Objective:To investigate the efficacy of self-prescribed Huoxue Shengjing Prescription as adjuvant therapy for varicocele-induced infertility and its impact on the outcomes of in vitro fertilization-embryo transfer/intracytoplasmic sperm injection (IVF-ET/ICSI).Methods:A randomized controlled trial was conducted. A total of 99 patients with varicocele-induced infertility in our hospital from January 2022 to July 2023 were selected as observation subjects and divided into three groups using a random number table method, with 33 patients in each group. The low ligation group received low ligation of varicocele under a microscope, the low ligation + conventional Western medicine treatment group received low ligation + conventional Western medicine therapy, and the combined group received low ligation + conventional Western medicine therapy + a self-prescribed Huoxue Shengjing Prescription. Among them, the low ligation of varicocele under a microscope was followed by IVF-ET/ICSI assisted reproductive technology 3 months after surgery; the conventional Western medicine therapy involved continuous administration of L-carnitine oral solution for 3 months; the self-prescribed Huoxue Shengjing Prescription was started on the first day after surgery and continued for 3 months. TCM syndrome scores were assessed before and after treatment, and semen routine analysis was performed using an automated semen quality analyzer. Mitochondrial activity of granulosa cells was measured using the Hrudka extraction method, and sperm nuclear DNA integrity was assessed using a modified alkaline single-cell gel electrophoresis method. Follow-up was conducted for 1 year to observe and record the outcomes of IVF-ET/ICSI and evaluate the clinical efficacy.Results:The total effective rate was 93.9% (31/33) in the combined group, 69.7% (23/33) in the low ligation group, and 75.8% (25/33) in the low ligation + conventional Western medicine treatment group, with statistical significance ( χ 2=6.52, P=0.039). After treatment, the scores for mild abdominal pain, testicular heavy pain, impotence, mental fatigue, and the total score in the combined group were lower than those in the low ligation + conventional Western medicine treatment group and the low ligation group ( F values were 89.29, 97.51, 136.36, 155.06, and 311.13, respectively, P<0.001). The sperm survival rate, sperm concentration, normal morphology rate, and progressive motility rate in the combined group were higher than those in the low ligation + conventional Western medicine treatment group and the low ligation group ( F values were 19.23, 11.85, 35.97, and 52.21, respectively, P<0.001). Mitochondrial grade I cell activity of granulosa cells was higher than that of the low ligation + conventional treatment group and low ligation group ( F=23.23, P<0.001), and grade Ⅲ cell activity was lower than that of the low ligation + conventional treatment group and low ligation group ( F=20.28, P<0.001). After treatment, the detection of grade Ⅰ and Ⅱ sperm nuclear DNA integrity in the combined group were higher than those in the low ligation + conventional Western medicine treatment group and the low ligation group ( F values were 17.73 and 18.39, respectively, P<0.001), while grades Ⅲ and Ⅳ were lower than those in the low ligation + conventional Western medicine treatment group and the low ligation group ( F values were 29.07 and 10.36, respectively, P<0.001). During follow-up, the excellent embryo rate and the spouse's clinical pregnancy rate in the combined group were higher than those in the low ligation + conventional Western medicine treatment group and the low ligation group ( χ2 values were 14.92 and 8.38, respectively; P values were 0.001 and 0.015, respectively). Conclusion:The adjuvant treatment with a self-prescribed Huoxue Shengjing Prescription can enhance sperm quality in patients with varicocele-related infertility, maintain DNA integrity, regulate seminal plasma mitochondrial function, increase the rate of high-quality embryos, and improve the spouse's pregnancy outcomes.

Benzylisoquinoline alkaloids (BIAs) are a structurally diverse group of plant metabolites renowned for their pharmacological properties. However, sustainable sources for these compounds remain limited. Consequently, researchers are focusing on elucidating BIA biosynthetic pathways and genes to explore alternative sources using synthetic biology approaches. CYP80B, a family of cytochrome P450 (CYP450) enzymes, plays a crucial role in BIA biosynthesis. Previously reported CYP80Bs are known to catalyze the 3'-hydroxylation of (S)-N-methylcoclaurine, with the N-methyl group essential for catalytic activity. In this study, we successfully cloned a full-length CYP80B gene (StCYP80B) from Stephania tetrandra (S. tetrandra) and identified its function using a yeast heterologous expression system. Both in vivo yeast feeding and in vitro enzyme analysis demonstrated that StCYP80B could catalyze N-methylcoclaurine and coclaurine into their respective 3'-hydroxylated products. Notably, StCYP80B exhibited an expanded substrate selectivity compared to previously reported wild-type CYP80Bs, as it did not require an N-methyl group for hydroxylase activity. Furthermore, StCYP80B displayed a clear preference for the (S)-configuration. Co-expression of StCYP80B with the CYP450 reductases (CPRs, StCPR1, and StCPR2), also cloned from S. tetrandra, significantly enhanced the catalytic activity towards (S)-coclaurine. Site-directed mutagenesis of StCYP80B revealed that the residue H205 is crucial for coclaurine catalysis. Additionally, StCYP80B exhibited tissue-specific expression in plants. This study provides new genetic resources for the biosynthesis of BIAs and further elucidates their synthetic pathway in natural plant systems.
Cytochrome P-450 Enzyme System/chemistry* ; Benzylisoquinolines/chemistry* ; Hydroxylation ; Plant Proteins/chemistry* ; Alkaloids/metabolism* ; Stephania tetrandra/genetics*

Objective:To systematically evaluate the influencing factors of retinal re-detachment after the first silicone oil removal.Methods:Chinese databases (CNKI, CBM, VIP, Wanfang) and English databases (PubMed, Cochrane, Embase, Web of science) were searched to retrieve the factors affecting the retinal re-detachment after the first pars plana vitrectomy (PPV) combined with silicone oil removal from the inception of the databases to August 20, 2023.The quality of literature was evaluated according to the Newcastle-Ottawa Scale (NOS).The influencing factors related to the retinal re-detachment after the first silicone oil removal were extracted from the literature, and the influencing factors mentioned in <3 literatures were excluded.RevMan5.3 software was used for quantitative and comprehensive analysis.Results:A total of 14 articles were included, including 3 393 eyes, with 498 eyes in the recurrent group, and 2 895 eyes in the non-recurrent group.The results of meta-analysis showed that high myopia (odds ratio [ OR]=1.40, 95% confidence interval [ CI]: 1.08-1.81), giant retinal hole( OR=2.36, 95% CI: 1.63-3.41), vitreous residue ( OR=130.02, 95% CI: 66.03-256.02), intraocular lens status before PPV ( OR=1.86, 95% CI: 1.26-2.75) were the risk factors for retinal re-detachment after silicone oil removal.Rhegmatogenous retinal detachment ( OR=0.68, 95% CI: 0.50-0.92), PPV combined with external scleral compression ( OR=0.63, 95% CI: 0.45-0.88) and fundus laser photocoagulation 2-4 weeks before silicone oil removal ( OR=0.25, 95% CI: 0.13-0.49) were protective factors for retinal detachment after silicone oil removal.The results of sensitivity analysis showed that there was no significant change in the analysis results after changing the analysis model.There was no publication bias among the included studies. Conclusions:High myopia, giant retinal detachment, vitreous residue and intraocular lens status before PPV increased the risk of retinal re-detachment after the first silicone oil removal, Rhegmatogenous retinal detachment, PPV combined with external scleral pressure and fundus laser photocoagulation 2-4 weeks before silicone oil removal may be protective factors.

Objective:To systematically evaluate the influencing factors of retinal re-detachment after the first silicone oil removal.Methods:Chinese databases (CNKI, CBM, VIP, Wanfang) and English databases (PubMed, Cochrane, Embase, Web of science) were searched to retrieve the factors affecting the retinal re-detachment after the first pars plana vitrectomy (PPV) combined with silicone oil removal from the inception of the databases to August 20, 2023.The quality of literature was evaluated according to the Newcastle-Ottawa Scale (NOS).The influencing factors related to the retinal re-detachment after the first silicone oil removal were extracted from the literature, and the influencing factors mentioned in <3 literatures were excluded.RevMan5.3 software was used for quantitative and comprehensive analysis.Results:A total of 14 articles were included, including 3 393 eyes, with 498 eyes in the recurrent group, and 2 895 eyes in the non-recurrent group.The results of meta-analysis showed that high myopia (odds ratio [ OR]=1.40, 95% confidence interval [ CI]: 1.08-1.81), giant retinal hole( OR=2.36, 95% CI: 1.63-3.41), vitreous residue ( OR=130.02, 95% CI: 66.03-256.02), intraocular lens status before PPV ( OR=1.86, 95% CI: 1.26-2.75) were the risk factors for retinal re-detachment after silicone oil removal.Rhegmatogenous retinal detachment ( OR=0.68, 95% CI: 0.50-0.92), PPV combined with external scleral compression ( OR=0.63, 95% CI: 0.45-0.88) and fundus laser photocoagulation 2-4 weeks before silicone oil removal ( OR=0.25, 95% CI: 0.13-0.49) were protective factors for retinal detachment after silicone oil removal.The results of sensitivity analysis showed that there was no significant change in the analysis results after changing the analysis model.There was no publication bias among the included studies. Conclusions:High myopia, giant retinal detachment, vitreous residue and intraocular lens status before PPV increased the risk of retinal re-detachment after the first silicone oil removal, Rhegmatogenous retinal detachment, PPV combined with external scleral pressure and fundus laser photocoagulation 2-4 weeks before silicone oil removal may be protective factors.

Objective·To verify the performance and explore the clinical application value of a multi-modal pulmonary nodule diagnosis model combined with metabolic fingerprints,protein biomarker CEA and Image-AI via random forest(MPI-RF).Methods·This study enrolled 289 patients with pulmonary nodules who were admitted to the Shanghai Chest Hospital,Shanghai Jiao Tong University School of Medicine and were detected by low-dose helical computed tomography(LDCT).The patients were divided into malignant nodule group(n=197)and benign nodule group(n=92)based on postoperative pathological results,and the basic information of the two groups was collected and compared.Electrochemiluminescence was used to detect the preoperative serum CEA levels of the patients in the two groups,matrix-assisted laser desorption/ionization mass spectrometry(MALDI-MS)was used to detect the serum metabolic fingerprints,and the CT image artificial intelligence model Image-AI was used to calculate the image scores.CEA data,serum metabolic fingerprints data and image scores were integrated and input into MPI-RF to calculate the malignant probability score of each patient.The receiver operator characteristic curve(ROC curve)and area under the curve(AUC)were used to evaluate the performance of different models,and the DeLong test was used for comparative analysis,including the diagnostic performance of MPI-RF in different types(solid nodule,pure ground-glass nodule and part-solid nodule)and sizes(diameter<8 mm and diameter≥8 mm)of pulmonary nodules,the diagnostic performance comparison of MPI-RF with Mayo Clinic model,veterans administration(VA)model and Brock model,and the diagnostic performance comparison of MPI-RF with lung imaging reporting and data system(Lung-RADS)in benign and malignant nodules.Results·MPI-RF had good diagnostic performance in the differentiation of benign and malignant pulmonary nodules(AUC=0.887,95%CI 0.848?0.925,sensitivity 81.22%,specificity 83.70%).Among them,the AUC of MPI-RF for solid nodules was 0.877(95%CI 0.820?0.934),for part-solid nodules was 0.858(95%CI 0.771?0.946),and for pure ground-glass nodules was 0.978(95%CI 0.923?1.000).The AUC of MPI-RF was 0.840(95%CI 0.716?0.963)for nodules within 8 mm diameter and 0.891(95%CI 0.849?0.933)for nodules larger than 8 mm diameter.Compared with the existing models,the diagnostic performance of MPI-RF was better than that of Mayo Clinic model,VA model and Brock model(all P=0.000).Compared with Lung-RADS,MPI-RF had better diagnostic performance in the total samples and different types of nodules(all P=0.000).Conclusion·MPI-RF is a model for the differential diagnosis of benign and malignant pulmonary nodules with excellent performance,and has potential clinical application value.

Patellofemoral pain syndrome(PFPS)is one of the main diseases leading to patellofemoral joint dysfunction,which seriously affects the quality of life of patients.This disease is classified as"knee impediment"and"tendon impediment"in TCM,and acupuncture treatment has a significant effect on this disease.This article combed the clinical studies on acupuncture treatment of PFPS in recent years around filiform needling,warm acupuncture and moxibustion,fire needle,needle knife,electro-acupuncture and other acupuncture treatments,and discussed the clinical effects and application scope of different treatments.Studies have shown that acupuncture therapy can effectively improve the symptoms and function of PFPS through a variety of mechanisms,such as regulating the function of the central nervous system,promoting the absorption of inflammatory factors and the clearance of joint effusion,and improving local blood circulation.These findings provide an important reference for the clinical treatment of PFPS.

Objective:To investigate the tissue methylation features of adenocarcinoma patients presenting as pulmonary nodules on CT scans.Methods:A retrospective analysis was conducted on 70 adenocarcinoma patients with pulmonary nodules diagnosed at the Shanghai General Hospital from June 1, 2022 to January 20, 2024. Participants were assigned to two groups using the random number table, with 40 in the discovery group and 30 in the validation group. In the discovery group, tissue samples were analyzed using reduced representation bisulfite sequencing (RRBS) technology to compare the average methylation levels between cancer tissues and paired adjacent non-cancerous tissues. Differentially methylated regions (DMRs) were screened for analysis of their distribution across various genomic functional elements, and hierarchical clustering was plotted. GO and KEGG pathway enrichment analyses were further conducted on the DMRs. Subsequently, candidate DMRs associated with lung adenocarcinoma were validated using TCGA lung adenocarcinoma cohort and targeted bisulfite sequencing technology in the validation group. The comparison of methylation levels between groups was conducted using t-tests or non-parametric tests, while rates and composition ratios were analyzed using chi-square tests or Fisher′s exact test.Results:In discovery cohort, the average methylation level in cancer tissues was lower compared to adjacent normal tissues [(42.369±4.627) vs (44.370±4.046), t=?2.059, P=0.043]. A total of 37 995 DMRs were identified, including 16 889 upregulated regions and 21 106 downregulated regions, predominantly locating in promoter regions (48.917%), introns (36.457%), and exons (10.812%). The DMR clustering heatmap revealed two distinct clusters corresponding to cancer tissues and adjacent non-cancerous tissues. GO analysis showed that DMRs associated genes were mainly located in the cell membrane and nuclear chromatin, and were primarily involved in RNA polymerase Ⅱ-related transcription and regulation. KEGG pathway enrichment analysis indicated that DMRs associated genes were mainly involved in neuroactive ligand-receptor interaction, cancer pathways, calcium signaling pathway, cAMP signaling pathway, and MAPK signaling pathway. Validation in the TCGA cohort confirmed 11 potential characteristic DMRs. In the validation group, TBS confirmed that the methylation levels of DMRs associated with MIR10B, DMRTA2, HOPX, TFAP2B and MARCH11 in cancer tissues were significantly higher than those in adjacent non-cancerous tissues [11.200(4.305, 27.088) vs 2.650(1.298, 4.645), Z=?4.539, P<0.05; 18.610(13.600, 33.025) vs 8.675(5.488, 13.085), Z=?4.554, P<0.05; 17.600(2.183, 76.015) vs 1.085(0.898, 1.835), Z=?5.131, P<0.05; 5.250(3.220, 7.693) vs 3.495(2.165, 4.383), Z=?2.861, P<0.05; 11.515(7.525, 21.033) vs 7.830(5.518, 11.488), Z=?2.440, P<0.05 ], and the differences were statistically significant. Conclusions:Lung adenocarcinoma tissue exhibits different methylation patterns compared with adjacent normal lung tissue. The identified DMRs are involved in the regulation of several key pathways. Results from the TCGA cohort and an independent validation group support the potential diagnostic value of DMRs such as MIR10B, DMRTA2, HOPX, TFAP2B, and MARCH11 in lung adenocarcinoma, though their clinical application requires further validation.

Objective:This study aims to explore the application value of the "liftoff" modular method in robot-assisted laparoscopic surgery for complex adrenal tumors.Methods:We retrospectively analyzed the clinical data of 15 patients with complex adrenal tumors treated at the General Hospital of Southern Theater Command from May 2022 to June 2023. The cohort comprised 5 males and 10 females with an average age of (47.6±7.8) years and a body mass index (BMI) of 26.5 (23.8-27.9) kg/m 2. Among the patients, 3 had a BMI ≥28 kg/m 2, 2 had diabetes, 6 had hypertension, and 1 had coronary heart disease. Preoperative endocrine hormone examination revealed abnormal blood catecholamines in 5 cases and abnormal blood cortisol in 2 cases. Ultrasound and CT scans indicated that 9 tumors were located on the left side and 6 on the right, with 4 cases showing tumor compression on adjacent large blood vessels or organs. The average tumor diameter was (7.61±2.79) cm, with 10 cases having a diameter ≥ 6 cm. All patients underwent laparoscopic adrenalectomy assisted by robots through the transperitoneal approach. The surgeries were performed in a lateral position under general anesthesia. The "liftoff" modular method was utilized to separate the treatment of adrenal tumors into lateral, medial, dorsal, cephalic, and adrenal renal plane sides. Tumors were appropriately manipulated during the operations to achieve a "liftoff" shape. Different modular dissociation steps were adopted based on the size and location of the left and right adrenal tumors. The left adrenal gland was dissected in the order of medial and dorsal, adrenal renal plane side, and lateral and cephalic sides, while the right adrenal gland was dissected in the order of lateral and dorsal, adrenal renal plane side, and medial and cephalic sides. Postoperative related indicators and follow-up status of patients were recorded and analyzed. Results:All 15 surgeries were successfully completed without any conversions to open adrenalectomy, with an average operation time of 118 (102-130) minutes and an average intraoperative blood loss of 102 (69-163) ml. The postoperative drainage time was 4 (3-5) days, and the postoperative hospital stay was 6 (4-7) days. The postoperative pathological diagnoses included 5 cases of pheochromocytoma, 3 cases of macronodular adrenal hyperplasia, 6 cases of adrenocortical adenoma, and 1 case of myelolipoma. Follow-up for 6-12 months after surgery showed good recovery and no recurrence.Conclusions:The application of the "liftoff" modular method in robot-assisted laparoscopic surgery for complex adrenal tumors is safe and feasible. It efficiently aids in tumor removal and holds significant clinical application value.

Objective:To verify the effect of Fu′s massage combined with physical therapy technology in rapidly relieving neck and low back pain caused by long-haul flight.Methods:Forty-two male volunteers were divided into 8, 12, 16, 24 and 48 h groups according to the simulated flying hours. After the completion of the simulated long-haul flight, the 5 groups of volunteers were immediately treated with Fu′s massage combined with physical factors for neck and low back pain. The Visual Analogue Scale (VAS) was used to evaluate the cervical and lumbar pain of volunteers after simulated flight and after treatment, and the treatment effect was before treatment analyzed.Results:There were significant differences in the VAS scores of cervical and lumbar regions before treatment among volunteers with different flying hours ( H=-30.15, -28.25, both P<0.001). The VAS scores of cervical and lumbar regions of volunteers in the 24 h and 48 h groups were higher than those in the 8 h group ( P=0.002, <0.001, =0.002, <0.001). The VAS scores of cervical and lumbar regions of volunteers in the 48 h group were higher than those in the 12 h group ( P=0.016, 0.001). The VAS score of cervical region of volunteers in the 48 h group was higher than that in the 16 h group ( P=0.033). After the intervention of Fu's massage combined with physical therapy, the VAS scores of cervical and lumbar regions in each group were lower than those before treatment, and the differences were significant ( t/ Z=-3.00-17.00, all P<0.05 or 0.01). Conclusions:Fu′s massage manipulation combined with physical treatment can effectively relieve the neck and low back pain caused by long-haul flight, which can be widely used as a relief method.

Objective:To verify the effect of Fu′s massage combined with physical therapy technology in rapidly relieving neck and low back pain caused by long-haul flight.Methods:Forty-two male volunteers were divided into 8, 12, 16, 24 and 48 h groups according to the simulated flying hours. After the completion of the simulated long-haul flight, the 5 groups of volunteers were immediately treated with Fu′s massage combined with physical factors for neck and low back pain. The Visual Analogue Scale (VAS) was used to evaluate the cervical and lumbar pain of volunteers after simulated flight and after treatment, and the treatment effect was before treatment analyzed.Results:There were significant differences in the VAS scores of cervical and lumbar regions before treatment among volunteers with different flying hours ( H=-30.15, -28.25, both P<0.001). The VAS scores of cervical and lumbar regions of volunteers in the 24 h and 48 h groups were higher than those in the 8 h group ( P=0.002, <0.001, =0.002, <0.001). The VAS scores of cervical and lumbar regions of volunteers in the 48 h group were higher than those in the 12 h group ( P=0.016, 0.001). The VAS score of cervical region of volunteers in the 48 h group was higher than that in the 16 h group ( P=0.033). After the intervention of Fu's massage combined with physical therapy, the VAS scores of cervical and lumbar regions in each group were lower than those before treatment, and the differences were significant ( t/ Z=-3.00-17.00, all P<0.05 or 0.01). Conclusions:Fu′s massage manipulation combined with physical treatment can effectively relieve the neck and low back pain caused by long-haul flight, which can be widely used as a relief method.