Chronic visceral pain is a persistent and debilitating condition arising from dysfunction or sensitization of the visceral organs and their associated nervous pathways. Increasing evidence suggests that imbalances in central nervous system function play an essential role in the progression of visceral pain, but the exact mechanisms underlying the neural circuitry and molecular targets remain largely unexplored. In the present study, the ventral tegmental area (VTA) was shown to mediate visceral pain in mice. Visceral pain stimulation increased c-Fos expression and Ca²⁺ activity of glutamatergic VTA neurons, and optogenetic modulation of glutamatergic VTA neurons altered visceral pain. In particular, the upregulation of NMDA receptor 2A (NR2A) subunits within the VTA resulted in visceral pain in mice. Administration of a selective NR2A inhibitor decreased the number of visceral pain-induced c-Fos positive neurons and attenuated visceral pain. Pharmacology combined with chemogenetics further demonstrated that glutamatergic VTA neurons regulated visceral pain behaviors based on NR2A. In summary, our findings demonstrated that the upregulation of NR2A in glutamatergic VTA neurons plays a critical role in visceral pain. These insights provide a foundation for further comprehension of the neural circuits and molecular targets involved in chronic visceral pain and may pave the way for targeted therapies in chronic visceral pain.
Animals ; Male ; Visceral Pain/metabolism* ; Up-Regulation/physiology* ; Ventral Tegmental Area/metabolism* ; Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors* ; Neurons/drug effects* ; Mice, Inbred C57BL ; Mice ; Proto-Oncogene Proteins c-fos/metabolism* ; Chronic Pain/metabolism* ; Glutamic Acid/metabolism*

BACKGROUND: A growing body of research is exploring the role of antioxidant and anti-inflammatory dietary supplements in the treatment of osteoarthritis, highlighting an increasing emphasis on non-pharmacological interventions. Although more patients are turning to supplements to manage osteoarthritis, their actual effectiveness remains uncertain. OBJECTIVE: This study aims to provide a comprehensive evaluation of the available evidence concerning the efficacy of various dietary supplements in osteoarthritis treatment. SEARCH STRATEGY: We searched PubMed, Embase, Cochrane Library and Web of Science for studies on the use of various dietary supplements in the treatment of osteoarthritis from the creation of each database until Jan 20, 2025. INCLUSION CRITERIA: (1) Research object: osteoarthritis. (2) Intervention measures: patients in the treatment group received dietary supplements, while the control group received placebos. (3) Research type: randomized controlled trials (RCTs). DATA EXTRACTION AND ANALYSIS: Two researchers independently examined the literature and retrieved data based on predefined criteria. The information gathered included the first author, year of publication, sample size, participant demographics, length of the follow-up period, intervention and control measures, and inclusion indications. RCTs comparing dietary supplements to placebo with the pain and function subscales of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) among patients with osteoarthritis were included. The optimal dietary supplement was identified based on the total ranking by summing the surface under the cumulative ranking curve (SUCRA) of these two scores. Furthermore, the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) was used to confirm the quality of the evidence. RESULTS: Overall, 23 studies covering 21 dietary supplements and involving 2455 participants met the inclusion criteria. In the WOMAC pain score, the SUCRA of passion fruit peel extract was 91% (mean difference [MD]: -9.2; 95% confidence interval [CI]: [-16.0, -2.3]), followed by methylsulfonylmethane (89%), undenatured type II collagen (87%), collagen (84%), and Lanconone (82%). The SUCRA (99%) of passion fruit peel extract (MD: -41.0; 95% CI: [-66.0, -16.0]) ranked first in terms of the WOMAC function score, followed by Lanconone (95%), collagen (86%), ParActin (84%), and Lactobacillus casei strain Shirota (83%). The top three total rankings are passion fruit peel extract (95.0%), Lanconone (88.5%), and collagen (85.0%). However, the GRADE revealed low evidence quality. CONCLUSION Passion fruit peel extract was the best supplement for improving WOMAC pain and function scores in patients with osteoarthritis, followed by Lanconone and collagen. However, further large-scale, well designed RCTs are required to substantiate these promising findings. Please cite this article as: Chen CS, Wen L, Yang F, Deng YC, Ji JH, Chen RJ, Chen Z, Chen G, Gu JY. Effects of dietary supplements on patients with osteoarthritis: A systematic review and network meta-analysis. J Integr Med. 2025; 23(4): 357-369.
Humans ; Dietary Supplements ; Osteoarthritis/drug therapy* ; Randomized Controlled Trials as Topic

Objective To analyze the influencing factors of postoperative live birth in patients with tubal ectopic pregnancy who had received fresh double cleavage-stage embryo transfer through in vitro fertilization/intracytoplasmic sperm injection(IVF/ICSI).Methods A retrospective cohort study was performed by analyzing clinical data of patients receiving laparoscopic salpingectomy for clinical diagnosed tubal ectopic pregnancy who had undergone double fresh cleavage-stage embryo transfer in our department from January 2016 to June 2018.A follow-up study was performed in terms of pregnancy outcomes in patients who were willing to conceive or attempt pregnancy for 6 years after the operation.The patients were categorized into two groups according to postoperative pregnancy outcomes.A logistic regression analysis was performed to analyze the influencing factors of postoperative live births.Results A total of 188 patients were included,110 of which had live birth within 6 years after surgery,with a live birth rate of 58.5％(110/188).A multivariate logistic regression analysis was conducted on variables with P＜0.2 in the univariate analysis(age,duration of infertility,ovarian reserve dysfunction,number of egg retrieval after laparoscopic resection,endometrial thickness,pelvic adhesions,and fimbrial morphology of the fallopian tube)and the baseline antral follicle count in the last transplantation cycle of the live birth cycle(P=0.205),which would affect the outcome of subsequent pregnancy.The analysis showed that pelvic single site and multiple site dense adhesions were independent prognostic factors affecting the live birth again(OR=0.185,95％ CI:0.046-0.736,P=0.017;OR=0.124,95％ CI:0.024-0.640,P=0.013).Conclusions Intraoperative pelvic adhesion negatively affects the pregnancy outcomes of patients diagnosed with tubal ectopic pregnancy who have received fresh double cleavage-stage embryo transfer,and is an independent prognosis factor for postoperative live birth within 6 years.Improving pelvic adhesion and preventing pelvic inflammatory disease are beneficial for refining fertility outcome after surgery.

Objective:To investigate the clinical efficacy of combination of a Flow-through anterolateral thigh myocutaneous flap with a contralateral great saphenous vein grafting in reconstruction of Gustilo ⅢC foot and ankle injury in emergency surgery.Methods:This retrospective study analysed the clinical data of 9 patients who were admitted in the Department of Wound Repair Surgery, Suzhou Ruihua Orthopaedic Hospital between September 2021 and October 2023. All patients were diagnosed with Gustilo ⅢC foot and ankle injury and met the predefined inclusion criteria. The average age of the patients was 45 (26-64) years. The mean of Mangled Extremity Severity Score (MESS) was 8.2 points, with a range from 5 to 10 points. The wound area after debridement ranged from 15.5 cm×6.0 cm to 24.5 cm×12.5 cm, with the vascular occlusion or defect at 4.0-20.0 (mean, 6.3) cm in length. The size of the flap was 16.5 cm×7.0 cm-25.5 cm×13.5 cm. During surgery, segments of the great saphenous vein were excised in the length of 5.0-21.0 cm, at an approximately 6.5 cm in length. The Flow-through anterolateral thigh myocutaneous flap was employed to reconstruct the soft tissue defect and to establish vascular connections between the anterior or posterior tibial arteries and veins, with the vessels carried by the flap. Additionally, the contralateral great saphenous vein was taken to bridge the posterior or anterior tibial arteries and veins. Follow-ups were carried out by outpatient visits, telephone calls and WeChat interviews. The flap viability, limb blood circulation, wound healing at both donor and recipient sites, as well as functional recovery of the affected limbs was observed. Sensation recovery of the flap was assessed according to the rating standard established by the British Medical Research Council (BMRC) , while the function recovery of foot and ankle was evaluated using the American Orthopaedic Foot and Ankle Society (AOFAS) scale.Results:All flaps successfully survived without vascular complication. Eight affected limbs were effectively cured, while a calf that had an infection and necrosis of a long segment of tibia and fibula was amputated below-the-knee in the stage-II surgery. One of the donor sites of flap was covered with a medium-thickness skin graft from lower abdomen due to the large size of the flap, while the other donor sites were directly sutured and healed at first intention. One patient developed postoperative bone infection, which was successfully treated through re-debridement and antibiotic bone cement filling. Another patient experienced partial necrosis at the distal hallux due to a prolonged limb ischemia, and a stump repair surgery was performed. All patients were entered into the postoperative follow-up for 15.3 (6-24) months. At the final follow-up visit, satisfactory colour and texture were observed on all flaps, although minor oedema was present. Donor sites healed well and the donor limb function was not affected. Sensory evaluation rated S 2 in 5 flaps and S 3 in 3 flaps according to BMRC. Functional assessment of foot and ankle of the affected limb yielded excellent in 2 patients, good in 5 patients and fair in 1 patient according to AOFAS. Conclusion:Flow-through anterolateral thigh myocutaneous flap combined with a contralateral great saphenous vein grafting enables one-stage reconstruction for soft tissue defect and blood circulation of the affected limb. It is a good method in the treatment of Gustilo ⅢC foot and ankle injury in emergency surgery.

Objective:To explore the clinical effects of free bilateral turbocharged anterolateral thigh flaps in tandem in repairing extensive wounds in the foot and ankle.Methods:The study was a retrospective observational study. From April 2020 to June 2023, 12 patients with extensive wounds in the foot and ankle who met the inclusion criteria were admitted to the Department of Wound Repair Surgery of Suzhou Ruihua Orthopedic Hospital, including 8 males and 4 females, aged 21 to 65 years. The wound area after debridement ranged from 27 cm×14 cm to 37 cm×20 cm. The bilateral perforator flaps pedicled with either oblique or descending branches of the lateral circumflex femoral artery were designed and harvested based on the size and shape of the wounds. The individual flap incision area ranged from 16 cm×9 cm to 34 cm×12 cm. The non-homologous perforator of the flap on the one side was turbocharged by anastomosing it with the gross muscular branch or main vessel of the oblique or descending branch of the lateral circumflex femoral artery from the flap. Subsequently, the proximal end of the oblique or descending branch of the lateral circumflex femoral artery and its accompanying vein from the flap on the one side were connected end-to-end with either the anterior tibial artery and vein, posterior tibial artery and vein, or dorsal foot artery and vein in the recipient area, the distal end of the oblique or descending branch of the lateral circumflex femoral artery and its accompanying vein from the flap on the one side were anastomosed end-to-end with a source vessel originating from flap on the other side. The wounds in the flap donor areas were sutured directly. The number and source of perforators carried by the flaps and the duration of the flap repair surgery were recorded. The survival of the flap, the occurrence of vascular crisis, and the wound healing at both donor and recipient areas were observed after surgery. The flap condition, appearance and function of the affected limb were observed during follow-up. At the last follow-up, the sensory function of the flap was assessed using the British Medical Research Council's sensory rating standard, the foot and ankle function of the affected limb was evaluated according to the American Orthopedic Foot and Ankle Society scoring standard.Results:A total 24 flaps were successfully harvested, carrying 60 perforators, including 34 perforators from the oblique branch of the lateral circumflex femoral artery, 24 perforators from the descending branch of the lateral circumflex femoral artery, one perforator from the transverse branch of the lateral circumflex femoral artery, and one perforator from the direct branch of the femoral artery. The duration of the flap repair surgery ranged from 4.2 to 9.0 hours. The flaps of 12 patients exhibited complete survival after surgery. A total of two flaps of two patients experienced venous crisis after surgery but survived through emergency exploration. One patient encountered undesirable wound healing at the donor area of flap on the one side after surgery, which healed after dressing change, debridement, and suturing. The remaining patients' donor area wounds healed. Two patients displayed impaired wound healing in the recipient area, which improved after dressing change and resection of residual sequestrum, and the wounds in the recipient area of other patients healed successfully. During the follow-up of 4-26 months, the flaps demonstrated favorable color and texture, slight edematous appearance, and partial sensory recovery, as well as good aesthetic and functional restoration of the affected limbs. At the last follow-up, the sensory function of the flap was assessed as grade S2 in 9 cases and grade S3 in 3 cases; the foot and ankle function of the affected limb was evaluated as excellent in two cases, good in 9 cases, and fair in one case.Conclusions:The bilateral turbocharged anterolateral thigh flaps have numerous sources of perforators. By implementing supercharging of non-homologous perforators within the flap, the vascular supply to the flap is turbocharged, thereby mitigating the risk of extensive flap necrosis. The flap is an effective approach for repairing extensive wounds in the foot and ankle, resulting in improved function of the affected limb after repair.

BACKGROUND:Hemivertebra deformity should be treated surgically at an early age,but the risk factors for progression of deformity after hemivertebral resection have not been established.OBJECTIVE:To investigate the curative effect of one-stage posterior hemivertebrae resection and pedicle screw fixation in the treatment of congenital scoliosis,and to further explore the risk factors causing the progression of postoperative deformity.METHODS:The medical records of patients who underwent pedicle screw-rod fixation for unilateral hemivertebral deformity from January 2012 to February 2020 and were followed up for at least 2 years were retrospectively analyzed,and a total of 116 patients met the inclusion criteria.All patients were treated with standing anterior and lateral spinal radiographs taken before,after and at each follow-up time point.The segment Cobb angle,the total scoliosis Cobb angle,the proximal complementary Cobb angle,the distal complementary Cobb angle,and the coronal balance distance,apical vertebra distance,upper instrumented vertebra tilt,upper instrumented vertebra disc angle,lower instrumented vertebra tilt,lower instrumented vertebra disc angle,segmental kyphosis/lordosis,thoracic kyphosis,lumbar lordosis and sagittal vertical axis were measured.The progression of deformity and complications were also recorded.RESULTS AND CONCLUSION:(1)Segment Cobb,total scoliosis Cobb,segmental kyphosis,proximal complementary Cobb,and distal complementary Cobb were significantly corrected after operation(P＜0.05),and remained corrected at the last follow-up.Thoracic kyphosis,lumbar lordosis,coronal balance distance,and sagittal vertical axis were all in the normal range pre-operation,after operation and at the last follow-up.(2)During follow-up,10 patients developed coronary decompensation,which was characterized by abnormal progression.(3)Independent sample t-test showed that preoperative total scoliosis Cobb,preoperative apical vertebra distance,age,Risser sign,postoperative upper instrument vertebra tilt and postoperative lowest instrumented vertebra tilt were correlated with postoperative malformation progression(P＜0.05).(4)Multivariate Logistic regression analysis showed that postoperative lowest instrumented vertebra tilt was an independent risk factor for postoperative malformation progression(P=0.002,OR=1.526).(5)Receiver operating characteristic curve analysis showed that a postoperative lowest instrumented vertebra tilt of 8.14° was the optimal threshold for deformity progression after hemivertebrae resection and pedicle rod fixation(sensitivity 0.900,specificity 0.906,area under curve:0.926).(6)It is indicated that the treatment of congenital scoliosis with one-stage posterior hemivertebrae resection and pedicle nail fixation can achieve satisfactory orthopedic effect.Postoperative lowest instrumented vertebra tilt greater than 8.14° was an independent risk factor for postoperative coronal decompensation.

Objective To explore the molecular mechanism by which SOS Ras/Rac guanine nucleotide exchange factor 1-intronic transcript 1(SOS1-IT1)affects enhancer of zeste homolog 2(EZH2)protein expression in endometrial cancer cells Ishikawa and RL95-2.Methods Lentiviral transfection of short hairpin RNA(shRNA)and overexpression plasmid were used in Ishikawa and RL95-2 cell lines to knock down and overexpress SOS1-IT1.The mechanism of EZH2 expression regulation was studied using Real-time PCR,Western blotting,and chromatin immunoprecipitation.Results The expression of SOS1-IT1 and EZH2 genes was positively correlated in endometrial cancer tissues.Knocking down SOS1-IT1 significantly reduces the expression of EZH2,inhibited the proliferation and migration of Ishikawa and RL95-2 cells,and could reduced the acetylation of histone H3 at position 27(H3K27)and the enrichment of CREB binding protein(CBP)in the EZH2 gene promoter region.Overexpression of SOS1-IT1 could increased the expression of EZH2 and enhance the acetylation of H3K27 and the enrichment of CBP.CBP could bind to SOS1-IT1 RNA,and this binding ability was weakened when CBP was knocked down.Conclusion SOS1-IT1 can promote the expression level of EZH2 in endometrial cancer cells Ishikawa and RL95-2 by regulating the acetylation modification level of the EZH2 gene promoter region,thereby affecting the proliferation and migration ability of endometrial cancer cells.

Aim To explore the mechanism of baicalin combined with heat stimulation in treating acute lym-phoblastic leukemia(ALL)based on network pharma-cology and in vitro experiments.Methods The CCK-8 assay was used to screen the suitable conditions for heat stimulation to interfere ALL cell lines Jurkat,CCRF-CEM,Hut-78 and a normal lymphocyte HMy2.CIR,and the effects of baicalin combined with heat stimulation on the proliferation of three ALL cell lines and a normal lymphocyte were tested.The key targets of baicalin combined with fever stimulation for the treatment of ALL were obtained based on network phar-macological analysis,and the potential mechanisms were predicted by gene ontology(GO)annotation and kyoto encyclopedia of genes and genomes(KEGG)en-richment.The expression levels of TNF-α,AKT1,TYMS and CASP3 mRNA in ALL cell lines Jurkat and CCRF-CEM were examined by RT-qPCR with baicalin alone and baicalin combined with heat stimulation.Results The optimal conditions for heat stimulation to intervene ALL cells were 41 ℃ for 24 h,and heat stimulation combined with baicalin synergistically inhibited the growth of ALL cell lines and effectively reduced the cy-totoxicity of baicalin.Based on the network pharmaco-logical analysis,55 intersecting targets of baicalin with ALL diseases and 77 intersecting targets of baicalin with fever were obtained.The results of GO annotation and KEGG enrichment suggested that baicalin com-bined with fever stimulation to intervene ALL might be associated with influencing intracellular reactive oxygen species metabolism,DNA transcription and apoptotic processes involved in cysteine enzymes.Apoptosis,TNF and IL-17 signaling pathways were the key pathways for baicalin combined with heat stimulation in treating ALL.Under heat stimulation at 41 ℃ using SDHA gene as housekeeping gene,in vitro experiments showed that baicalin significantly up-regulated the expression of TNF-α and CASP3,and down-regulated the expression of TYMS in ALL cells.Conclusions Based on net-work pharmacologic analyses and in vitro experiments,baicalin combined with heat stimulation can regulate TNF-α and CASP3 gene levels in ALL cells and de-stroy cellular structure to promote cell apoptosis,thus synergistically treating ALL.

Objective To explore the efficacy differences between 3 Tesla magnetic resonance imaging with zero echo time(3T MRI ZTE)and high resolution computed tomography(HRCT)in the detection of pulmonary nodules and the classification diagnosis of the lung imaging reporting and data system(Lung-RADS)in sub-health populations.Methods Clinical and imaging data of 93 patients with pulmonary nodules(126 nodules in total)admitted to some hospital from July to December 2023 were retrospectively analyzed.The 126 nodules were categorized into a benign nodule group(n=51)and a malignant nodule group(n=75)using pathological findings as the gold standard.All the patients underwent examinations by 3T MRI ZTE and HRCT to compare the detection rates of the two measures for pulmonary nodules;the missed and misdiagnosis rates of 3T MRI ZTE,HRCT and Lung-RADS grading were contrasted with the postoperative pathological diagnosis results as the gold standard;comparison analyses of 3T MRI ZTE signs and HRCT signs were performed between the two groups and the patients with different Lung-RADS grades;3T MRI ZTE,HRCT and Lung-RADS grading were compared with the receiver operating characteristic(ROC)curve in terms of diagnosis efficacy for pulmonary nodules,and the consistency analysis was carried out.Results No discernible statistical variation was observed in the detection rates of pulmonary nodules between 3T MRI ZTE and HRCT(P>0.05).Lung-RADS grading had the highest rates of missed diagnosis and misdiagnosis,and 3T MRI ZTE and HRCT had similar detection rates.The malignant nodule group was different from the benign nodule group in the 3T MRI ZTE and HRCT signs in terms of lesion size,spiculation sign,lobulation sign,calcifica-tion,pleural indentation sign,cavity sign,boundary and bronchial cut-off sign,with the differences being statistically signi-ficant(all P<0.05).For the patients of Lung-RADS grade 3,the 3T MRI ZTE and HRCT signs had significant differences in terms of lesion size,spiculation sign,lobulation sign,calcification,pleural indentation sign,cavity sign and bronchial cut-off sign(all P<0.05).For the patients of Lung-RADS grade 4A,the 3T MRI ZTE and HRCT signs had significant differen-ces in terms of lesion size,calcification,boundary and bronchial cut-off sign(all P<0.05).For the patients of Lung-RADS grade 4B,the 3T MRI ZTE and HRCT signs had significant differences in terms of lesion size and calcification(all P<0.05).For the patients of Lung-RADS grade 4X,there were no significant differences found between the 3T MRI ZTE and HRCT signs(all P>0.05).HRCT had the highest sensitivity,specificity,accuracy,AUC value,predictive values and Kappa value for benign and malignant nodules,3T MRI ZTE had the values slightly lower than those of HRCT,and Lung-RADS grading had the lowest values when compared with HRCT and 3T MRI ZTE.Conclusion HRCT and 3T MRI ZTE are complementary for the evaluation of pulmonary nodules,and the differences in imaging signs between them show graded dependence.3T MRI ZTE and HRCT have no significant differences in the detection rate of pulmonary nodules,while HRCT gains advanta-ges in differentiating benign and malignant pulmonary nodules,and references are provided for the screening and clinical early diagnosis of pulmonary nodules.[Chinese Medical Equipment Journal,2025,46(9):52-59]

Objective:To investigate the role of platelet-derived zyxin in promoting tumor migration by platelets.Methods:The gene expression profile of platelets was analyzed from cancer patients by using the GEO database.Isolated platelets from wild-type(WT)and Zyx-/-mice were co-cultured with B16F10 cells labeled with green fluorescence to investigate the influence of zyxin deficiency on tumor cell migration,invasion,and wound healing.Optical microscopy was employed to evaluate the impact of zyxin deficiency on epithelial-mesenchymal transition(EMT)in B16F10 cells induced by platelets.Employing specific markers to label platelets,fluorescence confocal microscopy was utilized to investigate the impact of platelet-derived zyxin on the binding between tumor cells and platelets.And an aggregometer was employed to observe the influence of zyxin deficiency on tumor cell-induced platelet aggregation.Results:Compared to platelets from healthy volunteers,zyxin was upregulated in platelets from cancer patients.Zyx-/-mouse platelets exhibited a significant reduction in tumor cell invasion and migration,impaired wound healing,and delayed tumor cell EMT compared to WT mouse platelets.Additionally,zyxin deficiency attenuated the interaction between platelets and tumor cells,and diminished the capacity for tumor cell-induced platelet aggregation.Conclusion:Platelet-derived zyxin deficiency diminishes platelet-tumor cell interactions and weakens the ability of tumor cell-induced platelet aggregation,ultimately suppressing tumor cell migration.