Objective To explore the clinical value of albumin-globulin ratio(AGR)combined with prostate-specific antigen(PSA)and Gleason score in predicting biochemical recurrence(BCR)after radical resection in patients with localized prostate cancer, and to provide reference for early identification of BCR high-risk patients and individualized treatment. Methods The clinical data of 114 patients with localized prostate cancer treated during Sep.2019 and Sep.2023 were retrospectively analyzed.According to postoperative BCR status, patients were divided into the BCR group(n=43)and non-BCR group(n=71).Preoperative clinical and pathological data were compared between the two groups.Univariate and multivariate Cox regression analyses were used to assess the correlation between these indicators and BCR.The predictive performance of the combined model was evaluated using receiver operating characteristic(ROC)curve.The Kaplan-Meier method was used to compare biochemical recurrence-free survival(BFS)among patients with different AGR, PSA levels and Gleason scores.Results Compared with the non-BCR group, the BCR group had significantly higher PSA level and ISUP grading, but significantly lower AGR level(P＜0.001).Multivariate Cox regression analyses showed that AGR was negatively correlated with BCR(HR=0.031, 95%CI:0.008-0.119, P＜0.001), PSA was positively correlated with BCR(HR=1.009, 95%CI:1.002-1.016, P=0.017), and Gleason score was positively correlated with BCR(HR=1.551, 95%CI:1.199-2.005, P＜0.001).The area under the ROC curve(AUC)for the combined prediction model(AGR + PSA + Gleason score)was 0.886, with a sensitivity of 90.7% and a specificity of 78.9%.Kaplan-Meier analyses showed that patients in the low AGR group, high PSA group, and high Gleason score group had significantly lower BFS than those in the high AGR group, low PSA group and low Gleason score group, respectively(all P＜0.0001).Conclusion The combination of AGR, PSA and Gleason score is closely associated with postoperative BCR in patients with localized prostate cancer.The combined prediction model demonstrates high predictive efficacy and can provide an important reference for the early identification of high-risk BCR patients and for guiding individualized postoperative treatment.

Objective:To evaluate the safety and effectiveness of fuzuloparib for the treatment of ovarian epithelial cancer patients in the real world setting.Methods:A retrospective analysis was conducted on the baseline data of 4 620 ovarian cancer patients who had received fuzuloparib monotherapy or combination therapy. Another 224 ovarian cancer patients who were willing to receive fuzuloparib monotherapy or combination therapy were prospectively enrolled, and their baseline characteristics, drug effectiveness, and safety data were analyzed.Results:(1) Among the 4 620 patients in the retrospective cohort, the median age of patients was 60 years; tumor types: 89.8% (4 149/4 620) had ovarian cancer. Among patients with clearly documented information, the vast majority had a histological type of serous carcinoma (82.9%, 3 770/4 546) and International Federation of Gynecology and Obstetrics (FIGO) staging of Ⅲ-Ⅳ (90.9%, 1 537/1 691). (2) Among the 224 patients in the prospective cohort, the median age of patients was 57 years; tumor types: 83.9% (188/224) had ovarian cancer. Among patients with clearly documented records, the predominant pathologic type was serous carcinoma (91.9%, 193/210), and FIGO stage was Ⅲ-Ⅳ in 79.9% (139/174). (3) Among the 224 prospective patients: 84 patients received first-line fluzoparib maintenance therapy, 92 patients received fluzoparib maintenance therapy after platinum-sensitive recurrence, 23 patients received direct fluzoparib treatment after platinum-sensitive recurrence, 19 patients received direct fluzoparib treatment after platinum-resistant recurrence. The median follow-up durations were 8.5, 8.7, 7.9, and 6.7 months, respectively. The median durations of fluzoparib treatment were 6.7, 4.8, 3.1, and 1.9 months, respectively. The median progression-free survival (PFS) times were not reached during follow-up, 12.6 months, not reached during follow-up, and 4.8 months, respectively. The 1-year PFS rates were 84.1%, 55.0%, 69.8%, and 45.5%, respectively. The remaining 6 patients received other fluzoparib regimens. (4) Among the 224 patients in the prospective dataset, 205 had safety data recorded. Of these, 127 patients (62.0%, 127/205) experienced treatment-related adverse events, with common events including anemia (24.4%, 50/205), thrombocytopenia (21.0%, 43/205), and leukopenia (19.5%, 40/205). Among the 205 patients, 43 (21.0%, 43/205) experienced grade 3 or higher treatment-related adverse events, with common events including anemia (8.3%, 17/205) and thrombocytopenia (8.3%, 17/205).Conclusions:The effectiveness of fuzuloparib in clinical application is generally consistent with other drugs in the same class, with good safety. This study provids new clinical evidence for the treatment of ovarian cancer with fuzuloparib.

Objective:To evaluate the safety and effectiveness of fuzuloparib for the treatment of ovarian epithelial cancer patients in the real world setting.Methods:A retrospective analysis was conducted on the baseline data of 4 620 ovarian cancer patients who had received fuzuloparib monotherapy or combination therapy. Another 224 ovarian cancer patients who were willing to receive fuzuloparib monotherapy or combination therapy were prospectively enrolled, and their baseline characteristics, drug effectiveness, and safety data were analyzed.Results:(1) Among the 4 620 patients in the retrospective cohort, the median age of patients was 60 years; tumor types: 89.8% (4 149/4 620) had ovarian cancer. Among patients with clearly documented information, the vast majority had a histological type of serous carcinoma (82.9%, 3 770/4 546) and International Federation of Gynecology and Obstetrics (FIGO) staging of Ⅲ-Ⅳ (90.9%, 1 537/1 691). (2) Among the 224 patients in the prospective cohort, the median age of patients was 57 years; tumor types: 83.9% (188/224) had ovarian cancer. Among patients with clearly documented records, the predominant pathologic type was serous carcinoma (91.9%, 193/210), and FIGO stage was Ⅲ-Ⅳ in 79.9% (139/174). (3) Among the 224 prospective patients: 84 patients received first-line fluzoparib maintenance therapy, 92 patients received fluzoparib maintenance therapy after platinum-sensitive recurrence, 23 patients received direct fluzoparib treatment after platinum-sensitive recurrence, 19 patients received direct fluzoparib treatment after platinum-resistant recurrence. The median follow-up durations were 8.5, 8.7, 7.9, and 6.7 months, respectively. The median durations of fluzoparib treatment were 6.7, 4.8, 3.1, and 1.9 months, respectively. The median progression-free survival (PFS) times were not reached during follow-up, 12.6 months, not reached during follow-up, and 4.8 months, respectively. The 1-year PFS rates were 84.1%, 55.0%, 69.8%, and 45.5%, respectively. The remaining 6 patients received other fluzoparib regimens. (4) Among the 224 patients in the prospective dataset, 205 had safety data recorded. Of these, 127 patients (62.0%, 127/205) experienced treatment-related adverse events, with common events including anemia (24.4%, 50/205), thrombocytopenia (21.0%, 43/205), and leukopenia (19.5%, 40/205). Among the 205 patients, 43 (21.0%, 43/205) experienced grade 3 or higher treatment-related adverse events, with common events including anemia (8.3%, 17/205) and thrombocytopenia (8.3%, 17/205).Conclusions:The effectiveness of fuzuloparib in clinical application is generally consistent with other drugs in the same class, with good safety. This study provids new clinical evidence for the treatment of ovarian cancer with fuzuloparib.

The clinical data of an infant with chondrodysplasia accompanied by early-onset epilepsy and medial temporal lobe dysgenesis due to the FGFR3 gene mutation, who was treated in the Affiliated Hospital of Jining Medical University in March 2024 were retrospectively analyzed.The 9-day-old male infant presented with frequent apnea at 5 hours after birth and experienced first seizure at 24 hours after birth.Physical examination revealed short limbs.Magnetic resonance imaging (MRI) showed abnormal changes in bilateral temporal lobes, hippocampal structure and bilateral lateral ventricular temporal angles, so cerebral developmental abnormalities were considered in this child.Whole exome sequencing confirmed a heterozygous variation in the FGFR3 gene [c.1620C>A(p.Asn540Lys)].After receiving Phenobarbital monotherapy, the child still had frequent seizures, but the seizure was completely controlled after the additional use of Lvetiracetam.To August 2024, a total of 14 patients with achondroplasia, epilepsy, and medial temporal lobe dysplasia caused by FGFR3 gene mutations were identified.These patients typically experienced frequent seizures in early infancy, which could be accompanied by apnea and psychomotor retardation.MRI consistently showed abnormal development of bilateral temporal lobes and hippocampus.Seizures were hardly controlled by anti-seizure medications, and Phenobarbital was effective in some cases.Whole exome sequencing revealed gene variations of c.1620C>A or c. 1620C>G (p.Asn540Lys).Patients with achondroplasia caused by FGFR3 gene mutations may present with early-onset epilepsy and medial temporal lobe dysplasia.Early seizures are frequent and difficult to control, and Phenobarbital is effective in some cases.

The clinical data of an infant with chondrodysplasia accompanied by early-onset epilepsy and medial temporal lobe dysgenesis due to the FGFR3 gene mutation, who was treated in the Affiliated Hospital of Jining Medical University in March 2024 were retrospectively analyzed.The 9-day-old male infant presented with frequent apnea at 5 hours after birth and experienced first seizure at 24 hours after birth.Physical examination revealed short limbs.Magnetic resonance imaging (MRI) showed abnormal changes in bilateral temporal lobes, hippocampal structure and bilateral lateral ventricular temporal angles, so cerebral developmental abnormalities were considered in this child.Whole exome sequencing confirmed a heterozygous variation in the FGFR3 gene [c.1620C>A(p.Asn540Lys)].After receiving Phenobarbital monotherapy, the child still had frequent seizures, but the seizure was completely controlled after the additional use of Lvetiracetam.To August 2024, a total of 14 patients with achondroplasia, epilepsy, and medial temporal lobe dysplasia caused by FGFR3 gene mutations were identified.These patients typically experienced frequent seizures in early infancy, which could be accompanied by apnea and psychomotor retardation.MRI consistently showed abnormal development of bilateral temporal lobes and hippocampus.Seizures were hardly controlled by anti-seizure medications, and Phenobarbital was effective in some cases.Whole exome sequencing revealed gene variations of c.1620C>A or c. 1620C>G (p.Asn540Lys).Patients with achondroplasia caused by FGFR3 gene mutations may present with early-onset epilepsy and medial temporal lobe dysplasia.Early seizures are frequent and difficult to control, and Phenobarbital is effective in some cases.

Objective: Despite the availability of numerous treatment options, managing patients with platinum-resistant ovarian cancer (PROC) remains challenging, and the prognosis of PROC is notably unfavorable. This retrospective study aimed to assess the efficacy and safety of combined anlotinib-oral etoposide treatment for patients with PROC. Methods: Data of 23 patients who were diagnosed with PROC from January 2020 to November 2022 and treated with anlotinib combined with oral etoposide for at least 2 cycles were retrospectively analyzed. Results: Among per-protocol patients, 9 (45.0%; 95% confidence interval [CI]=21.1–68.9) of 20 patients achieved partial response and 17 (85.0%, 95% CI=67.9–100.0) of 20 patients achieved disease control. The median progression-free survival was 8.7 months (95% CI=5.3–11.6).The incidence of adverse events (any grade) was 100%, and the incidence of grade 3–4 adverse events was 54.5%. Conclusion Anlotinib combined with etoposide emerged effective for the treatment of PROC.

Objective:To explore regulatory effects of short-chain fatty acids (SCFA) on hypoxia-induced oxidative stress and activation of pancreatic stellate cells (PSCs) .Methods:PSCs were cultured in normoxia or hypoxia conditions to establish normoxia or hypoxia group. PSCs were pre-treated with SCFA working solution (10 mmol/L sodium acetate, 0.5 mmol/L sodium propionate and 0.5 mmol/L sodium butyrate), and then cultured in hypoxia conditions to establish the hypoxia-SCFA group. PSCs pre-treated by normal saline was set as the hypoxia-control group. The relative growth viability of the cells was detected by the CCK-8 assay. Relative levels of reactive oxygen species (ROS) were detected by DCFH-DA fluorescence probe method. The mitochondrial membrane potential was detected by JC-1 fluorescence probe. Protein expression of cyclin-associated marker cyclin A and cyclin D, hypoxic marker HIF1α, activation marker α-SMA, and antioxidant marker NRF2 and HO-1 was detected by western blotting.Results:The relative viability of PSCs in hypoxia group was significantly higher than that in normoxia group at 48 h (1.23±0.05 vs 0.99±0.04), but the relative viability of hypoxia-SCFA group was significantly lower than that of the hypoxic-control group at both 36 h and 48 h (0.69±0.01 vs 0.86±0.03, 0.86±0.02 vs 1.25±0.05). The relative level of ROS was significantly higher in hypoxia group than normoxia group (1.74±0.11 vs 1.00±0.10). The relative level of ROS was significantly lower in the hypoxia-SCFA group than the hypoxia-control group (1.39±0.14 vs 1.66±0.11). The fluorescence signals of JC-1 polymer in hypoxia group were significantly higher than those in normoxia group (1.36±0.05 vs 1.00±0.11), whereas the fluorescence signals of JC-1 polymer were significantly lower in hypoxia-SCFA group than in hypoxia-control group (1.11±0.03 vs 1.32±0.06). The expression of cyclin A, cyclin D, HIF1α, α-SMA, NRF2, and HO-1 was significantly higher in hypoxia group than those in normoxia group (1.19±0.01 vs 0.63±0.02, 0.93±0.02 vs 0.83±0.03, 1.18±0.07 vs 0.41±0.02, 1.19±0.14 vs 0.66±0.04, 1.22±0.11 vs 0.61±0.04, 1.28±0.12 vs 0.68±0.02), but the expression of cyclin A, cyclin D, α-SMA, NRF2, and HO-1 in Hypoxia-SCFA group was significantly lower than those in hypoxia-control group (0.79±0.04 vs 1.15±0.03, 0.88±0.01 vs 0.95±0.03, 0.87±0.01 vs 1.18±0.05, 0.84±0.01 vs 1.22±0.04, and 0.92±0.02 vs 1.27±0.06). All these differences were statistically significant (all P values <0.05) . Conclusions:SCFA significantly improves the oxidative stress state of PSCs under hypoxic conditions, maintains the stability of mitochondrial membrane potential, and inhibites hypoxia-induced activation of PSCs.

Objective: Despite the availability of numerous treatment options, managing patients with platinum-resistant ovarian cancer (PROC) remains challenging, and the prognosis of PROC is notably unfavorable. This retrospective study aimed to assess the efficacy and safety of combined anlotinib-oral etoposide treatment for patients with PROC. Methods: Data of 23 patients who were diagnosed with PROC from January 2020 to November 2022 and treated with anlotinib combined with oral etoposide for at least 2 cycles were retrospectively analyzed. Results: Among per-protocol patients, 9 (45.0%; 95% confidence interval [CI]=21.1–68.9) of 20 patients achieved partial response and 17 (85.0%, 95% CI=67.9–100.0) of 20 patients achieved disease control. The median progression-free survival was 8.7 months (95% CI=5.3–11.6).The incidence of adverse events (any grade) was 100%, and the incidence of grade 3–4 adverse events was 54.5%. Conclusion Anlotinib combined with etoposide emerged effective for the treatment of PROC.

Objective: Despite the availability of numerous treatment options, managing patients with platinum-resistant ovarian cancer (PROC) remains challenging, and the prognosis of PROC is notably unfavorable. This retrospective study aimed to assess the efficacy and safety of combined anlotinib-oral etoposide treatment for patients with PROC. Methods: Data of 23 patients who were diagnosed with PROC from January 2020 to November 2022 and treated with anlotinib combined with oral etoposide for at least 2 cycles were retrospectively analyzed. Results: Among per-protocol patients, 9 (45.0%; 95% confidence interval [CI]=21.1–68.9) of 20 patients achieved partial response and 17 (85.0%, 95% CI=67.9–100.0) of 20 patients achieved disease control. The median progression-free survival was 8.7 months (95% CI=5.3–11.6).The incidence of adverse events (any grade) was 100%, and the incidence of grade 3–4 adverse events was 54.5%. Conclusion Anlotinib combined with etoposide emerged effective for the treatment of PROC.

bjective To mine signals of post-marketing adverse drug events(ADEs)associated with dapagliflozin,and to provide insights for safe medication in clinical settings.Methods Data on ADEs related to dapagliflozin from U.S.Food and Drug Administration Adverse Event Reporting System(FAERS)were collected from the first quarter of 2013 to the third quarter of 2024.The analyses involved data mining and signal monitoring using disproportionality analysis techniques including the reporting odds ratio(ROR)method,Medicines and Healthcare Products Regulatory Agency(MHRA)method,Bayesian confidence propagation neural network(BCPNN)method,and multi-item gamma Poisson shrinker(MGPS)method.Results After data cleaning,a total of 55 832 qualified dapagliflozin case reports were obtained,involving 25 090 patients,with a slightly higher percentage of males(44.99％)than females(41.18％).The predominant age group was 45 to 64 years(20.78％).A total of 379 ADE signals were detected across 22 system-organ classes(SOC).The ADEs of dapagliflozin were mainly concentrated in the SOC such as infections and infestations,general disorders and administration sites conditions,and metabolism and nutrition disorders,aligning with information provided in the drug instructions.Additionally,the ADE signals were not documented in drug inserts such as scrotal gangrene,periperineal cellulitis,scrotal abscess,hyperglycemia,ketonuria,and pancreatitis.Conclusion When clinically using dapagliflozin,it is essential to conduct a thorough medication assessment.In addition to closely monitoring diabetes ketoacidosis,fungal infection,and acute renal injury.The latent ADEs that are not mentioned in the instructions to should be noticed ensure safe medication.