The expanded clinical trial system is designed to provide clinical trial drugs for patients suffering from serious or life-threatening diseases for which there is no effective treatment， essentially seeking a balance between the accessibility of drugs to patients and the soundness of the development of the pharmaceutical industry， as well as between the risk of expanding the use of clinical trial drugs and the need to safeguard the rights and interests of patients’ lives and health. Article 23 of China's Drug Administration Law provides only a principled description of the applicable standards and operating procedures for this system， with no implementing regulations， making it difficult for the system to function effectively in practice. The United States， Japan， and Canada have made detailed provisions on the conditions of application， applicants， review subjects and contents， and safeguards of the system through laws， regulations， and guidelines. Based on China's legislative environment and regulatory reality， and considering that the system is still in the initial stage in China， it is recommended that appropriate reference be made to the beneficial experience of foreign countries and that regulations and normative documents be promulgated as soon as possible to clarify the types of expanded clinical trials， applicants， review subjects etc.， and to determine the responsibilities of all the parties involved， to promote the standardization of China’s expanded clinical trial system， to promote the availability of medicines to patients， and to effectively safeguard the rights and interests of patients’ lives and health， and the soundness and safety of the development of the pharmaceutical industry.

Objective To evaluate clinical efficacy of lung transplantation for lung chronic graft-versus-host disease (cGVHD) after hematopoietic stem cell transplantation (HSCT). Methods Clinical data of 12 patients undergoing lung transplantation for lung cGVHD were retrospectively analyzed. Preoperative clinical manifestations and involved organs of patients were analyzed. The lung function before and after lung transplantation was compared, and the survival of patients after lung transplantation was analyzed. Results Eleven patients underwent HSCT due to primary hematological malignancies, including 9 cases of leukemia, 1 case of myelodysplastic syndrome, 1 case of lymphoma. And 1 case underwent HSCT for systemic lupus erythematosus. Among 12 cGVHD patients, skin involvement was found in 8 cases, oral cavity involvement in 5 cases, gastrointestinal tract involvement in 4 cases and liver involvement in 3 cases. All 12 patients developed severe respiratory failure caused by cGVHD before lung transplantation, including 9 cases of typeⅡ respiratory failure and 3 cases of type Ⅰ respiratory failure. Two patients underwent right lung transplantation, 2 cases of left lung transplantation and 8 cases of bilateral lung transplantation. The interval from HSCT to lung transplantation was 75 (19-187) months. Upon the date of submission, postoperative follow-up time was 18 (7-74) months. Ten patients survived, 1 died from severe hepatitis at postoperative 22 months, and 1 died from gastrointestinal bleeding at postoperative 6 months. No recurrence of primary diseases was reported in surviving patients. Conclusions Lung transplantation is an efficacious treatment for lung cGVHD after HSCT, which may prolong the survival time and improve the quality of life of the recipients.

【Objective】 To investigate the protective effects of aflexible sleeve penile protection device on reducing postoperative pain and wound edema in patients after circumcision. 【Methods】 A total of 54 patients who underwent circumcision at Yan’an Branch of Peking University Third Hospital during Feb.1 and May 31, 2023 were enrolled.The patients were randomly divided into the experimental group and control group, with 27 patients in either groups.Patients in the experimental group were treated with a flexible sleeve penis protection device after surgery, and patients in the control group were treated with traditional gauze bandage after surgery.Postoperative pain, wound edema and complications were compared between the two groups. 【Results】 In terms of pain, the visual analogue scale of the experimental group was significantly lower at 6 hours [(1.7±0.9) vs.(3.3±1.9), P<0.001] and 2 days [(2.0±1.3) vs.(3.3±1.3), P<0.001] after surgery than that of the control group, but there were no statistically significant differences between the two groups on the 4th and 7th postoperative days (P>0.05).In terms of edema, the edema score of the experimental group was significantly lower than that of the control group on the 2nd postoperative day [(2.0±1.0) vs.(4.0±0.8), P<0.001] , the 4th postoperative day [(1.5±1.2) vs.(2.6±0.9), P<0.001] , and the 7th postoperative day [(0.9±1.3) vs.(2.3±1.5), P<0.001] .There was no statistically significant difference in the incidence of complications between the two groups (P>0.05). 【Conclusion】 The flexible sleeve penile protection device has significant effects of reducing early postoperative pain and reducing edema in patients undergoing circumcision.

Objective:To investigate the prognostic factors for all-cause mortality in patients with muscle-invasive bladder cancer(MIBC)with intermediate-to-high-risk primary prostate cancer.Methods:From January 2012 to October 2023,the clinical data of the patients with MIBC with intermediate-to-high-risk primary prostate cancer in Peking University Third Hospital were retrospectively analyzed.All the patients were monitored and the occurrence of all-cause death was documented as the outcome event in the prognostic study.Univariate and multivariate Cox proportional risk regression analysis models were implemented to search for independent influences on the prognosis of patients.For significant influencing factors(pathological T stage,M stage and perineural invasion of bladder cancer),survival curves were plotted before and after multifactorial Cox regression adjusting for confounding factors.Results:A total of 32 patients were included in this study.The mean age was(72.5±6.6)years;the median preoperative total prostate specific antigen(tPSA)was 6.68(2.47,6.84)μg/L;the mean preoperative creatinine was(95±36)μmol/L,and the median survival time was 65 months.The majority of the patients(87.5％)had high-grade bladder cancer,53.1％had lymphatic invasion,and 31.3％had perineural invasion.Prostate involvement was observed in 25.0％of the cases,and the positive rate of soft-tissue surgical margin was 37.5％.Multivariate Cox analysis revealed that preoperative creatinine level(HR=1.02,95％CI:1.01-1.04),pathological stage of bladder cancer T3(HR=11.58,95％CI:1.38-97.36)and T4(HR=19.53,95％CI:4.26-89.52)metastasis of bladder cancer(HR=9.44,95％CI:1.26-70.49)and perineural invasion of bladder cancer(HR=6.26,95％CI:1.39-28.27)were independent prognostic factors(P＜0.05).Survival curves with Log-rank test after adjusting for confounding factors demonstrated that bladder cancer pathology T3,T4,M1,and perineural invasion were unfavorable factors affecting the patients'survival prognosis(P＜0.05).Conclusion:Patients with MIBC with intermediate-to-high risk primary prostate cancer generally portends a poor prognosis.High preoperative serum creatinine,T3 or T4 pathological stage of bladder cancer,metastasis of bladder cancer and bladder cancer perineural invasion are poor prognostic factors for patients with MIBC with intermediate-to-high risk primary prostate cancer.

Objective:This study aimed to assess the awareness of trainees in physician standardized training towards the consequences of scientific misconduct and identify the main influencing factors, additionally, to provide targeted suggestions.Methods:A questionnaire survey was conducted among 6 200 trainees from 17 National standardized training bases for residencies in Guangxi. The cognitive status of the consequences of scientific misconduct were analyzed and factors affecting trainees' cognition were examined in terms of grade, education level, research experience, publication experience, research integrity training experience, and research integrity knowledge level.Results:The findings indicated that the awareness of trainees towards the consequences of scientific misconduct requires improvement. Notably, trainees from the 2020 and 2021 grade cohorts, with a master′s degree or above, having led research projects, having participated in research integrity training, and with a high level of research integrity knowledge scored higher on the cognitive assessment of the impact of research misconduct.Conclusions:Training bases should prioritize the education of research integrity among trainees, enhance their identification with scientific research integrity, raise their awareness of the seriousness of the consequences of scientific misconduct, and uphold the belief of adhering to the bottom line of academic ethics.

Heterotypic cell-in-cell structures (heCICs) are closely related to tumor development and progression, and have become a new frontier in life science research. Ras-related C3 botulinum toxin substrate 1 (Rac1) belongs to the classic Rho GTPase, which plays a key role in regulating the cytoskeleton and cell movement. To investigate the role and mechanism of Rac1 in the formation of heCICs, tumor cells and immune killer cells were labeled with cell-tracker, respectively, to establish the heCICs model. Upon treatment with the Rac1 inhibitor NSC23766, the formation of heCICs between tumor and immune cells was significantly reduced. The plasmid pQCXIP-Rac1-EGFP constructed by gene cloning was packaged into pseudoviruses that subsequently infect tumor cells to make cell lines stably expressing Rac1. As a result, the formation of heCICs was significantly increased upon Rac1 overexpression. These results demonstrated a promotive role of Rac1 in heCICs formation, which may facilitate treating cell-in-cell related diseases, such as tumors, by targeting Rac1.

Objective:To assess the efficacy and safety of 100 units of botulinum toxin A (BTX-A) intradetrusor injection in patients with overactive bladder.Methods:From April 2016 to December 2018, 17 tertiary hospitals were selected to participate in this prospective, multicenter, randomized, double-blind, placebo-controlled study. Two phases of study were conducted: the primary phase and the extended phase. This study enrolled patients aged 18 to 75 years who had been inadequately managed by anticholinergic therapy (insufficient efficacy or intolerable side effects) and had spontaneous voiding with overactive bladder. Exclusion criteria included patients with severe cardiac, renal and hepatic disorders, patients with previous botulinum toxin treatment for 6 months or allergic to BTX-A, patients with urinary tract infections, patients with urinary stones, urinary tract tumors, diabetes mellitus, and bleeding tendency. Eligible patients were randomly assigned to BTX-A group and placebo control group in a ratio of 2∶1. Two groups of patients received 20 intradetrusor injections of BTX-A 100U or placebo at the depth of the submucosal muscle layer respectively under cystoscope, including 5 injections at the base of the bladder, 3 injections to the bladder triangle, 5 injections each to the left and right walls and 2 injections to the top, sparing the bladder neck. As a placebo control group, patients received same volume of placebo containing no BTX-A and only adjuvant freeze-dried preparations for injection with the same method. A combination of gelatin, sucrose, and dextran served as adjuvants. Average micturition times per 24 hours, urinary incontinence (UI) episodes per day, average micturition volume per day, OAB symptom score(OABSS), and quality of life (QOL) score were recorded at baseline and the 2nd, 6th and 12th week after treatment. The primary efficacy endpoint was the change from baseline in the average micturition times per 24 hours at the 6th week after treatment. The secondary efficacy endpoints included the change from baseline in the average micturition times per 24 hours at 2nd and 12th week, as well as the change from baseline in the OABSS, QOL score, average frequency of urgency and UI episodes per day, urgency score, average micturition volume per day at 2nd, 6th and 12th week after treatment. Patients were followed for 12 weeks to assess adverse events (AEs). After assessed at week 12, if the micturition times has decreased less than 50% compared to baseline and the patient is willing to receive retreatment, then patients could enter the extended trial phase. In that phase, patients in both groups were injected with 100 units BTX-A from 12th week onwards and then followed up the same indicators for 12 weeks.Results:216 patients were enrolled in this trial (144 cases in the BTX-A group and 72 cases in the placebo control group). Baseline characteristics such as age (47.75±14.20 in the BTX-A group and 46.39±15.55 in the control group), sex (25 male/117 female in the BTX-A group and 10/61 in the control group), and disease duration (0.51 years in the BTX-A group and 0.60 years in the control group) were balanced between the two groups( P>0.05). A marked reduction from baseline in average micturition times per 24 hours was observed in all treatment groups at the 6th week and the reduction of the two groups was statistically different ( P<0.001 and P=0.008 respectively). Compared with the baseline, the average micturition times per 24 hours at the 6th week decreased from baseline by 2.40(0.70, 4.60)times for the BTX-A group and 0.70(-1.00, 3.30) times for the placebo control group respectively, and the difference between the two groups was considered to be statistically significant ( P=0.003). The change rates of average micturition times per 24 hours from baseline at the 6th week of the two groups were (16±22)% and (8±25)% respectively, and the difference between the two groups was statistically significant ( P=0.014). Compared with the baseline, the average micturition times per 24 hours at 2nd and 12th week decreased by 2.00(0.00, 4.00)and 3.30(0.60, 5.03)for the BTX-A group, 1.00(-1.00, 3.00)and 1.70(-1.45, 3.85)for the placebo control group respectively. The difference between two groups was considered to be statistically significant ( P=0.038 and P=0.012); the changes of average urgency times per day for the BTX-A group and the control group at the 2nd, 6th and 12th week were 2.00(0.00, 4.30)and 2.40(0.30, 5.00), 3.00(0.30, 5.70)and 0.70(-1.30, 2.70), 0.70(-1.30, 3.00) and 1.35(-1.15, 3.50), respectively. There were significant differences between two groups at the 2nd, 6th and 12th week, ( P=0.010, P=0.003 and P=0.025, respectively). The OABSS of the BTX-A group and the control group at the 6th week decreased by 1.00(0.00, 4.00)and 0.50(-1.00, 2.00) compared with the baseline, and the difference between the two groups was statistically significant ( P=0.003). 47 cases of BTX-A group and 34 cases of placebo control group entered the extended trial phase, and 40 and 28 cases completed the extended trial phase, respectively. The average micturition volume per 24 hours changed by -16.60(-41.60, -0.60)ml and -6.40(-22.40, 13.30)ml, (-35.67±54.41)ml and(-1.76±48.69)ml, (-36.14±41.51)ml and (-9.28±44.59)ml, (-35.85±43.35)ml and(-10.41±40.29)ml for two groups at the 12th, 14th, 18th and 24th week, and the difference between two groups was statistically significant at each follow-up time ( P=0.01, 0.006, 0.012 and 0.016, respectively). There was no significant difference in other parameters( P>0.05). However, adverse reactions after intradetrusor injection included increased residual urine volume (27 in the BTX-A group and 3 in the control group), dysuria (21 in the BTX-A group and 6 in the control group), urinary infection (19 in the BTX-A group and 6 in the control group), bladder neck obstruction (3 in the BTX-A group and 0 in the control group), hematuria (3 in the BTX-A group and 1 in the control group), elevated alanine aminotransferase (3 in the BTX-A group and 0 in the control group), etc. During the follow-up period, there was no significant difference in the other adverse events between two groups except the increase of residual urine volume( P<0.05). In the primary trial phase, among the 27 cases with increased residual urine volume in BTA group, only 1 case (3.70%) with PVR more than 300 ml; the PVR of 3 patients in the placebo group was less than 100 ml. The increase of residual urine volume caused by the injection could be improved or disappeared with the passage of time. Conclusions:Intradetrusor injection of Chinese BTX-A improved the average micturition times per 24 hours, the average daily urgent micturition times, OABSS, and average micturition volume per time, and reduced the adverse effects in patients with overactive bladder.Chinese BTX-A at dose of 100U demonstrated durable efficacy and safety in the management of overactive bladder.

Objective:To disiuss the application of liver free technique in renal cell carcinoma patients with Mayo Ⅱ-Ⅳ tumor thrombus.Methods:The clinical data of renal cell carcinoma patients with MayoⅡ-Ⅳ IVC tumor thrombus in our hospital from January 2014 to December 2019 were retrospectively analyzed. 25 patients underwent right part of liver or hepatic portal part dissection via open abdominal approach. There were 20 males and 5 females, aged 45-74 years (mean 61±6 years). All patients underwent urinary tract CTU or MRU examination, vena cava enhanced magnetic resonance angiography.There were left 8 cases, right 17 cases; the median length of tumor was 7 cm (3.6-12.1 cm). There were 1 case of Mayo grade Ⅱ tumor thrombus, 7 cases of Mayo grade Ⅲ tumor thrombus, and 17 cases of Mayo grade Ⅳ tumor thrombus. There were 7 cases of distant metastasis, including 6 cases of lung metastasis and 1 case of bone metastasis. After multi-disciplinary consultation (MDT), 19 patients underwent radical nephrectomy and 6 patients underwent tumor reducing nephrectomy. During the operation, the ligaments around the liver were completely dissociated and the space between the liver and kidney was opened. The bare area of the liver was fully dissociated, to expose the inferior vena cava. For Mayo grade Ⅳ tumor thrombus, 11 cases were treated with free diaphragmatic thrombus removal without thoracotomy, and 6 cases were treated with open chest cardiopulmonary bypass.Results:The median operation time was 444(258-694)min, the median intraoperative blood loss was 2 000(250-10 000)ml, and the median value of suspended red blood cell transfusion was 1 300(400-10 400)ml. The median postoperative hospital stay was 10(4-25)days.15 patients (60%) had postoperative complications, including 8 cases of liver injury, 5 cases of respiratory complications, 4 cases of kidney injury, 3 cases of anemia, 3 cases of infection and 1 case of thrombosis. Three patients died during perioperative period.Conclusions:The application of total liver free technique might obtain good exposure of surgical field, effectively control the hemorrhage of inferior vena cava, which is helpful for safe resection of tumor.

Objective:To evaluate the short-term influence of bilateral subthalamic deep brain stimulation (STN-DBS) in anxiety symptoms and quality of life in patients with Parkinson's disease (PD).Methods:Thirty-nine PD patients underwent bilateral STN-DBS in our hospital from August 2017 to August 2018 were chosen in our study. Beck Anxiety Inventory (BAI) and Beck Depression Inventory (BDI) scales were performed in these patients before and one month after surgery, and at the last follow-up, respectively. Parkinson's Disease Questionnaire-8 (PDQ-8) was performed before surgery and at the last follow-up. Statistical methods were used to analyze the differences of the above scores at different time points, and correlations between each two improvement degrees of above scores. The participants were subsequently divided into four groups based on preoperative BAI scores: no anxiety group ( n=18), mild anxiety group ( n=10), moderate anxiety group ( n=8), and severe anxiety group ( n=3); the above scales were performed. Results:(1) The BAI scores of 39 patients one month after surgery and at the last follow-up (14 [8, 20] and 9 [3, 14]) were significantly lower than those before surgery (16 [9, 27]), and the BDI scores (8[6, 16]) and PDQ-8 scores (3 [2, 6]) at the last follow-up were significantly lower than those before surgery (15 [8, 21] and 9 [6, 13], P<0.05). (2) Correlation analysis revealed that the improvement degree of BAI scores was positively correlated with that of BDI scores ( r s=0.722, P=0.000), and negatively correlated with preoperative baseline scores of BDI and PDQ-8, respectively ( r s=-0.714, P=0.000; r s=-0.378, P=0.018). (3) The BAI scores in the mild and moderate anxiety groups at the last follow-up were significantly lower as compared with the preoperative baseline BAI scores ( P<0.05). The improvement degree of BAI scores in mild, moderate, and severe anxiety groups was significantly higher than that in the no anxiety group ( P<0.05). Conclusion:The bilateral STN-DBS has considerable benefit effect on anxiety symptoms and health-related quality of life in PD patients during short-term follow-up, suggesting an involvement of STN in the pathogenesis of anxiety in PD.

Zoster sine herpete (ZSH) is one of the atypical clinical manifestations of herpes zoster (HZ), which stems from infection and reactivation of the varicella-zoster virus (VZV) in the cranial nerve, spinal nerve, viscera, or autonomic nerve. Patients with ZSH display variable symptoms, such as neuralgia, however, different from HZ, ZSH show no zoster, which makes clinical diagnosis difficult. ZSH not only causes initial symptoms, such as neuropathic pain in the affected nerve, Bell palsy, and Ramsay Hunt syndrome, but also postherpetic neuralgia and fatal complications such as VZV encephalitis and stroke. The misdiagnosis of ZSH and tardy antiviral treatment may lead to severe ZSH sequelae. We review the publications related to ZSH, especially its diagnosis with VZV DNA and/or anti-VZV immunoglobulin (IgG and IgM). More work about ZSH, especially ZSH epidemiological survey and guidelines for its diagnosis and treatment, are needed because most of the present studies are case reports.