Objective:To explore the impact of tislelizumab on renal function in bladder cancer patients with hydronephrosisMethods:A retrospective analysis of 34 bladder cancer patients with hydronephrosis treated at the Second Hospital of Tianjin Medical University from July 2020 to September 2023. Among them, 27 were male, and 7 were female, with an average age of (67.41±11.06)years and a body mass index (BMI) of (29.00±7.34) kg/m 2. 18 patients (52.9%) had hypertension, 5 (14.7%) had diabetes, and 5 (14.7%) had coronary heart disease. The baseline serum creatinine (SCr) was 81.15(69.18, 108.90)μmol/L, and the estimated glomerular filtration rate (eGFR) was 73.86(62.17, 91.12)ml/(min·1.73m 2). Of these, 26 patients (76.5%) had eGFR ≥60 ml/(min·1.73m 2)(G60+ group), and 8 patients (23.5%) had eGFR <60 ml/(min·1.73m 2)(G60- group). 10 patients (29.4%) had non-muscle invasive bladder cancer (NMIBC), and 24(70.6%) had muscle-invasive bladder cancer (MIBC). Eleven patients received surgical interventions within 1 month before baseline data collection that might affect hydronephrosis. All 34 patients received tislelizumab (200 mg, intravenous infusion every 3 weeks) combined with albumin-paclitaxel (200 mg, intravenous infusion every 3 weeks). Serum creatinine values were recorded before cycles 1, 2, and 3, and 21 days after cycle 3 (Cr1, Cr2, Cr3, CrE), and corresponding eGFR values (eGFR1, eGFR2, eGFR3, eGFRE) were calculated. A reduction in eGFR >25% from baseline at any of these points was defined as a decline in renal function (DRF), and an increase in eGFR >25% was defined as improvement in renal function (IRF). Differences in renal function changes and IRF, DRF incidence rates were compared between baseline subgroups Results:After 3 cycles of tislelizumab treatment, there was no significant change in eGFR []eGFR1 vs. eGFRE, 73.86 (62.16, 91.12)ml/(min·1.73m 2) vs. 83.82 (60.32, 90.62) ml/(min·1.73m 2), P=0.197]. Subgroup analysis showed that patients with diabetes had a significant increase in CrE compared to Cr1 (88.90 μmol/L vs. 69.40 μmol/L, P=0.043) and a significant decrease in eGFRE compared to eGFR1 [76.47 ml/(min·1.73m 2) vs. 87.73 ml/(min·1.73m 2), P=0.043]. No significant differences were observed in the other subgroups for SCr and eGFR within or between groups. DRF occurred in 4 patients (11.8%), with 1 diagnosed with acute renal injury, but not immune-related. IRF occurred in 8 patients (22.9%). In the subgroup analysis, the IRF incidence was significantly higher in the G60-group compared to the G60+ group (50.0% vs. 15.4%, P=0.044). No other factors were found to be associated with DRF or IRF. Conclusions:Tislelizumab treatment is safe for renal function in bladder cancer patients with hydronephrosis. Most patients with baseline poor renal function or underlying conditions like hypertension, diabetes, or coronary heart disease showed stable renal function during treatment.

Objective:To investigate the causal relationship between trimethylamine N-oxide (TMAO) and its precursors (betaine, carnitine, and choline) and pancreatic diseases based on the Mendelian randomization (MR) method.Methods:Genome-wide association study data of TMAO, betaine, carnitine, choline, acute pancreatitis (AP), chronic pancreatitis (CP), pancreatic cancer (PC), and circulating immune cell characteristics (white blood cell, lymphocyte, monocyte, neutrophil, eosinophil and basophil) were collected. According to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE)-MR reporting guidelines, the available genetic variants [single nucleotide polymorphism (SNP)] were strictly screened. The causal relationship between exposure (TMAO and its precursors) and outcomes (pancreatic diseases and circulating immune cell characteristics) was evaluated using inverse variance weighting (IVW), MR-Egger regression and weighted median. The reliability of the results was evaluated by sensitivity analysis based on MR-Egger regression, MR-PRESSO, Cochrane's Q test and leave-one-out method. Results:A total of 36 SNP associated with TMAO and its precursors were included. Five of these were associated with TMAO, 13 with betaine, 12 with carnitine, and 6 with choline. ① MR analysis showed that TMAO may increase the risk of AP [odds ratio ( OR) = 1.100, 95% confidence interval (95% CI) was 1.008-1.200, P = 0.032], and choline may reduce the risk of alcoholic acute pancreatitis (AAP; OR = 0.743, 95% CI was 0.585-0.944, P = 0.015). The analysis results of MR-Egger regression and weighted median were consistent with the IVW results. There is no evidence to support a causal relationship between TMAO and its precursors and the risk of CP and PC. Sensitivity analysis indicated that SNP analyzed by MR showed no heterogeneity and low pleiotropy. The leave-one-out method analysis determined that after excluding any SNP, the effect intervals of the remaining SNP on the results were similar to the overall effect intervals, which suggested the robustness of MR results. ② There was a positive causal relationship between plasma TMAO level and circulating monocyte count ( OR = 1.017, 95% CI was 1.000*-1.034, P = 0.048, * represented that the data was obtained by correcting to 3 decimal places from 1.000 1). The causal effect obtained by MR-Egger regression and weighted median analysis was consistent with the results of IVW. Sensitivity analysis illustrated SNP analyzed by MR showed no heterogeneity and pleiotropy. The leave-one-out method analysis determined that after excluding any SNP, the effect intervals of the remaining SNP on the results were similar to the overall effect intervals, which suggested the robustness of MR results. Conclusion:TMAO and choline may change the risk of AP, and TMAO may contribute to the increase of circulating monocyte count in AP.

Objective:To explore the impact of tislelizumab on renal function in bladder cancer patients with hydronephrosisMethods:A retrospective analysis of 34 bladder cancer patients with hydronephrosis treated at the Second Hospital of Tianjin Medical University from July 2020 to September 2023. Among them, 27 were male, and 7 were female, with an average age of (67.41±11.06)years and a body mass index (BMI) of (29.00±7.34) kg/m 2. 18 patients (52.9%) had hypertension, 5 (14.7%) had diabetes, and 5 (14.7%) had coronary heart disease. The baseline serum creatinine (SCr) was 81.15(69.18, 108.90)μmol/L, and the estimated glomerular filtration rate (eGFR) was 73.86(62.17, 91.12)ml/(min·1.73m 2). Of these, 26 patients (76.5%) had eGFR ≥60 ml/(min·1.73m 2)(G60+ group), and 8 patients (23.5%) had eGFR <60 ml/(min·1.73m 2)(G60- group). 10 patients (29.4%) had non-muscle invasive bladder cancer (NMIBC), and 24(70.6%) had muscle-invasive bladder cancer (MIBC). Eleven patients received surgical interventions within 1 month before baseline data collection that might affect hydronephrosis. All 34 patients received tislelizumab (200 mg, intravenous infusion every 3 weeks) combined with albumin-paclitaxel (200 mg, intravenous infusion every 3 weeks). Serum creatinine values were recorded before cycles 1, 2, and 3, and 21 days after cycle 3 (Cr1, Cr2, Cr3, CrE), and corresponding eGFR values (eGFR1, eGFR2, eGFR3, eGFRE) were calculated. A reduction in eGFR >25% from baseline at any of these points was defined as a decline in renal function (DRF), and an increase in eGFR >25% was defined as improvement in renal function (IRF). Differences in renal function changes and IRF, DRF incidence rates were compared between baseline subgroups Results:After 3 cycles of tislelizumab treatment, there was no significant change in eGFR []eGFR1 vs. eGFRE, 73.86 (62.16, 91.12)ml/(min·1.73m 2) vs. 83.82 (60.32, 90.62) ml/(min·1.73m 2), P=0.197]. Subgroup analysis showed that patients with diabetes had a significant increase in CrE compared to Cr1 (88.90 μmol/L vs. 69.40 μmol/L, P=0.043) and a significant decrease in eGFRE compared to eGFR1 [76.47 ml/(min·1.73m 2) vs. 87.73 ml/(min·1.73m 2), P=0.043]. No significant differences were observed in the other subgroups for SCr and eGFR within or between groups. DRF occurred in 4 patients (11.8%), with 1 diagnosed with acute renal injury, but not immune-related. IRF occurred in 8 patients (22.9%). In the subgroup analysis, the IRF incidence was significantly higher in the G60-group compared to the G60+ group (50.0% vs. 15.4%, P=0.044). No other factors were found to be associated with DRF or IRF. Conclusions:Tislelizumab treatment is safe for renal function in bladder cancer patients with hydronephrosis. Most patients with baseline poor renal function or underlying conditions like hypertension, diabetes, or coronary heart disease showed stable renal function during treatment.

Bacteria-mediated anti-tumor therapy has received widespread attention due to its natural tumor-targeting ability and specific immune-activation characteristics. It has made significant progress in breaking the limitations of monotherapy and effectively eradicating tumors, especially when combined with traditional therapy, such as radiotherapy. According to their different biological characteristics, bacteria and their derivatives can not only improve the sensitivity of tumor radiotherapy but also protect normal tissues. Moreover, genetically engineered bacteria and bacteria-based biomaterials have further expanded the scope of their applications in radiotherapy. In this review, we have summarized relevant researches on the application of bacteria and its derivatives in radiotherapy in recent years, expounding that the bacteria, bacterial derivatives and bacteria-based biomaterials can not only directly enhance radiotherapy but also improve the anti-tumor effect by improving the tumor microenvironment (TME) and immune effects. Furthermore, some probiotics can also protect normal tissues and organs such as intestines from radiation via anti-inflammatory, anti-oxidation and apoptosis inhibition. In conclusion, the prospect of bacteria in radiotherapy will be very extensive, but its biological safety and mechanism need to be further evaluated and studied.

BACKGROUND: Exposure to the ionizing radiation (IR) encountered outside the magnetic field of the Earth poses a persistent threat to the reproductive functions of astronauts. The potential effects of space IR on the circadian rhythms of male reproductive functions have not been well characterized so far. METHODS: Here, we investigated the circadian effects of IR exposure (3 Gy X-rays) on reproductive functional markers in mouse testicular tissue and epididymis at regular intervals over a 24-h day. For each animal, epididymis was tested for sperm motility, and the testis tissue was used for daily sperm production (DSP), testosterone levels, and activities of testicular enzymes (glucose-6-phosphate dehydrogenase (G6PDH), sorbitol dehydrogenase (SDH), lactic dehydrogenase (LDH), and acid phosphatase (ACP)), and the clock genes mRNA expression such as Clock, Bmal1, Ror-α, Ror-β, or Ror-γ. RESULTS: Mice exposed to IR exhibited a disruption in circadian rhythms of reproductive markers, as indicated by decreased sperm motility, increased daily sperm production (DSP), and reduced activities of testis enzymes such as G6PDH, SDH, LDH, and ACP. Moreover, IR exposure also decreased mRNA expression of five clock genes (Clock, Bmal1, Ror-α, Ror-β, or Ror-γ) in testis, with alteration in the rhythm parameters. CONCLUSION These findings suggested potential health effects of IR exposure on reproductive functions of male astronauts, in terms of both the daily overall level as well as the circadian rhythmicity.
ARNTL Transcription Factors/genetics* ; Acid Phosphatase ; Animals ; CLOCK Proteins/genetics* ; Circadian Rhythm/radiation effects* ; Epididymis/radiation effects* ; Gene Expression/radiation effects* ; Genitalia, Male/radiation effects* ; Glucosephosphate Dehydrogenase ; L-Iditol 2-Dehydrogenase ; L-Lactate Dehydrogenase ; Male ; Mice ; Mice, Inbred C57BL ; Models, Animal ; Nuclear Receptor Subfamily 1, Group F, Member 1/genetics* ; Nuclear Receptor Subfamily 1, Group F, Member 2/genetics* ; Nuclear Receptor Subfamily 1, Group F, Member 3/genetics* ; RNA, Messenger/genetics* ; Radiation Exposure ; Radiation, Ionizing ; Reproductive Physiological Phenomena/radiation effects* ; Sperm Motility/radiation effects* ; Spermatozoa/radiation effects* ; Testis/radiation effects*

Objective To evaluate the methods of standard patient (SP)combined with case-based learning (CBL ) in humanistic quality cultivation for interns in the department of thoracic surgery. Methods Medical interns in the department of thoracic surgery were divided randomly into experimental(n=30)and control group(n=30)respectively. In experimental group,SP combined with CBL was used while in control group traditional teaching was used. At the end of the study,teaching effect was assessed by the final examination and questionnaires and the data were processed by t test andX2 test. P<0.05 signifies statistical differences. Results There was no significant difference in test scores between the two groups (P>0.05). Scores of history-taking,medical check-up,paper writing quality in the final examination in experimental group were significantly higher than those in control group(P<0.01). Satisfaction degrees of doctor-patient communication,responsibility and service attitude in experimental group were better than those of control group(X2=16.484,10.335,20.376,32.851,P<0.01). Conclusions SP combined with CBL teaching method can stimulate the students' interests in thoracic surgery practice,improve the doctor-patient relationship and strengthen the ability of human-istic concern. It is a better clinical thoracic practice teaching method and it is beneficial to cultivating medical students with humanistic concern.

Objective To study the chemical constituents from mycelium of marine fungus Aspergillus versicolor.Methods The compounds were separated by column chromatography and their structures were elucidated based on chemical and spectral analysis. Results Seven compounds have been isolated from the acetone and methanol extracts from the mycelia of Aspergillus versicolor. Their structures were determined as sterigmatocystin (I), 6-methoxysterigmatocystin (II), averufin (III), tyrosine (IV), 3-methyl-pyrrolopiperazine-2, 5-dione (V), 3-isopropyl-pyrrolopiperazine-2, 5-dione (VI), carbamide (VII). Conclusion Compounds IV,V and VI were isolated for the first time from this genus of marine fungi.

Object To study the chemical constituents from the roots of Stellera chamaejasme L. Methods Chemical constituents were isolated by chromatographic methods and identified by physiochemical and spectral analysis. Results One lignan and three biflavonoids were purified and determined as bursehernin (Ⅰ), chamaejasmenin B (Ⅱ), isoneochamaejasmin A (Ⅲ),and (+)-chamaejasmin (Ⅳ). Conclusion Compound Ⅲ and Ⅳ are determined as new optical compounds. Compound I is first isolated from Stellera L. species.