Polycystic ovary syndrome （PCOS） is one of the most prevalent gynecological diseases， and its incidence is increasing year by year， seriously affecting the physical and mental health of female patients. The pathogenesis of this disease is complex and has not been fully clarified. At present， PCOS is mainly treated by Western medicine， which， however， has poor efficacy and induces various adverse reactions. Therefore， developing safe and effective therapies has become a difficult problem that needs to be solved. Studies have confirmed that traditional Chinese medicine （TCM） can regulate phosphatidylinositol 3-kinase/protein kinase B（PI3K/Akt）， mitogen-activated protein kinase/extracellular signal-regulated kinase （MAPK/ERK）， Toll-like receptor 4/nuclear factor-κB （TLR4/NF-κB）， transforming growth factor-β （TGF-β）/Smads， secreted glycoprotein/β-catenin （Wnt/β-catenin）， adenosine monophosphate-activated protein kinase （AMPK）， and advanced glycation endproduct/receptor for advanced glycation endproducts （AGE/RAGE） signaling pathways to ameliorate insulin resistance， inhibit inflammation and oxidative stress， regulate endocrine hormone disorders， and intervene in apoptosis and autophagy， thus alleviating the symptoms， slowing down the disease progression， and improving the ovarian function. The treatment of PCOS with TCM has demonstrated definite effects and high safety. Therefore， exploring this disease from cellular and molecular perspectives can provide a theoretical basis for its clinical treatment and new drug development. However， there is a lack of systematic reviews on the modulation of relevant signaling pathways by TCM in the treatment of PCOS. This article reviews the research progress in the treatment of PCOS with the active ingredients and compound prescriptions of TCM by regulating relevant signaling pathways in recent years， with the aim of providing evidence to support the promotion of TCM for treating PCOS in the future.

BACKGROUND: Arsenic trioxide (ATO) is indicated as a broad-spectrum medicine for a variety of diseases, including cancer and cardiac disease. While the role of ATO in hepatic ischemia/reperfusion injury (HIRI) has not been reported. Thus, the purpose of this study was to identify the effects of ATO on HIRI. METHODS: In the present study, we established a 70% hepatic warm I/R injury and partial hepatectomy (30% resection) animal models in vivo and hepatocytes anoxia/reoxygenation (A/R) models in vitro with ATO pretreatment and further assessed liver function by histopathologic changes, enzyme-linked immunosorbent assay, cell counting kit-8, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay. Small interfering RNA (siRNA) for extracellular signal-regulated kinase (ERK) 1/2 was transfected to evaluate the role of ERK1/2 pathway during HIRI, followed by ATO pretreatment. The dynamic process of autophagic flux and numbers of autophagosomes were detected by green fluorescent protein-monomeric red fluorescent protein-LC3 (GFP-mRFP-LC3) staining and transmission electron microscopy. RESULTS: A low dose of ATO (0.75 μmol/L in vitro and 1 mg/kg in vivo ) significantly reduced tissue necrosis, inflammatory infiltration, and hepatocyte apoptosis during the process of hepatic I/R. Meanwhile, ATO obviously promoted the ability of cell proliferation and liver regeneration. Mechanistically, in vitro  studies have shown that nontoxic concentrations of ATO can activate both ERK and phosphoinositide 3-kinase-serine/threonine kinase (PI3K-AKT) pathways and further induce autophagy. The hepatoprotective mechanism of ATO, at least in part, relies on the effects of ATO on the activation of autophagy, which is ERK-dependent. CONCLUSION Low, non-toxic doses of ATO can activate ERK/PI3K-AKT pathways and induce ERK-dependent autophagy in hepatocytes, protecting liver against I/R injury and accelerating hepatocyte regeneration after partial hepatectomy.
Animals ; Arsenic Trioxide ; Autophagy/physiology* ; Reperfusion Injury/prevention & control* ; Mice ; Male ; Proto-Oncogene Proteins c-akt/physiology* ; Arsenicals/therapeutic use* ; Oxides/therapeutic use* ; Liver/metabolism* ; Extracellular Signal-Regulated MAP Kinases/metabolism* ; Mice, Inbred C57BL

Objective:To explore the application effect of microsurgical thinning optimized anterolateral thigh flap in the repair of limb tumor wounds.Methods:A retrospective analysis was conducted on the clinical data of patients with limb tumors at the Microsurgery and Reconstruction Department of Xuzhou Renci Hospital from January 2019 to January 2021. All patients underwent surgical resection of the lesions and were repaired with microsurgical thinning optimized anterolateral thigh flap. The outpatient follow-up was conducted after surgery. One year after surgery, limb function and appearance were evaluated using the Musculoskeletal Tumor Society (MSTS) bone tumor limb salvage surgery limb energy scale and efficacy satisfaction score. The total score is 30 points, and a higher score indicates better function. The limb appearance was evaluated using a satisfaction score scale, with a total score of 5-10 points being satisfactory, 0-4 points being average, and -5 to -1 points considered unsatisfactory. Descriptive methods were used for statistical analysis, and normally distributed measurement data were expressed as Mean±SD.Results:A total of 11 patients were included, comprising 7 males and 4 females, aged between 19 and 55 years, with an average age of 31.5 years. Among them, there were 3 cases of dermatofibrosarcoma protuberans, 4 cases of invasive fibroma, 1 case of mucinous fibrosarcoma, 2 cases of malignant fibrous histiocytoma, and 1 case of squamous cell carcinoma of the skin. The tumor lesion ranged from 5.5 cm × 8.0 cm to 9.0 cm × 19.0 cm, and the tumor resection range during surgery was from 6.5 cm × 9.0 cm to 10.0 cm × 20.0 cm. The size of the skin flap ranged from 7.5 cm × 11.0 cm to 10.0 cm × 22.5 cm. The average thickness of the flap before thinning was 2.2 cm (1.6-3.5 cm), and the average thickness after thinning was 1.2 cm (0.9-1.7 cm). One case of superficial necrosis occurred at the edge of the flap measuring 1.5 cm × 2.0 cm after surgery, and the wound healed after dressing changes. One case of arterial crisis occurred 48 hours after surgery, and thrombus formation was detected at the distal end of the anastomosis during exploration. After reanastomosis, blood flow was restored. The remaining flaps survived well, and the incisions healed in one stage. The average postoperative follow-up period was 14.5 months (12-18 months) with no tumor recurrence. The MSTS score for limb function was (25.2±2.1) points, and the satisfaction score for limb appearance efficacy was (7.4±1.6) points, with a satisfaction rate of 10 out of 11.Conclusion:The application of microsurgical thinning optimized anterolateral thigh flap in the plastic surgery of limb tumors can restore satisfactory limb function and appearance, making it an ideal surgical method.

Objective To investigate the risk factors affecting the malignancy of amorphous calcifications in the breast and to establish a predictive nomogram.Methods Patients with amorphous calcifications detected by mammography were retrospectively collected,clinical data were obtained from electronic medical record(EMR),and the mammographic features of the patients were assessed by diagnostic physicians.The risk factors affecting the malignancy of amorphous calcifications were analyzed to develop a predictive model and to assess the performance of the model.Results A total of 153 amorphous calcifications in 144 patients were included in the study,and the overall malignancy rate of calcifications was 20.92％.Patient's age ≥45 years,linear distribution of calcifications,unilateral single or unilateral multiple calcifications,and a larger maximum ratio of calcification extent all predicted a higher probability of malignancy,establishing a nomogram based on these 4 risk factors,with a 3.65％predicted probability of malig-nancy as the cut-off,33.99％(52/153)of patients were allowed to be spared biopsy.Conclusion Patient's age and the distribution,number,and maximum ratio of calcifications may be the risk predictors of malignancy for amorphous calcifications,with nomogram con-struction for distinguishing benignity from malignancy of amorphous calcifications via combining with mammographic features and clinical data.

Objective:To explore the application effect of microsurgical thinning optimized anterolateral thigh flap in the repair of limb tumor wounds.Methods:A retrospective analysis was conducted on the clinical data of patients with limb tumors at the Microsurgery and Reconstruction Department of Xuzhou Renci Hospital from January 2019 to January 2021. All patients underwent surgical resection of the lesions and were repaired with microsurgical thinning optimized anterolateral thigh flap. The outpatient follow-up was conducted after surgery. One year after surgery, limb function and appearance were evaluated using the Musculoskeletal Tumor Society (MSTS) bone tumor limb salvage surgery limb energy scale and efficacy satisfaction score. The total score is 30 points, and a higher score indicates better function. The limb appearance was evaluated using a satisfaction score scale, with a total score of 5-10 points being satisfactory, 0-4 points being average, and -5 to -1 points considered unsatisfactory. Descriptive methods were used for statistical analysis, and normally distributed measurement data were expressed as Mean±SD.Results:A total of 11 patients were included, comprising 7 males and 4 females, aged between 19 and 55 years, with an average age of 31.5 years. Among them, there were 3 cases of dermatofibrosarcoma protuberans, 4 cases of invasive fibroma, 1 case of mucinous fibrosarcoma, 2 cases of malignant fibrous histiocytoma, and 1 case of squamous cell carcinoma of the skin. The tumor lesion ranged from 5.5 cm × 8.0 cm to 9.0 cm × 19.0 cm, and the tumor resection range during surgery was from 6.5 cm × 9.0 cm to 10.0 cm × 20.0 cm. The size of the skin flap ranged from 7.5 cm × 11.0 cm to 10.0 cm × 22.5 cm. The average thickness of the flap before thinning was 2.2 cm (1.6-3.5 cm), and the average thickness after thinning was 1.2 cm (0.9-1.7 cm). One case of superficial necrosis occurred at the edge of the flap measuring 1.5 cm × 2.0 cm after surgery, and the wound healed after dressing changes. One case of arterial crisis occurred 48 hours after surgery, and thrombus formation was detected at the distal end of the anastomosis during exploration. After reanastomosis, blood flow was restored. The remaining flaps survived well, and the incisions healed in one stage. The average postoperative follow-up period was 14.5 months (12-18 months) with no tumor recurrence. The MSTS score for limb function was (25.2±2.1) points, and the satisfaction score for limb appearance efficacy was (7.4±1.6) points, with a satisfaction rate of 10 out of 11.Conclusion:The application of microsurgical thinning optimized anterolateral thigh flap in the plastic surgery of limb tumors can restore satisfactory limb function and appearance, making it an ideal surgical method.

Objective To explore the relationship of the preoperative serum alanine aminotransferase(ALT)/aspartate aminotransferase(AST)ratio and imaging features to the prognosis of patients with hepatocellular carcinoma(HCC)after receiving transarterial chemoembolization(TACE),and to develop a nomogram model used for predicting the patient's overall survival(OS).Methods A total of 211 patients,who were diagnosed as HCC and were treated with TACE as the initial therapy at the Guangci Branch of the First Affiliated Hospital of Soochow University of China between July 2016 and July 2020,were enrolled in this study.The patients were randomly divided into the modeling group(n=139)and validation group(n=72).The receiver operating characteristic(ROC)curve was used to determine the optimal cutoff value of AST/ALT ratio.The univariate and multivariate Cox regression analyses were conducted in the modeling group to screen out the independent predictors affecting HCC patient's OS and to establish a prognostic model.Harrell consistency index(C-index)was used to evaluate the predictive ability of the nomogram model for OS in HCC patients,and the calibration curves were plotted to assess the predictive accuracy of the nomogram model.Results No statistically significant difference in the baseline feature distribution existed between the modeling group and validation group(P＞0.05).The median OS of the modeling group and validation group was 28.5 months(95％CI:22.1-34.9)and 25.1 months(95％CI:19.2-29.0)respectively,the difference was not statistically significant(x2=1.395,P=0.322).The optimal cutoff value of AST/ALT ratio for predicting OS was 1.10,and the area under curve(AUC)value was 0.674(95％CI:0.604-0.753).The Cox regression analysis indicated that the tumor number(HR=2.080,95％CI=1.245-3.475,P=0.005),tumor capsule(HR=1.771,95％CI=1.128-2.780,P=0.013),irregular marginal enhancement(HR=1.884,95％CI=1.190-2.984,P=0.007),and AST/ALT ratio(HR=2.450,95％CI=1.506-3.987,P＜0.01)were the independent prognostic factors for HCC patients receiving TACE treatment.Based on the above variables,a nomogram model for predicting OS was established,and the C-index values in the modeling group and validation group were 0.733(95％CI:0.650-0.826)and 0.770(95％CI:0.688-0.862)respectively.The calibration curves showed that no significant deviations existed between the predictive curves of the prognostic model and the ideal reference curves for one-,2-and 3-year OS.Conclusion The nomogram model,which is established based on the tumor number,imaging features and preoperative AST/ALT ratio,has an excellent value in predicting the prognosis of HCC patients treated with TACE.

Objective:To investigate the effects of gelatin methacrylate anhydride (GelMA) hydrogel loaded with small extracellular vesicles derived from human umbilical cord mesenchymal stem cells (hUCMSCs-sEVs) in the treatment of full-thickness skin defect wounds in mice.Methods:This study was an experimental study. hUCMSCs-sEVs were extracted by ultracentrifugation, their morphology was observed through transmission electron microscope, and the expression of CD9, CD63, tumor susceptibility gene 101 (TSG101), and calnexin was detected by Western blotting. The human umbilical vein endothelial cells (HUVECs), the 3 rd and 4 th passages of human epidermal keratinocytes (HEKs) and human dermal fibroblasts (HDFs) were all divided into blank control group (routinely cultured) and hUCMSC-sEV group (cultured with the cell supernatant containing hUCMSCs-sEVs). The cell scratch test was performed and the cell migration rates at 6, 12, and 24 h after scratching were calculated, the cell Transwell assay was performed and the number of migration cells at 12 h after culture was calculated, and the proportion of proliferating cells was detected by 5-acetylidene-2'-deoxyuridine and Hoechst staining at 24 h after culture, with sample numbers being all 3. The simple GelMA hydrogel and the GelMA hydrogel loaded with hUCMSCs-sEVs (hereinafter referred to as hUCMSC-sEV/GelMA hydrogel) were prepared. Then the micromorphology of 2 kinds of hydrogels was observed under scanning electron microscope, the distribution of hUCMSCs-sEVs was observed by laser scanning confocal microscope, and the cumulative release rates of hUCMSCs-sEVs at 0 (immediately), 2, 4, 6, 8, 10, and 12 d after soaking hUCMSC-sEV/GelMA hydrogel in phosphate buffer solution (PBS) were measured and calculated by protein colorimetric quantification ( n=3). Twenty-four 6-week-old male C57BL/6J mice were divided into PBS group, hUCMSC-sEV alone group, GelMA hydrogel alone group, and hUCMSC-sEV/GelMA hydrogel group according to the random number table, with 6 mice in each group, and after the full-thickness skin defect wounds on the back of mice in each group were produced, the wounds were performed with PBS injection, hUCMSC-sEV suspenson injection, simple GelMA coverage, and hUCMSC-sEV/GelMA hydrogel coverage, respectively. Wound healing was observed on post injury day (PID) 0 (immediately), 4, 8, and 12, and the wound healing rates on PID 4, 8, and 12 were calculated, and the wound tissue was collected on PID 12 for hematoxylin-eosin staining to observe the structure of new tissue, with sample numbers being both 6. Results:The extracted hUCMSCs-sEVs showed a cup-shaped structure and expressed CD9, CD63, and TSG101, but barely expressed calnexin. At 6, 12, and 24 h after scratching, the migration rates of HEKs (with t values of 25.94, 20.98, and 20.04, respectively), HDFs (with t values of 3.18, 5.68, and 4.28, respectively), and HUVECs (with t values of 4.32, 19.33, and 4.00, respectively) in hUCMSC-sEV group were significantly higher than those in blank control group ( P<0.05). At 12 h after culture, the numbers of migrated HEKs, HDFs, and HUVECs in hUCMSC-sEV group were 550 ±23, 235 ±9, and 856 ±35, respectively, which were significantly higher than 188 ±14, 97 ±6, and 370 ±32 in blank control group (with t values of 22.95, 23.13, and 17.84, respectively , P<0.05). At 24 h after culture, the proportions of proliferating cells of HEKs, HDFs, and HUVECs in hUCMSC-sEV group were significantly higher than those in blank control group (with t values of 22.00, 13.82, and 32.32, respectively, P<0.05). The inside of simple GelMA hydrogel showed a loose and porous sponge-like structure, and hUCMSCs-sEVs was not observed in it. The hUCMSC-sEV/GelMA hydrogel had the same sponge-like structure, and hUCMSCs-sEVs were uniformly distributed in clumps. The cumulative release rate curve of hUCMSCs-sEVs from hUCMSC-sEV/GelMA hydrogel tended to plateau at 2 d after soaking, and the cumulative release rate of hUCMSCs-sEVs was (59.2±1.8)% at 12 d after soaking. From PID 0 to 12, the wound areas of mice in the 4 groups gradually decreased. On PID 4, 8, and 12, the wound healing rates of mice in hUCMSC-sEV/GelMA hydrogel group were significantly higher than those in the other 3 groups ( P<0.05); the wound healing rates of mice in GelMA hydrogel alone group and hUCMSC-sEV alone group were significantly higher than those in PBS group ( P<0.05). On PID 8 and 12, the wound healing rates of mice in hUCMSC-sEV alone group were significantly higher than those in GelMA hydrogel alone group ( P<0.05). On PID 12, the wounds of mice in hUCMSC-sEV/GelMA hydrogel group showed the best wound epithelization, loose and orderly arrangement of dermal collagen, and the least number of inflammatory cells, while the dense arrangement of dermal collagen and varying degrees of inflammatory cell infiltration were observed in the wounds of mice in the other 3 groups. Conclusions:hUCMSCs-sEVs can promote the migration and proliferation of HEKs, HDFs, and HUVECs which are related to skin wound healing, and slowly release in GelMA hydrogel. The hUCMSC-sEV/GelMA hydrogel as a wound dressing can significantly improve the healing speed of full-thickness skin defect wounds in mice.

Objective To investigate the effect of growth hormone(GH)pretreatment on the improvement of eu-ploid and pregnancy outcome.Methods A prospective analysis was conducted on 134 patients undergoing preim-plantation genetic testing for aneuploidy(PGT-A),among whom 30 patients were self-controlled and 104 patients were inter-group controlled.According to whether GH was added,the patients were divided into GH pretreatment group and GH non-pretreatment group.GH pretreatment included subcutaneous injection of GH 2U/day for 4-6 weeks before the start of gonadotropin(Gn),and the dose was doubled on the day of Gn until the trigger day.GH non-pretreatment meant no GH treatment,GH pretreatment was given when the previous PGT-A cycle failed within one year when the PGT-A was performed again,forming the self-control group.The basic situation,blastocyst situa-tion and pregnancy outcome were compared between the groups by inter-group and self-control.Results No matter in the group control or self-controlled group,the endometrial thickness on the day of HCG,ovarian sensitivity index(OSI),number of oocytes obtained,MII oocytes,2PN number,2PN fertilization rate,available oocyte rate,num-ber of biopsy blastocysts,number of euploid blastocysts,euploid blastocyst rate,and at least one euploid rate sig-nificantly increased after GH pretreatment,with statistically significant differences(P＜0.05).The total amount of Gn,Gn days,number of mosaic blastocysts,and mosaic blastocyst rate were not significantly changed after GH pretreatment,with no statistically significant differences.The implantation rate and clinical pregnancy rate in-creased after GH pretreatment,but with no statistically significant differences.Conclusion GH pretreatment can significantly improve the number and rate of euploid embryos in patients undergoing PGT-A,and has a tendency to improve pregnancy outcome.