Objective:To compare the clinical application of the anterolateral thigh perforator flap (ALTPF) and the calf pedicled propeller perforator flap (PPPF) in reconstruction of soft tissue defect of foot and ankle.Methods:A retrospective observational study was conducted. From March 2013 to June 2019, 48 patients with soft tissue defect around ankle and in foot were reconstructed with ALTPF and PPPF in the Department of Orthopaedics, 920th Hospital of the Joint Logistic Support Force, People's Liberation Army of China. According to the types of flap, the patients were divided into 2 groups: ALTPF group (21 patients,13 males and 8 females, aged 16-67 years, mean 38.71 years±15.30 years. Donor sites were all directly sutured.) and PPPF group (27 patients, 12 males and 15 females, aged 12-69 years, mean 35.18 years±13.96 years. Five cases in the donor site required partial skin grafting, and the rest 22 cases were repaired by directly suture.). The wound size of the former was 5 cm×6 cm-15 cm×18 cm, and at 2 cm×3 cm-14 cm×17 cm for the latter. The surgical time and flap size of the 2 groups were recorded during the surgery. The survival and complications of the flap were observed, and the days of hospital stay were recorded after surgery. Follow-ups were conducted by outpatient clinic and via telephone and WeChat interviews. The colour, texture, appearance, donor scar, complications and thinning of the flap were observed during the follow-up. The ankle function was evaluated according to the score of American Orthopaedic Foot and Ankle Society (AOFAS), and the donor scar was evaluated according to the score of Vancouver Scar Scale (VSS). SPSS 22.0 statistical software was used for data analysis, and P<0.05 was considered statistically significant. Results:The surgical time for the ALTPF group was 118-203 (154.71±25.42) min, and that for the PPPF group was 52-92 (72.78±10.04) min. The size of the flap in the ALTPF group was 5 cm×8 cm-8 cm×18 cm (75.00 cm 2±8.69 cm 2), while it was 3 cm×7 cm-7 cm×17 cm (53.56 cm 2±19.49 cm 2) in the PPPF group. In the ALTPF group, 3 flaps had vascular complications within 24 hours after surgery, which survived after exploration and thrombectomy. Partial necrosis occurred in 1 flap. The rest 17 flaps survived uneventfully. In the PPPF group, 2 flaps had partial necrosis due to infection and they healed after dressing changes, 3 flaps had venous occlusion and survived after phlebotomy, partial suture removal and massage. The rest 22 flaps in 2 groups survived uneventfully. The postoperative days of hospital stay for the ALTPF group was 6-14 (8.71±2.03) days, and that was 4-12 (6.03±2.16) days in the PPPF group. Flap thinning was performed on 19 flaps in the ALTPF group and 2 in the PPPF group. Follow-up was performed for 7 to 21 months. All the flaps were good in colour, shape and texture. All donor sites healed well. At the final follow-up, 19 patients achieved ankle function of excellent, 1 of good and 1 of fair in the ALTPF group, and 21 patients achieved ankle function of excellent, 4 of good and 2 of fair in the PPPF group, according to the AOFAS. According to the VSS, scores of donor site scar was rated 4-8 (6.33±1.35) points for the ALTPF group, and 3-10 (5.92±1.80) points for the PPPF group. Statistical analysis showed no significant differences between the 2 groups in terms of early postoperative complications, flap survival rate, ankle function, and VSS scores ( P>0.05). However, there were statistically significant differences between the 2 groups in terms of surgical time, hospital stay, flap size, and the number of flap thinning ( P<0.05). Conclusion:Both ALTPF and PPPF have good clinical effects in reconstruction of soft tissue defect of foot and ankle. For small to medium-sized wounds, PPPF is the preferred choice due to the advantages in surgical time and postoperative hospital stay. For larger wounds, the ALTPF is the first choice with multiple surgery.

OBJECTIVE: To observe the protective effect of Fisetin on sepsis-associated brain injury and explore its possible mechanism from the perspective of ferroptosis. METHODS: Sprague-Dawley (SD) rats (6-8-week-old male) were randomly divided into three groups: sham operation group (Sham group), colonic ligation and puncture (CLP) induced sepsis model group (CLP group) and Fisetin preprocessing group (CLP+Fisetin group), with 18 rats in each group (12 for observing survival rate and 6 for indicator testing). The CLP+Fisetin group was given Fisetin solution 50 mg×kg^-1×d^-1 by gavage continuously for 5 days before CLP, with dimethyl sulfoxide (DMSO) as the solute, while Sham group and CLP group were given the same dose of DMSO. The model was established at 2 hours after the last gavage. The general condition of each group of rats were observed, and the 10-day mortality were record. The behavioral testing (new object recognition experiment, elevated cross maze experiment) were performed after 7 days of modeling. After 24 hours of modeling, nerve reflex scoring was performed, and then the rats were euthanized and brain tissue was collected. The pathological changes of brain tissue were observed under a microscope by hematoxylin-eosin (HE) staining, the deposition of iron ion in brain tissue was observed by Prussian blue staining. The content of iron in brain tissue was determined by tissue iron kit, and the content of malondialdehyde (MDA) in brain tissue was determined by colorimetry. The expressions of tumor necrosis factor-α (TNF-α), neuron damage marker S100β, nuclear factor E2-related factor 2 (Nrf2), heme oxygenases-1 (HO-1) and glutathione peroxidase 4 (GPX4) were detected by Western blotting. RESULTS: On day 10 post-operation, 12, 3, and 7 animals survived in the Sham group, CLP group, and CLP+Fisetin group, respectively. Compared with the Sham group, rats in the CLP group showed significantly decreased nerve reflex score, new object discrimination index and open arm dwell time. HE staining showed arranged disorderly of neuronal cells, cytoplasm deep staining, nuclear condensation, unclear structures, neuron loss, and significant inflammation in the hippocampus in the hippocampus. Prussian blue staining showed iron ion deposition in the brain tissue. The contents of iron and MDA in brain tissue were elevated, and the expressions of TNF-α and S100β were up-regulated, while the expressions of Nrf2, HO-1, and GPX4 were down-regulated. Compared with the CLP group, the CLP+Fisetin group showed significantly increased neurological reflex score (7.33±1.15 vs. 4.67±1.53), improved new object discrimination index (0.44±0.02 vs. 0.32±0.04), and longer open arm dwell time (minutes: 78.33±9.29 vs. 41.15±9.64). Neuronal cells in the hippocampus were more organized, with less cytoplasmic staining, nuclear condensation, reduced neuronal loss, and fewer inflammatory cells. Iron ion deposition was reduced, and the contents of iron ions and MDA in brain tissue were decreased [iron ion (μg/g): 151.27±14.90 vs. 224.69±17.64, MDA (μmol/g): 470.0±44.3 vs. 709.3±65.4]. The expressions of TNF-α and S100β were significantly decreased (TNF-α/GAPDH: 0.651±0.060 vs. 0.896±0.022, S100β/GAPDH: 0.685±0.032 vs. 0.902±0.014), while the expressions of Nrf2, HO-1, and GPX4 were significantly increased (Nrf2/GAPDH: 0.708±0.108 vs. 0.316±0.112, HO-1/GAPDH: 0.694±0.022 vs. 0.538±0.024, GPX4/GAPDH: 0.620±0.170 vs. 0.317±0.039). All differences were statistically significant (all P < 0.05). CONCLUSION Fisetin pretreatment can inhibit ferroptosis and reduce sepsis-associated brain injury by Nrf2/HO-1/GPX4 pathway.
Animals ; Ferroptosis/drug effects* ; Rats, Sprague-Dawley ; NF-E2-Related Factor 2/metabolism* ; Sepsis/complications* ; Male ; Rats ; Phospholipid Hydroperoxide Glutathione Peroxidase ; Neurons/drug effects* ; Signal Transduction ; Brain Injuries/metabolism* ; Flavonols ; Flavonoids/pharmacology* ; Heme Oxygenase-1/metabolism* ; Heme Oxygenase (Decyclizing)

Objective To investigate the effect and mechanism of melatonin in alleviating hypoxia-induced apoptosis in ovarian gra-nulosa cells.Methods Rat ovarian granulosa cells were isolated and divided into normoxic,hypoxic,and melatonin groups.Hypoxia-induced injury models were established in the hypoxic and melatonin groups,and granulosa cells in the melatonin group were treated with melatonin.A total of 24 rats were randomized into the control,model,and intervention groups(n=8 per group).Rat models of declining ovarian function induced by long-term hypoxia were established in the model and intervention groups.The rats in the intervention group were intraperitoneally injected with melatonin.Cell proliferation was measured using a CCK-8 assay,and lactate secretion and HIF-1αprotein with a specific kit,respectively.The levels of estradiol and progesterone in the cell supernatant and rat serum were detected using ELISA.Granulosa cell apoptosis was detected by flow cytometry,ovarian morphology by HE staining,and Bax and caspase-3 expression by Western blotting.Results Compared with the normoxic group,the hypoxic group exhibited decreased granulosa cell proliferation,increased apoptosis,elevated lactate and HIF-1α levels,and reduced estradiol and progesterone levels(P＜0.05).Compared with hypoxic group,these changes were significantly reversed in the molatonin group(P＜0.05).Compared with the control group,the model group showed increased lactate,HIF-1α,Bax,and caspase-3 levels,decreased estradiol and progesterone levels,and reduced follicles.Compared with the model group,all the indicators were ameliorated in the intervention group(P＜0.05).Conclusion Melatonin alleviated hypoxia-induced granulosa cell apoptosis and promoted the recovery of ovarian function.

Objective To investigate the effect and mechanism of melatonin in alleviating hypoxia-induced apoptosis in ovarian gra-nulosa cells.Methods Rat ovarian granulosa cells were isolated and divided into normoxic,hypoxic,and melatonin groups.Hypoxia-induced injury models were established in the hypoxic and melatonin groups,and granulosa cells in the melatonin group were treated with melatonin.A total of 24 rats were randomized into the control,model,and intervention groups(n=8 per group).Rat models of declining ovarian function induced by long-term hypoxia were established in the model and intervention groups.The rats in the intervention group were intraperitoneally injected with melatonin.Cell proliferation was measured using a CCK-8 assay,and lactate secretion and HIF-1αprotein with a specific kit,respectively.The levels of estradiol and progesterone in the cell supernatant and rat serum were detected using ELISA.Granulosa cell apoptosis was detected by flow cytometry,ovarian morphology by HE staining,and Bax and caspase-3 expression by Western blotting.Results Compared with the normoxic group,the hypoxic group exhibited decreased granulosa cell proliferation,increased apoptosis,elevated lactate and HIF-1α levels,and reduced estradiol and progesterone levels(P＜0.05).Compared with hypoxic group,these changes were significantly reversed in the molatonin group(P＜0.05).Compared with the control group,the model group showed increased lactate,HIF-1α,Bax,and caspase-3 levels,decreased estradiol and progesterone levels,and reduced follicles.Compared with the model group,all the indicators were ameliorated in the intervention group(P＜0.05).Conclusion Melatonin alleviated hypoxia-induced granulosa cell apoptosis and promoted the recovery of ovarian function.

Objective:To compare the clinical application of the anterolateral thigh perforator flap (ALTPF) and the calf pedicled propeller perforator flap (PPPF) in reconstruction of soft tissue defect of foot and ankle.Methods:A retrospective observational study was conducted. From March 2013 to June 2019, 48 patients with soft tissue defect around ankle and in foot were reconstructed with ALTPF and PPPF in the Department of Orthopaedics, 920th Hospital of the Joint Logistic Support Force, People's Liberation Army of China. According to the types of flap, the patients were divided into 2 groups: ALTPF group (21 patients,13 males and 8 females, aged 16-67 years, mean 38.71 years±15.30 years. Donor sites were all directly sutured.) and PPPF group (27 patients, 12 males and 15 females, aged 12-69 years, mean 35.18 years±13.96 years. Five cases in the donor site required partial skin grafting, and the rest 22 cases were repaired by directly suture.). The wound size of the former was 5 cm×6 cm-15 cm×18 cm, and at 2 cm×3 cm-14 cm×17 cm for the latter. The surgical time and flap size of the 2 groups were recorded during the surgery. The survival and complications of the flap were observed, and the days of hospital stay were recorded after surgery. Follow-ups were conducted by outpatient clinic and via telephone and WeChat interviews. The colour, texture, appearance, donor scar, complications and thinning of the flap were observed during the follow-up. The ankle function was evaluated according to the score of American Orthopaedic Foot and Ankle Society (AOFAS), and the donor scar was evaluated according to the score of Vancouver Scar Scale (VSS). SPSS 22.0 statistical software was used for data analysis, and P<0.05 was considered statistically significant. Results:The surgical time for the ALTPF group was 118-203 (154.71±25.42) min, and that for the PPPF group was 52-92 (72.78±10.04) min. The size of the flap in the ALTPF group was 5 cm×8 cm-8 cm×18 cm (75.00 cm 2±8.69 cm 2), while it was 3 cm×7 cm-7 cm×17 cm (53.56 cm 2±19.49 cm 2) in the PPPF group. In the ALTPF group, 3 flaps had vascular complications within 24 hours after surgery, which survived after exploration and thrombectomy. Partial necrosis occurred in 1 flap. The rest 17 flaps survived uneventfully. In the PPPF group, 2 flaps had partial necrosis due to infection and they healed after dressing changes, 3 flaps had venous occlusion and survived after phlebotomy, partial suture removal and massage. The rest 22 flaps in 2 groups survived uneventfully. The postoperative days of hospital stay for the ALTPF group was 6-14 (8.71±2.03) days, and that was 4-12 (6.03±2.16) days in the PPPF group. Flap thinning was performed on 19 flaps in the ALTPF group and 2 in the PPPF group. Follow-up was performed for 7 to 21 months. All the flaps were good in colour, shape and texture. All donor sites healed well. At the final follow-up, 19 patients achieved ankle function of excellent, 1 of good and 1 of fair in the ALTPF group, and 21 patients achieved ankle function of excellent, 4 of good and 2 of fair in the PPPF group, according to the AOFAS. According to the VSS, scores of donor site scar was rated 4-8 (6.33±1.35) points for the ALTPF group, and 3-10 (5.92±1.80) points for the PPPF group. Statistical analysis showed no significant differences between the 2 groups in terms of early postoperative complications, flap survival rate, ankle function, and VSS scores ( P>0.05). However, there were statistically significant differences between the 2 groups in terms of surgical time, hospital stay, flap size, and the number of flap thinning ( P<0.05). Conclusion:Both ALTPF and PPPF have good clinical effects in reconstruction of soft tissue defect of foot and ankle. For small to medium-sized wounds, PPPF is the preferred choice due to the advantages in surgical time and postoperative hospital stay. For larger wounds, the ALTPF is the first choice with multiple surgery.

Objective To study the relationship between serum urine regulator protein and cystatin C levels and pathological characteristics and prognosis in patients with hypertensive nephropathy.Methods A total of 100 patients admitted in the hospital from August 2021 to October 2022 were selected as the study group,and 40 healthy persons who underwent the physical examination in the hospital were selected as the control group,complete data of all patients were collected and analyzed,the levels of serum urinary regulatory protein and cystatin C in each group were tested,and the relationship between serum urinary regulatory protein and cysta-tin C levels,pathological characteristics,and prognosis was analyzed.Results The urine regulatory protein and glomerular filtration rate in the study group were lower than those in the control group,but cystatin C,u-rea nitrogen,and blood creatinine were all higher than those in the control group,and the differences were sta-tistically significant(P＜0.05).Urinary regulatory protein was negatively correlated with urea nitrogen and blood creatinine,but positively correlated with glomerular filtration rate(P＜0.05).Cystatin C was positively correlated with urea nitrogen and blood creatinine,but negatively correlated with glomerular filtration rate(P＜0.05).Urinary regulatory protein level was related to crescent formation,renal tubular atrophy/intersti-tial fibrosis(P＜0.05),while level the expression of cystatin C was related to glomerular segmental sclerosis,glomerular glomerular sclerosis,and glomerular ischemic shrinkage(P＜0.05).The survival rate of the high urinary regulatory protein level group(≥126.49 ng/mL)was higher than that of the low urinary regulatory protein level group(＜126.49 ng/mL),while the survival rate of the high cystatin C level group(≥2.43 mg/L)was lower than that of the low cystatin C level group(＜2.43 mg/L)(P＜0.05).Urinary regulatory protein,cystatin C,renal tubular atrophy/interstitial fibrosis were factors that affected the occurrence of end-stage renal disease in hypertensive nephropathy(P＜0.05).Conclusion Hypertensive kidney disease patients u-sually have higher levels of cystatin C and lower levels of urinary regulatory protein,among which cystatin C is closely related to pathological features of glomerular segmental sclerosis,glomerular glomerular sclerosis,and glomerular is-chemic shrinkage,and urinary regulatory protein is closely related to crescent formation,renal tubular atrophy/intersti-tial fibrosis.In addition,urinary regulatory protein and cystatin C have a significant impact on the development of hy-pertensive nephropathy into end-stage renal disease,and could become important indicators for evaluating patient prognosis.

Objective To analyze the influencing factors of clinical pregnancy and live birth rates in patients undergoing frozen-thawed embryo transfer(FET)for the first time.Methods The clinical data of 1 458 patients who underwent FET cycle-assisted pregnancy for the first time were retrospectively analyzed and divided into four groups according to clinical pregnancy and live bith outcomes.The clini-cal data were compared to analyze the factors affecting clinical pregnancy and live birth rates in FET cycles that were included in multiple logistic regression analysis.Results Of the 1458 cycles,the clinical pregnancy and live birth rates were 44.0% and 34.0%,respectively.The mean age of the clinical pregnancy and live birth groups was lower than that in non-clinical pregnancy and stillbirth groups(P<0.05).The clinical pregnancy and live birth rates of patients aged<35 years were higher than those aged≥35 years(P<0.05).The clinical preg-nancy and live birth rates of patients with≥8 mm endometrial thickness were higher than those with<8 mm endometrial thickness(P<0.05).The clinical pregnancy rate of natural cycles of endometrial preparation regimen was higher than that of HRT cycles(P<0.05).The clinical pregnancy and live birth rates of double-embryo transfers were higher than that of single-embryo transfers(P<0.05).The clinical pregnancy and live birth rates of blastocyst transfers were higher than those of cleavage stage(P<0.05).Conclusion Age,endometrial thickness,number of transplanted embryos,and embryo morphology were the independent factors influencing clinical pregnancy and live birth outcomes during FET cycle transplantation.

Objective To investigate the effect of resveratrol(RES)on ovarian function in mice and elucidate the potential mechanism involving miR-23a.Methods Thirty mice were randomly divided into control,premature ovarian failure(POF)model,and treatment(RES)groups,with n=10 per group.The body weight and ovarian mass of the mice were measured,and the ovarian index was calculated.Hematoxylin and eosin staining was performed to observe pathological changes in mouse ovarian tissue.Real-time quantitative PCR and Western blotting were performed to measure the mRNA and protein levels of miR-23a,X-linked inhibitor of apoptosis protein(XIAP),and caspase-3 in the ovarian tissue.Results Compared with the control group,the POF group exhibited significant decreases in ovarian mass(P＜0.05),ovarian index(P＜0.05),number of primary follicles,and XIAP mRNA expression(P＜0.05),alongside significant increases in miR-23a and caspase-3 mRNA expression(P＜0.05).Compared with the POF group,the RES group exhibited significant increases in the ovarian mass(P＜0.05),ovarian index(P＜0.05),number of primary follicles,and XIAP mRNA expression(P＜0.05),as well as significant decreases in miR-23a and caspase-3 mRNA expression(P＜0.05).XIAP protein expression was significantly lower and caspase-3 protein expression was significantly higher in the POF group than in the control group(P＜0.05).Conversely,XIAP protein expression was significantly higher and caspase-3 protein expression was significantly lower in the RES group than in the POF group(P＜0.05).Conclusion RES exerts a protective effect on weakened ovarian function in mice,potentially mediated through its effect on miR-23a targeting the XIAP-caspase-3 signaling pathway.

Diabetic nephropathy （DN） is one of the common chronic kidney diseases （CKD） worldwide and a major cause of end-stage renal disease （ESRD）， seriously threatening and affecting the life and health of the global population. Currently， the pathogenesis of DN is considered to be closely related to factors such as glucose metabolism disorders， abnormal lipid metabolism， oxidative stress， activation of inflammatory factors， autophagy， and cell apoptosis in the continuous high-glucose environment of the body. Renal fibrosis is an important pathological feature and ultimate pathological outcome of DN. Timely intervention in renal fibrosis is of significant clinical and practical importance for the prevention and treatment of DN. Due to the limitations of western medicine in treating DN， traditional Chinese medicine （TCM） intervention in the process of renal fibrosis in DN has been widely used as a routine and potential treatment method due to its multi-component， multi-effect， and multi-target effects， effectively delaying the progression of the disease. It has been found that the Notch signaling pathway plays an important role in the development and maintenance of homeostasis in the body， and abnormal activation of the Notch signaling pathway is associated with DN. Activation of this signaling pathway plays a key role in the process of renal fibrosis. This article reviewed the regulatory mechanism of the Notch signaling pathway in renal fibrosis in DN， focusing on the relationship between targeting Notch signaling pathway by Chinese medicinal monomers and prescriptions and renal fibrosis in DN in order to provide a theoretical basis for the development of new drugs， basic research， and clinical application of TCM in the prevention and treatment of DN.

Diabetic kidney disease （DKD）， a chronic kidney disease with unique pathological structural and functional alterations in the kidney， is a common complication of diabetes mellitus （DM）. The majority of researchers believe that the occurrence of this disease is associated with glucose metabolism disorders， oxidative stress， inflammation， endoplasmic reticulum stress， autophagy， and disorders of lipid metabolism and exosome release. The mammalian target of rapamycin （mTOR） signaling pathway， which can maintain glomerular podocyte homeostasis and participate in autophagy， renal fibrosis， oxidative stress， lipid metabolism disorders， and inflammatory response in DKD， has been discovered to play a key role in DKD. Therefore， it has emerged as a novel target for the treatment of DKD. Studies have demonstrated that traditional Chinese medicine can prevent the renal damage in DKD by regulating the mTOR signaling pathway to delay the disease progression and improve the prognosis and the quality of life of the patients. This article summarizes the structure and role of the mTOR signaling pathway in DKD and briefs the research progress in the prevention and treatment of DKD via this signaling pathway by the active components， extracts， and compound prescriptions of Chinese medicines， aiming to present new ideas and approaches for the clinical treatment of DKD with traditional Chinese medicine.