OBJECTIVES: To compare the anti-inflammatory, antibacterial and analgesic effects of Yinqiao Powder (YQS) formulated granules and decoction. METHODS: We first evaluated the anti-inflammatory effects of the two dosage forms of YQS in a LPS-induced RAW 264.7 cell model using RT-qPCR and Western blotting. We further constructed zebrafish models of inflammation by copper sulfate exposure, caudal fin transection, or LPS and Poly (I:C) microinjection, and evaluated anti-inflammatory effects of YQS granules and decoction by examining neutrophil aggregation and HE staining findings. In a mouse model of acute lung injury (ALI) induced by intratracheal LPS instillation, the effects of YQS gavage at 10, 15, and 20 g/kg on lung pathologies were evaluated by calculating lung wet-dry weight ratio and using HE staining, ELISA and Western blotting. The microbroth dilution method was used to evaluate the antibacterial effect of YQS. Mouse pain models established by hot plate and intraperitoneal injection of glacial acetic acid were used to evaluate the analgesic effects of YQS at 10, 15, and 20 g/kg. RESULTS: Both YQS granules and decoction significantly reduced TNF-α, IL-6, and IL-1β expressions and p-STAT3 (Tyr 705) phosphorylation level in LPS-induced RAW 264.7 cells, and obviously inhibited neutrophil aggregation in the zebrafish models. In ALI mice, YQS granules and decoction effectively ameliorated lung injury, lowered lung wet-dry weight ratio, and reduced p-STAT3 (Tyr 705) expression and TNF-α and IL-6 levels. YQS produced obvious antibacterial effect at the doses of 15.63 and 31.25 mg/mL, and significantly reduced body torsion and increased pain threshold in the mouse pain models. CONCLUSIONS The two dosage forms of TQS have similar anti-inflammatory, antibacterial and analgesic effects with only differences in their inhibitory effect on TNF-α, IL-6 and IL-1β mRNA expressions in LPS-induced RAW 264.7 cells.
Animals ; Mice ; Drugs, Chinese Herbal/pharmacology* ; Anti-Inflammatory Agents/pharmacology* ; Analgesics/pharmacology* ; RAW 264.7 Cells ; Zebrafish ; Anti-Bacterial Agents/pharmacology* ; Powders ; Tumor Necrosis Factor-alpha/metabolism* ; Acute Lung Injury/drug therapy* ; Interleukin-6/metabolism* ; Lipopolysaccharides

BACKGROUND:Previous studies have indicated that cathepsin K can intervene with the occurrence and development of osteoporosis by regulating bone mineral density in middle-aged and older adults. However,whether there is a causal relationship between the cathepsin family and bone mineral density in other populations remains unknown. OBJECTIVE:To investigate the causal relationship between cathepsin and bone mineral density.METHODS:Genetic loci associated with eight cathepins were extracted from the IEU Open GWAS database as instrumental variables,and bone mineral density values in five age groups acted as an outcome. The causal relationship between cathepin and bone mineral density was assessed by two-way Mendelian randomization analysis. Heterogeneity of the genetic instrumental variables was assessed using Cochran's Q test,pleiotropy was assessed using the MR-Egger intercept test,and the sensitivity of single nucleotide polymorphisms used as instrumental variables to the causal effect of exposure and outcome was assessed using the leave-one-out method. RESULTS AND CONCLUSION:The results of the inverse variance weighting method with positive Mendelian randomization showed that cathepin H was negatively associated with bone mineral density in people aged 45-60 years[odds ratio (95％ confidence interval)=0.965(0.94-0.99),P=0.04];cathepin Z was negatively associated with bone mineral density in people aged 30-45 year[odds ratio (95％ confidence interval)=1.06 (1.00-1.11),P=0.03]. The results of sensitivity analysis showed a stable causal relationship,and MR-Egger intercept analysis did not detect potential horizontal pleiotropy. The inverse Mendelian randomization results showed that bone mineral density had no significant inverse effect on cathepin. The above results confirm that cathepin can affect bone mineral density in some age groups,which may increase the risk of osteoporosis and should be given more attention.

Objective:To compare the mydriatic effects of a combination of 1% tropicamide and 2.5% phenylephrine with a 0.5% tropicamide and 0.5% phenylephrine combination in patients with type 2 diabetes.Methods:A randomized, double-blind, controlled trial was conducted.Ninety Chinese patients (90 eyes) with dark irises and type 2 diabetes who needed mydriasis examination at the Fundus Disease Clinic of Tianjin Medical University Eye Hospital from June to September 2024 were included.The subjects were divided into control group (30 patients 30 eyes), high concentration group (30 patients 30 eyes) and half-dilution group (30 patients 30 eyes) using the random number table method, which received 2 drops of a mixture of 0.5% tropicamide and 0.5% phenylephrine, 2 drops of a mixture of 1% tropicamide and 2.5% phenylephrine, 1 drop of a mixture of 1% tropicamide and 2.5% phenylephrine+ 1 drop of saline respectively.The pupil diameter of the patients was measured with a pupillometer 40 minutes before and after instillation.The study adhered to the Declaration of Helsinki and the study protocol was approved by the Ethics Committee of Tianjin Medical University Eye Hospital (No.2024KY-16).Written informed consent was obtained from all participants.Results:The proportions of patients whose pupil diameters reached 7 mm 40 minutes after the initial administration in the control group, high-concentration group, and half-dilution group were 56.7%(17/30), 86.7%(26/30) and 66.7%(20/30), respectively, with a statistically significant overall difference ( χ2=6.667, P=0.036).The proportion of patients in the high-concentration group whose pupil diameter reached 7 mm 40 minutes after the initial administration was higher than that in the control group, and the difference was statistically significant ( P<0.05).The pupil diameters 40 minutes after the initial administration in the control group, the high-concentration group and the half-dilution group were (7.01±0.86), (7.64±0.61) and (7.49±1.15)mm, respectively, with a statistically significant overall difference ( F=4.019, P=0.021), and the pupil diameter of the high-concentration group was significantly higher than that of the control group ( P=0.024).Changes in pupil diameter 40 minutes after the initial administration in the control group, high-concentration group and half-dilution group were (3.23±0.81), (3.82±0.60) and (3.62±0.75)mm, respectively, with a statistically significant overall difference ( F=5.121, P=0.008), and the change in pupil diameter in the high-concentration group was higher than that in the control group ( P=0.007). Conclusions:The combination of 1% tropicamide and 2.5% phenylephrine has better pupil dilation than the combination of 0.5% tropicamide and 0.5% phenylephrine.It is recommended that pupil dilation be performed with a high-concentration mydriatic drug prior to outpatient fundus examination for diabetic patients.

Objective To investigate the prevalence of hyperuricemia among ethnic groups in Gongshan county,Yunnan province through a cross-sectional study.Methods A total of 229 residents aged ≥ 18 years from Dulong,Nu,Tibetan,Bai and Lisu ethnic groups were randomly selected in Gongshan County of Yunnan Province for questionnaire survey,physical examinations and laboratory tests.SPSS 22.0 was used for t test,Chi-square test,correlation analysis,and multivariate logistic regression analysis.Results A total of 107 cases of hyperuricemia were identified,with a detection rate of 46.7％,among which the prevalence was 43.9％in males,52.63％in female,48％in the Dulong,51％in the Lisu,47％in the Nu,37.5％in the Bai,52％in the Tibetan and 50％in the Han.There were no statistically significant differences in prevalence among all nationalities(P＞0.05).The proportion of individuals with a history of diabetes,as well as levels of urea nitrogen and serum creatinine,were significantly higher in the hyperuricemia group compared to the non-hyperuricemia group(P＜0.05).Correlation analysis showed a positive correlation between hyperuricemia and diabetes,urea nitrogen and serum creatinine.(P＜0.05).Multivariate regression analysis showed that diabetes and elevated serum creatinine were independent risk factors for the onset of hyperuricemia(P＜0.05).Conclusion The detection rate of hyperuricemia is relatively high in Gongshan County,Yunnan Province,and there is no significant differences in prevalence among ethnic groups.Diabetes and elevated serum creatinine are associated with hyperuricemia,which increase the risk of developing hyperuricemia.

Objective:To investigate the short-term efficacy and safety of rituximab (RTX) in children with calcineurin inhibitor (CNI) resistant steroid resistant nephrotic syndrome (SRNS).Methods:A retrospective case analysis was conducted. Thirteen children with CNI resistant SRNS who were regularly treated with RTX (375 mg/m 2 per dose (maximum dose 500 mg), 1 dose per week, a total of 4 doses) in Department of Nephrology, Children′s Hospital of Fudan University from January 2016 to December 2023 were enrolled. The general data, disease related information, urinary protein/creatinine, serum albumin, blood creatinine before RTX treatment, immunosuppressants, adverse events, and monthly urinary protein/creatinine, serum albumin, and blood creatinine indexes within 6 months after RTX treatment were collected. The changes of urinary protein/creatinine, serum albumin and estimated glomerular filtration rate (eGFR) before and after RTX at 3 and 6 months were analyzed by using paired sample t test and Wilcoxon signed-rank test. Results:Among the 13 patients, 8 were male and 5 were female. The age of disease onset was 4.0 (2.9, 6.8) years and the age of RTX treatment was 9.8 (5.9, 13.6) years. There were 8 cases of focal segmental glomerulosclerosis, 3 cases of minimal change disease and 2 cases of mesangial proliferative glomerulonephritis. No clinically significant gene variation was detected in 12 cases and the other one did not receive gene test. Before RTX treatment, 11 cases were in chronic kidney disease stage G1, and 1 case each was in stage G2 and stage G3. Ten children completed 4 doses of RTX treatment, 1 patient completed 3 doses, and 2 patients completed 2 doses. Urinary protein/creatinine in 13 children at 3 and 6 months after RTX treatment was significantly lower than baseline (0.60 (0.13, 2.04), 0.49 (0.28, 1.10) vs. 1.44 (0.76, 4.11) mg/mg, Z=-2.34, -2.34, both P<0.05), and serum albumin was significantly higher than baseline ((35±8), (34±7) vs. (30±6) g/L, t=2.30, 2.60, both P<0.05). The eGFR at 6 months after RTX treatment was not significantly different from the baseline ((110±32) vs. (113±35) ml/(min·1.73 m 2), t=-0.76, P>0.05)). No serious adverse reactions occurred in this study. Conclusion:RTX could reduce urinary protein and increase serum albumin in short-term treatment in children with CNI resistant SRNS without significant side effects.

Objective:To compare the mydriatic effects of a combination of 1% tropicamide and 2.5% phenylephrine with a 0.5% tropicamide and 0.5% phenylephrine combination in patients with type 2 diabetes.Methods:A randomized, double-blind, controlled trial was conducted.Ninety Chinese patients (90 eyes) with dark irises and type 2 diabetes who needed mydriasis examination at the Fundus Disease Clinic of Tianjin Medical University Eye Hospital from June to September 2024 were included.The subjects were divided into control group (30 patients 30 eyes), high concentration group (30 patients 30 eyes) and half-dilution group (30 patients 30 eyes) using the random number table method, which received 2 drops of a mixture of 0.5% tropicamide and 0.5% phenylephrine, 2 drops of a mixture of 1% tropicamide and 2.5% phenylephrine, 1 drop of a mixture of 1% tropicamide and 2.5% phenylephrine+ 1 drop of saline respectively.The pupil diameter of the patients was measured with a pupillometer 40 minutes before and after instillation.The study adhered to the Declaration of Helsinki and the study protocol was approved by the Ethics Committee of Tianjin Medical University Eye Hospital (No.2024KY-16).Written informed consent was obtained from all participants.Results:The proportions of patients whose pupil diameters reached 7 mm 40 minutes after the initial administration in the control group, high-concentration group, and half-dilution group were 56.7%(17/30), 86.7%(26/30) and 66.7%(20/30), respectively, with a statistically significant overall difference ( χ2=6.667, P=0.036).The proportion of patients in the high-concentration group whose pupil diameter reached 7 mm 40 minutes after the initial administration was higher than that in the control group, and the difference was statistically significant ( P<0.05).The pupil diameters 40 minutes after the initial administration in the control group, the high-concentration group and the half-dilution group were (7.01±0.86), (7.64±0.61) and (7.49±1.15)mm, respectively, with a statistically significant overall difference ( F=4.019, P=0.021), and the pupil diameter of the high-concentration group was significantly higher than that of the control group ( P=0.024).Changes in pupil diameter 40 minutes after the initial administration in the control group, high-concentration group and half-dilution group were (3.23±0.81), (3.82±0.60) and (3.62±0.75)mm, respectively, with a statistically significant overall difference ( F=5.121, P=0.008), and the change in pupil diameter in the high-concentration group was higher than that in the control group ( P=0.007). Conclusions:The combination of 1% tropicamide and 2.5% phenylephrine has better pupil dilation than the combination of 0.5% tropicamide and 0.5% phenylephrine.It is recommended that pupil dilation be performed with a high-concentration mydriatic drug prior to outpatient fundus examination for diabetic patients.

BACKGROUND:Previous studies have indicated that cathepsin K can intervene with the occurrence and development of osteoporosis by regulating bone mineral density in middle-aged and older adults. However,whether there is a causal relationship between the cathepsin family and bone mineral density in other populations remains unknown. OBJECTIVE:To investigate the causal relationship between cathepsin and bone mineral density.METHODS:Genetic loci associated with eight cathepins were extracted from the IEU Open GWAS database as instrumental variables,and bone mineral density values in five age groups acted as an outcome. The causal relationship between cathepin and bone mineral density was assessed by two-way Mendelian randomization analysis. Heterogeneity of the genetic instrumental variables was assessed using Cochran's Q test,pleiotropy was assessed using the MR-Egger intercept test,and the sensitivity of single nucleotide polymorphisms used as instrumental variables to the causal effect of exposure and outcome was assessed using the leave-one-out method. RESULTS AND CONCLUSION:The results of the inverse variance weighting method with positive Mendelian randomization showed that cathepin H was negatively associated with bone mineral density in people aged 45-60 years[odds ratio (95％ confidence interval)=0.965(0.94-0.99),P=0.04];cathepin Z was negatively associated with bone mineral density in people aged 30-45 year[odds ratio (95％ confidence interval)=1.06 (1.00-1.11),P=0.03]. The results of sensitivity analysis showed a stable causal relationship,and MR-Egger intercept analysis did not detect potential horizontal pleiotropy. The inverse Mendelian randomization results showed that bone mineral density had no significant inverse effect on cathepin. The above results confirm that cathepin can affect bone mineral density in some age groups,which may increase the risk of osteoporosis and should be given more attention.

Objective:To investigate the short-term efficacy and safety of rituximab (RTX) in children with calcineurin inhibitor (CNI) resistant steroid resistant nephrotic syndrome (SRNS).Methods:A retrospective case analysis was conducted. Thirteen children with CNI resistant SRNS who were regularly treated with RTX (375 mg/m 2 per dose (maximum dose 500 mg), 1 dose per week, a total of 4 doses) in Department of Nephrology, Children′s Hospital of Fudan University from January 2016 to December 2023 were enrolled. The general data, disease related information, urinary protein/creatinine, serum albumin, blood creatinine before RTX treatment, immunosuppressants, adverse events, and monthly urinary protein/creatinine, serum albumin, and blood creatinine indexes within 6 months after RTX treatment were collected. The changes of urinary protein/creatinine, serum albumin and estimated glomerular filtration rate (eGFR) before and after RTX at 3 and 6 months were analyzed by using paired sample t test and Wilcoxon signed-rank test. Results:Among the 13 patients, 8 were male and 5 were female. The age of disease onset was 4.0 (2.9, 6.8) years and the age of RTX treatment was 9.8 (5.9, 13.6) years. There were 8 cases of focal segmental glomerulosclerosis, 3 cases of minimal change disease and 2 cases of mesangial proliferative glomerulonephritis. No clinically significant gene variation was detected in 12 cases and the other one did not receive gene test. Before RTX treatment, 11 cases were in chronic kidney disease stage G1, and 1 case each was in stage G2 and stage G3. Ten children completed 4 doses of RTX treatment, 1 patient completed 3 doses, and 2 patients completed 2 doses. Urinary protein/creatinine in 13 children at 3 and 6 months after RTX treatment was significantly lower than baseline (0.60 (0.13, 2.04), 0.49 (0.28, 1.10) vs. 1.44 (0.76, 4.11) mg/mg, Z=-2.34, -2.34, both P<0.05), and serum albumin was significantly higher than baseline ((35±8), (34±7) vs. (30±6) g/L, t=2.30, 2.60, both P<0.05). The eGFR at 6 months after RTX treatment was not significantly different from the baseline ((110±32) vs. (113±35) ml/(min·1.73 m 2), t=-0.76, P>0.05)). No serious adverse reactions occurred in this study. Conclusion:RTX could reduce urinary protein and increase serum albumin in short-term treatment in children with CNI resistant SRNS without significant side effects.

Background The benchmark dose (BMD) method calculates the dose associated with a specific change in response based on a specific dose-response relationship. Compared with the traditional no observed adverse effect level (NOAEL) method, the BMD method has many advantages, and the 95% lower confidence limit of benchmark dose lower limit (BMDL) is recommended to replace NOAEL in deriving biological exposure limits. No authority has yet published any health-based guideline for rare earth elements. Objective To evaluate genotoxicity threshold induced by acute exposure to neodymium nitrate in mice using BMD modeling through micronucleus test and comet assay. Methods SPF grade mice (n=90) were randomly divided into nine groups, including seven neodymium nitrate exposure groups, one control group (distilled water), and one positive control group (200 mg·kg⁻¹ ethyl methanesulfonate), 10 mice in each group, half male and half female. The seven dose groups were fed by gavage with different concentrations of neodymium nitrate solution (male: 14, 27, 39, 55, 77, 109, and 219 mg·kg⁻¹; female: 24, 49, 69, 97, 138, 195, and 389 mg·kg⁻¹) twice at an interval of 21 h. Three hours after the last exposure, the animals were neutralized by cervical dislocation. The bone marrow of mice femur was taken to calculate the micronucleus rate of bone marrow cells, and the liver and stomach were taken for comet test. Results The best fitting models for the increase of polychromatophil micronucleus rate in bone marrow of female and male mice induced by neodymium nitrate were the exponential 4 model and the hill model, respectively. The BMD and the BMDL of female mice were calculated to be 31.37 mg·kg⁻¹ and 21.90 mg·kg⁻¹, and those of male mice were calculated to be 58.62 mg·kg⁻¹ and 54.31 mg·kg⁻¹, respectively. The best fitting models for DNA damage induced by neodymium nitrate in female and male mouse hepatocytes were the exponential 5 model and the exponential 4 model, respectively, and the calculated BMD and BMDL were 27.15 mg·kg⁻¹ and 11.99 mg·kg⁻¹ for female mice, and 16.28 mg·kg⁻¹ and 10.47 mg·kg⁻¹ for male mice, respectively. The hill model was the best fitting model for DNA damage of gastric adenocytes in both female and male mice, and the calculated BMD and BMDL were 36.73 mg·kg⁻¹ and 19.92 mg·kg⁻¹ for female mice, and 24.74 mg·kg⁻¹ and 14.08 mg·kg⁻¹ for male mice, respectively. Conclusion Taken the micronucleus rate of bone marrow cells, DNA damage of liver cells and gastric gland cells as the end points of genotoxicity, the BMDL of neodymium nitrate is 10.47 mg·kg⁻¹, which can be used as the threshold of genotoxic effects induced by acute exposure to neodymium nitrate in mice.