OBJECTIVE: To investigate the effectiveness of tibial transverse transport (TTT) in treating Wagner grade 3-4 type 2 diabetic foot ulcers and analyze dynamic changes in immunoglobulin levels. METHODS: The clinical data of 68 patients with Wagner grade 3-4 type 2 diabetic foot ulcers treated with TTT between May 2022 and September 2023 was retrospectively analyzed. The cohort included 49 males and 19 females, aged 44-91 years (mean, 67.3 years), with 40 Wagner grade 3 and 28 grade 4 ulcers. The duration of type 2 diabetes ranged from 5 to 23 years, with an average of 10 years. The number of wound healing cases, healing time, amputation cases, death cases, and complications were observed and recorded. Serum samples were collected at 6 key time points [1 day before TTT and 3 days, 7 days (the first day of upward transverse transfer), 14 days (the first day of downward transverse transfer), 21 days (the first day after the end of transfer), 36 days (the first day after the removal of the transfer device)], and the serum immunoglobulin levels were detected by flow cytometry including immunoglobulin G (IgG), IgA, IgM, IgE, complement C3 (C3), C4, immunoglobulin light chain κ (KAP), immunoglobulin light chain λ (LAM). RESULTS: All the 68 patients were followed up 6 months. Postoperative pin tract infection occurred in 3 cases and incision infection in 2 cases. Amputation occurred in 5 patients (7.4%) at 59-103 days after operation, and 8 patients (11.8%) died at 49-77 days after operation; the wounds of the remaining 55 patients (80.9%) healed in 48-135 days, with an average of 80 days. There was no recurrence of ulcer, peri-osteotomy fracture, or local skin necrosis during follow-up. The serum immunoglobulin levels of 55 patients with wound healing showed that the levels of IgG and IgM decreased significantly on the 3rd and 7th day after operation compared with those before operation ( P<0.05), and gradually returned to the levels before operation after 14 days, and reached the peak on the 36th day. IgA levels continued to decrease with time, and there were significant differences at all time points when compared with those before operation ( P<0.05). The level of IgE significantly decreased at 21 days after operation compared with that before operation ( P<0.05), while it was higher at other time points than that before operation, but the difference was not significant ( P>0.05). The level of C3 showed a clear treatment-related increase, which was significantly higher on the 7th, 14th, and 21st days after operation than that before operation ( P<0.05), and the peak appeared on the 14th day. The change trend of C4 level was basically synchronous with that of C3, but the amplitude was smaller, and the difference was significant at 7 and 14 days after operation compared with that before operation ( P<0.05). There was no significant difference in KAP/LAM between different time points before and after operation ( P>0.05). CONCLUSION TTT can accelerate wound healing, effectively treat diabetic foot ulcer, and reduce amputation rate, and has definite effectiveness. The potential mechanisms of TTT in the treatment of diabetic foot ulcers include the dynamic regulation of IgG, IgA, IgM, and IgE levels to balance the process of inflammation and repair, and the periodic increase of C3 and C4 levels may promote tissue cleaning, angiogenesis, and anti-infection defense.
Humans ; Male ; Female ; Middle Aged ; Aged ; Diabetic Foot/immunology* ; Wound Healing ; Adult ; Retrospective Studies ; Aged, 80 and over ; Treatment Outcome ; Tibia/transplantation* ; Diabetes Mellitus, Type 2/complications* ; Amputation, Surgical ; Immunoglobulins/blood* ; Immunoglobulin G/blood*

Objective:To compare the efficacy and safety of robotic surgery and open surgery in the treatment of hilar cholangiocarcinoma.Methods:PubMed, Embase, Cochrane Library, Web of Science, CNKI and Wanfang database were searched to compare the treatment of hilar cholangiocarcinoma by robotic surgery and traditional open surgery. Literatures were searched from the establishment of the database to July 2023. Compare operation time, intraoperative blood transfusion rate, R 0 resection rate, lymph node metastasis rate, postoperative complication rate and hospital stays between the two groups. The combined odds ratio ( OR) and mean difference ( MD) and 95% confidence interval (95% CI) were calculated using RevMan 5.4 software. Results:A total of 4 studies were included, including 267 patients with hilar cholangiocarcinoma. There were 177 males and 90 females, aged (58.8±5.7) years. A total of 267 patients were divided into open surgery group ( n=165) and robotic surgery group ( n=102) according to the surgical formula. The extract results show: operative time ( MD=-103.96, 95% CI: -216.90-8.98, P=0.070) and intraoperative blood transfusion rate ( OR=1.32, 95% CI: 0.43-4.07, P=0.630), R 0 resection rate ( OR=1.41, 95% CI: 0.71-2.81, P=0.330), lymph node metastasis rate ( OR=1.62, 95% CI: 0.46-5.63, P=0.450), postoperative complications ( OR=0.60, 95% CI: 0.28-1.31, P=0.200), and postoperative hospital stay ( MD=2.17, 95% CI: -11.56-15.90, P=0.760). Conclusion:In the treatment of hilar cholangiocarcinoma, robotic surgery is as safe and feasible as open surgery. However, due to the limited number and quality of included studies, the above conclusions need to be verified by more high-quality studies.

Background and purpose:Human epidermal growth factor receptor 2(HER2)is closely associated with drug efficacy and prognosis in urothelial carcinoma(UC).HER2 is a significant biomarker and therapeutic target in various tumors.In recent years,anti-HER2 antibody-drug conjugates have shown significant clinical efficacy in UC patients with HER2 overexpression.Therefore,an in-depth understanding of HER2 expression and its characteristics in Chinese UC patients is crucial to guide treatment decision-making,optimize treatment strategies and achieve personalized therapy.This study aimed to thoroughly investigate correlation of HER2 expression and clinicopathological characteristics in Chinese patients with UC.Methods:This study was a multicenter study that retrospectively included UC patients from urology departments of 8 tertiary hospitals in 5 geographical regions of China(North China,East China,South China,Central China and Northwest)whose tissue samples were collected from January 2023 to March 2024.Inclusion criteria:① age above 18 years;② UC diagnosed by histopathological or cytological examination;③ complete results of HER2 expression detection using immunohistochemistry(IHC)in the primary tumor site were required.Exclusion criteria:① diagnosed patients with tumors in other parts of the body;② physicians evaluated other situations that were not suitable for inclusion in this study.IHC results for HER2 expression and clinicopathological data were collected.HER2 expression was determined according to the criteria outlined in"Clinical pathological expert consensus on HER2 testing in urothelial carcinoma in China",with HER2 2+and 3+defined as HER2 overexpression.The HER2 expression and clinicopathological features were analyzed.This study was approved by the medical ethics committee of Fudan University Shanghai Cancer Center(ethical number:2301268-12)and was registered at China Clinical Trial Registry(registration number:ChiCTR2300069746).Results:A total of 1054 patients with UC were included.Most of the tumors were bladder UC(n=807,76.6%).The mean age of patients was(66.8±10.5)years,and the majority were male(78.5%).The HER2 overexpression rate was 58.4%(n=616),with an additional 23%of patients having HER2 1+expression(n=242),and a small proportion exhibiting negative HER2 expression(n=196,18.6%).HER2 expression was significantly associated with various clinical and pathological characteristics such as Eastern Cooperative Oncology Group(ECOG)performance status,history of cardiovascular disease,history of metabolic disorders,smoking,UC disease location,differentiation grade,pathological type,and tumor stage.Conclusion:Retrospective analysis of multi-center data shows that HER2 expression is frequently observed in Chinese UC patients,with an overexpression rate of up to 58.4%.Furthermore,HER2 expression is closely associated with various clinical and pathological features of UC patients.This study underscores the critical importance of accurately assessing HER2 expression in UC patient to guide personalized therapies.

Objective To investigate the effects of pretreatment with Xuebijing injection on renal tubular injury in rats with contrast-induced acute kidney injury(CI-AKI).Methods Twenty-four Sprague-Dawley(SD)rats were selected and divided into normal group,model group,control group,and treatment group according to the random number table method,with 6 rats in each group.The animal model of CI-AKI was prepared by adopting iohexol,and the normal group was not subjected to any treatment.The rats in the treatment group were injected with Xuebijing injection via the tail vein 15 hours before modeling until 24 hours after modeling.The injection volume was 10 mL/kg for every 6 hours.The control group was injected with normal saline at the same time point.After 24 hours of modeling,the urine of rats in each group was collected to determine the levels of blood urea nitrogen(BUN)and urine N-acetyl-β-D-gluco-aminidase(uNAG),and the blood was collected to determine the levels of serum creatinine(SCr).Then the rats were killed and the kidney tissues were extracted,and then stained with hematoxylin-eosin(HE),and the pathological changes of the kidney tissues were observed under the light microscope.Results BUN,SCr and uNAG were significantly higher in the model group than those in the normal group[BUN(μmol/L):37.29±6.18 vs.6.37±1.19,SCr(mmol/L):30.43±4.44 vs.14.90±1.61,uNAG(U/L):47.77±4.71 vs.11.32±3.62,all P<0.01];BUN,SCr and uNAG levels were obviously decreased in the treatment group compared to the model group[BUN(μmol/L):9.45±3.04 vs.37.29±6.18,SCr(mmol/L):19.83±2.16 vs.30.43±4.44,uNAG(U/L):21.70±6.21 vs.47.77±4.71,all P<0.05],however,BUN and uNAG in the treatment group were still significantly higher than those in the normal group[BUN(μmol/L):9.45±3.04 vs.6.37±1.19,uNAG(U/L):21.70±6.21 vs.11.32±3.62,P<0.05 or P<0.01];SCr in the treatment group was not statistically significant compared to the normal group(μmol/L:19.83±2.16 vs.14.90±1.61,P>0.05).Under the light microscope,the renal tubular epithelial cells at the junction of cortex and dermatomedulla in the kidneys of the model group were obviously vacuolated,accompanied by cell detachment and necrosis,and the tubules were dilated,with no obvious lesions in the glomeruli.The degree of damage in the control group and the treatment group was reduced compared with that in the model group.The degree of renal tubular damage in the model group was higher than that in the normal group;while the degree of renal tubular damage in the control group was significantly lower than that in the model group;and the degree of renal tubular damage in the treatment group was lower than that in the model group.There was no statistically significant difference in the degree of renal tubular damage between the treatment group and the control group.Conclusion Xuebijing injection may exert a protective effect on renal function in rats with CI-AKI by attenuating renal tubular injury.

OBJECTIVES: To investigate the prevalence of pathogenic germline mutations of mismatch repair (MMR) genes in prostate cancer patients and its relationship with clinicopathological characteristics. METHODS: Germline sequencing data of 855 prostate cancer patients admitted in Fudan University Shanghai Cancer Center from 2018 to 2022 were retrospectively analyzed. The pathogenicity of mutations was assessed according to the American College of Medical Genetics and Genomics (ACMG) standard guideline, Clinvar and Intervar databases. The clinicopathological characteristics and responses to castration treatment were compared among patients with MMR gene mutation (MMR⁺ group), patients with DNA damage repair (DDR) gene germline pathogenic mutation without MMR gene (DDR⁺MMR^－ group) and patients without DDR gene germline pathogenic mutation (DDR^－ group). RESULTS: Thirteen (1.52%) MMR⁺ patients were identified in 855 prostate cancer patients, including 1 case with MLH1 gene mutation, 6 cases with MSH2 gene mutation, 4 cases with MSH6 gene mutation and 2 cases with PMS2 gene mutation. 105 (11.9%) patients were identified as DDR gene positive (except MMR gene), and 737 (86.2%) patients were DDR gene negative. Compared with DDR^－ group, MMR⁺ group had lower age of onset (P<0.05) and initial prostate-specific antigen (PSA) (P<0.01), while no significant differences were found between the two groups in Gleason score and TMN staging (both P>0.05). The median time to castration resistance was 8 months (95%CI: 6 months-not achieved), 16 months (95%CI: 12-32 months) and 24 months (95%CI: 21-27 months) for MMR⁺ group, DDR⁺MMR^－ group and DDR^－ group, respectively. The time to castration resistance in MMR⁺ group was significantly shorter than that in DDR⁺MMR^－ group and DDR^－ group (both P<0.01), while there was no significant difference between DDR⁺MMR^－ group and DDR^－ group (P>0.05). CONCLUSIONS MMR gene mutation testing is recommended for prostate cancer patients with early onset, low initial PSA, metastasis or early resistance to castration therapy.
Male ; Humans ; Prostate-Specific Antigen/genetics* ; Germ-Line Mutation ; Retrospective Studies ; DNA Mismatch Repair/genetics* ; DNA-Binding Proteins/metabolism* ; China ; Prostatic Neoplasms/pathology*

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone

Objective:To explore the influences of Xingnao Tongdu acupuncture combined with Brunnstrom staging training on rehabilitation effect in stroke patients during recovery.Methods:According to random number table method, 82 patients with stroke during recovery who met inclusion criteria in Rehabilitation Medicine Department of the hospital were divided into control group (receiving routine rehabilitation training combined with Xingnao Tongdu acupuncture) and observation group (Brunnstrom staging training on basis of control group) between February 2020 and February 2021, 41 cases in each group. Both groups were continuously treated for 4 weeks. Before and after treatment, the severity of neurological deficits was evaluated by National Institute of Health Stroke Scale (NIHSS). The limb motor function was evaluated by Fugl-Meyer Assessment (FMA). The self-care ability was assessed by Barthel Index (BI). IL-6 was detected by ELISA. CRP level was detected by immunoturbidimetry. The WBC was detected by blood analyzer. The adverse reactions during treatment were observed. The clinical curative effect was evaluated.Results:There 40 cases in observation group and 41 cases in the control group were included into the statistics. The difference in total response rate between observation group and control group was not statistically significant [90.0% (36/40) vs. 75.6% (31/41)] ( χ2=2.93, P=0.087). After treatment, NIHSS score (6.65±1.79 vs. 8.71±2.61, t=4.13) in observation group was significantly lower than that of the control group ( P<0.01), while FMA score (69.56±9.64 vs. 61.77±10.33, t=3.51) and BI (73.72±8.34 vs. 65.86±7.36, t=4.50) were significantly higher than those in the control group ( P<0.01). The levels of serum IL-6 and CRP in observation group were significantly lower than those in the control group ( t values were 5.95, 5.61, respectively, all Ps<0.01). There were no adverse reactions in either group during treatment. Conclusion:The Xingnao Tongdu acupuncture combined with Brunnstrom staging training can improve rehabilitation effect and reduce levels of serum inflammatory cytokines in stroke patients during recovery.

Objective:To examine the clinical features and prognostic value of TP53 mutation in circulating tumor DNA(ctDNA) of Chinese prostate cancer patients. Methods:A prospective cohort of 239 prostate cancer patients diagnosed in the Department of Urology, Fudan University Shanghai Cancer Center from May 2018 to June 2019 was included. The age of diagnosis was(65.4±7.6) years(range: 45 to 85 years). Clinical data were collected from patient diagnosis and treatment records as well as follow-up surveys. TP53 mutations in plasma were detected by target sequence capture and second-generation sequencing. The relationship between TP53 mutation status and progression-free survival(PFS) was analyzed in patients who received any treatment lines. Kaplan-Meier analysis was performed in different subgroups, survival curves were drawn, and Log-rank test was used for comparison. Cox regression models were used to estimate multivariate adjusted HR and 95 %CI associated with PFS. Results:In the cohort, 15.9%(38/239) patients had TP53 mutation. Patients with TP53 mutations had a higher rate of metastases initially diagnosed with prostate cancer (78.9% (30/38) vs. 60.2% (121/201), χ2=4.829, P=0.028), as well as a higher rate of castration resistance (68.4% (26/38) vs. 42.8% (86/201), χ2=8.434, P=0.004). Kaplan-Meier analysis revealed a median androgen-deprivation therapy-PFS of 13.0 months in patients with TP53 mutation and 17.0 months in patients with TP53 wild-type. The median abiraterone-PFS was 4.7 months for patients with TP53 mutation and 11.0 months for TP53 wild-type patients. The median docetaxel-PFS was 3.0 months in patients with TP53 mutation and 5.0 months in patients with TP53 wild-type. TP53 mutation was the undependent prognosis factor of PFS in patients treated with abiraterone( HR=2.23, 95 %CI: 1.26 to 3.94, P=0.006) and docetaxel( HR=1.92, 95 %CI: 1.01 to 3.66, P=0.047) had significant differences in PFS. Conclusions:TP53 mutations were associated with the presence of metastasis and castration resistance, and were also an independent prognostic factor for progression-free survival in patients treated with abiraterone and docetaxel.

Objective:To examine the clinical features and prognostic value of TP53 mutation in circulating tumor DNA(ctDNA) of Chinese prostate cancer patients. Methods:A prospective cohort of 239 prostate cancer patients diagnosed in the Department of Urology, Fudan University Shanghai Cancer Center from May 2018 to June 2019 was included. The age of diagnosis was(65.4±7.6) years(range: 45 to 85 years). Clinical data were collected from patient diagnosis and treatment records as well as follow-up surveys. TP53 mutations in plasma were detected by target sequence capture and second-generation sequencing. The relationship between TP53 mutation status and progression-free survival(PFS) was analyzed in patients who received any treatment lines. Kaplan-Meier analysis was performed in different subgroups, survival curves were drawn, and Log-rank test was used for comparison. Cox regression models were used to estimate multivariate adjusted HR and 95 %CI associated with PFS. Results:In the cohort, 15.9%(38/239) patients had TP53 mutation. Patients with TP53 mutations had a higher rate of metastases initially diagnosed with prostate cancer (78.9% (30/38) vs. 60.2% (121/201), χ2=4.829, P=0.028), as well as a higher rate of castration resistance (68.4% (26/38) vs. 42.8% (86/201), χ2=8.434, P=0.004). Kaplan-Meier analysis revealed a median androgen-deprivation therapy-PFS of 13.0 months in patients with TP53 mutation and 17.0 months in patients with TP53 wild-type. The median abiraterone-PFS was 4.7 months for patients with TP53 mutation and 11.0 months for TP53 wild-type patients. The median docetaxel-PFS was 3.0 months in patients with TP53 mutation and 5.0 months in patients with TP53 wild-type. TP53 mutation was the undependent prognosis factor of PFS in patients treated with abiraterone( HR=2.23, 95 %CI: 1.26 to 3.94, P=0.006) and docetaxel( HR=1.92, 95 %CI: 1.01 to 3.66, P=0.047) had significant differences in PFS. Conclusions:TP53 mutations were associated with the presence of metastasis and castration resistance, and were also an independent prognostic factor for progression-free survival in patients treated with abiraterone and docetaxel.

Objective: To explore the causes and management of the complications in diabetic foot treated with tibial transverse transport (TTT). Methods: Between September 2015 and September 2019, 196 patients with diabetic foot were treated with TTT. There were 109 males and 87 females, with an average age of 67.6 years (range, 45-86 years). According to Wagner's classification, there were 124 cases of grade 3, 62 cases of grade 4, and 10 cases of grade 5; the course of disease was 1-12 months, with an average of 2.6 months. All patients underwent the minimally invasive tibial osteotomy. The osteotomy site was the middle and lower tibia in 62 cases and the middle and upper tibia in 134 cases. The area of osteotomy was 20 cm 2 in 83 cases and 7.5 cm 2 in 113 cases. The osteotomy block was moved back and forth once in 92 cases and twice in 104 cases. The complications were recorded, including secondary fracture at tibial osteotomy, skin necrosis in osteotomy area, and pin tract infection. Results: Among 196 patients, 41 cases (20.9%) had complications. Nine cases (4.6%) had secondary fracture at tibial osteotomy, among which 6 cases (9.6%) of middle and lower segment osteotomies and 3 cases (2.2%) of middle and upper segment osteotomies. The incidence between the patients with different osteotomy sites was significant ( χ2=5.354, P=0.021). The area of osteotomy was 20 cm 2 in 5 cases (6.0%) and 7.5 cm 2 in 4 cases (3.5%). There was no significant difference in the incidence between patients with different areas ( χ2=0.457, P=0.499). Skin necrosis occurred in the osteotomy area in 12 cases (6.1%), all of which were moved back and forth once. There was a significant difference in the incidence between patients who were treated with transport once and twice ( P=0.001). There were 18 cases (9.1%) with pin tract infection, including 12 cases (6.1%) with mild infection and 6 cases (3.0%) with severe infection. There was no significant difference in the incidence between the patients with mild and severe infections ( P=0.107). Conclusion: TTT is an effective method to treat diabetic foot, but there are complications such as secondary fracture at tibial osteotomy, skin necrosis in osteotomy area, and pin tract infection during transport. Preoperative evaluation of indication, standardization of osteotomy mode, size and position of osteotomy block, establishment of individualized removal plan, and strengthening of pin track nursing after operation can effectively reduce complications.