Diabetic kidney disease(DKD)with increasing global prevalence lacks effective therapeutic targets to halt or reverse its progression.Therapeutic targets supported by causal genetic evidence are more likely to succeed in randomized clinical trials.In this study,we integrated large-scale plasma proteomics,genetic-driven causal inference,and experimental validation to identify prioritized targets for DKD using the UK Biobank(UKB)and FinnGen cohorts.Among 2844 diabetic patients(528 with DKD),we identified 37 targets significantly associated with incident DKD,supported by both observational and causal evi-dence.Of these,22％(8/37)of the potential targets are currently under investigation for DKD or other diseases.Our prospective study confirmed that higher levels of three prioritized targets-insulin-like growth factor binding protein 4(IGFBP4),family with sequence similarity 3 member C(FAM3C),and prostaglandin D2 synthase(PTGDS)—were associated with a 4.35,3.51,and 3.57-fold increased likeli-hood of developing DKD,respectively.In addition,population-level protein-altering variants(PAVs)analysis and in vitro experiments cross-validated FAM3C and IGFBP4 as potential new target candidates for DKD,through the classic NLR family pyrin domain containing 3(NLRP3)-caspase-1-gasdermin D(GSDMD)apoptotic axis.Our results demonstrate that integrating omics data mining with causal inference may be a promising strategy for prioritizing therapeutic targets.

Objective:To analyze the related factors of biochemical recurrence after laparoscopic radical prostatectomy (LRP).Methods:Clinical data of 312 patients with prostate cancer who received LRP in Hunan Provincial People's Hospital (the First Affiliated Hospital of Hunan Normal University) from September 2020 to September 2023 were retrospectively analyzed. Those patients were followed up for 1 year after surgery. According to whether biochemical recurrence occurred after surgery, the above patients were divided into biochemical recurrence group ( n=61) and non-biochemical recurrence group ( n=251). Compare the clinical data [including age, smoking history, drinking history, history of diabetes, postoperative Gleason score, body mass index (BMI), tumor stage, presence or absence of seminal vesicle invasion, and positive surgical margins] and laboratory indicators [including fasting blood glucose after admission, hemoglobin, prostate volume, prostate mass, and preoperative prostate-specific antigen (PSA)] levels between the two groups of patients. Measurement data with normal distribution were presented as Mean±SD, comparison between the two groups was performed by the independent samples t-test. Categorical data were expressed as case (%), comparison between groups was performed by the χ2 test, multivariate analysis was performed by Logistic regression model. Results:The difference in smoking history between groups was not statistically significant( P>0.05). The proportions of patients with age≥65 years old [85.25% (52/61) vs. 68.13% (171/251)], alcohol drinking history[73.77% (45/61) vs. 68.53% (172/251)], diabetes mellitus[50.82% (31/61) vs. 40.24% (101/251)], Gleason score >7 points[72.13% (44/61) vs. 30.68% (77/251)], BMI≥30 kg/m 2[32.79% (20/61) vs. 14.34% (36/251)], disease stage ≥T2a[67.21% (41/61) vs. 23.11% (58/251)], seminal vesicle invasion[32.79% (20/61) vs. 13.55% (34/251)], and postoperative positive incisal margin[24.59% (15/61) vs. 3.59% (9/251)] in the biochemical recurrence group were higher than those in the non-biochemical recurrence group, and the differences were statistically significant ( χ2=393.22, 34.58, 74.28, 36.70, 725.49, 48.09, 171.37, 30.49, respectively, all P<0.001). The differences in fasting blood glucose [(6.81±0.89) mmol/L vs. (6.63±0.78) mmol/L], prostate volume[37.19±4.23) mL vs. (36.87±4.36) mL], prostate weight[(48.21±5.11) g vs. (47.82±5.13) g], and hemoglobin level[(134.08±15.62) g/L vs. (133.26±16.24) g/L] between both groups of patients were not statistically significant ( t=1.57,0.52,0.53,0.36, P=0.117,0.606,0.594,0.722, respectively). The preoperative prostate-specific antigen (PSA) level was higher in the biochemical recurrence group than that in the non-biochemical recurrence group [(45.13±5.26) μg/L vs. (28.87±3.18) μg/L, t=30.99, P<0.001). Multivariate Logistic regression analysis results indicated that postoperative Gleason score >7 points, preoperative PSA and seminal vesicle invasion were risk factors for postoperative biochemical recurrence in patients undergoing LRP ( OR=5.39, 95% CI:1.57-18.48, P=0.008; OR=4.32, 95% CI:1.32-14.10, P=0.016; OR=12.76, 95% CI:1.47-111.03, P=0.022). Conclusion:Patients with prostate cancer are prone to biochemical recurrence after LRP, which is affected by postoperative Gleason score, preoperative PSA level and seminal vesicle invasion. It is necessary to take targeted measures to prevent biochemical recurrence.

OBJECTIVE To explore the indexes affecting the prognosis of the ICU patients with sepsis,establish the nomogram model for prediction of 28-day mortality rate,and validate it.METHODS On the basis of criteria for diagnosis of sepsis(3.0 version),the related data of the sepsis patients were extracted from Medical Information Mart for Intensive Care-Ⅳ(MIMIC-Ⅳ)database for retrospective study and were randomly divided into the train-ing set and the validation set in a 7∶3 ratio.Univariate analysis and multivariate Cox proportional risk regression analysis were performed for the screening of influencing factors for prediction of 28-day mortality of the sepsis pa-tients.The nomogram prediction model was established based on the screened factors and was validated by the val-idation set,and the effect was evaluated.RESULTS A total of 7 955 sepsis patients were included.Seven variables were selected to establish the nomogram model for prediction of the 28-day mortality rate.The nomogram showed favorable performance in identification between the two cohorts,the area under receiver operating characteristic curves(AUROCs)were 0.748 and 0.721,respectively.Calibration curves and Hosmer-Lemeshow test(x2=8.689,10.614;P=0.369,0.225)indicated that the model had remarkable effect on correction.With the per-formance of decision curve analysis(DCA)and clinical impact curve(CIC),the model was considered to have high clinical application value.CONCLUSIONS The nomogram model shows favorable performance in prediction of the 28-day mortality rate and calibration capability.It is worthy to be further promoted and applied.

Objective:To evaluate the safety, feasibility, and technical advantages of the domestic Jingfeng single-port robotic surgical system in transoral and transaxillary approach surgeries for multisite diseases. Methods:A retrospective analysis was conducted on the clinical data of 6 patients who underwent Jingfeng SP1000 single-port robotic-assisted surgery at our hospital from June 2025 to July 2025. They were divided into the transoral robotic surgery group（4cases） and the transaxillary approach thyroid cancer radical resection group（2cases） based on surgical approaches. The transoral robotic surgery group included extended resection of right tonsillar cancer with cervical lymph node dissection, epiglottic cyst resection, extended resection of right pyriform sinus cancer with cervical lymph node dissection, and surgery for epiglottic cyst and obstructive sleep apnea（OSA）. For each case, parameters including operative time, intraoperative blood loss, perioperative complications, robotic operation performance, and postoperative recovery were recorded. Results:All 6 surgeries were successfully completed without conversion to open surgery or system failure. In the transoral robotic surgery group, the mean robotic operation time was（60.00±34.88） minutes, and the mean intraoperative blood loss was 20.00（5.75，20.00）mL. In the transaxillary robotic surgery group, the robotic operation time was respectively 60.00 and 40.00 minutes, and the intraoperative blood loss was 10.00 and 5.00 mL, respectively. One case of minor perioperative complication（in the flap dissection area） occurred, with no severe complications reported. All patients recovered smoothly after surgery, with a median follow-up of 1.9 months showing no residual lesions, recurrence, or functional impairment. Conclusion:This case series confirms the safety and feasibility of the domestic Jingfeng single-port robot in transoral and axillary approach surgeries in oropharyngeal-head and neck surgery. Its single-port design reduces trauma and the risk of robotic arm collision, adapts to minimally invasive needs, and its domestic production attribute lowers costs to facilitate popularization, providing a new option for such patients.
Humans ; Robotic Surgical Procedures/methods* ; Retrospective Studies ; Operative Time ; Middle Aged ; Male ; Female ; Neck/surgery* ; Sleep Apnea, Obstructive/surgery* ; Adult ; Head and Neck Neoplasms/surgery* ; Oropharynx/surgery* ; Oropharyngeal Neoplasms/surgery*

Objective: To explore the cross sectional and longitudinal associations between 24 hour movement behaviors and physical fitness in preschool children, and to adopt the method of equal time substitution analysis to evaluate the impact of time redistribution of different activity behaviors on physical fitness scores,so as to provide a scientific basis for promoting the health of preschool children. Methods: A total of 193 preschool children aged 3-6 years were selected from three Shanghai districts (Jing an, Baoshan, Jiading) from October to December 2023 by the stratified cluster random sampling method. The 24 hour movement behaviors were monitored via 7 day accelerometry, and physical fitness was measured according to the National Physical Fitness Measurement Standards (Revised 2023, preschool section). From October to December 2024, the follow up of physical fitness among preschool children used the same testing method. The comparison between groups was conducted by t-test. Compositional regression analyses evaluated the relationship of 24 hour movement behaviors and physical fitness among preschool children. Results: At baseline, moderate to vigorous physical activity (MVPA) time was significantly higher in boys [(84.10±25.78)min/d] than in girls [( 70.44± 25.98)min/d]; the composite physical fitness score was significantly higher in boys (71.65±8.69) than in girls (68.84±9.89), and the differences were statistically significant ( t =3.65, 2.10, both P <0.01). After adjusting for gender, age and body mass index, the results of component multiple linear regression analysis showed that MVPA time proportion was positively correlated with the composite physical fitness score at baseline among preschool children ( β =6.61), but was negatively correlated with two legged continuous hopping time at 1 year ( β =-1.12) (both P <0.05). Light physical activity (LPA) time proportion was negatively correlated with walking on the balance beam time at 1 year ( β =-4.44), and sedentary behavior (SB) time proportion was negatively correlated with the composite score of physical fitness at baseline ( β =-6.55) (both P <0.05). Isotemporal substitution analysis revealed that replacing 10 minutes of sleep (SP), SB, and LPA with MVPA increased the baseline physical fitness composite score by 0.750, 0.689 and 0.575 units, respectively; at 1 year follow up, the composite score increased by 1.440, 1.419 and 1.430 units, respectively (all P <0.05). Conversely, replacing MVPA with 10 minutes of SP, SB, and LPA,resulted in decreases in baseline physical fitness composite scores of 0.836, 0.777 and 0.669 units, and reductions of 1.613, 1.592 and 1.598 units at 1 year follow up (all P < 0.05 ). Conclusions Preschool children s 24 hour movement behaviors, especially MVPA, are closely related to physical health. Implementing appropriate strategies to increase physical activity and reduce sedentary time may improve the physical fitness of preschoolers.

OBJECTIVE To explore the indexes affecting the prognosis of the ICU patients with sepsis,establish the nomogram model for prediction of 28-day mortality rate,and validate it.METHODS On the basis of criteria for diagnosis of sepsis(3.0 version),the related data of the sepsis patients were extracted from Medical Information Mart for Intensive Care-Ⅳ(MIMIC-Ⅳ)database for retrospective study and were randomly divided into the train-ing set and the validation set in a 7∶3 ratio.Univariate analysis and multivariate Cox proportional risk regression analysis were performed for the screening of influencing factors for prediction of 28-day mortality of the sepsis pa-tients.The nomogram prediction model was established based on the screened factors and was validated by the val-idation set,and the effect was evaluated.RESULTS A total of 7 955 sepsis patients were included.Seven variables were selected to establish the nomogram model for prediction of the 28-day mortality rate.The nomogram showed favorable performance in identification between the two cohorts,the area under receiver operating characteristic curves(AUROCs)were 0.748 and 0.721,respectively.Calibration curves and Hosmer-Lemeshow test(x2=8.689,10.614;P=0.369,0.225)indicated that the model had remarkable effect on correction.With the per-formance of decision curve analysis(DCA)and clinical impact curve(CIC),the model was considered to have high clinical application value.CONCLUSIONS The nomogram model shows favorable performance in prediction of the 28-day mortality rate and calibration capability.It is worthy to be further promoted and applied.

Diabetic kidney disease (DKD) with increasing global prevalence lacks effective therapeutic targets to halt or reverse its progression. Therapeutic targets supported by causal genetic evidence are more likely to succeed in randomized clinical trials. In this study, we integrated large-scale plasma proteomics, genetic-driven causal inference, and experimental validation to identify prioritized targets for DKD using the UK Biobank (UKB) and FinnGen cohorts. Among 2844 diabetic patients (528 with DKD), we identified 37 targets significantly associated with incident DKD, supported by both observational and causal evidence. Of these, 22% (8/37) of the potential targets are currently under investigation for DKD or other diseases. Our prospective study confirmed that higher levels of three prioritized targets-insulin-like growth factor binding protein 4 (IGFBP4), family with sequence similarity 3 member C (FAM3C), and prostaglandin D2 synthase (PTGDS)-were associated with a 4.35, 3.51, and 3.57-fold increased likelihood of developing DKD, respectively. In addition, population-level protein-altering variants (PAVs) analysis and in vitro experiments cross-validated FAM3C and IGFBP4 as potential new target candidates for DKD, through the classic NLR family pyrin domain containing 3 (NLRP3)-caspase-1-gasdermin D (GSDMD) apoptotic axis. Our results demonstrate that integrating omics data mining with causal inference may be a promising strategy for prioritizing therapeutic targets.

Peroxisome proliferator activated receptor-α (PPAR-α) is significantly expressed in various tissues such as the liver, kidney, myocardium, and skeletal muscle, which plays a central role in the development of various diseases by regulating key physiological processes such as energy homeostasis, redox balance, inflammatory response, and ferroptosis. As an important metabolic and excretory organ of the body, renal dysfunction can lead to water and electrolyte imbalance, toxin accumulation, and multiple system complications. The causes of kidney injury are complex and diverse, including acute injury factors (such as ischemia/reperfusion, nephrotoxic drugs, septic shock, and immune glomerulopathy), as well as chronic progressive causes [such as metabolic disease-related nephropathy, hypertensive nephropathy (HN)], and risk factors such as alcohol abuse, obesity, and aging. This review briefly describes the structure, function, and activity regulation mechanism of PPAR-α, systematically elucidates the molecular regulatory network of PPAR-α in the pathological process of kidney injury including acute kidney injury (AKI) such as renal ischemia/reperfusion injury (IRI), drug-induced AKI, sepsis-associated acute kidney injury (SA-AKI), glomerulonephritis, chronic kidney disease (CKD) such as diabetic nephropathy (DN), HN, and other kidney injury, and summarizes the mechanisms related to PPAR-α regulation of kidney injury, including regulation of metabolism, antioxidation, anti-inflammation, anti-fibrosis, and anti-ferroptosis. This review also evaluates PPAR-α's medical value as a novel therapeutic target, and aims to provide theoretical basis for the development of kidney protection strategies based on PPAR-α targeted intervention.
Humans ; PPAR alpha/metabolism* ; Acute Kidney Injury/therapy* ; Animals ; Kidney/metabolism*

Objective:To describe the clinical characteristics of the urinary system involvement in patients with IgG4-related disease (IgG4-RD), and to identify the risk factors for progression to glomerular filtration rate (GFR) less than 60 ml/min.Methods:A retrospective review was carried out using the medical records of 71 cases with IgG4-RD complicated with renal and urinary lesions diagnosed in the First Affiliated Hospital of Zhejiang University School of Medicine between January 2017 and December 2021. Cox proportional hazards model was performed to assess the factors associated with the risk of GFR<60 ml/min.Results:We studied 71 patients with IgG4-RD who had renal and urinary lesions with a mean follow-up of (31.5±19.5)months. Among these, 60 patients were male, and the mean disease onset age was (63.1±10.8)years, and 41(57.7%) patients had IgG4-related kidney disease (IgG4-RKD). Twenty-four patients had IgG4-RKD confirmed after kidney biopsy, with all biopsies showing tubulointerstitial nephritis and one showing membranous nephropathy. Urine immunoglobulin G[ HR(95% CI)=1.218(1.026, 1.446), P=0.025] was associated with a higher risk of GFR less than 60 ml/min. Conclusion:The most common type of urinary system involvement in patients with IgG4-RD is IgG4-RKD. Meanwhile the most common pathological type of IgG4-RKD is TIN. Urine immunoglobulin G is associated with a higher GFR less than 60 ml/min rate.

Objective:To analyze the related factors of biochemical recurrence after laparoscopic radical prostatectomy (LRP).Methods:Clinical data of 312 patients with prostate cancer who received LRP in Hunan Provincial People's Hospital (the First Affiliated Hospital of Hunan Normal University) from September 2020 to September 2023 were retrospectively analyzed. Those patients were followed up for 1 year after surgery. According to whether biochemical recurrence occurred after surgery, the above patients were divided into biochemical recurrence group ( n=61) and non-biochemical recurrence group ( n=251). Compare the clinical data [including age, smoking history, drinking history, history of diabetes, postoperative Gleason score, body mass index (BMI), tumor stage, presence or absence of seminal vesicle invasion, and positive surgical margins] and laboratory indicators [including fasting blood glucose after admission, hemoglobin, prostate volume, prostate mass, and preoperative prostate-specific antigen (PSA)] levels between the two groups of patients. Measurement data with normal distribution were presented as Mean±SD, comparison between the two groups was performed by the independent samples t-test. Categorical data were expressed as case (%), comparison between groups was performed by the χ2 test, multivariate analysis was performed by Logistic regression model. Results:The difference in smoking history between groups was not statistically significant( P>0.05). The proportions of patients with age≥65 years old [85.25% (52/61) vs. 68.13% (171/251)], alcohol drinking history[73.77% (45/61) vs. 68.53% (172/251)], diabetes mellitus[50.82% (31/61) vs. 40.24% (101/251)], Gleason score >7 points[72.13% (44/61) vs. 30.68% (77/251)], BMI≥30 kg/m 2[32.79% (20/61) vs. 14.34% (36/251)], disease stage ≥T2a[67.21% (41/61) vs. 23.11% (58/251)], seminal vesicle invasion[32.79% (20/61) vs. 13.55% (34/251)], and postoperative positive incisal margin[24.59% (15/61) vs. 3.59% (9/251)] in the biochemical recurrence group were higher than those in the non-biochemical recurrence group, and the differences were statistically significant ( χ2=393.22, 34.58, 74.28, 36.70, 725.49, 48.09, 171.37, 30.49, respectively, all P<0.001). The differences in fasting blood glucose [(6.81±0.89) mmol/L vs. (6.63±0.78) mmol/L], prostate volume[37.19±4.23) mL vs. (36.87±4.36) mL], prostate weight[(48.21±5.11) g vs. (47.82±5.13) g], and hemoglobin level[(134.08±15.62) g/L vs. (133.26±16.24) g/L] between both groups of patients were not statistically significant ( t=1.57,0.52,0.53,0.36, P=0.117,0.606,0.594,0.722, respectively). The preoperative prostate-specific antigen (PSA) level was higher in the biochemical recurrence group than that in the non-biochemical recurrence group [(45.13±5.26) μg/L vs. (28.87±3.18) μg/L, t=30.99, P<0.001). Multivariate Logistic regression analysis results indicated that postoperative Gleason score >7 points, preoperative PSA and seminal vesicle invasion were risk factors for postoperative biochemical recurrence in patients undergoing LRP ( OR=5.39, 95% CI:1.57-18.48, P=0.008; OR=4.32, 95% CI:1.32-14.10, P=0.016; OR=12.76, 95% CI:1.47-111.03, P=0.022). Conclusion:Patients with prostate cancer are prone to biochemical recurrence after LRP, which is affected by postoperative Gleason score, preoperative PSA level and seminal vesicle invasion. It is necessary to take targeted measures to prevent biochemical recurrence.