According to the latest global cancer burden data for 2020 released by the WHO's International Agency for Research on Cancer, breast cancer has become the malignant tumor with the highest incidence worldwide. Based on existing internal medicine treatment means like chemotherapy, targeted therapy and endocrine therapy, the development of immunotherapy provides novel solutions for the treatment of breast cancer. To date, the clinical research of immunotherapy in various molecular types and stages of breast cancer has reached certain achievements. In addition, the exploration of joint application with other therapies, predictive markers for efficacy, and immune-related adverse effects is also ongoing. The research and development in the field of breast cancer immunotherapy holds a promising prospect, and approaching research advances will promote the further application of immunotherapy in breast cancer.

【Objective】 To explore the learning curve of single-surgeon robot-assisted laparoscopic radical prostatectomy (RARP), which provides a reference for physicians who intend to carry out RARP. 【Methods】 The clinical data of 65 prostate cancer patients who underwent RARP in our hospital during Sep.2022 and Dec.2023 were retrospectively analyzed.The patients’ median age was 67.5(58.1-82.4) years, median total prostate-specific antigen (PSA) was 15.6 (6.7-98.4) ng/mL, median body mass index (BMI) was 20.8(17.4-27.3) and preoperative clinical stage of tumor was T2aN0M0-T3bN1M0.The cumulative sum (CUSUM) method was used to fit the learning curves of machine installation time and operation time.According to the inflection points, the learning curves were divided into different learning stages, and the clinical data of patients at different learning stages were compared. 【Results】 The learning curve of RARP was 12 cases.The 65 cases were divided into three stages: 1st-12th cases in the learning stage, 13rd-43rd cases in the mastery stage, and 44th-65th cases in the proficiency stage.With the increase of the number of surgical cases, the median operation time [191(100-360) min vs. 116(83-165) min vs. 90(75-105) min] and median intraoperative blood loss [403(180-900) mL vs. 236(180-305) mL vs. 94(30-200) mL] in the three stages showed a gradual downward trend (P<0.05).The median machines installation time of the learning stage was significantly longer than that in the mastery stage and the proficiency stage [25(21-28) min vs. 12(11-15) min vs. 12(11-14) min] (P<0.05).The positive surgical marginrate (PSM) in the learning stage was significantly higher than that in the mastery stage and proficiency stage (41.7% vs.22.6% vs.22.7%) (P<0.05). 【Conclusion】 For surgeons with rich experience in traditional laparoscopic surgery, the learning curve of RARP is about 12 cases, and after 43 cases, the operation time and intraoperative blood loss can be further reduced.

The mesencephalic astrocyte-derived neurotrophic factor (MANF) has been recently identified as a neurotrophic factor, but its role in hepatic fibrosis is unknown. Here, we found that MANF was upregulated in the fibrotic liver tissues of the patients with chronic liver diseases and of mice treated with CCl₄. MANF deficiency in either hepatocytes or hepatic mono-macrophages, particularly in hepatic mono-macrophages, clearly exacerbated hepatic fibrosis. Myeloid-specific MANF knockout increased the population of hepatic Ly6C^high macrophages and promoted HSCs activation. Furthermore, MANF-sufficient macrophages (from WT mice) transfusion ameliorated CCl₄-induced hepatic fibrosis in myeloid cells-specific MANF knockout (MKO) mice. Mechanistically, MANF interacted with S100A8 to competitively block S100A8/A9 heterodimer formation and inhibited S100A8/A9-mediated TLR4-NF-κB signal activation. Pharmacologically, systemic administration of recombinant human MANF significantly alleviated CCl₄-induced hepatic fibrosis in both WT and hepatocytes-specific MANF knockout (HKO) mice. This study reveals a mechanism by which MANF targets S100A8/A9-TLR4 as a "brake" on the upstream of NF-κB pathway, which exerts an impact on macrophage differentiation and shed light on hepatic fibrosis treatment.

Objective:To summarize the ideal strategy for the treatment of female hypospadias.Methods:The data of 12 female patients with hypospadias admitted to the Sixth People's Hospital Affiliated to Shanghai Jiaotong University School of Medicine from December 2011 to December 2019 were retrospectively analyzed. The patients was (31.0±16.6) years old (7-67 years old). Among them, 3 cases had a history of pelvic fracture trauma, 3 cases had a history of birth trauma, and the remaining 6 cases had no history of trauma and surgery. Among them, there were 6 cases of congenital hypospadias and 6 cases of acquired hypospadias. The clinical manifestations were urinary incontinence in 6 cases and dysuria in 6 cases. Examination of the normal position of the external opening of the genital urethra did not show the opening of the urethra, but moved down to different parts of the anterior wall of the vagina. All patients underwent urethral lengthening. For congenital hypospadias, the urethral plate is used to cut the coiled tube during the operation to prolong the urethra. For acquired hypospadias, the stenotic urethra was enlarged and lengthened with a labial pedicled flap coil. The subcutaneous fat pad of the labia majora was mobilized and transferred to the outside of the newly constructed urethra to prevent the occurrence of urethro-vaginal fistula and increase the pressure of the urethra. Five patients with significant urinary incontinence underwent bladder neck reconstruction at the same time. Anatomical success of the procedure was defined as the appearance of a normal-shaped external urethral opening beneath the clitoris. Functional success was defined as the absence of moderate to severe urinary incontinence after surgery, and the maximum urinary flow rate was >15ml/s during the 12-month follow-up period.Results:All operations were successfully completed. All patients had no perioperative complications, and were followed up for 18-96 months, with an average of 57.3±32.5 months. All patients were able to urinate spontaneously after operation, 4 cases of urinary incontinence disappeared, and 2 cases improved significantly; 4 cases of patients with strenuous urination urinated smoothly. The remaining 2 cases still complained of dysuria after operation, which was solved by subsequent urethral dilatation. The anatomical repair success rate was 100.0%(12/12) and the functional success rate was 83.3% (10/12).Conclusions:Urethral lengthening is an effective method for female hypospadias. The pedicled fat pad helps to increase urethral pressure and prevent fistulas. For female patients with hypospadias and severe urinary incontinence, bladder neck reconstruction is an ideal method. of the technique.

【Objective】 To evaluate the safety and efficacy of transobturator bulbourethral suspension with modified four-armed pelvic sling for post-prostatectomy incontinence (PPI). 【Methods】 The clinical data of 78 male PPI patients treated during Jan.2012 and Dec.2017 in our hospital were collected. The incontinence quality of life (I-QOL) score, daily use of urine pad, 1-hour urine pad test, residual urine volume (RUV), and maximum flow rate (Qmax) were assessed before and after surgery. 【Results】 The total success rate was 79.5%, of which the cure rate was 56.4% and the improvement rate was 23.1%. The preoperative I-QOL score was (54.6±3.9), daily use of urinary pad was (3.6±0.7), and increase in weight of the 1-hour urine pad test was (33.6±5.0) g. Three years after surgery, the I-QOL score was (80.4±5.7), daily use of a urinary pad was (1.9±0.4), and increase in weight of the 1-hour urine pad test was (7.4±1.3) g. Compared to preoperative status, the I-QOL score, daily use of urine pad, and increase in weight of the 1-hour urine pad test 3 years after surgery improved significantly (P<0.05). During the mean follow-up of (61.4±20.5) months, no significant changes in the I-QOL score, daily use of a urinary pad, 1-hour urinary pad test, RUV or Qmax were observed, and no complications occurred. 【Conclusion】 Transobturator bulbourethral suspension with modified four-armed pelvic sling is an effective and safe procedure to treat post-prostatectomy incontinence. The long-term efficacy is satisfactory.

Four new triterpenoids, together with six known analogues, were isolated from an aqueous extract of the Ziziphus jujuba var. spinosa seeds, by multiple column chromatographic separation methods using stationary phases of macroporous adsorption resin, MCI resin, normal phase silica gel, Sephadex LH-20, and Toyopearl HW-40C as well as preparative thin-layer chromatography and reversed-phase HPLC. Their structures were determined by spectroscopic data analysis, the new structures were trivially named jujubaceanothoside A (1), 23-epijujuboside A (2), and jujubosides J and K (3 and 4), while the known analogues were identified as jujubosides A-C (5-7) and II (8), alphitolic acid (9), and betulinic acid (10). The structure of 1 was confirmed by single crystal X-ray diffraction.

Objective:To investigate the effect of modified York-Mason technique on urethrorectal fistula after radical prostatectomy.Methods:A retrospective analysis of clinical data from 20 patients with urethrorectal fistula after radical prostatectomy admitted to Shanghai Sixth People's Hospital from May 2016 to October 2022 was conducted. Patients’ average age was (76.6±4.2) years. The etiology was rectal injury during radical prostatectomy. Patients present urine leakage from the anus during micturition. 2 cases also had bladder neck stenosis, and 1 case had urinary incontinence.3 cases had radiotherapy history because of prostate cancer. The average duration of urethrorectal fistula was (1.8±2.3)years. Preoperative imaging confirmed the presence of contrast agent flowing from the bladder neck into the rectum. Three suspicious patients also underwent CT three-dimensional reconstruction. Urethroscopy revealed a depression at the bladder neck in five cases. Anorectal examination in five cases showed the formation of gas bubbles in the lower anterior wall of the rectum, along with a concave anterior wall. The distance from the fistula to the anal margin was (6.0±2.1) cm, with fistula diameters ≥1 cm in twelve cases, <1 cm in eight cases. Twelve patients had previously undergone cystotomy, and seventeen patients had undergone colostomy. The modified York-Mason procedure was adopted for all 20 cases. The patients were under general anesthesia and placed in the prone jackknife position, with the buttocks spread and fixed to the sides to expose the anus. An 8 cm-long incision was made from two points near the sacrococcygeal joint to the anal edge, representing the modified York-Mason approach. After dividing the anal sphincter muscle, both sides were marked using 3-0 chromium thread for subsequent anal reconstruction. The urethrorectal fistula was exposed, and the urethral side of the fistula was sutured with 4-0 absorbable thread, while the anterior rectal wall side was sutured with 3-0 absorbable thread. In cases of bladder neck stenosis, urethral internal incision was performed, and a urethral catheter was retained for 3 weeks postoperatively. Perianal incision drainage tubes were removed after three days. Patients had colostomy repair could eat the day after surgery, while those who didn’t were fast for five days and received intravenous nutrition.Results:All 20 cases in this group were successfully completed without complications during surgery. Follow-up ranged from 10 to 48 months after surgery. Seventeen (17/20)cases had unobstructed urination, with a maximum urine flow rate >15 ml, and no urine leakage from the anus. Postoperative urethrography and cystourethroscopy showed there were no urethrorectal fistulas in 15 cases. None of the patients experienced fecal incontinence after the surgery, except for three patients with a history of radiotherapy who continued to experience anal leakage. One patient underwent a second modified York-Mason procedure and achieved complete recovery three months after the second surgery. Another patient had anal discharge, and the fistula healed after two weeks of urethral catheter retention. One patient refused further treatment due to advanced age and frailty but still had anal leakage. Another patient experienced regular urethral dilation for urination difficulties, while one patient continued to have urinary incontinence.Conclusions:The modified York-Mason technique could be an effective method for urethrorectal fistula after radical prostatectomy with high success rate and few side effects.

Objective: To investigate the prevalence of allergic rhinitis (AR) in 3 central cities (Chifeng, Hohhot, Ordos) and the surrounding rural areas of Inner Mongolia region, and to look for possible risk factors related to the disease. Methods: From March to October of 2019, a multi-stage stratified random sampling epidemiological survey was conducted in Chifeng, Hohhot, Ordos and rural areas. The AR-related factors of the population were obtained in the form of face-to-face questionnaire survey, and the skin prick test (SPT) was taken for the participants. AR disease was diagnosed according to the "Guidelines for the Diagnosis and Treatment of Allergic Rhinitis (2015, Tianjin)". The daily airborne pollen situation in the three regions was monitored during the same period. SPSS 23.0 was used to analyze all survey results. Results: A total of 6 818 questionnaires were recovered, with 6 393 valid questionnaires. The self-reported prevalence of AR was 27.72% (1 772/6 393) and the confirmed prevalence of AR was 17.10% (1 093/6 393). The prevalence of perennial AR was 1.83% (117/6 393) while the prevalence of seasonal AR was 15.27% (976/6 393). The prevalence of AR diagnosed in females was higher than that in males (19.19% vs 15.34%, χ²=16.594, P<0.001) and the prevalence of females in the two age groups of 36-45 years and 46-55 years was significantly higher than that of males (18.17% vs 9.73%, 14.13% vs 7.25%, χ² value was 23.848, 18.772, respectively, all P<0.001). The prevalence of confirmed diagnoses in ethnic minorities was higher than that of Han nationality, and the prevalence of confirmed diagnoses in urban areas was higher than that in rural areas (23.13% vs 16.20%, 27.27% vs 9.71%, χ² value was 24.516, 336.024, respectively, all P<0.001). The main nasal symptoms of AR patients were sneezing (91.31%), nasal congestion (85.91%) and nasal itching (85.00%). The most common concomitant disease of AR was allergic conjunctivitis (73.99%). Asthma (OR=6.629), food allergy (OR=3.236), drug allergy (OR=1.786), application of antibiotics (OR=1.553), recent home decoration (OR=2.307), and smoking (OR=1.322) were the AR related risk factors. The highest proportion of SPT positive reactions was Artemisia annua (80.15%). The peak period of clinical symptoms of AR patients in Inner Mongolia region was July to September, which was consistent with the second peak period of airborne pollen monitoring. Conclusions: The prevalence of AR in central cities and the surrounding rural areas of Inner Mongolia region is 17.10%, and Artemisia species is the most important pollen allergen in this area. History of asthma, food allergy, drug allergy, antibiotic use, home decoration and smoking history are the related risk factors for AR.
Adult ; Allergens ; China/epidemiology* ; Female ; Humans ; Male ; Middle Aged ; Pollen ; Prevalence ; Rhinitis, Allergic/epidemiology* ; Rhinitis, Allergic, Seasonal ; Urbanization

Objective:To compare the outcomes of combined lingual mucosal graft with buccal mucosal graft urethroplasty and combined lingual mucosal graft with ADM (acellular dermal matrix) urethroplasty for the treatment of repair failed hypospadias.Methods:From February 2017 to February 2019, 26 patients with failed hypospadias repairs were treated with combined lingual mucosal graft with buccal mucosal graft urethroplasty (14 cases in Group A), and combined lingual mucosal graft with ADM urethroplasty (12 cases in Group B). The mean age of Group A was (29.5±1.2) years (range 18.0-41.0 years), and (26.5±0.8) years (range 20.0-38.0 years) in Group B. The previous operation times was mean (3.6±0.7)(range 2-5 times) and (4.6±0.8)(range 3-5 times) in Group A and Group B respectively. Operation method: All patients were nasally intubated, the remaining curvature was corrected, the fibrous tissue or scar was removed, and the defected urethra was measured. In Group A, the lingual mucosa was spread and fixed to the corpora cavernosa over the midline as the urethral plate, the buccal mucosa was covered the lingual mucosa as ventral urethra, both the mucosa lateral edges was sutured. In Group B, the lingual mucosa was harvested and fixed to the corpora cavernosa the same as in Group A, the ADM was made appropriate length and width, covered and sutured with the lingual mucosa. The lingual mucosa was harvested mean (5.0±0.2)cm(range 4-6cm)long, mean (1.2±0.2)cm (range 1.0-1.5cm)wide and mean (5.0±0.2)cm(range 5-6cm)long, mean (1.2±0.2)cm (range 1.0-1.5cm)wide in Group A and Group B respectively( P<0.05). In Group A, the buccal mucosa was harvested mean (4.1±0.2)cm(range 3.5-5.5cm)long, mean (1.2±0.2)cm wide. Criteria for successful repair of hypospadias were set as: ①The appearance of the penis is nearly normal; ②The penis curvature was corrected; ③Urethra orifice in normal position; ④Urine flow line is normal. The outcomes of the two groups were analyzed and compared, statistical analysis was done using SPSS 18.0 software. Results:The mean follow-up time was (16.3±1.6)(8-24) months. The age, number of preoperative surgeries, number of previous oral mucous membranes, and length of urethral defects were no statistically significant differences between the two groups in A and B( P>0.05). The length of oral mucosa was harvested during the operation between group A and Group B were statistically significant differences( P<0.05). The incidence of oral complications in group A and B: Oral pain 7/14, 1/12; The feeling of tension in mouth 8/14, 1/12; The numbness in the oral 8/14, 1/12, A and Group B were statistically significant differences( P<0.05). The incidence of urethral complications in group A and Group B: the urethra fistula 1/14, 4/12; the urethral stricture 2/14, 6/12, there were statistically significant differences between the two groups ( P<0.05). Penile curvature 2/14, 1/12, ( P>0.05). The success rate was 12/14 and 5/12 in Group A and B respectively, with statistical difference( P<0.05). Conclusions:Combined lingual mucosal graft with buccal mucosal graft urethroplasty could be a good choice for repeated failed hypospadias repairs. Combined lingual mucosal graft with ADM urethroplasty has many complications and less success, should be performed in caution.

Objective:To investigate the characteristics and the management of male genital lichen sclerosus (MGLSc)accompanied by urethral carcinoma.Methods:A retrospective analysis was performed on 16MGLSc accompanied by urethral carcinoma patients who were referred to Shanghai Sixth People’s Hospital between June 2000 and August 2019. The average age was 53.7 (45-69) years. All of the patients had a mean history of MGLSc 15(6-35) years, anterior urethral stricture received urethral dilatation and other inappropriate urethrotomy treatment for 10 (8-15) years. There were 5 cases of solid mass 4.5 (3-7) cm in scrotum, accompanied by obviously pain. There were 11 cases of infective masses 6(4-10)cm in the perineum, and the masses were ulcerated with purulent secretions and residue-like pus mixed with necrotic tissues draining from the wounds. Urethrocutaneous fistula developed in 9 cases, and the secretions in the fistula cannot heal. The diseased tissue was confirmed by pathology as the metastasis of invasive urothelial carcinoma in 12 patients and urethral squamous cell carcinoma in 4 patients. 9 cases of tumor invaded corpus spongiosum or corpus cavernosum, 5 cases invaded corpus spongiosum or corpus cavernosum, with enlarged firm one side inguinal node. 2 cases of tumor invaded corpus cavernosum, beyond prostatic capsule and bladder neck, bilateral palpable inguinal lymph nodes metastasis were found, one case found tumor involved the left testis. 9 cases were T 2-3N 0M 0, 5 cases T 2-3N 1M 0, 1 case T 3N 2M 0, 1 case T 4N 2M 1. 5 patients with substantial tumors located in the scrotum, penile-sparing scrotum tumor, urethral tumor resection and urethrostomy was performed in 2 patients. Partial phallectomy, urethral tumor resection and perineal urethrostomy were performed in 3 patients. 11 patients with urethral cancer complicated with perineal infectious mass, 2 patients underwent extensive resection of the tumor and suprapubic cystostomy. 8 cases with perineal tumor infection complicated with urethrocutaneous fistulas formation, of which 2 patients received perineal mass, urethral tumor, fistula resection and suprapubic cystostomy, 4 patients with unilateral inguinal lymph node metastasis and received perineal mass, urethral tumor, fistula, lymph node resection and suprapubic cystostomy. 2 patients with bilateral inguinal node metastasis underwent total phallectomy and urethrectomy, inguinal lymph node resection and suprapubic cystostomy. One case of perineal infectious mass with urethral cutaneous fistula and unilateral inguinal lymph node metastasis (T 2-3N 1M 0) gave up tumor resection. Results:The pathological examination of surgical resection of the glans and urethra showed typical MGLSc manifestations as epithelial keratinization, basal cell vacuoles degeneration, dermis lymphocyte infiltration. The pathological examination of the surgical excised diseased urethra and surrounding tumor tissue showed invasive urothelial carcinoma in 12 patients. Immunohistochemical staining showed positive expression of P53, Ki-67 and GATA3. 4 patients of urethral squamous carcinoma and immunohistochemical staining showed positive expression of Ki-67, P40 and GATA3. All patients received cisplatin combined with gemcitabine chemotherapy for an average of 4.8 (2-6)courses and received local radiotherapy (50-70Gy/5w). The mean postoperative survival time of the 16 patients was 26 (3-48) months, and the survival time of urethral transitional cell carcinoma and squamous cell carcinoma was 29 (18-48) months and 18 (3-24) months, respectively. All patients died of tumor metastasis, with 6 patients of lung metastsis, 2 patients of lumbar and bone metastasis, 3 patients of liver metastasis, 2 patients of brain metastasis and 3 patients of lung combined with bone metastasis.Conclusions:MGLSc can cause urethal stricture and urethral carcinoma. The clinical manifestations are dysuria, urinary tumor, repeated infection and urethral fistula. Tumor excision and urinary diversion are common surgical methods. Urethral transitional cell carcinoma and squamous cell carcinoma are common pathological types. Postoperative combined radiotherapy and chemotherapy can be used, but the overall prognosis is poor.