Objective:To explore the clinical effects of end-to-side anastomosis of non-primary perforating vessels carried by free anterolateral thigh perforator flap (ALTPF) in reconstruction of soft tissue of limb.Methods:Between February 2020 and July 2021, 14 patients with soft tissue defect of limb were admitted in the Department of Hand and Foot Surgery, the First Affiliated Hospital of Wannan Medical College. The patients were 12 males and 2 females, aged between 30 and 69 years old, with a median age of 52 years old. One defect was found in left hand, 7 in left foot and ankle and 6 in right foot and ankle. Wound sizes were 7 cm×7 cm-9 cm×22 cm, all accompanied with exposed tendons, nerves or bone tissue. The size of flaps ranged from 8 cm×8 cm to 10 cm×23 cm. ALTPFs carrying non-primary source vessels were applied in reconstruction of soft tissue defects. The non-primary perforating vessels of ALTPF was anastomosed with the artery in recipient site in an end-to-side fashion and the vein of ALTPF was end-to-end anastomosed with the accompanying vein of the recipient artery. All donor sites were sutured directly. The follow-up was conducted by online reviews via WeChat or by visit of outpatient clinics. Appearance of flap and donor site were observed and the aesthetic satisfaction of the patients recipient sites were assessed subjectively using Likert scale.Results:All 14 ALTPFs survived uneventfully. Wound exudation occurred in 1 flap, and healed after dressing change and drainage. All patients received 9-18 (mean 12.6) months of follow-up. The ALTPFs were in good texture and shape. According to the Likert scale, appearance were excellent in 4 flaps, good in 8 flaps and fair in 2 flaps.Conclusion:Application of free ALTPF of non-primary source vessels with end-to-side anastomosis is not only effective in the reconstruction of limb defects, but also has advantages of reliable blood perfusion and cosmetic appearance.

[Objective]To explore the effects of electricity on sperm quality,sex hormone levels,and related proteins in TGF-β 1/smads signaling in testicular tissue.[Methods]Forty male SD rats were randomly divided into blank group,model group,electroacupuncture group,and positive drug group.Adenine gavage method was used to establish the model,in the electroacupuncture group,rats received electroacupuncture treatment at the acupoints Zhongji,Guanyuan,Zusanli,and Sanyinjiao once daily for 30 minutes;in the positive drug group,rats were administered L-carnitine oral solution via gavage at a dosage of 10 mL/kg,both intervention groups underwent continuous treatment for 28 days.After treatment,the changes of sperm number,sperm motility rate,follicle-stimulating hormone(FSH),luteizing hormone(LH)and serum sex hormone testosterone(T)were detected by HE staining,and the expression of TGF-β-1/smads signaling pathway in testicular tissue was examined by Western Blot.[Results]Compared to the blank group,the model group showed a significant decrease in sperm count and sperm motility rate(P<0.05),both the electroacupuncture group and the positive drug group exhibited significant increases compared to the model group(P<0.05).Compared to the blank group,the model group had a significant decrease in serum testosterone(T)levels(P<0.05),and significant increases in serum FSH and LH levels(P<0.05);in comparison to the model group,the electroacupuncture group and the positive drug group showed significant increases in serum T levels(P<0.05),and significant decreases in serum FSH and LH levels(P<0.05).The HE staining results showed typical pathological features of AR in the testicular tissue of model group rats,with varying degrees of improvement observed in electroacupuncture and positive drug group rats.Western Blot analysis revealed that in the model group,the protein levels of TGF-β,p-smad2,and p-smad3 in the TGF-β1/smads pathway in testicular tissue were significantly increased(P<0.05);in comparison to the model group,the electroacupuncture group and the positive drug group showed significant decreases in the protein levels of TGF-β,p-smad2,and p-smad3(P<0.05).[Conclusion]Acupuncture can improve the sperm number and sperm motility rate,regulate sex hormone level and improve the spermatogenic environment,and affect the spermatogenesis process via TGF-β 1/smads signaling pathway.

Prostate cancer(PCa)is one of the common tumors in the genitourinary system,with an increasing morbidity and mortality in China.Recent studies show that autophagy plays an important pathophysiological role in many diseases,including cancers.Besides,some miRNAs are also key regulatory factors for autophagy in PCa cells,and play an important role in the development,pro-gression,diagnosis and treatment of PCa.In-depth studies of miRNAs may contribute to the discovery of some valuable diagnostic methods and novel treatment strategies.This article reviews the progress in researches on the role of autophagy-related miRNAs in PCa,aiming to provide some reference for the diagnosis and treatment of the malignancy.

OBJECTIVE: To explore the effect of "Zhibian" (BL 54)-to-"Shuidao" (ST 28) needle insertion on the ovarian function in the rats with primary ovarian insufficiency (POI) and the potential effect mechanism based on the Fas/FADD/Caspase-8 of death receptor pathway. METHODS: Forty-eight female SD rats were randomly divided into a blank group, a model group, a medication group and an acupuncture group, with 12 rats in each group. Except in the blank group, the rats in the other groups were intraperitoneally injected with cyclophosphamide to establish the POI model. In the acupuncture group, after successful modeling, the intervention was given with "Zhibian" (BL 54)-to- "Shuidao" (ST 28) needle insertion, once daily, 30 min in each intervention; and the duration of intervention was 4 weeks. In the medication group, estradiol valerate tablets were administered intragastrically, 0.09 mg•kg^-1•d^-1, for 4 weeks. The general situation and the estrous cycle of the rats were compared among groups. Using ELISA, the levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH) and estradiol (E₂) in the serum were detected. HE staining was adopted to observe the morphological changes of ovarian tissue of rats. The protein expression of Fas, FADD and Caspase-8 in ovarian tissue was detected with immunohistochemistry and Western blot. RESULTS: After modeling, except the rats of the blank group, the rats of the other groups had dry fur, lost hair, low spirits, reduced food intake, increased urination and loose stool. After intervention, the stool became regular gradually in the acupuncture group and the medication group. The percentage of estrous cycle disturbance was increased in the rats of the model group when compared with the blank group (P<0.01); in comparison with the model group, the percentages of estrous cycle disturbance were reduced in the acupuncture group and the medication group after intervention (P<0.01). When compared with the blank group, the body mass and E₂ content in the serum were lower (P<0.01), the levels of FSH and LH in the serum and the protein expression levels of Fas, FADD and Caspase-8 were increased (P<0.01) in the model group. Compared with the model group, the body mass and E₂ contents in the serum were higher (P<0.01), the levels of FSH and LH in the serum and the protein expression levels of Fas, FADD and Caspase-8 were reduced (P<0.01) in the acupuncture group and the medication group. CONCLUSION "Zhibian" (BL 54)-to-"Shuidao" (ST 28) needle insertion can effectively improve the ovarian function of POI rats, and its effect mechanism may be related to regulating the serum sex hormone levels, reducing the expression of Fas, FADD and Caspase-8 in ovarian tissue and retarding apoptosis of ovarian cells.
Female ; Animals ; Rats ; Needles ; Signal Transduction ; Receptors, Death Domain/metabolism*

Objective: To provide survival evidence of anthracycline-free neoadjuvant chemotherapy for patients with stages Ⅱ-Ⅲ human epidermal growth factor receptor-2 (HER-2) positive and hormone receptor (HR) negative breast cancer. Methods: The prospective cohort study was conducted at the Department of Medical Oncology of Cancer Hospital, Chinese Academy of Medical Sciences. Patients with HER-2 positive and HR negative breast cancer in stages Ⅱ-Ⅲ were enrolled to receive neoadjuvant therapy (NAT) of dose-dense paclitaxel (175 mg/m(2)) plus carboplatin (AUC=4.0) biweekly for 6 cycles in combination with trastuzumab (PCbH), and matched patients who received standard adjuvant therapy of physicians' choice were recruited for survival and safety comparison. Results: From July 2013 to November 2019, 166 patients were included (neoadjuvant 51, adjuvant 115). Compared with those who received adjuvant therapy, patients receiving NAT were younger (<35 years: 19.6% vs 5.2%, P=0.014), had larger tumors (T3: 62.7% vs 7.8%, P<0.001) and more advanced diseases (stage ⅡA: 2.0% vs 41.7%, P<0.001). Patients in the neoadjuvant group all received surgery, and 96 (83.5%) in the adjuvant group received anthracycline-and-taxane-containing regimens. A total of 98 patients (49 pairs) were matched, and the covariates between the two groups were acceptably balanced. Within a median follow-up of 46.5 (range, 14-87) months, the 4-year recurrence-free survival (RFS) rate among patients who received NAT was 73.3% (95% CI: 59.0%-87.6%), versus 80.6% (95% CI: 67.9%-93.3%) among those in the adjuvant group without statistical difference (P=0.418). A similar result was observed for the 4-year overall survival (OS) [neoadjuvant versus adjuvant: 91.5% (95% CI: 81.7%-100.0%) vs 97.8% (95% CI: 93.5%-100.0%), P=0.314]. Compared with standard adjuvant therapy, PCbH was related to less neutropenia and better cardiac safety. Conclusions: These results support the consideration of anthracycline-free neoadjuvant chemotherapy combined with anti-HER-2 therapy for patients with stages Ⅱ-Ⅲ HER-2-positive and HR-negative breast cancer. Optimized regimens with both efficacy and safety are needed and to be further investigated.
Female ; Humans ; Anthracyclines/therapeutic use* ; Antibiotics, Antineoplastic/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Carboplatin/therapeutic use* ; Chemotherapy, Adjuvant ; Hormones/therapeutic use* ; Neoadjuvant Therapy ; Paclitaxel/therapeutic use* ; Prospective Studies ; Receptor, ErbB-2/metabolism* ; Trastuzumab/therapeutic use* ; Triple Negative Breast Neoplasms/drug therapy*

Objective: To provide survival evidence of anthracycline-free neoadjuvant chemotherapy for patients with stages Ⅱ-Ⅲ human epidermal growth factor receptor-2 (HER-2) positive and hormone receptor (HR) negative breast cancer. Methods: The prospective cohort study was conducted at the Department of Medical Oncology of Cancer Hospital, Chinese Academy of Medical Sciences. Patients with HER-2 positive and HR negative breast cancer in stages Ⅱ-Ⅲ were enrolled to receive neoadjuvant therapy (NAT) of dose-dense paclitaxel (175 mg/m(2)) plus carboplatin (AUC=4.0) biweekly for 6 cycles in combination with trastuzumab (PCbH), and matched patients who received standard adjuvant therapy of physicians' choice were recruited for survival and safety comparison. Results: From July 2013 to November 2019, 166 patients were included (neoadjuvant 51, adjuvant 115). Compared with those who received adjuvant therapy, patients receiving NAT were younger (<35 years: 19.6% vs 5.2%, P=0.014), had larger tumors (T3: 62.7% vs 7.8%, P<0.001) and more advanced diseases (stage ⅡA: 2.0% vs 41.7%, P<0.001). Patients in the neoadjuvant group all received surgery, and 96 (83.5%) in the adjuvant group received anthracycline-and-taxane-containing regimens. A total of 98 patients (49 pairs) were matched, and the covariates between the two groups were acceptably balanced. Within a median follow-up of 46.5 (range, 14-87) months, the 4-year recurrence-free survival (RFS) rate among patients who received NAT was 73.3% (95% CI: 59.0%-87.6%), versus 80.6% (95% CI: 67.9%-93.3%) among those in the adjuvant group without statistical difference (P=0.418). A similar result was observed for the 4-year overall survival (OS) [neoadjuvant versus adjuvant: 91.5% (95% CI: 81.7%-100.0%) vs 97.8% (95% CI: 93.5%-100.0%), P=0.314]. Compared with standard adjuvant therapy, PCbH was related to less neutropenia and better cardiac safety. Conclusions: These results support the consideration of anthracycline-free neoadjuvant chemotherapy combined with anti-HER-2 therapy for patients with stages Ⅱ-Ⅲ HER-2-positive and HR-negative breast cancer. Optimized regimens with both efficacy and safety are needed and to be further investigated.
Female ; Humans ; Anthracyclines/therapeutic use* ; Antibiotics, Antineoplastic/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Carboplatin/therapeutic use* ; Chemotherapy, Adjuvant ; Hormones/therapeutic use* ; Neoadjuvant Therapy ; Paclitaxel/therapeutic use* ; Prospective Studies ; Receptor, ErbB-2/metabolism* ; Trastuzumab/therapeutic use* ; Triple Negative Breast Neoplasms/drug therapy*

Aim To explore the effect of Buyang Huanwu Decoction on cerebral ischemia-reperfusion injury in rats by regulating autophagy through PI3K/AKT pathway. Methods The rats were randomly divided into five groups(n=10): sham operation group(Sham), model group(Model), Buyang Huanwu Decoction group(BYHWD), PI3K inhibitor group(LY294002)and Vehicle group(Vehicle). Except Sham group, the other groups were treated with 2h ischemia and 72 h reperfusion for modeling. The Zea Longa score was used to assess the neurological defects, HE was used to observe brain injury in the ischemic penumbra(IP), immunofluorescence was employed to detect LC3, and Western blot was used to detect pathway and autophagy marker proteins. Results Compared BYHWD group with model group, the neurological score of rats decreased, cerebral infarction volume decreased, the pathological lesions of brain IP were relieved, PI3K and p-AKT/AKT expression increased, and LC3Ⅱ/ decreased and p62 increased(P<0.05). The regulatory effect of BYHWD was weakened by LY294002(P<0.05). Conclusion Buyang Huanwu Decoction alleviates cerebral ischemia-reperfusion injury in rats by activating PI3K/AKT pathway to inhibit autophagy.

Objective:To verify the effect and safety of low-intensity extracorporeal shockwave therapy(Li-ESWT)in improving the symptoms of ED,and provide some reference for further related large-scale clinical trials.Methods:Twenty-six patients diag-nosed with ED received Li-ESWT with an energy of 0.09 mJ/mm2 for 20 minutes once a week for 6 four-week courses.Before and at 3,6,9,and 12 months after treatment,we obtained the IIEF-5 and Erectile Hardness Scale(EHS)scores of the patients using question-naires,recorded the incidence of treatment-related adverse reactions,compared the erectile function of the patients before and after treatment,and evaluated the effect and safety of Li-ESWT in improving ED-related symptoms.Results:Compared with the baseline,the IIEF-5 scores of the patients were significantly increased(P＜0.01)while the EHS scores slightly increased at 3 months after Li-ESWT treatment(P＞0.05),both IIEF-5 and EHS scores were dramatically increased at 6 months(P＜0.01),and both signifi-cantly higher than at 3 months.At 9 months,EHS scores remained remarkably higher than the baseline(P＜0.01)although IIEF-5 scores slightly lower than at 6 months.At 12 months,however,IIEF-5 scores decreased,though still significantly higher than the base-line(P＜0.01),and EHS scores became lower than at 6 and 9 months(P＜0.05)but still markedly higher than before treatment(P＜0.05).Adverse reactions observed during the intervention mainly included pruritus(4.35％),pain(2.90％),paresthesia(2.17％),and petechiae/ecchymosis(2.90％).Conclusion:Li-ESWT can increase the IIEF-5 and EHS scores and improve the clinical symptoms of ED patients,with a low incidence of adverse reactions during the treatment.

Objective:To evaluate the consistency of the Gleason scores of PCa patients based on preoperative biopsy with those from postoperative pathology,identify the possible factors influencing results of scoring,and construct a risk scoring model.Meth-ods:We collected the demographic and clinical data on the patients with PCa confirmed by preoperative prostate biopsy or postoperative pathology and treated by radical prostatectomy within 6 months after diagnosis.Using paired sample t-test,we identified the difference between the Gleason scores based on preoperative biopsy and those from postoperative pathology,analyzed the demographic and clinical data on the patients for relevant factors affecting the consistency of the Gleason scores,and calculated and visualized the relative risk values of the factors through Poisson regression.From the continuous variables with statistical significance,we screened independent risk factors for the difference in the Gleason scores by Lasso regression analysis,established a risk scoring model,generated risk coeffi-cients,and evaluated the predictive ability of the model using the ROC curve.Based on the results of imaging examination with statisti-cally significant differences,we constructed a column chart by logistic regression and evaluated the predictive validity of the chart using calibration curves,decision curves and ROC curves.Results:The results of paired sample t-test for 210 PCa patients showed statisti-cally significant differences between the Gleason scores from preoperative biopsy and those from postoperative pathology(P＜0.001).There were significant differences in the body weight,BMI and PSA level as well as in all other factors but prostate calcification be-tween the patients with consistent and those with inconsistent Gleason scores(all P＜0.05).An 8-factor prediction model was suc-cessfully constructed,which could predict the consistency of Gleason scores,with a better predicting performance than the single indi-cator within the model.The nomogram exhibited a C-index value of 0.85,with the calibration curve similar to the standard one,the threshold of the decision curve 0.10-0.92,and the area under the ROC curve higher than other predictive indicators.Conclusion:Based on the demographic and clinical data on PCa patients,a risk prediction model and a column chart were successfully constructed,which could effectively predict the difference between the Gleason scores from preoperative prostate biopsy and those from postoperative pathology.

OBJECTIVE To ev aluate the economical efficiency of nivolumab versus everolimus in the second-line treatment of metastatic clear cell renal cell carcinoma. METHODS From the perspective of China ’s health system ，cost-effectiveness analysis of the two therapies was carried out by developing a three-state partitioned survival model. The clinical parameters were from the updated CheckMate 025 study，and the cost and health utility were from relevant websites and published literatures. The model adopted a 2-week cycle and a lifetime research time. The robustness of the results was verified by sensitivity analysis. The economical efficiency of two therapy schemes were evaluated in the scenario of model simulation time of 80 months and charitable drug donation scheme. RESULTS The results of basic analysis showed that compared with everolimus ，the incremental cost-effectiveness ratio （ICER）of nivolumab was 586 982.60 yuan/quality-adjusted life year （QALY），which was far higher than 3 times of China ’s per capita gross domestic product （GDP）in 2020. The results of single-factor sensitivity analysis showed that the 3 parameters that had the greatest impact on the economic evaluation results were the cost of nivolumab ，the utility value of nivolumab group and everolimus group in progressive disease state. The results of probability sensitivity analysis verified the robustness of the basic analysis results. Results of scenario analysis showed that in the first scenario analysis ，in which model simulation time lasted for 80 months，ICER of nivolumab was 417 204.52 yuan/QALY；in the second scenario analysis ，in which nivolumab charitable drug donation program for low-income people was considered ，ICER of nivolumab was 124 988.58 yuan/QALY. CONCLUSIONS Under the threshold of 1-3 times of China ’s per capita GDP in 2020，compared with everolimus ，it is not economical to use nivolumab as the second-line treatment for metastatic clear cell renal cell carcinoma ； nivolumab is economical when considering its charitable drug donation program for low-income people.