In this study, we explored the pharmacological effects of Siwu Decoction in treating premature ovarian insufficiency(POI) and its molecular mechanism based on the mitophagy pathway modulated and mediated by estrogen receptor(ER) subtypes. Female Balb/c mice were divided into a control group, model group, as well as high-dose and low-dose groups of Siwu Decoction. The POI mice model was constructed by intraperitoneal injection of cisplatin. The high-dose and low-dose groups of Siwu Decoction were administered intragastrically with Siwu Decoction each day for 14 days. During this period, we monitored the estrous cycle and body weight of the mice and calculated the ovarian index. The morphology of the ovaries was detected by hematoxylin-eosin(HE) staining, and the number of primordial follicles was counted. The apoptosis of the ovarian tissue was detected by TUNEL staining. The expression levels of anti-Müllerian hormone(AMH), apoptosis-associated and mitophagy-associated proteins, ER subtypes, and the expression levels of key proteins of its mediated molecular pathways were detected by Western blot and immunohistochemistry. KGN cells were divided into a control group, model group, Siwu Decoction group, and gene silencing group. The apoptosis model was induced by H_2O_2, and PTEN-induced putative kinase 1(PINK1) gene silencing was induced by siRNA transfection. The Siwu Decoction group and gene silencing group were added to the medium containing Siwu Decoction. Cell viability was detected by CCK-8 assay. Cell senescence was detected by senescence-associated-β-galactosidase. The expression levels of apoptosis-associated and mitophagy-associated proteins were detected by Western blot. The results of in vivo experiments showed that compared with the model group, the mice in the high-dose and low-dose groups of Siwu Decoction significantly recovered the rhythm of the estrous cycle, and the levels of ovarian index, number of primordial follicles, and expression of AMH, representative indexes of ovarian function, were significantly higher, suggesting that the level of ovarian function was significantly improved. The expression levels of the apoptosis-related proteins, cytochrome C(Cyt C), cysteinyl aspartate specific proteinase 3(caspase 3), B-cell lymphoma-2(Bcl-2)-associated X(Bax), and mitophagy-associated indicator(Beclin 1) were significantly decreased, and the expression levels of Bcl-2 was significantly elevated. The positive area of TUNEL was significantly reduced, suggesting that the apoptosis level of the ovaries was significantly reduced. The expression levels of PINK1, Parkin, and sequestosome 1(p62) were significantly reduced, suggesting that the level of ovarian mitophagy was significantly down-regulated. The expression levels of ERα and ERβ were significantly elevated, and the ratio of ERα/ERβ was significantly reduced. The expression levels of key proteins in the pathway, phosphoinositide 3-kinase(PI3K) and protein kinase B(Akt), were significantly reduced, suggesting that the regulation of ER subtypes and the mediation of PI3K/Akt pathway were the key mechanisms. In vitro experiments showed that compared with the model group, the proportion of senescent cells in the Siwu Decoction group was significantly reduced. Cyt C, caspase 3, Beclin 1, Parkin, and p62 were significantly reduced, which was in line with in vivo experimental results. The proportion of senescent cells and the expression level of the above proteins were further significantly reduced after PINK1 silencing. It can be seen that Siwu Decoction can regulate the expression level and proportion of ER subtypes in KGN cells, then mediate the PI3K/Akt pathway to inhibit excessive mitophagy and apoptosis, and exert therapeutic effects of POI.
Animals ; Female ; Drugs, Chinese Herbal/administration & dosage* ; Mitophagy/drug effects* ; Primary Ovarian Insufficiency/physiopathology* ; Mice ; Mice, Inbred BALB C ; Humans ; Receptors, Estrogen/genetics* ; Apoptosis/drug effects* ; Ovary/metabolism* ; Signal Transduction/drug effects* ; Anti-Mullerian Hormone/genetics*

OBJECTIVE: To explore the effectiveness of free paraumbilical perforator flaps in repairing skin and soft tissue defects in children. METHODS: Between February 2018 and March 2024, 12 children with skin and soft tissue defects were treated with the free paraumbilical perforator flaps. There were 7 boys and 5 girls with an average age of 6.3 years (range, 2-12 years). The defects located on the upper limbs in 6 cases, lower limbs in 5 cases, and neck in 1 case. The causes of wounds included 7 cases of electrical burns, 1 case of thermal burn, 2 cases of scar release and excision due to scar contraction after burns, 1 case of scar ulcer at the amputation stump after severe burns, and 1 case of skin necrosis after a traffic accident injury. The size of defects after debridement ranged from 7.0 cm×4.0 cm to 18.0 cm×10.0 cm. According to the defect size, 11 cases were repaired with unilateral paraumbilical perforator flaps centered on the umbilicus, among which 3 cases with larger defects were designed as "L"-shaped flaps along the lateral and lower ends of the perforator; the donor sites were directly closed. One case with extensive defect after scar excision and release was repaired with bilateral expanded paraumbilical perforator flaps; the donor sites were repaired with autologous split-thickness skin grafts. The size of flaps ranged from 9.0 cm×4.0 cm to 20.0 cm×11.0 cm. Postoperatively, analgesia and sedation were provided, and the blood supply of the flaps was observed. RESULTS: All operations were successfully completed. The operation time was 4-7 hours, with an average of 5.0 hours. After postoperative analgesia and sedation, the visual analogue scale (VAS) score for pain in all children was less than or equal to 3, and there was no non-cooperation due to pain. All flaps and skin grafts survived completely, and the wounds healed by first intention. Ten children underwent 1-4 times of flap de-fatting, finger separation, and trimming. All children were followed up 6-48 months (mean, 26.6 months). No obvious swelling of the flaps occurred, and the texture was soft. At last follow-up, among the 6 children with upper limb defects, 2 had upper limb function grade Ⅳ and 4 had upper limb function grade Ⅴ according to the Carroll upper limb function assessment method. The 4 children with lower limb defects had no limitation of joint movement. The neck flexion and rotation in the 1 child with neck defect significantly improved when compared with that before operation. The 1 child with residual ulcer at the amputation stump could wear a prosthesis and move without limitation, and no new ulcer occurred. Linear scars were left at the donor sites, and no abdominal wall hernia was formed. CONCLUSION The free paraumbilical perforator flap has abundant blood supply and can be harvested in large size. It can be used to repair skin and soft tissue defects in children and has the advantages of short operation time, minimal injury, high safety, and minimal impact on the growth and development of children.
Humans ; Perforator Flap/transplantation* ; Child ; Male ; Female ; Soft Tissue Injuries/surgery* ; Child, Preschool ; Plastic Surgery Procedures/methods* ; Burns/surgery* ; Umbilicus/surgery* ; Skin Transplantation/methods* ; Skin/injuries* ; Cicatrix/surgery* ; Treatment Outcome

Objective:To evaluate the safety and efficiency of China-made Toumai Robot-assisted laparoscopic radical prosta-tectomy(LRP).Methods:This study included 40 cases of PCa treated from January 2023 to May 2023 by robot-assisted LRP with preservation of the bladder neck and maximal functional urethral length,15 cases with the assistance of Toumai Robot(the TMR group)and the other 25 with the assistance of da Vinci Robot as controls(the DVR group).We recorded the docking time,laparo-scopic surgery time,vesico-urethral anastomosis time,intraoperative blood loss and postoperative urinary continence,and compared them between the two groups.Results:Operations were successfully completed in all the cases.No statistically significant differ-ences were observed between the TMR and DVR groups in the docking time(6 min vs 5 min,P＞0.05)or intraoperative blood loss(200 ml vs 150 ml,P＞0.05).The TMR group,compared with the DVR group,showed a significantly longer median laparoscopic surgery time(146 min vs 130 min,P＜0.05)and median vesico-urethral anastomosis time(19 min vs 16 min,P＜0.05).There were no statistically significant differences between the TMR and DVR groups in the rates of urinary continence recovery immediately af-ter surgery(60.0％[9/15]vs 64.0％[16/25],P＞0.05)or at 1 month(80.0％[12/15])vs(76.0％[19/25],P＞0.05),3 months(93.3％[14/15])vs(92.0％[23/25],P＞0.05)and 6 months postoperatively(100％[15/15])vs(96％[24/25],P＞0.05).Conclusion:China-made Toumai? Robot surgical system is safe and reliable for laparoscopic radical prosta-tectomy,with satisfactory postoperative recovery of urinary continence.

Objective To explore the relevant factors of new-onset conduction disturbance(NOCD)after transcatheter aortic valve replacement(TAVR),such as anatomical structure,device type,surgical strategies,etc.,discover relevant predictive factors,and establish a predictive model to assess the risk of conduction blockages.Methods From January 2016 to March 2022,clinical data of symptomatic patients with severe aortic valve stenosis or severe regurgitation who underwent TAVR at Xiangya Second Hospital of Central South University were collected through the hospital information system and imaging database.ECG,echocardiography,CTA,surgical materials,etc.,were extracted and analyzed by specialists.SPSS software was used for statistical analysis,and a multi-factor regression prediction model for NOCDwas built.Results A total of 184 patients were included,the occurrence rate of NOCD after TAVR was 31.0%,pure regurgitation patients'NOCD occurrence rate was 63.6%(7/11).The NOCD group had a larger aortic angles[(57.7±10.3)°vs.(52.0±9.0)°,P＜0.001],larger Oversizing[(129±28)%vs.(120±21)%,P=0.018],deeper implantation depth[(7.2±5.1)mm vs.(4.8±4.2)mm,P=0.001],and higher pure regurgitation patients'proportion[12.3%vs.3.1%,P=0.037]than the non-NOCD group.Multifactorial Logistic regression analysis indicated that an aorta angle＞54.5°(OR 3.78,95%CI 1.86-7.63,P＜0.001)or implantation depth＞5.7 mm(OR 3.39,95%CI 1.68-6.85,P＜0.001)are independent risk factors for new onset conduction disturbances after TAVR,and a predictive model was established with aortic angle,implantation depth,and Oversizing ratio as variables.The receiver operating characteristics curve showed area under ROC curve 0.709,95%CI 0.623-0.795,predicting NOCD after TAVR.Conclusions A retrospective analysis carried out at a single center discovered that the aortic angle in the NOCD group was larger than that in the non-NOCD group,the Oversizing ratio was higher,the implantation location was deeper,and there was a higher proportion of patients with pure regurgitation lesions.An aortic angle greater than 54.5°or an implantation depth more than 5.7 mm were identified as independent risk factors for NOCD after TAVR.

Objective:This study discusses the job preferences of Center for Disease Control and Prevention(CDC)staffs at the prefectural-level,and provides a basis for the development of an effective incentive mechanism.Method:This study used a combination of stratified sampling and purposive sampling to research online 455 staffs from six prefectural-level CDCs in Shandong Province,analyzed the data using a mixed logit model and latent class model,and calculated willingness to pay and relative importance.Result:In the mixed logit model,income,benefit level,establishment,workload,recognition and respect from the public,personal career development opportunities,and training opportunities all had significant influences(P<0.05)on the job selection preferences of the CDC staffs,with hygiene factors such as establishment(β =2.636)and income(β =0.083)having a greater degree of influence than motivation factors.The latent class model shows that relatively young CDC staffs with lower monthly incomes value income more;older CDC staffs with higher monthly incomes value establishment more.Conclusion:Prefectural-level CDC staffs prefer jobs with establishment,higher incomes,very good benefit levels,recognition and respected from the public,lower workloads,many opportunities for personal career advancement and abundant training opportunities.It is recommended that the total number of establishments be rationally controlled and dynamically adjusted to balance the differences between working conditions within and outside the establishment and that the financial input to CDC be increased and the pay performance system be improved;that attention be paid to both hygiene factors and motivation factors,and that a variety of measures work together to incentivize CDC staffs development;and that differentiated incentives be adopted for different categories of CDC staffs.

Objective To evaluate the effects of anterior cruciate ligament (ACL) reconstruction timing on the motor performance and proprioception by clinical evaluation as well as proprioception and motor performance tests on the patients more than 2 years after ACL reconstruction. Methods The patients who underwent ACL reconstruction in the National Institute of Sports Medicine,General Administration of Sport of China from January 2015 to January 2021 and met the inclusion criteria were followed up,and the postoperative data were collected retrospectively.Fifty-six patients who met the inclusion criteria were included in this study and categorized into two groups:early surgery (n=28,who underwent ACL reconstruction ≤3 weeks after injury) and delayed surgery (n=28,who underwent ACL reconstruction >3 weeks after injury).The basic information,clinical evaluation results,proprioception,and motor performance were compared between the two groups. Results The ACL return to sport after injury scale (ACL-RSI) score in the early surgery group was higher than that in the delayed surgery group [(68.68±22.04)scores vs. (55.82±24.87)scores,P=0.045].There was no difference in the range of motion of the knee joint,the positive rate of pivot shift test,or the scores of Tegner,Marx,Lysholm,knee injury and osteoarthritis outcome score (KOOS),and international knee documentation committee (IKDC) between the two groups (all P>0.05).Although there was no significant difference in range of motion of the knee joint between the two groups,the proportion of knee flexion and extension affected in the early surgery group was smaller than that in the delayed surgery group.Neither motor performance (isokinetic strength test,Y-balance test,and single-leg jump test) nor proprioception had difference between the two groups (all P>0.05). Conclusions Early ACL reconstruction outperformed delayed ACL reconstruction in improving the psychological health,emotions,and confidence in returning to sport,accelerating functional recovery of the patients.The timing of ACL reconstruction has no significant effect on the short-term postoperative knee stability,knee function,motor performance,or proprioceptive recovery of the patients.Early ACL reconstruction is recommended for improving the clinical outcomes.
Humans ; Anterior Cruciate Ligament Reconstruction/methods* ; Proprioception/physiology* ; Retrospective Studies ; Male ; Female ; Range of Motion, Articular ; Anterior Cruciate Ligament Injuries/physiopathology* ; Adult ; Postoperative Period ; Time Factors ; Return to Sport ; Recovery of Function ; Knee Joint/physiopathology* ; Young Adult

Objective To evaluate the effects of knee flexor and extensor strength on the subjective function and motor performance of knees after anterior cruciate ligament reconstruction. Methods A total of 53 patients who underwent anterior cruciate ligament reconstruction in the National Institute of Sports Medicine,General Administration of Sport of China from June 2015 to June 2021 and met the inclusion criteria were enrolled in this study.The patients were followed up time for at least 2 years.An isometric muscle strength test system was used to measure the strength of bilateral quadriceps and hamstring muscles.The patients were grouped according to whether the limb symmetry index (LSI) of peak torque of quadriceps and hamstring muscle reached 85% at an angular velocity of 60°/s.Specifically,26 patients were classified into group A (LSI≥85%) and 27 patients were classified into group B (LSI<85%).The subjective function and motor performance of knees were compared between the two groups. Results In terms of subjective function of knees,the international knee documentation committee (IKDC) score (88.76±9.93 vs. 81.08±12.57,P=0.017) and knee injury and osteoarthritis outcome score (KOOS) (86.27±8.96 vs. 80.22±11.31,P=0.036) were different between groups A and B.There was no significant difference in Lysholm score [95.0 (79.8,100.00) vs. 86.00 (66.00,100.00),P=0.238],ACL return to sports after injury scale score (66.08±22.25 vs. 61.12±23.53,P=0.434),Marx score [6.00 (4.75,7.00) vs. 6.00 (4.00,7.00),P=0.805] or Tegner activity score [8.00 (4.00,12.00) vs. 4.00 (2.00,12.00),P=0.566] between the two groups.In terms of motor performance,the single-leg triple hop LSI (0.92±0.13 vs. 0.81±0.18,P=0.016) and single-leg crossover hop LSI (0.96±0.12 vs. 0.84±0.22,P=0.021) showed significant differences between groups A and B,while there was no significant difference in single-leg hop LSI (0.90±0.18 vs. 0.79±0.25,P=0.116) between the two groups.In addition,there was no statistical significance in proprioception [30°:8.83±4.66 vs. 10.73±4.63,P=0.143;45°:6.94±3.82 vs. 7.66±3.93,P=0.504;60°:4.10 (3.20,4.72) vs. 3.90 (2.30,5.20),P=0.493] or Y-balance test results [anterior LSI:0.98 (0.84,1.02) vs. 0.94 (0.86,0.98),P=0.328;posterolateral LSI:1.00±0.08 vs. 0.97±0.07,P=0.249;posteromedial LSI:1.00 (0.97,1.03) vs. 0.96 (0.93,1.03),P=0.179] between groups A and B. Conclusion The patients with good symmetry of quadriceps and hamstring muscle strength after anterior cruciate ligament reconstruction had better subjective function and movement performance of knees than the patients with poor symmetry,which was mainly reflected in the IKDC score,KOOS,single-leg triple hop,and single-leg crossover hop.
Humans ; Anterior Cruciate Ligament Reconstruction ; Muscle Strength/physiology* ; Male ; Quadriceps Muscle/physiology* ; Female ; Adult ; Anterior Cruciate Ligament Injuries/physiopathology* ; Hamstring Muscles/physiopathology* ; Knee Joint/physiopathology* ; Anterior Cruciate Ligament/physiopathology* ; Torque ; Knee/physiopathology*

Objectives: To investigated the safety and efficacy of treating patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) and elevated levels of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) with levosimendan within 24 hours of first medical contact (FMC). Methods: This multicenter, open-label, block-randomized controlled trial (NCT03189901) investigated the safety and efficacy of levosimendan as an early management strategy of acute heart failure (EMS-AHF) for patients with NSTEMI and high NT-proBNP levels. This study included 255 patients with NSTEMI and elevated NT-proBNP levels, including 142 males and 113 females with a median age of 65 (58-70) years, and were admitted in the emergency or outpatient departments at 14 medical centers in China between October 2017 and October 2021. The patients were randomly divided into a levosimendan group (n=129) and a control group (n=126). The primary outcome measure was NT-proBNP levels on day 3 of treatment and changes in the NT-proBNP levels from baseline on day 5 after randomization. The secondary outcome measures included the proportion of patients with more than 30% reduction in NT-proBNP levels from baseline, major adverse cardiovascular events (MACE) during hospitalization and at 6 months after hospitalization, safety during the treatment, and health economics indices. The measurement data parameters between groups were compared using the t-test or the non-parametric test. The count data parameters were compared between groups using the χ² test. Results: On day 3, the NT-proBNP levels in the levosimendan group were lower than the control group but were statistically insignificant [866 (455, 1 960) vs. 1 118 (459, 2 417) ng/L, Z=-1.25,P=0.21]. However, on day 5, changes in the NT-proBNP levels from baseline in the levosimendan group were significantly higher than the control group [67.6% (33.8%,82.5%)vs.54.8% (7.3%,77.9%), Z=-2.14, P=0.03]. There were no significant differences in the proportion of patients with more than 30% reduction in the NT-proBNP levels on day 5 between the levosimendan and the control groups [77.5% (100/129) vs. 69.0% (87/126), χ²=2.34, P=0.13]. Furthermore, incidences of MACE did not show any significant differences between the two groups during hospitalization [4.7% (6/129) vs. 7.1% (9/126), χ²=0.72, P=0.40] and at 6 months [14.7% (19/129) vs. 12.7% (16/126), χ²=0.22, P=0.64]. Four cardiac deaths were reported in the control group during hospitalization [0 (0/129) vs. 3.2% (4/126), P=0.06]. However, 6-month survival rates were comparable between the two groups (log-rank test, P=0.18). Moreover, adverse events or serious adverse events such as shock, ventricular fibrillation, and ventricular tachycardia were not reported in both the groups during levosimendan treatment (days 0-1). The total cost of hospitalization [34 591.00(15 527.46,59 324.80) vs. 37 144.65(16 066.90,63 919.00)yuan, Z=-0.26, P=0.80] and the total length of hospitalization [9 (8, 12) vs. 10 (7, 13) days, Z=0.72, P=0.72] were lower for patients in the levosimendan group compared to those in the control group, but did not show statistically significant differences. Conclusions: Early administration of levosimendan reduced NT-proBNP levels in NSTEMI patients with elevated NT-proBNP and did not increase the total cost and length of hospitalization, but did not significantly improve MACE during hospitalization or at 6 months.
Male ; Female ; Humans ; Aged ; Natriuretic Peptide, Brain ; Simendan/therapeutic use* ; Non-ST Elevated Myocardial Infarction ; Heart Failure/drug therapy* ; Peptide Fragments ; Arrhythmias, Cardiac ; Biomarkers ; Prognosis

In May 16 th, 2019, a male patient (aged 51 years) with a rare giant ulcer caused by skin diffuse large B-cell lymphoma in the axilla was admitted to Tongren Hospital of Wuhan University & Wuhan Third Hospital, and the ulcer wound was confirmed by biopsy and immunohistochemical analysis after extensive excision. Ultimately, a good prognosis was obtained by transplantation of flap and skin graft in combination with radiotherapy and chemotherapy.

Objective:To investigate the clinical effects of expanded flaps in reconstructing scar contracture deformities in the face and neck after extensive burns.Methods:A retrospective observational study was conducted. From May 2016 to September 2022, 17 patients with scar contracture deformities in the face and neck after extensive burns were admitted to Tongren Hospital of Wuhan University & Wuhan Third Hospital, including 13 males and 4 females, aged 23 to 55 years, with 3 patients having degree Ⅱ cervical contracture, 14 patients having degree Ⅲ cervical contracture, and 12 patients having facial scar contracture deformity. In the first stage, 34 rectangular skin and soft tissue expanders (hereinafter referred to as expanders) with rated capacity of 100-600 mL were inserted into the face, chest, shoulder, and abdomen, and then the normal saline was injected for expansion. In the second stage, the scar tissue was removed and the contracture was released to correct the deformity. Two expanded facial flaps were transplanted in local fashion, 17 expanded flaps were transplanted in pedicled fashion, and 15 expanded flaps were freely transplanted to repair the secondary wounds after release, with artery pressurization was performed in 7 flaps. Indocyanine green fluorescence imaging was used to evaluate the arterial blood perfusion and venous return of the flaps during transplantation. The incision area of 32 flaps except 2 facial flaps was 10 cm×8 cm-36 cm×16 cm. The wounds of 31 flap donor sites were closed by direct suture, and the wound of 1 flap donor site was repaired by autologous split-thickness scalp transplantation. The skin condition of inserted place, expansion time, and total amount of normal saline injection of expanders, complications of skin and soft tissue expansion surgery, and survival of flap after the second stage surgery were observed and recorded. The long-term face and neck reconstruction effect and recovery of flap donor area were followed up. At the last follow-up, the 5-level Likert scale was used to evaluate the efficacy satisfaction of patients.Results:Of the 34 expander inserted places in 17 patients, 22 places were superficial scar skin after deep partial-thickness burns, 8 places were superficial scar skin after multiple skin donations, and 4 places were normal skin. After 4 to 15 months of expansion, the total normal saline injection volume was 238 to 2 000 mL, with no complications occurred. After the second stage surgery, the distal part of 2 pedicled flaps was partially necrotic, and the necrotic wounds were healed after flap dressing and free transplantation of contralateral expanded triangular flaps, respectively; the other flaps survived completely. During 6 to 18 months of follow-up, except for 2 expanded paraumbilical flaps and 1 expanded groin flap, which were bloated and improved by flap thinning, the appearance and texture of the other flaps were good, and all the flap donor sites recovered well. At the last follow-up, the face and neck scar contracture deformities were significantly improved in all patients, and the satisfaction of curative effect of patient was very satisfactory in 8 patients and relatively satisfactory in 9 patients.Conclusions:The expanded flaps of chest, abdomen, and other parts, combined with local advance, pedicled, and free transplantation, can effectively reconstruct scar contracture deformities in the face and neck after extensive burns, restore the function of operative area and improve the appearance simultaneously, with high degree of patient satisfaction, which is worthy of promotion in clinic.