In order to investigate whether the effect of Yuxuebi Tablets on the peripheral and central inflammation resolution of mice with inflammatory pain is related to their regulation of G protein-coupled receptor 37(GPR37), an inflammatory pain model was established by injecting complete Freund's adjuvant(CFA) into the paws of mice, with a sham-operated group receiving a similar volume of normal saline. The mice were assigned randomly to the sham-operated group, model group, ibuprofen group(91 mg·kg~(-1)), and low-, medium-, and high-dose groups of Yuxuebi Tablets(60, 120, and 240 mg·kg~(-1)). The drug was administered orally from days 1 to 19 after modeling. Von Frey method and the hot plate test were used to detect mechanical pain thresholds and heat hyperalgesia. The levels of interleukin-10(IL-10) and transforming growth factor-beta(TGF-β) in the spinal cord were quantified using enzyme-linked immunosorbent assay(ELISA), and the mRNA and protein expression of GPR37 in the spinal cord was measured by real-time quantitative reverse transcription PCR(qRT-PCR) and Western blot. Additionally, immunofluorescence was used to detect the expression of macrosialin antigen(CD68), mannose receptor(MRC1 or CD206), and GPR37 in dorsal root ganglia, as well as the expression of calcium-binding adapter molecule 1(IBA1), CD206, and GPR37 in the dorsal horn of the spinal cord. The results showed that compared with those of the sham-operated group, the mechanical pain thresholds and hot withdrawal latency of the model group significantly declined, and the expression of CD68 in the dorsal root ganglia and the expression of IBA1 in the dorsal horn of the spinal cord significantly increased. The expression of CD206 and GPR37 significantly decreased in the dorsal root ganglion and dorsal horn of the spinal cord, and IL-10 and TGF-β levels in the spinal cord were significantly decreased. Compared with those of the model group, the mechanical pain thresholds and hot withdrawal latency of the high-dose group of Yuxuebi Tablets significantly increased, and the expression of CD68 in the dorsal root ganglion and IBA1 in the dorsal horn of the spinal cord significantly decreased. The expression of CD206 and GPR37 in the dorsal root ganglion and dorsal horn of the spinal cord significantly increased, as well as IL-10 and TGF-β levels in the spinal cord. These findings indicated that Yuxuebi Tablets may reduce macrophage(microglial) infiltration and foster M2 macrophage polarization by enhancing GPR37 expression in the dorsal root ganglia and dorsal horn of the spinal cord of CFA-induced mice, so as to improve IL-10 and TGF-β levels, promote resolution of both peripheral and central inflammation, and play analgesic effects.
Inflammation/genetics* ; Pain/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Animals ; Mice ; Freund's Adjuvant/pharmacology* ; Ibuprofen ; Pain Threshold/drug effects* ; Hyperalgesia/genetics* ; Ganglia, Spinal ; Interleukin-10/genetics* ; Transforming Growth Factor beta/genetics* ; Reverse Transcriptase Polymerase Chain Reaction ; Tablets ; Receptors, G-Protein-Coupled

BACKGROUND: The use of inserted sham acupuncture as a placebo in randomized controlled trials (RCTs) is controversial, because it may produce specific effects that cause an underestimation of the effect of acupuncture treatment. OBJECTIVE: This systematic survey investigates the magnitude of insert-specific effects of sham acupuncture and whether they affect the estimation of acupuncture treatment effects. SEARCH STRATEGY: PubMed, Embase and Cochrane Central Register of Controlled Trials were searched to identify acupuncture RCTs from their inception until December 2022. INCLUSION CRITERIA: RCTs that evaluated the effects of acupuncture compared to sham acupuncture and no treatment. DATA EXTRACTION AND ANALYSIS: The total effect measured for an acupuncture treatment group in RCTs were divided into three components, including the natural history and/or regression to the mean effect (controlled for no-treatment group), the placebo effect, and the specific effect of acupuncture. The first two constituted the contextual effect of acupuncture, which is mimicked by a sham acupuncture treatment group. The proportion of acupuncture total effect size was considered to be 1. The proportion of natural history and/or regression to the mean effect (PNE) and proportional contextual effect (PCE) of included RCTs were pooled using meta-analyses with a random-effect model. The proportion of acupuncture placebo effect was the difference between PCE and PNE in RCTs with non-inserted sham acupuncture. The proportion of insert-specific effect of sham acupuncture (PIES) was obtained by subtracting the proportion of acupuncture placebo effect and PNE from PCE in RCTs with inserted sham acupuncture. The impact of PIES on the estimation of acupuncture's treatment effect was evaluated by quantifying the percentage of RCTs that the effect of outcome changed from no statistical difference to statistical difference after removing PIES in the included studies, and the impact of PIES was externally validated in other acupuncture RCTs with an inserted sham acupuncture group that were not used to calculate PIES. RESULTS: This analysis included 32 studies with 5492 patients. The overall PNE was 0.335 (95% confidence interval [CI], 0.255-0.415) and the PCE of acupuncture was 0.639 (95% CI, 0.567-0.710) of acupuncture's total effect. The proportional contribution of the placebo effect to acupuncture's total effect was 0.191, and the PIES was 0.189. When we modeled the exclusion of the insert-specific effect of sham acupuncture, the acupuncture treatment effect changed from no difference to a significant difference in 45.45% of the included RCTs, and in 40.91% of the external validated RCTs. CONCLUSION The insert-specific effect of sham acupuncture in RCTs represents 18.90% of acupuncture's total effect and significantly affects the evaluation of the acupuncture treatment effect. More than 40% of RCTs that used inserted sham acupuncture would draw different conclusions if the PIES had been controlled for. Considering the impact of the insert-specific effect of sham acupuncture, caution should be taken when using inserted sham acupuncture placebos in RCTs. Please cite this article as: Luo XC, Liu JL, Yao MH, Chen YM, Fan AY, Liang FR, Zhao JP, Zhao L, Zhou X, Zhong XY, Yang JH, Li B, Zhang Y, Sun X, Li L. Specific effect of inserted sham acupuncture and its impact on the estimation of acupuncture treatment effect in randomized controlled trials: A systematic survey. J Integr Med. 2025; 23(6):630-640.
Acupuncture Therapy/methods* ; Humans ; Randomized Controlled Trials as Topic ; Placebo Effect ; Placebos ; Treatment Outcome

OBJECTIVE: Hepatocellular carcinoma (HCC) is sensitive to ferroptosis, a new form of programmed cell death that occurs in most tumor types. However, the mechanism through which ferroptosis modulates HCC remains unclear. This study aimed to investigate the oncogenic role and prognostic value of FANCD2 and provide novel insights into the prognostic assessment and prediction of immunotherapy. METHODS: Using clinicopathological parameters and bioinformatic techniques, we comprehensively examined the expression of FANCD2 macroscopically and microcosmically. We conducted univariate and multivariate Cox regression analyses to identify the prognostic value of FANCD2 in HCC and elucidated the detailed molecular mechanisms underlying the involvement of FANCD2 in oncogenesis by promoting iron-related death. RESULTS: FANCD2 was significantly upregulated in digestive system cancers with abundant immune infiltration. As an independent risk factor for HCC, a high FANCD2 expression level was associated with poor clinical outcomes and response to immune checkpoint blockade. Gene set enrichment analysis revealed that FANCD2 was mainly involved in the cell cycle and CYP450 metabolism. CONCLUSION To the best of our knowledge, this is the first study to comprehensively elucidate the oncogenic role of FANCD2. FANCD2 has a tumor-promoting aspect in the digestive system and acts as an independent risk factor in HCC; hence, it has recognized value for predicting tumor aggressiveness and prognosis and may be a potential biomarker for poor responsiveness to immunotherapy.
Humans ; Carcinoma, Hepatocellular/diagnosis* ; Liver Neoplasms/diagnosis* ; Immunotherapy ; Fanconi Anemia Complementation Group D2 Protein/metabolism* ; Prognosis ; Male ; Female ; Middle Aged ; Biomarkers, Tumor/metabolism*

OBJECTIVE: Coronavirus disease 2019 (COVID-19) can result in fatigue and post-exertional malaise; however, whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection exacerbates lower urinary tract symptoms (LUTS) is unclear. This study investigated the association between prenatal SARS-CoV-2 infection and postpartum LUTS. METHODS: A multicenter, retrospective cohort study was conducted at two tertiary hospitals in China from November 1, 2022, to November 1, 2023. Participants were classified into infected and uninfected groups based on SARS-CoV-2 antigen results. LUTS prevalence and severity were assessed using self-reported symptoms and the Incontinence Impact Questionnaire-Short Form (IIQ-7). Pelvic floor muscle activity was measured using electromyography following the Glazer protocol. Group comparisons were performed to evaluate the association of SARS-CoV-2 infection with LUTS and electromyography parameters, with stratified analyses conducted using SPSS version 26.0. RESULTS: Among 3,652 participants (681 infected, 2,971 uninfected), no significant differences in LUTS prevalence or IIQ-7 scores were observed. However, SARS-CoV-2 infection was an independent factor influencing the electromyographic activity of the pelvic floor muscles (mean tonic contraction amplitudes), regardless of delivery mode ( P = 0.001). CONCLUSION Prenatal SARS-CoV-2 infection was not significantly associated with an increased risk of postpartum LUTS but independently altered pelvic floor muscle electromyographic activity, suggesting potential neuromuscular effects.
Humans ; Female ; COVID-19/epidemiology* ; Retrospective Studies ; Adult ; Pregnancy ; Lower Urinary Tract Symptoms/virology* ; Postpartum Period ; Pregnancy Complications, Infectious/virology* ; China/epidemiology* ; Electromyography ; SARS-CoV-2/physiology* ; Pelvic Floor/physiopathology* ; Prevalence

Objective:To detect the levels of sex hormones and insulin in follicular fluid(FF)and the expression level of phosphatase and tensin homolog deleted on chromosome ten(PTEN)in granulosa cells in the infertile patients with polycystic ovary syndrome(PCOS),and to preliminarily explain the correlations between the insulin level and the expression level of PTEN mRNA.Methods:Seventy infertile patients were selected as the subjects and divided into PCOS group and control group(tubal obstruction or infertility due to male factors)according to infertility factors.All patients received in vitro fertilization-embryo transfer(IVF-ET)treatment.FF and ovarian granulosa cells were collected on the day of ovulation.The expression levels of PTEN mRNA in ovarian granulosa cells of the patients in two groups were detected by real-time fluorescence quantitative PCR(RT-qPCR)method.The levels of sex hormone and insulin in FF were measured by electrochemiluminescence.The correlations of the PTEN mRNA expression level in ovarian granulosa cells and testosterone(T)in FF with the level of insulin in FF were analyzed by Spearman correlation analysis method.Results:There were no significant differences in age,infertility years,body mass index(BMI),basic sex hormone,total dose of gonadotropin(Gn)and days of ovulation induction in two groups(P＞0.05).Compared with control group,the anti-Mullerian hormone(AMH)and antral follicle counting(AFC)of the patients in PCOS group were significantly increased(P＜0.05).The RT-qPCR results showed that the PTEN mRNA expression level in ovarian granulosa cells of the patients in the PCOS group was higher than that in control group(P＜0.001).The electrochemiluminescence results showed that the levels of T and insulin in FF of the patients in PCOS group were higher than those in control group(P＜0.05),whereas the estrogen and progesterone levels were lower than those in control group(P＜0.05).The Spearman correlation analysis showed that that T level in FF was positively correlated with the insulin level of the patients in PCOS group(r=0.577,P＜0.001),and the PTEN mRNA expression level in ovarian granulosa cells was positively correlated with the insulin levels in FF(r=0.616,P＜0.001);in control group,there was no correlation between T level and insulin level in FF(r=0.266,P=0.123),and there was no correlation between the expression level of PTEN mRNA in granulosa cells and the insulin level in FF in control group(r=-0.214,P=0.216).Conclusion:The high expression of PTEN in granulosa cells of the infertile patients with PCOS may be related to the local hyperinsulin level in the ovary,and PTEN participates in the occurrence and development of PCOS.

Chest low-dose computed tomography (LDCT) is a widely utilized modality for lung cancer screening and follow-up in high-risk populations, owing to its low radiation dose. However, the diagnostic accuracy of LDCT is significantly constrained by inherent limitations, including elevated image noise and reduced contrast resolution. The potential for deep learning technologies to address these challenges through data-driven LDCT image denoising approaches has been demonstrated. In this review, the advantages and limitations of deep learning models were introduced, including supervised, unsupervised, and self-supervised learning. The potential and challenges of these models in clinical applications were analyzed, thereby providing a reference for subsequent research and clinical practice.

Objective To investigate the effects of modified Banxia Baizhu Tianma Decoction(BBTD)on blood pressure and lipid metabolism in patients with metabolic hypertension and dyslipidemia of phlegm-damp obstruction syndrome,guided by Professor Tong Xiaolin's"state-target differentiation and treatment"theory.Methods Sixty eligible patients treated at Chongqing Beibei Hospital of Traditional Chinese Medicine from February 2024 to February 2025 were randomly assigned to treatment group(n=30,receiving conventional therapy plus modified BBTD)and control group(n=30,conventional therapy alone)for 4 weeks.The changes in blood pressure,lipid profiles,body mass index(BMI),fasting blood glucose(FBG),serum uric acid(SUA)were observed,and the antihypertensive efficacy and traditional Chinese medicine(TCM)syndrome efficacy were evaluated.Results(1)Regarding participant dropout,during the study,2 cases in the treatment group were lost to follow-up,while no dropouts occurred in the control group.Ultimately,58 patients were included in the efficacy analysis(28 in the treatment group,30 in the control group).(2)In terms of antihypertensive efficacy,after 4 weeks of treatment,the total effective rate was 92.86％(26/28)in the treatment group versus 36.67％(11/30)in the control group.The intergroup comparison(by chi-square test)demonstrated significantly superior antihypertensive efficacy in the treatment group(P＜0.05).(3)For TCM syndrome efficacy,the marked improvement rate and total effective rate in the treatment group were 60.71％(17/28)and 92.86％(26/28)respectively,compared to 0.00％(0/30)and 33.33％(10/30)in the control group.The treatment group showed significantly better outcomes in marked improvement rate(by chi-square test),total effective rate(by chi-square test),and overall efficacy(by rank-sum test)(all P＜0.05).(4)Regarding blood pressure,post-treatment systolic blood pressure(SBP)and diastolic blood pressure(DBP)were significantly decreased in the treatment group(P＜0.05)but remained unchanged in the control group(P＞0.05).The treatment group exhibited significantly greater reductions in both SBP and DBP compared to controls(P＜0.05).(5)For lipid profiles,the treatment group showed significant post-treatment reductions in total cholesterol(TC),triglycerides(TG),and low-density lipoprotein cholesterol(LDL-C)(P＜0.05).The control group demonstrated increased TG(P＜0.05),with nonsignificant decreases in TC and LDL-C,and a slight increase of HDL-C(P＞0.05).The treatment group achieved significantly greater TC and TG reductions versus controls(P＜0.05).(6)The treatment group showed decreased BMI,fasting glucose,and serum uric acid(P＜0.05),whereas the control group had unchanged BMI and fasting glucose(P＞0.05)but increased uric acid(P＜0.05).The treatment group's reductions in fasting glucose and uric acid were significantly superior to those of control group(P＜0.05).Conclusion State-target-guided modified BBTD effectively treats metabolic hypertension with dyslipidemia of phlegm-damp obstruction syndrome,demonstrating comprehensive metabolic benefits beyond blood pressure control.

Objective To explore the relationship between levels of vascular endothelial growth factor(VEGF),insulin-like growth factor 1(IGF-1),and transforming growth factor-β1(TGF-β1)in the synovial fluid of children with avascular necrosis of the femoral head(also known as Perthes disease)and the efficacy of postoperative revascularization,aiming to provide a basis for subsequent diagnosis and treatment.Methods A retrospective study was conducted on 262 children with Perthes disease admitted to the Affiliated Hospital of Gansu University of Chinese Medicine from January 2023 to June 2024.Based on postoperative revascularization efficacy,patients were divided into good revascularization group(n=228)and poor revascularization group(n=34).For poor revascularization group,a 1:2 matched case-control design was used to select 68 age-matched children with hip synovitis who underwent hip joint fluid puncture as control group.Additionally,82 children with Perthes disease treated at the hospital from June 2024 to January 2025 were enrolled as a validation cohort for nomogram model verification.The expression levels of VEGF,IGF-1 and TGF-β1 in the synovial fluid of three groups were compared.Confounding biases were controlled through univariate and stratified analyses.Binary logistic regression analysis was used to identify independent factors affecting the revascularization effect.R software was utilized to draw and verify the nomogram model for predicting the postoperative revascularization effect.Results The levels of VEGF,IGF-1 and TGF-β1 in the synovial fluid of children in poor revascularization group were all higher than those in control group and good revascularization group(P<0.05).After three types of reconstructive surgeries,the levels of VEGF,IGF-1 and TGF-β1 in the synovial fluid of children with poor revascularization were all higher than those in children with good revascularization(P<0.05);however,there was no statistically significant difference in the above indicators among different surgical types(P>0.05).Binary logistic regression analysis showed that the levels of VEGF,IGF-1,and TGF-β1 in the synovial fluid were independent risk factors for poor postoperative revascularization in children with Perthes disease.The area under the ROC curve of the nomogram model established accordingly for predicting poor postoperative revascularization in children with Perthes disease was 0.875(95%CI 0.805-0.945),with a sensitivity of 0.874 and a specificity of 0.851.Moreover,the calibration curve and decision curve analysis(DCA)indicated that the model had good clinical applicability.Conclusions The increased levels of VEGF,IGF-1 and TGF-β1 in synovial fluid are associated with poor postoperative revascularization in children with Perthes disease.These three factors are expected to become prognostic indicators for children with Perthes disease.

Objective To explore the spatiotemporal expression patterns of Patched 1(Ptch1)and insulin enhancer binding protein-1(Isl 1)in mouse embryonic foregut and their relationship with the early development of trachea-main bronchus.Methods The foregut of 60 mouse embryos at E9.5-12.5 was separated for the detection of Isl1 and sonic hedgehog(Shh)protein by Western blotting.Serial paraffin sections of 6 mouse embryos at E9.5-14.5 were taken for immunohistochemical staining and immunofluorescence double staining with Isl1,Ptch1,forkhead box protein A2(Foxa2),type Ⅱ collagen α1 chain(Col2a1)and α-smooth muscle actin(α-SMA),as well as HE staining and Masson staining.Results The expression trend of Isl1 and Shh in foregut endoderm at E9.5-12.5 was similar,and the peak of Shh expression was later than Isl1.The foregut developed into the trachea at E9.5-12.5,Ptch1 was expressed in the thickening and protrusion of the respiratory endoderm,the laryngal-tracheal groove and the solid cell cord,accompanied by the increase and aggregation of Isl1-positive mesenchymal cells,forming a characteristic pyramidal structure centered on the respiratory endoderm and the solid cell cord;The main bronchus appeared at E12.5-13.5,Ptch1 was only expressed in its lateral wall,accompanied by the accumulation of Isl1-positive mesenchymal cells;The trachea-main bronchial epithelium lost Ptch1 expression and the surrounding Isl 1-positive mesenchymal cells also decreased rapidly at E13.5-14.5.Co12a1-positive chondrocytes first appeared in the Isl1-positive mesenchymal area adjacent to the Ptch1-positive epithelium at E12.5;Col2a1-positive cartilage was nested within the Isl1-positive mesenchymic area in a"C"shape and expanded in a proximal-distal pattern at E12.5-13.5;Col2a1-positive cartilage extended to the dorsal trachea beyond the Isl1-positive mesenchyma and encircles α-SMA positive smooth muscle in a circular manner at E14.5.Conclusion The expression of Ptch1 in the foregut endoderm is involved in the development and morphogenesis of the trachea-main bronchus epithelium,and is closely related to the proliferation and aggregation of Isl1-positive mesenchyme in the trachea-main bronchial wall,Subsequently,they jointly determine the time,location and extent of airway cartilage.

Objective:To characterize the etiological and genetic features of pediatric influenza outbreaks in Changzhou between 2021 and 2024，with the goal of informing evidence-based prevention strategies and guiding effective management of influenza outbreaks in school settings.Methods:During the period of 2021 to 2024，throat swabs of influenza-like cases from school outbreaks in Changzhou were collected. These samples underwent real-time reverse transcription-polymerase chain reaction（RT-PCR）testing and virus isolation. Epidemiological data were integrated to conduct pathogenetic analysis. The HA genes of isolated strains were amplified and sequenced to perform genetic characterization.Results:Between 2021 and 2024，a total of 256 influenza outbreaks were reported in schools in Changzhou. A total of 3 201 specimens were collected，of which 2 245 were tested positive for influenza viruses，resulting in a positivity rate of 70.13%. The outbreak season was primarily concentrated from December to February each year，with settings predominantly distributed in primary schools（accounting for 73.83%）. The predominant epidemic strains were influenza A viruses，including 118 outbreaks caused by H1N1 and 104 by H3N2. A total of 74 influenza virus strains were successfully isolated from positive specimens，and sequencing of the hemagglutinin（HA）gene was completed. Phylogenetic analysis revealed that certain B/Victoria lineage strains（e.g.，B/Changzhou/01/2021）clustered closely with the vaccine strain B/Austria/3594/17（bootstrap support：99%）. Among influenza H1N1 strains，multiple isolates from 2023—2024 clustered within the same major branch as A/Victoria/4897/2022（bootstrap support：100%）. In contrast，the H3N2 strains exhibited a complex evolutionary pattern，showing variable genetic distances to vaccine strains from different years（e.g.，A/Massachusetts/18/2022，A/Darwin/6/2021）；some isolates were closely related to vaccine strains，while others were more distantly related and scattered across the phylogenetic tree.Conclusions:The influenza outbreak situation in schools was severe and has significant public health implications. Continuous surveillance is essential，and preventive strategies should be promptly adjusted based on the epidemiological and genetic characteristics of circulating strains.