Objective:To investigate effect of cedrol on radiosensitivity of prostate cancer(PCa)cells and its mechanism.Methods:mRNA and protein expressions of cGAS and STING in PCa tissues and cells were detected by qRT-PCR and Western blot,respectively.Human PCa cells PC-3 were divided into control group,radiation group,cedrol group,combination group and inhibitor group.Radiosensitivity of cells in each group was detected by plate cloning test;apoptosis,migration and invasion were detected by flow cytometry,scratch test and Transwell chamber,respectively;γ-H2AX immunofluorescence staining was used to analyze effect of cedrol on DNA damage repair;after PC-3 cells and CD8+T cells were co-cultured,cells were divided into T cell group,co-culture group,cedrol group and inhibitor group,MTT and flow cytometry were used to detect proliferation and apoptosis of CD8+T cells,IFN-γ,IL-2 and TNF-α levels in supernatant of CD8+T cells were detected by ELISA;Western blot was used to detect prolife-rating cell nuclear antigen(PCNA),Bcl-2 associated protein(Bax),programmed death recepter ligand 1(PD-L1)and cGAS-STING signal pathway protein.Results:cGAS and STING protein and mRNA expressions in PCa tissues and cells were decreased(P<0.05),which were lowest in PC-3 cells.Compared with control group,colony formation rate,cell survival rate,scratch healing rate and cell inva-sion rate of PC-3 cells in radiation group and cedrol group were decreased obviously,apoptosis rate and number of γ-H2AX focus were increased obviously(P<0.05);compared with radiation group and cedrol group,combined group inhibited proliferation,migration and invasion of PC-3 cells,and induced DNA damage and apoptosis(P<0.05);inhibitor group attenuated inhibitory effect of com-bined group on proliferation,migration and invasion of PC-3 cells,and promoted DNA damage and apoptosis(P<0.05);compared with T cell group,A490,levels of IFN-γ,IL-2 and TNF-α in CD8+T cells in co-culture group were decreased,apoptosis rate was in-creased(P<0.05);compared with co-culture group,A490,levels of IFN-γ,IL-2 and TNF-α in CD8+T cells in cedrol group were in-creased,apoptosis rate was decreased(P<0.05);compared with cedrol group,A490,levels of IFN-γ,IL-2 and TNF-α in CD8+T cells in inhibitor group were decreased,apoptosis rate was increased(P<0.05).Compared with control group,expressions of PCNA and PD-L1 proteins in PC-3 cells in cedrol group were reduced obviously,expressions of Bax,cGAS and STING proteins were increased obviously(P<0.05);inhibitors of cGAS-STING pathway could reverse effect of cedrol on above proteins(P<0.05).Conclusion:Cedrol may enhance radiosensitivity of PCa cells by activating cGAS-STING signal pathway and inhibiting immune escape.

Objective:To investigate effect of cedrol on radiosensitivity of prostate cancer(PCa)cells and its mechanism.Methods:mRNA and protein expressions of cGAS and STING in PCa tissues and cells were detected by qRT-PCR and Western blot,respectively.Human PCa cells PC-3 were divided into control group,radiation group,cedrol group,combination group and inhibitor group.Radiosensitivity of cells in each group was detected by plate cloning test;apoptosis,migration and invasion were detected by flow cytometry,scratch test and Transwell chamber,respectively;γ-H2AX immunofluorescence staining was used to analyze effect of cedrol on DNA damage repair;after PC-3 cells and CD8+T cells were co-cultured,cells were divided into T cell group,co-culture group,cedrol group and inhibitor group,MTT and flow cytometry were used to detect proliferation and apoptosis of CD8+T cells,IFN-γ,IL-2 and TNF-α levels in supernatant of CD8+T cells were detected by ELISA;Western blot was used to detect prolife-rating cell nuclear antigen(PCNA),Bcl-2 associated protein(Bax),programmed death recepter ligand 1(PD-L1)and cGAS-STING signal pathway protein.Results:cGAS and STING protein and mRNA expressions in PCa tissues and cells were decreased(P<0.05),which were lowest in PC-3 cells.Compared with control group,colony formation rate,cell survival rate,scratch healing rate and cell inva-sion rate of PC-3 cells in radiation group and cedrol group were decreased obviously,apoptosis rate and number of γ-H2AX focus were increased obviously(P<0.05);compared with radiation group and cedrol group,combined group inhibited proliferation,migration and invasion of PC-3 cells,and induced DNA damage and apoptosis(P<0.05);inhibitor group attenuated inhibitory effect of com-bined group on proliferation,migration and invasion of PC-3 cells,and promoted DNA damage and apoptosis(P<0.05);compared with T cell group,A490,levels of IFN-γ,IL-2 and TNF-α in CD8+T cells in co-culture group were decreased,apoptosis rate was in-creased(P<0.05);compared with co-culture group,A490,levels of IFN-γ,IL-2 and TNF-α in CD8+T cells in cedrol group were in-creased,apoptosis rate was decreased(P<0.05);compared with cedrol group,A490,levels of IFN-γ,IL-2 and TNF-α in CD8+T cells in inhibitor group were decreased,apoptosis rate was increased(P<0.05).Compared with control group,expressions of PCNA and PD-L1 proteins in PC-3 cells in cedrol group were reduced obviously,expressions of Bax,cGAS and STING proteins were increased obviously(P<0.05);inhibitors of cGAS-STING pathway could reverse effect of cedrol on above proteins(P<0.05).Conclusion:Cedrol may enhance radiosensitivity of PCa cells by activating cGAS-STING signal pathway and inhibiting immune escape.

Accurately assessing and positioning the current development status of disciplines can help hospitals formulate targeted disciplinary development strategies and achieve disciplinary development goals. In 2022, a large tertiary public hospital established a discipline-demand-oriented " pyramid" hierarchical discipline evaluation system based on Maslow′s need-hierarchy theory. The discipline evaluation system set six levels of evaluation indicators from low to high, including medical quality and safety, department operation, sub specialty construction, scientific and educational achievements, platform construction, and talent cultivation(including 6 primary indicators, 21 secondary indicators, and 44 tertiary indicators). By applying the evaluation system and providing feedback on the evaluation results in the form of " disciplinary diagnostic reports" and " disciplinary evaluation conferences, " the hospital′s discipline construction had been improved at six levels. From 2022 to 2023, the hospital added five national clinical key specialties; The number of sub major construction disciplines increased from 18 in 2021 to 61 in 2023, and patient satisfaction increased from 94.64% to 96.25%. This evaluation system could objectively reflect the level of discipline development, lead the high-quality development of disciplines, and provide references for other public hospitals to promote discipline development.

Aristolochic acid (AA), extracted from Aristolochiaceae plants, plays an essential role in traditional herbal medicines and is used for different diseases. However, AA has been found to be nephrotoxic and is known to cause aristolochic acid nephropathy (AAN).AA-induced acute kidney injury (AKI) is a syndrome in AAN with a high morbidity that manifests mitochondrial damage as a key part of its pathological progression. Melatonin primarily serves as a mitochondria-targeted antioxidant. However, its mitochondrial protective role in AA-induced AKI is barely reported. In this study, mice were administrated 2.5 mg/kg AA to induce AKI. Melatonin reduced the increase in Upro and Scr and attenuated the necrosis and atrophy of renal proximal tubules in mice exposed to AA. Melatonin suppressed ROS generation, MDA levels and iNOS expression and increased SOD activities in vivo and in vitro. Intriguingly, the in vivo study revealed that melatonin decreased mitochondrial fragmentation in renal proximal tubular cells and increased ATP levels in kidney tissues in response to AA. In vitro, melatonin restored the mitochondrial membrane potential (MMP) in NRK-52E and HK-2 cells and led to an elevation in ATP levels. Confocal immunofluorescence data showed that puncta containing Mito-tracker and GFP-LC3A/B were reduced, thereby impeding the mitophagy of tubular epithelial cells. Furthermore, melatonin decreased LC3A/B-II expression and increased p62 expression. The apoptosis of tubular epithelial cells induced by AA was decreased. Therefore, our findings revealed that melatonin could prevent AA-induced AKI by attenuating mitochondrial damage, which may provide a potential therapeutic method for renal AA toxicity.

Objective:To explore the effect of venetoclax-based therapy on relapsed/refractory multiple myeloma (MM) patients harboring t(11;14).Methods:The data of a relapsed/refractory MM patient harboring t(11;14) treated with venetoclax-based regimen admitted to Shanghai Changzheng Hospital in June 2019 was retrospectively analyzed and the literatures were reviewed.Results:The relapsed/refractory MM patient harboring t(11;14) had progression of disease after 3 lines of therapies, and then was treated with the selective bcl-2 inhibitor venetoclax combined with daratumumab and dexamethasone. As a result, the patient achieved partial remission and better hemogram recovery. The Eastern Cooperative Oncology Group (ECOG) score of physical status decreased from 3 to 1, and the quality of life was improved significantly.Conclusions:The relapsed/refractory MM patients harboring t(11;14) could benefit from venetoclax-based therapy. In the future, the safety, sensitivity and other performances of venetoclax in the treatment of MM should be further explored.

Objective:To evaluate the clinical efficacy and safety of SpyGlass-guided laser lithotripsy for large common bile duct (CBD) stones with diameter>2 cm.Methods:From August 2015 to August 2018, a total of 157 patients with large CBD stones at the First Affiliated Hospital of Shandong First Medical University who met the inclusion criteria were randomly divided into SpyGlass group ( n=78, underwent SpyGlass-guided laser lithotripsy) and laparoscopic common bile duct exploration (LCBDE) group ( n=79, underwent LCBDE) by using random numbers. Non-inferiority test was used for rates of one-time stone removal and total stone removal, and the non-inferiority margin was set to 10%. The transform rate, incidence of short-term complications, hospital stay, and quality of life (assessed by the gastrointestinal quality of life index) were compared between the two groups. Results:The total success rates of stone clearance were 92.3% (72/78) and 96.2% (76/79) in the SpyGlass group and LCBDE group, respectively ( P=0.023), with valid non-inferiority hypothesis. The one-time stone removal rates were 83.3% (65/78) and 96.2% (76/79), respectively ( P=0.124), with invalid non-inferiority hypothesis. There were no significant differences in the incidence of transform [7.7% (6/78) VS 3.8% (3/79), P=0.294] or short-term complications [5.1% (4/78) VS 10.1% (8/79), P=0.246] between the two groups. Compared with the LCBDE group, the SpyGlass group had a shorter hospital stay (5.65±0.94 d VS 8.84±1.54 d, P=0.001) and higher scores of gastrointestinal quality of life index (1 month after operation: 99.85±4.36 VS 91.51±5.47, P=0.001; 3 months after operation: 131.24±3.32 VS 112.32±7.77, P=0.001). Conclusion:For large CBD stones, the efficacy of SpyGlass-guided laser lithotripsy is not inferior to LCBDE, and it is less invasive. In the future, SpyGlass-guided laser lithotripsy could be an important option for the treatment of large CBD stones.

Objective:To summarize the clinical characteristics and prognosis of 51 patients with Waldenstr?m’s macroglobulinemia (WM) and evaluate the efficacy and adverse reactions of ibrutinib in the treatment of WM.Methods:We carried out a single-center retrospective study, including 51 patients with WM of our single center from November 2008 to October 2019.Results:The median age at diagnosis was 65 years with a male-to-female ratio of 2.64∶1. There were 9 (18%) , 21 (41%) , and 21 (41%) ISSWM stage low-, intermediate- and high-risk patients identified, respectively. A total of 27 (73%) patients harbored MYD88 L265P mutation. The median follow-up time was 38.6 (0.3-120.0) months, the median progression free survival was 46.4 months, and the median overall survival was not reached. The overall remission and major remission rates of patients who received ibrutinib were 87% and 80%, respectively. The median time to achieve at least partial remission of patients treated with ibrutinib was 8 weeks, which was earlier than those treated with other drugs ( P<0.05) . Conclusion:WM is often seen in elderly men. MYD88 L265P had a high frequency in WM. The findings of our study validate the efficacy of ibrutinib monotherapy. Even in patients with advanced age and at high risk of ISSWM, the overall remission rate and major remission rate are high. Ibrutinib is a safe and effective therapy because of its rapid onset and rare serious adverse reactions.

Objective To explore the value of ultrasound in differential diagnosis of hepatic hilar cyst in neonates and infants. Methods The ultrasonographic characteristics of 93 children with hilar cysts under 6 months of age admitted to the General Surgery Department of Beijing Children′s Hospital. Affiliated to Capital Medical University from January 2014 to December 2018 were retrospectively analyzed. According to the surgical results,they were divided into two groups:cystic biliary atresia ( CBA) group and congenital choledochal cyst (CC) group,21 cases in the CBA group and 72 cases in the CC group. The size of cyst in hepatic portal area,the shape of gallbladder in empty stomach,the expansion of intrahepatic and extrahepatic bile ducts,the deposition of biliary sludge and the communication between cyst and intrahepatic bile duct were observed by ultrasound. Results The cyst volume of CBA group was 0. 4 ( 0. 1, 1. 3 ) cm3 , and that of CC group was 18. 3(5. 4,50. 3) cm3. The cyst volume of CBA group was significantly smaller than that of CC group (P<0. 01);19 cases had abnormal gallbladder morphology in CBA group and 4 cases in CC group (P<0. 01);1 case had biliary sludge in hilar cyst in CBA group and 51 cases had biliary sludge in cyst in CC group ( P <0. 01);no intrahepatic bile duct dilatation was observed in CBA group,and 54 cases had intrahepatic bile duct dilatation in CC group (P<0. 01);no cyst communicated with intrahepatic bile duct in CBA group,and all cysts communicated with intrahepatic bile duct in CC group (P <0. 01). Conclusion Gallbladder shape,cyst size,biliary sludge deposition,intrahepatic bile duct dilatation and the communication between cyst and intrahepatic bile duct can be used as sonographic features to differentiate CBA from CC.

Objective To investigate the efficacy of prophylactic pancreatic stent placement and nonsteroidal antiinflammatory drugs( NSAIDs) for the prevention of post?endoscopic retrograde cholangiopan?creatography(ERCP) pancreatitis(PEP). Methods A total of 623 patients with high risk factors for PEP were treated with prophylactic pancreatic stent placement ( 145 patients, group A) or rectal NSAIDs( 478 pa?tients, group B) for PEP prevention by using the propensity score matching( PSM) analysis. Incidence of PEP, moderate and severe PEP were investigated. According to risk factors of PEP, indications of prophy?lactic pancreatic stent placement were analysed. Results Of 623 patients with high risk factors, 145 pairs were generated after PSM.Pancreatitis occurred in 32 patients,10 (6?9%) in group A and 22 (15?2%) in group B( P<0?05 ) . Moderate?to?severe pancreatitis developed in 5 ( 3?4%) patients in group A and 14 (9?7%) patients in group B(P<0?05).Risk factors of post?ERCP PEP were cannulation attempts duration longer than 10 minutes, precut sphincterotomy, more than one pancreatic guidewire passages and history of ampullectomy. Conclusion Although the NSAIDs represent an easy, inexpensive treatment, prophylactic pancreatic stent placement is still a better prevention strategy for PEP.Prophylactic pancreatic stents should be recommended to those with risk factors including cannulation attempts duration longer than 10 minutes, precut sphincterotomy, more than one pancreatic guidewire passages and ampullectomy.

Objective:To investigate the effects of Liuweidihuang pill on the insulin levels in sera and pancreatic islets from spontaneous mouse models of human type 2 diabetes administrated with different doses .Methods:The 6-8 week-old KK-Ay mice were randomly divided into three groups including no drug control group ,low-dose group and high-dose group,in addition C57BL/6J mice were used as a genetic control group .All the animals were given with different dose Liuweidihuang pill solutions or sterile distilled water by intragastrical administration for fifteen weeks .The fasting blood glucose ,body mass and food consumption were measured weekly .The serum insulin levels were surveyed by ELISA .And the insulin levels in the pancreas islets were detected by immunofluorescence and immunohistochemistry .Results:Decreased fasting blood glucose ,controlled body mass and food consumption ,and lower levels of insulin in the sera and pancreas islets were confirmed from the KK-Ay mice administered with Liuweidihuang pill .Furthermore,the low dose program exhibits a stronger effect .Conclusion:Liuweidihuang pill has exhibited relatively therapeutic effects in the spontaneous type 2 diabetes mice including controls of hyperglycemia and body mass and relieving insulin resistance .In addition , the low-dose regimen showed even better treatment in controlling insulin levels in the sera and pancreas islets .