, 8 departments (stars) had strong medical service capabilities and high operational efficiency; 6 departments (cash cows) had poor medical service capabilities but high operational efficiency, and 8 departments (dogs) had poor medical service capabilities and operational efficiency; 2 departments (question marks) had strong medical service capabilities but low operational efficiency. Conclusions:This study comprehensively applied multiple data models to objectively and comprehensively evaluate the service capabilities and operational efficiency of surgical departments. Hospitals could develop corresponding resource allocation optimization strategies based on the Boston matrix classification results, combined with the disease characteristics and business scale configuration of each department.

Objective:To explore the clinical characteristics and genetic etiology of a child with Oral-facial-digital syndrome type Ⅰ(OFDSⅠ).Method:A child with OFDSⅠ who received treatment at the Women and Children′s Hospital Affiliated to Ningbo University in March 2023 was selected as the study subject. A retrospective research method was used to collect the clinical data of the child. Peripheral venous blood samples were collected from the child, her parents and sister. Genomic DNA was extracted, and whole exome sequencing (WES) was performed. Candidate variants were validated using Sanger sequencing for familial verification. According to the Standards and Guidelines for the Interpretation of Sequence Variants developed by the American College of Medical Genetics and Genomics (ACMG) (hereinafter referred to as the " ACMG Guidelines" ), the pathogenicity of the candidate variant was rated. This study was approved by the Medical Ethics Committee of Ningbo University Affiliated Women and Children′s Hospital (Ethic No.: EC 2024-063).Results:The child was a prematurely born female with deformities of the oral cavity, fingers, and toes. She was admitted to the Neonatal Department of the Hospital where she was born due to shortness of breath 15 minutes after birth. The WES results indicated that the child has harbored a heterozygous c. 710dup(p.Y238Vfs*2) frameshifting variant of the OFD1 gene. Sanger sequencing confirmed that neither of the child′s parents nor her sister had carried the same variant. According to the ACMG guidelines, the variant was rated as pathogenic (PVS1+ PS4_Moderate+ PM2-Supporting+ PM6_Supporting+ PP4). Conclusion:Children with OFDSⅠ have clinical features such as oral, finger, and toe deformities. The c. 710dup(p.Y238Vfs*2) variant of the OFD1 gene probably underlay the OFDSⅠ in this child. Above result has enriched the mutational spectrum of the OFD1 gene.

Objective:To evaluate the efficacy and safety of sintilimab combined with bevacizumab in the second-line treatment of malignant pleural mesothelioma(MPM).Methods:This was a longitudinal study. Patients with MPM who had progressed after first-line treatment and were admitted to the Day-Care Outpatient Department of Medical Oncology, Ningguo People′s Hospital from February 2019 to February 2022 were included. General clinical data of the patients were collected at baseline. The patients were treated with the second-line treatment regimen of sintilimab (200 mg)+bevacizumab (15 mg/kg) on a 21-day cycle. Enhanced CT scans were performed every 3 cycles to evaluate the efficacy until tumor progression or death. Follow-up period ended in December 2023. The primary endpoints were progression-free survival (PFS) and overall survival (OS). Efficacy was evaluated according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST), and the best response of each patient was recorded. The objective response rate (ORR) and disease control rate (DCR) were calculated. Adverse reactions were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), ranging from grade Ⅰto Ⅳ. Kaplan-Meier survival curves were used to analyze PFS and OS, and survival times were expressed as median values.Results:A total of 23 MPM patients were included, with the mean age of (55.04±13.27)years, 15 males, 8 females, 19 cases of epithelial type and 4 cases of non-epithelial type. The Eastern Cooperative Oncology Group (ECOG) performance status scores were 0-1 in 12 patients and 2 in 11 patients. There were 17 smokers and 6 non-smokers, 12 cases with PD-L1 positive and 11 cases with PD-L1 negative, and 6 cases with anti-angiogenic drugs and 17 cases without using anti-angiogenic drugs in the first-line treatment. Of the 23 patients, 1 achieved complete response (CR), 9 achieved partial response (PR), 7 had stable disease (SD), and 6 had progressive disease (PD). The ORR and DCR of the enrolled patients were 43.5% (10/23) and 73.9% (17/23), respectively. Kaplan-Meier survival analysis showed that the PFS of the enrolled patients was 7.50 (95% CI: 5.47-9.54) months, and the OS was 12.50 (95% CI: 1.07-23.93) months. The most common adverse reactions related to the treatment of sintilimab combined with bevacizumab were hypertension (14 cases (60.9%)), fatigue (10 cases (43.5%)), decreased appetite (8 cases (34.8%)), proteinuria (6 cases (26.1%)), pruritus (5 cases (21.7%)), constipation (4 cases (17.4%)) and nausea (3 cases (13.0%)), etc. Only 9 patients had grade Ⅲ adverse reactions (8 cases of hypertension and 1 case of nausea), and only 1 patient had grade Ⅳ adverse reaction (hypertension). Conclusion:Sintilimab combined with bevacizumab has some therapeutic effects on progressive MPM, and the adverse reactions are relatively mild.