Objective: This study aimed to systematically evaluate potential causal relationships between nine cathepsins and female infertility using Mendelian randomization (MR) methods. Methods: A bidirectional MR analysis was conducted utilizing single nucleotide polymorphisms as instrumental variables to investigate the potential causal effects between nine cathepsins and female infertility. Genetic data on female infertility were sourced from the FinnGen study, and cathepsin-related data were obtained from genome-wide association studies datasets of European ancestry. Results: Elevated levels of cathepsin E were significantly and inversely associated with the risk of female infertility, suggesting a potential protective role. This finding was further supported by multivariable MR analysis. However, no significant associations were observed between the other eight cathepsins and female infertility. Conclusion This study represents the first systematic MR analysis to identify a potential protective effect of cathepsin E on female infertility.

Objective: This study aimed to systematically evaluate potential causal relationships between nine cathepsins and female infertility using Mendelian randomization (MR) methods. Methods: A bidirectional MR analysis was conducted utilizing single nucleotide polymorphisms as instrumental variables to investigate the potential causal effects between nine cathepsins and female infertility. Genetic data on female infertility were sourced from the FinnGen study, and cathepsin-related data were obtained from genome-wide association studies datasets of European ancestry. Results: Elevated levels of cathepsin E were significantly and inversely associated with the risk of female infertility, suggesting a potential protective role. This finding was further supported by multivariable MR analysis. However, no significant associations were observed between the other eight cathepsins and female infertility. Conclusion This study represents the first systematic MR analysis to identify a potential protective effect of cathepsin E on female infertility.

Objective: This study aimed to systematically evaluate potential causal relationships between nine cathepsins and female infertility using Mendelian randomization (MR) methods. Methods: A bidirectional MR analysis was conducted utilizing single nucleotide polymorphisms as instrumental variables to investigate the potential causal effects between nine cathepsins and female infertility. Genetic data on female infertility were sourced from the FinnGen study, and cathepsin-related data were obtained from genome-wide association studies datasets of European ancestry. Results: Elevated levels of cathepsin E were significantly and inversely associated with the risk of female infertility, suggesting a potential protective role. This finding was further supported by multivariable MR analysis. However, no significant associations were observed between the other eight cathepsins and female infertility. Conclusion This study represents the first systematic MR analysis to identify a potential protective effect of cathepsin E on female infertility.

Objective: This study aimed to systematically evaluate potential causal relationships between nine cathepsins and female infertility using Mendelian randomization (MR) methods. Methods: A bidirectional MR analysis was conducted utilizing single nucleotide polymorphisms as instrumental variables to investigate the potential causal effects between nine cathepsins and female infertility. Genetic data on female infertility were sourced from the FinnGen study, and cathepsin-related data were obtained from genome-wide association studies datasets of European ancestry. Results: Elevated levels of cathepsin E were significantly and inversely associated with the risk of female infertility, suggesting a potential protective role. This finding was further supported by multivariable MR analysis. However, no significant associations were observed between the other eight cathepsins and female infertility. Conclusion This study represents the first systematic MR analysis to identify a potential protective effect of cathepsin E on female infertility.

Objective: This study aimed to systematically evaluate potential causal relationships between nine cathepsins and female infertility using Mendelian randomization (MR) methods. Methods: A bidirectional MR analysis was conducted utilizing single nucleotide polymorphisms as instrumental variables to investigate the potential causal effects between nine cathepsins and female infertility. Genetic data on female infertility were sourced from the FinnGen study, and cathepsin-related data were obtained from genome-wide association studies datasets of European ancestry. Results: Elevated levels of cathepsin E were significantly and inversely associated with the risk of female infertility, suggesting a potential protective role. This finding was further supported by multivariable MR analysis. However, no significant associations were observed between the other eight cathepsins and female infertility. Conclusion This study represents the first systematic MR analysis to identify a potential protective effect of cathepsin E on female infertility.

Purpose To explore the pathological features of angioimmunoblastic T-cell lymphoma(AITL)with bone marrow involvement and to improve awareness of bone marrow infiltration in AITL.Methods The tissue morphology of 32 cases of AITL with bone marrow involvement was retrospectively analyzed.Im-munohistochemistry using the EnVision method and ten-color flow cytometry were conducted to detect AITL-related immune markers.T cell clonality was analyzed through T cell receptor(TCR)gene rearrangement.Results The predominant pat-terns of tumor cell infiltration were nodular(20/32,62.5％)and interstitial or small clusters(10/32,31.3％).The nodules showed a mixture of cellular components.In some cases,the fo-ci contained a mixture of cells with characteristic"granuloma-toid"changes.The tumor cells were mainly small to medium-sized lymphocytes with inconspicuous atypia.Some cases showed plasma cell proliferation.19 cases were subject to immunohisto-chemical staining,which revealed a low count of CD4-positive T cells,with an average of 8.4％.The positive rates of T follic-ular helper cells(TFH)markers were as follows:CD10(7/14,50.0％),BCL6(6/19,31.6％),PD-1(13/19,68.4％),and CXCL13(13/19,68.4％).In most cases,tumor cells showed co-expression of PD-1 and CXCL13,but the number of positive cells was less than 1％.Flow cytometry analysis was performed in 24 cases,among which 22 cases all consistently expressed cytoplasmic CD3(cCD3),CD5,CD4,and CD2,with varying degrees of CD10 expression.In some cases,there was a lack of expression of surface CD3(sCD3)(12/22,54.5％),while there was a lack of expression of CD7(8/22,36.4％).and no abnormal T cells were found in 2 cases.TCR gene rearrangement analysis was performed in 7 cases,with 3 cases showing TCR clonality.Conclusion AITL with bone marrow involvement exhibits a lower proportion of tumor cells and less atypia,making it prone to misdiagnosis.The presence of lymphocytic foci with mixed cellular components in the bone marrow can indicate bone marrow involvement in AITL.Flow cy-tometry detection of abnormal T cells(double positive for CD4 and CD10)strongly suggests bone marrow infiltration in AITL.A comprehensive diagnosis of bone marrow involvement in AITL re-quires consideration of bone marrow biopsy,flow cytometry,and TCR gene rearrangement analysis.

Objective:To further investigate the safety and efficacy of Belimumab in the treatment of patients with systemic lupus erythematosus (SLE).Methods:All SLE patients treated with Belimumab from May 1, 2020 to February 1, 2022 in Peking Union Medical College Hospital were retrospectively collected and analyzed. The clinical manifestations, the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2000) score, and laboratory test such as levels of anti-dsDNA antibody, the medication before and after Belimumab treatment, adverse events were collected. Normally distributed data were tested using the t-test, otherwise the Wilcoxon paired signed rank test was used. Results:A total of 81 patients were enrolled in this study. The use of belimumab could significantly decrease the SLEDAI-2000 score [10.00(7.75, 12.00) vs. 4.00(3.75, 6.00), Z=-5.38, P<0.001], ESR of SLE patients [19.50(12.75, 32.25) mm/1 h vs. 14.00(7.75, 20.25) mm/1 h, Z=-3.71, P=0.003], anti-dsDNA titer detected by CLIFT [300.00 (117.00, 864.00) vs. 183.00(100.00, 471.00), Z=-4.15, P=0.001], meanwhile, increase the complement C3 [0.78 (0.62, 0.97)g/L vs. 0.69 (0.55, 0.84)g/L, Z=-4.68, P<0.001], and the complement C4 [0.12 (0.08, 0.19)g/L vs. 0.10 (0.05, 0.14)g/L, Z=-4.78, P<0.001]. We also observed that with the use of Belimumab, the dosage of Glucocorticoids decreased significantly, which were [10.00(7.50, 22.50) mg vs. 7.50(5.00, 10.00) mg, Z=-4.90, P<0.001]. In addition, the antibody of IgG, IgA and IgM decreased significantly. Only one patient stopped the administration of Belimumab due to the low level of immunoglobulin. Conclusion:Belimumab can alleviate disease activity of patients with SLE and help in safely tapering the daily dose of glucocorticoid with good safety.

Objective:To investigate urinary pH distribution and its influencing factors in gout patients, to provide insights for individualized treatment.Methods:This is a retrospective study. The gout patients in the Gout Outpatient Department of the Affiliated Hospital of Qingdao University from September 2019 to August 2021 were collected. Clinical data were collected and relevant indicators were measured. The patients were divided into different groups according to urinary pH. Clinical characteristics and factors related to urinary pH were compared among the groups. SPSS 23.0 software was used.Results:A total of 2 553 patients were enrolled. There were significant statistical differences in age, body mass index, triglyceride, alanine aminotransferase(ALT), blood urea nitrogen, serum creatinine, estimated glomerular filtration rate(eGFR), blood uric acid, urinary uric acid/creatinine ratio, fraction excretion of uric acid(FEUA) among groups with different urinary pH( F were 5.114, 4.772, 7.170, 4.721, 13.603, 2.812, 3.422, 22.834, 18.230, 26.332, all P<0.05). Urinary uric acid and FEUA in acute group were higher than those in remission group( Z were -2.295, -3.528, both P<0.05). After adjusting for gender, age, eGFR, logistics regression analysis showed that body mass index, triglyceride, total cholesterol, ALT, blood uric acid, and blood urea nitrogen were still risk factors. Multivariate logistic regression analysis showed that triglyceride, blood uric acid, and blood urea nitrogen were independent risk factors associated with acid urine. Linear correlation analysis showed that urinary pH was negatively correlated with body mass index, triglyceride, total cholesterol, blood uric acid, fasting glucose, blood urea nitrogen, ALT( r were -0.079, -0.106, -0.051, -0.186, -0.040, -0.122, -0.051, all P<0.05), but positively correlated with eGFR( r=0.058, P=0.003). Conclusion:The overall urine pH levels in patients with primary gout are below normal reference. Several metabolic components are related to it. Triglyceride, blood uric acid, and blood urea nitrogen are independent risk factors of acidic urine. In clinical practice, attention should be paid to timely alkalization of urine to prevent complications.

Objective:To investigate the relationship between intra-abdominal pressure (IAP) and respiratory function in mechanically ventilated children with severe pneumonia and its prognostic value.Methods:A case-series study.Ninety-two children with severe pneumonia who were treated with mechanical ventilation in the Intensive Care Unit of Children′s Hospital Affiliated to Zhengzhou University from May 2019 to May 2021 were taken as the study subjects.The IAP and respiratory function-related indexes of the children were monitored.Those with IAP ≥12 mmHg(1 mmHg=0.133 kPa) were divided into the study group, and those with IAP <12 mmHg were divided into the control group.The difference in respiratory function related indexes between the 2 groups was compared, and the relationship between IAP and respiratory function indexes was analyzed by Pearson correlation.The children were divided into a good prognosis group and a poor prognosis group according to their prognosis.The relevant clinical data of the children in the 2 groups were collected for univariate analysis, and multivariate Logistic regression was used to analyze the risk factors affecting the prognosis of children with mechanical ventilation for severe pneumonia.A receiver operating characteristic (ROC) curve was drawn to analyze the predictive value of IAP on the prognosis of mechanically ventilated children with severe pneumonia.Results:The arterial partial pressure of oxygen (PaO 2) [(80.15±8.23) mmHg], arterial blood oxygen saturation (SaO 2) [(91.32±2.13)%], and oxygenation index (PaO 2/FiO 2) [(198.29±20.25) mmHg] in the study group were lower than those in the control group [(85.74±8.42) mmHg, (97.05±2.47)%, and (234.84±25.24) mmHg], while the respiratory rate (RR) [(56.23±2.16) breaths/min vs. (50.41±2.24) breaths/min], partial pressure of carbon dioxide (PaCO 2) [(36.48±3.72) mmHg vs.(33.29±3.46) mmHg], fraction of inspired oxygen (FiO 2) [(40.42±4.25)% vs.(36.51±3.72)%], mean arterial pressure (MAP) [(55.98±5.69) mmHg vs.(52.79±5.43) mmHg], and positive end expiratory pressure (PEEP) [(5.03±0.52) cmH 2O vs.(4.52±0.47) cmH 2O, 1 cmH 2O=0.098 kPa] were higher than those in the control group, and the differences were all statistically significant (all P<0.05).The IAP of the children in the study group was (14.25±1.83) mmHg, and that in the control group was (10.38±1.14) mmHg.Pearson correlation analysis showed that IAP was negatively correlated with PaO 2, SaO 2, and PaO 2/FiO 2 ( r=-0.615, -0.587, and -0.647, all P<0.05), and was positively correlated with RR, PaCO 2, FiO 2, MAP, and PEEP ( r=0.618, 0.634, 0.579, 0.578, 0.593, all P<0.05).IAP [(14.76±1.58) mmHg], PaCO 2 [(39.95±4.21) mmHg], FiO 2 [(50.29±5.12)%], alanine aminotransferase[(42.08±4.15) U/L], and total bilirubin [(17.92±1.87) μmol/L] in the poor prognosis group were greater than those [(10.75±1.19) mmHg, (35.37±3.64) mmHg, (45.38±4.47)%, (39.87±4.06) U/L, and (17.09±1.75) μmol/L] in the good prognosis group, while PaO 2 [(65.42±7.86) mmHg vs.(76.42±7.51) mmHg], SaO 2 [(90.65±9.26)% vs.(96.21±2.19)%], and PaO 2/FiO 2 [(130.09±15.15) mmHg vs.(168.40±20.17) mmHg] were smaller than those in the good prognosis group, and the differences were statistically significant (all P<0.05).Logistic regression analysis showed that IAP, PaO 2, PaCO 2, and SaO 2 were risk factors affecting the prognosis of mechanically ventilated children with severe pneumonia (all P<0.05).The optimal cut-off point of IAP for predicting a poor prognosis in mechanically ventilated children with severe pneumonia was 14.55 mmHg, and the area under the ROC curve was 0.873, with a sensitivity of 88.10% and a specificity of 76.00%. Conclusions:IAP has a certain relationship with the respiratory function of mechanically ventilated children with severe pneumonia, and has a good predictive value for the prognosis of the children.

Objective:To observe the clinical effect of anal fistula incision, muscle layer suture, and internal drainage surgery in the treatment of low anal fistula.Methods:A retrospective study was conducted on 65 patients with low anal fistula admitted to Fifth Hospital of Zhangjiakou City From March 2021 to March 2023, and they were divided into two groups based on different surgical methods. The control group consisted of 32 patients who underwent traditional anal fistula incision and thread drainage, while the study group consisted of 33 patients who underwent anal fistula incision and muscle layer suture internal drainage. The duration of surgery, wound recovery, anal function, anal motility, degree of pain, and recurrence rate were compared.Results:The surgical time of the study group was longer than that of the control group: (34.86 ± 4.17) min vs. (25.21 ± 3.95) min ( P<0.05), the wound healing time was shorter than that of the control group: (15.72 ± 3.26) d vs. (18.94 ± 4.42) d ( P<0.05), and the wound area was smaller than that of the control group: (5.76 ± 1.72) cm 2 vs. (7.78 ± 1.89) cm 2 ( P<0.05). At 4 weeks after surgery, the Wexner scores in both groups were lower than those at 1 d after surgery ( P<0.05), and the study group was lower than the control group: (3.39 ± 1.08) scores vs. (4.15 ± 1.21) scores ( P<0.05). After surgery, the high pressure zone length, anal rest pressure and anal maximum contraction pressure in the control group were lower than before surgery ( P<0.05), and the study group were higher than the control group: (4.92 ± 1.11) cm vs. (3.64 ± 1.02) cm, (11.93 ± 1.22) kPa vs. (9.45 ± 1.08) kPa, (13.34 ± 3.42) kPa vs. (10.82 ± 2.75) kPa ( P<0.05). At 48 h after surgery, the visual analogue scale (VAS) scores of both groups were lower than those at 12 h after surgery ( P<0.05), and the study group was lower than the control group: (1.63 ± 0.21) scores vs. (2.25 ± 0.34) scores ( P<0.05). After 6 months of follow-up, neither group experienced any recurrence. Conclusions:Anal fistula incision, muscle layer suture and internal drainage surgery for low anal fistula can shorten the wound healing time, reduce the wound area, improve anal function and anal motility, alleviate pain, and avoid recurrence. However, the surgical time is longer.