OBJECTIVE To study the effects of sophoranone （SOP） on the biological behavior of nasopharyngeal carcinoma CNE-1 cells and mitogen-activated protein kinase （MAPK） signaling pathway. METHODS CNE-1 cells were divided into blank group and SOP low-， medium- and high-concentration groups （SOP-L group， SOP-M group， SOP-H group， 25， 50 and 100 μmol/L）. The number of invasive cells， the number of migratory cells， and the apoptosis rate of cells were detected. The expression levels of mitogen-activated protein kinase kinase （MEK）， extracellular signal-regulated kinase 1 （ERK1）， ERK2， and c-Jun N-terminal kinase （JNK） mRNA， as well as phosphorylation levels of ERK， JNK， and p38 mitogen-activated protein kinase （abbreviated as “p38”） proteins in cells were all detected. Additionally， cells were divided into blank group， SOP high-concentration group （SOP- H group， 100 μmol/L）， SOP high-concentration combined with p38 inhibitor group （SOP-H+SB group， 100 μmol/L SOP+10 μmol/L SB）， and SOP high-concentration combined with JNK inhibitor group （SOP-H+SP group， 100 μmol/L SOP+10 μmol/L SP）. The number of invasive cells， cell migration rate， and the protein phosphorylation levels of JNK and p38 in cells， as well as the protein expression levels of matrix metalloproteinase-9（MMP-9）， proliferating cell nuclear antigen Ki67， and cleaved-caspase-3 were measured. RESULTS Compared with the blank group， SOP for each concentration could significantly decrease the number of invasive cells， the number of migratory cells， and mRNA expressions of MEK， ERK1， ERK2 （except for the SOP-L group） and JNK， but increase the apoptosis rate of cells and phosphorylation levels of ERK， JNK， and p38 proteins （P＜0.05）. Compared with the SOP-H group， the protein phosphorylation levels of p38 and JNK， and the protein expression of cleaved-caspase-3 were decreased significantly in SOP-H+SB group and SOP-H+SP group， while the number of invasive cells， cell migration rate， and the protein expression levels of MMP-9 and Ki67 were all increased significantly （P＜0.05）. CONCLUSIONS SOP can inhibit the proliferation， migration and invasion of CNE-1 cells， and induce the apoptosis， the mechanisms of which may be associated with promoting the phosphorylation of proteins related to the MAPK signaling pathway.

Objective:To explore the association between uric acid and new-onset chronic kidney disease (CKD) in middle-aged and elderly hypertensive patients.Methods:This was a retrospective cohort study. Middle-aged and elderly hypertensive patients who had attended at least two annual health examinations at Yongshun Community Health Service Center in Tongzhou District, Beijing, from June 2016 to December 2020 were enrolled. The time interval between the two physical examinations was three years. The first physical examination time served as the baseline, and the second as the end of follow-up. Based on the uric acid level at baseline, the participants were divided into the normal uric acid group and the hyperuricemia group. The relevant clinical data of the participants were collected. The endpoint of the study was new-onset CKD. A multivariate logistic regression model was used to analyze the association between uric acid and new-onset CKD in hypertensive patients.Results:A total of 2 472 middle-aged and elderly hypertensive patients with an average age of (62.43±7.02) years were included. Of these, 733(29.7%) were male. There were 710 patients with hyperuricemia (hyperuricemia group) and 1 762 patients with normal uric acid levels (normal uric acid group).After adjusting for age, sex, body mass index (BMI), systolic blood pressure, diabetes mellitus, estimated glomerular filtration rate (eGFR), and uric acid-lowering treatment, multivariate logistic regression analysis showed that combined with hyperuricemia was an independent risk factor for new-onset CKD in middle-aged and elderly hypertensive patients ( OR=3.00, 95% CI: 1.87-4.80, P<0.001). The results of multivariate logistic analysis showed that elevated uric acid level was an independent risk factor for new-onset CKD in both male and female middle-aged and elderly hypertensive patients (both P<0.05), and there was no sex interaction ( P for interactio n>0.05). The results of multivariate logistic analysis showed that the combination of asymptomatic hyperuricemia was an independent risk factor for new-onset CKD in middle-aged and elderly hypertensive patients ( OR=3.00, 95% CI: 1.87-4.80, P<0.001), and there was no gender interaction ( P for interactio n>0.05). Conclusions:Hyperuricemia is an independent risk factor for new-onset CKD in middle-aged and elderly hypertensive patients, and elevated uric acid levels increase the risk of new-onset CKD in both male and female patients. Moreover, asymptomatic hyperuricemia may increase the risk of new-onset CKD.

Objective:To evaluate the outcomes of intensive conservative treatment compared to conventional conservative treatment in patients with acute aortic syndrome(AAS).Methods:The study prospectively enrolled consecutive patients with AAS who were admitted to Beijing Anzhen Hospital, affiliated with Capital Medical University, and Beijing Dawanglu Emergency Rescue Hospital from January 2024 to December 2024. These patients with surgical contraindications or refused surgery for various reasons opted for conservative treatment. A total of 282 patients were included, and 15 patients with missing data or those who died without any treatment were excluded. Finally, 267 patients were enrolled, of whom 94 received intensive conservative treatment, and 173 received conventional conservative treatment, the inverse probability of treatment weighting (IPTW) was used to reduce the influence of confoundings. After adjusting of baseline datas via IPTW, the survival outcomes of the two groups were compared at 14 days, 30 days, and at the end of follow-up.Results:The results showed significant differences in acute phase survival rates between the enhanced conservative treatment group and the conventional conservative treatment group at 14 days(82.40%vs.53.20%, P<0.0001). Significant survival differences were also observed at 30 days and at 276-day mid-term follow-up (96.29% vs.51.60%, P<0.0001; 78.50% vs.48.50%, P<0.0001). In the subgroup analysis, for type A aortic dissection, the enhanced conservative treatment group had higher survival rates compared to the conventional conservative treatment group at 14, 30 and 276 days (63.46% vs.41.35%, P<0.05; 52.17% vs.37.90%, P<0.05; 50.00% vs. 31.97%, P<0.05). However, for type B aortic dissection, although the enhanced conservative treatment group had higher survival rates than the conventional conservative treatment group, no statistically significant differences were observed (96.29% vs. 80.00%, P=0.054; 95.65% vs.78.37%, P=0.067; 94.12% vs.74.20%, P=0.088). Conclusion:For patients diagnosed with AAS are forced to choose conservative treatment if emergency surgery is not possible in the first place, intensive conservative treatment strategies can significantly reduce the mortality in the acute phase compared with conventional conservative treatment. Mid-term follow-up, intensive conservative treatment still has a significant survival advantage.

OBJECTIVE To evaluate the efficacy of sulbactam-durlobactam combined with meropenem in treating carbapenem-resistant Acinetobacter baumannii(CRAB)pulmonary infection.METHODS A total of 16 patients treated at China-Japan Friendship Hospital from Jan.1,2025 to Jun.1,2025 were included.Retrospective analy-sis was conducted on patients'basic situation,preliminary treatment regimens,infection-related diagnoses,etiolo-gy and clinical outcomes.Therapeutic drug monitoring(TDM)for sulbactam was also performed.RESULTS By the end of the treatment course,13 patients achieved etiological eradication of CRAB and clinical improvement,while 1 patient experienced CRAB recurrence within one month.Three patients showed treatment failure.TDM for sulbactam was performed in 13 patients.Except for one slightly lower,all achieved trough plasma concentra-tions above the minimum inhibitory concentration(MIC)(100％T＞MIC,MIC=4 mg/L based on clinical breakpoints).Dosage adjustments based on plasma concentrations were made for 4 patients,with 3 receiving re-duced doses and 1 receiving an increased dose.CONCLUSIONS Sulbactam-durlobactam combined with meropenem demonstrates superior efficacy in treating CRAB compared to other regimens.Under the recommended dosage,all patients can achieve the PK/PD target for sulbactam.

Objective:To explore the clinical efficacy of olapalib in the treatment of platinum-sensitive recurrent breast cancer susceptibility gene (BRCA)-mutated ovarian cancer.Methods:The clinical data of 105 patients with platinum-sensitive recurrent BRCA-mutated ovarian cancer confirmed by pathology/imaging from October 2020 to March 2023 in Baoding Second Central Hospital were selected retrospectively, and they were divided into the control group (52 cases) and the experimental group (53 cases) according to the treatment methods. The control group was treated with a platinum-containing regimen, followed by olaparib at the end of the treatment. The experimental group was treated with olaparib. The recent clinical outcomes, tumour marker levels, ovarian cancer functional assessment of treatment questionnaire (FACT-O) score, cancer fatigue scale (CFS) score, and adverse reaction were compared between the two groups. The survival curve was drawn by Kaplan-Meier, and the prognosis was compared.Results:The overall response rate clinical in the experimental group was higher than that in the control group: 64.15%(34/53) vs.44.23%(23/52), there was a statistical difference ( χ2 = 4.20, P<0.05). After treatment, the levels of serum glycoantigen (CA) 125, CA153, human epithelial protein 4 (HE4), and vascular endothelial growth factor (VEGF) in the experimental group were lower than those in the control group: (42.35 ± 6.85) kU/L vs. (46.64 ± 7.11) kU/L, (24.26 ± 4.58) kU/L vs. (26.74 ± 5.20) kU/L, (144.25 ± 19.85) pmol/L vs. (155.64 ± 21.26) pmol/L, (335.32 ± 38.41) μg/L vs. (359.47 ± 41.24) μg/L; the FACT-O scores in the experimental group was higher than that in the control group: (55.24 ± 6.85)scores vs. (51.26 ± 7.19) scores; the CFS scores in the experimental group was lower than that in the control group: (38.51 ± 6.11) scores vs. (44.94 ± 8.38) scores, there were statistical differences ( P<0.05).After treatment, the rate of dizziness, nausea, leukopenia, neutropenia, thrombocytopenia, and anemia in the experimental group were lower than those in the control group ( P<0.05). The results of the survival curve showed that the median progression-free survival in the experimental group was longer than that in the control group ( P<0.05). Conclusions:Single-agent olaparib is effective in treating platinum-sensitive recurrent BRCA-mutated ovarian cancer, and can improve quality of life, reduce anemia and adverse reaction, and prolong patients′ median survival.

BACKGROUND:Polycystic ovary syndrome is a common reproductive endocrine disease leading to infertility in women of reproductive age.Currently,there is no effective treatment.Human umbilical cord mesenchymal stem cells may help to repair ovarian function,but few studies have reported their role in the treatment of polycystic ovary syndrome.OBJECTIVE:To explore the effect and mechanism of human umbilical cord mesenchymal stem cells in the treatment of polycystic ovary syndrome.METHODS:3-week-old female ICR mice were divided into three groups(n=15).Normal control group was not treated.Model group was given letrozole for 21 days to induce polycystic ovary syndrome.Treatment group was given letrozole via intragastric administration for 21 consecutive days,and human umbilical cord mesenchymal stem cell suspension was injected through the tail vein.The body weight of mice was monitored before treatment,7 and 14 days after treatment.The estrous cycle of mice was detected by continuous vaginal smears for 10 consecutive days after treatment.Fourteen days after treatment,peripheral blood sex hormone levels of mice were detected by ELISA.Hematoxylin-eosin staining was used to observe ovarian morphological changes.Immunofluorescence and immunohistochemistry were used to detect the expression of Rab27A protein in ovarian tissues.RESULTS AND CONCLUSION:(1)Compared with the normal control group,the estrous cycle of mice in the model group was disturbed;body weight was significantly increased;follicle stimulating hormone was decreased;luteinizing hormone and testesterone were both increased;more follicles were found in the ovaries,and the relative expression level of Rab27A protein was decreased.(2)Compared with the model group,the treatment group had diminished body weight,increased follicle stimulating hormone,decreased luteinizing hormone and testesterone,decreased follicles with polycystic dilatation,and increased Rab27A protein relative expression level.(3)These findings suggest that human umbilical cord mesenchymal stem cells improve serum sex hormone levels and ovarian function in polycystic ovary syndrome mice by upregulating the expression of Rab27A.

Objective:The aim of this study is to analyze the clinical characteristics and genetic variants of a late-onset auditory neuropathy pedigree caused by maternally inherited- mitochondrial mutation.Methods:A male proband who presented with bilateral sensorineural hearing loss at Henan Children′s Hospital in September 2023 was chosen, along with his family members (4 generations, 20 individuals) as the study subjects. Data from this pedigree were collected, organized, and analyzed for clinical genetic characteristics. Medical histories were obtained from family members, pedigree charts were drawn, audiological, imaging, and physical examinations were conducted. Pathogenic genes and mutations were screened using high-throughput sequencing. Sanger sequencing was employed for variant confirmation and segregation validation in the family.Results:In this family, a total of 12 members (10 members collected) had sensorineural hearing loss, characterized by late-onset hearing impairment with an onset age ranging from 9 to 30 years. The patients exhibited poor speech recognition rates, and audiometric examinations are consistent with auditory neuropathy. There was no history of ototoxic drug use. High-throughput sequencing identified the variant NC_012920.1:m.7471dup in the mitochondrial MT-TS1 gene as the pathogenic variant. Sanger sequencing results confirmed that the pathogenic gene mutation site perfectly co-segregated with the auditory neuropathy phenotype in this family. According to the classification criteria and guidelines for genetic variations by the American College of Medical Genetics and Genomics, the variant was classified as a pathogenic mutation. Conclusion:The mitochondrial MT-TS1 gene mutation m.7471dup is considered to be the pathogenic cause in this late-onset auditory neuropathy pedigree.

OBJECTIVE To evaluate the efficacy of sulbactam-durlobactam combined with meropenem in treating carbapenem-resistant Acinetobacter baumannii(CRAB)pulmonary infection.METHODS A total of 16 patients treated at China-Japan Friendship Hospital from Jan.1,2025 to Jun.1,2025 were included.Retrospective analy-sis was conducted on patients'basic situation,preliminary treatment regimens,infection-related diagnoses,etiolo-gy and clinical outcomes.Therapeutic drug monitoring(TDM)for sulbactam was also performed.RESULTS By the end of the treatment course,13 patients achieved etiological eradication of CRAB and clinical improvement,while 1 patient experienced CRAB recurrence within one month.Three patients showed treatment failure.TDM for sulbactam was performed in 13 patients.Except for one slightly lower,all achieved trough plasma concentra-tions above the minimum inhibitory concentration(MIC)(100％T＞MIC,MIC=4 mg/L based on clinical breakpoints).Dosage adjustments based on plasma concentrations were made for 4 patients,with 3 receiving re-duced doses and 1 receiving an increased dose.CONCLUSIONS Sulbactam-durlobactam combined with meropenem demonstrates superior efficacy in treating CRAB compared to other regimens.Under the recommended dosage,all patients can achieve the PK/PD target for sulbactam.

Objective:To explore the clinical efficacy of olapalib in the treatment of platinum-sensitive recurrent breast cancer susceptibility gene (BRCA)-mutated ovarian cancer.Methods:The clinical data of 105 patients with platinum-sensitive recurrent BRCA-mutated ovarian cancer confirmed by pathology/imaging from October 2020 to March 2023 in Baoding Second Central Hospital were selected retrospectively, and they were divided into the control group (52 cases) and the experimental group (53 cases) according to the treatment methods. The control group was treated with a platinum-containing regimen, followed by olaparib at the end of the treatment. The experimental group was treated with olaparib. The recent clinical outcomes, tumour marker levels, ovarian cancer functional assessment of treatment questionnaire (FACT-O) score, cancer fatigue scale (CFS) score, and adverse reaction were compared between the two groups. The survival curve was drawn by Kaplan-Meier, and the prognosis was compared.Results:The overall response rate clinical in the experimental group was higher than that in the control group: 64.15%(34/53) vs.44.23%(23/52), there was a statistical difference ( χ2 = 4.20, P<0.05). After treatment, the levels of serum glycoantigen (CA) 125, CA153, human epithelial protein 4 (HE4), and vascular endothelial growth factor (VEGF) in the experimental group were lower than those in the control group: (42.35 ± 6.85) kU/L vs. (46.64 ± 7.11) kU/L, (24.26 ± 4.58) kU/L vs. (26.74 ± 5.20) kU/L, (144.25 ± 19.85) pmol/L vs. (155.64 ± 21.26) pmol/L, (335.32 ± 38.41) μg/L vs. (359.47 ± 41.24) μg/L; the FACT-O scores in the experimental group was higher than that in the control group: (55.24 ± 6.85)scores vs. (51.26 ± 7.19) scores; the CFS scores in the experimental group was lower than that in the control group: (38.51 ± 6.11) scores vs. (44.94 ± 8.38) scores, there were statistical differences ( P<0.05).After treatment, the rate of dizziness, nausea, leukopenia, neutropenia, thrombocytopenia, and anemia in the experimental group were lower than those in the control group ( P<0.05). The results of the survival curve showed that the median progression-free survival in the experimental group was longer than that in the control group ( P<0.05). Conclusions:Single-agent olaparib is effective in treating platinum-sensitive recurrent BRCA-mutated ovarian cancer, and can improve quality of life, reduce anemia and adverse reaction, and prolong patients′ median survival.

BACKGROUND:Polycystic ovary syndrome is a common reproductive endocrine disease leading to infertility in women of reproductive age.Currently,there is no effective treatment.Human umbilical cord mesenchymal stem cells may help to repair ovarian function,but few studies have reported their role in the treatment of polycystic ovary syndrome.OBJECTIVE:To explore the effect and mechanism of human umbilical cord mesenchymal stem cells in the treatment of polycystic ovary syndrome.METHODS:3-week-old female ICR mice were divided into three groups(n=15).Normal control group was not treated.Model group was given letrozole for 21 days to induce polycystic ovary syndrome.Treatment group was given letrozole via intragastric administration for 21 consecutive days,and human umbilical cord mesenchymal stem cell suspension was injected through the tail vein.The body weight of mice was monitored before treatment,7 and 14 days after treatment.The estrous cycle of mice was detected by continuous vaginal smears for 10 consecutive days after treatment.Fourteen days after treatment,peripheral blood sex hormone levels of mice were detected by ELISA.Hematoxylin-eosin staining was used to observe ovarian morphological changes.Immunofluorescence and immunohistochemistry were used to detect the expression of Rab27A protein in ovarian tissues.RESULTS AND CONCLUSION:(1)Compared with the normal control group,the estrous cycle of mice in the model group was disturbed;body weight was significantly increased;follicle stimulating hormone was decreased;luteinizing hormone and testesterone were both increased;more follicles were found in the ovaries,and the relative expression level of Rab27A protein was decreased.(2)Compared with the model group,the treatment group had diminished body weight,increased follicle stimulating hormone,decreased luteinizing hormone and testesterone,decreased follicles with polycystic dilatation,and increased Rab27A protein relative expression level.(3)These findings suggest that human umbilical cord mesenchymal stem cells improve serum sex hormone levels and ovarian function in polycystic ovary syndrome mice by upregulating the expression of Rab27A.