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.

Objective:To evaluate the diagnostic efficacy and practicality of the Jaundice color card (JCard) as a screening tool for neonatal jaundice.Methods:Following the standards for reporting of diagnostic accuracy studies (STARD) statement, a multicenter prospective study was conducted in 9 hospitals in China from October 2019 to September 2021. A total of 845 newborns who were admitted to the hospital or outpatient department for liver function testing due to their own diseases. The inclusion criteria were a gestational age of ≥35 weeks, a birth weight of ≥2 000 g, and an age of ≤28 days. The neonate′s parents used the JCard to measure jaundice at the neonate′s cheek. Within 2 hours of the JCard measurement, transcutaneous bilirubin (TcB) was measured with a JH20-1B device and total serum bilirubin (TSB) was detected. The Pearson′s correlation analysis, Bland-Altman plots and the receiver operating characteristic (ROC) curve were used for statistic analysis.Results:Out of the 854 newborns, 445 were male and 409 were female; 46 were born at 35-36 weeks of gestational age and 808 were born at ≥37 weeks of gestational age. Additionally, 432 cases were aged 0-3 days, 236 cases were aged 4-7 days, and 186 cases were aged 8-28 days. The TSB level was (227.4±89.6) μmol/L, with a range of 23.7-717.0 μmol/L. The JCard level was (221.4±77.0) μmol/L and the TcB level was (252.5±76.0) μmol/L. Both the JCard and TcB values showed good correlation ( r=0.77 and 0.80, respectively) and agreements (96.0% (820/854) and 95.2% (813/854) of samples fell within the 95% limits of agreement, respectively) with TSB. The JCard value of 12 had a sensitivity of 0.93 and specificity of 0.75 for identifying a TSB ≥205.2?μmol/L, and a sensitivity of 1.00 and specificity of 0.35 for identifying a TSB ≥342.0?μmol/L. The TcB value of 205.2?μmol/L had a sensitivity of 0.97 and specificity of 0.60 for identifying TSB levels of 205.2 μmol/L, and a sensitivity of 1.00 and specificity of 0.26 for identifying TSB levels of 342.0 μmol/L. The areas under the ROC curve (AUC) of JCard for identifying TSB levels of 153.9, 205.2, 256.5, and 342.0 μmol/L were 0.96, 0.92, 0.83, and 0.83, respectively. The AUC of TcB were 0.94, 0.91, 0.86, and 0.87, respectively. There were both no significant differences between the AUC of JCard and TcB in identifying TSB levels of 153.9 and 205.2 μmol/L (both P>0.05). However, the AUC of JCard were both lower than those of TcB in identifying TSB levels of 256.5 and 342.0 μmol/L (both P<0.05). Conclusions:JCard can be used to classify different levels of bilirubin, but its diagnostic efficacy decreases with increasing bilirubin levels. When TSB level are ≤205.2 μmol/L, its diagnostic efficacy is equivalent to that of the JH20-1B. To prevent the misdiagnosis of severe jaundice, it is recommended that parents use a low JCard score, such as 12, to identify severe hyperbilirubinemia (TSB ≥342.0 μmol/L).

This study aims to explore the mechanism of Qingkailing(QKL) Oral Preparation's heat-clearing, detoxifying, mind-tranquilizing effects based on "component-target-efficacy" network. To be specific, the potential targets of the 23 major components in QKL Oral Preparation were predicted by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) and SwissTargetPrediction. The target genes were obtained based on UniProt. OmicsBean and STRING 10 were used for Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment of the targets. Cytoscape 3.8.2 was employed for visualization and construction of "component-target-pathway-pharmacological effect-efficacy" network, followed by molecular docking between the 23 main active components and 15 key targets. Finally, the lipopolysaccharide(LPS)-induced RAW264.7 cells were adopted to verify the anti-inflammatory effect of six monomer components in QKL Oral Preparation. It was found that the 23 compounds affected 33 key signaling pathways through 236 related targets, such as arachidonic acid metabolism, tumor necrosis factor α(TNF-α) signaling pathway, inflammatory mediator regulation of TRP channels, cAMP signaling pathway, cGMP-PKG signaling pathway, Th17 cell differentiation, interleukin-17(IL-17) signaling pathway, neuroactive ligand-receptor intera-ction, calcium signaling pathway, and GABAergic synapse. They were involved in the anti-inflammation, immune regulation, antipyretic effect, and anti-convulsion of the prescription. The "component-target-pathway-pharmacological effect-efficacy" network of QKL Oral Preparation was constructed. Molecular docking showed that the main active components had high binding affinity to the key targets. In vitro cell experiment indicated that the six components in the prescription(hyodeoxycholic acid, baicalin, chlorogenic acid, isochlorogenic acid C, epigoitrin, geniposide) can reduce the expression of nitric oxide(NO), TNF-α, and interleukin-6(IL-6) in cell supernatant(P<0.05). Thus, the above six components may be the key pharmacodynamic substances of QKL Oral Preparation. The major components in QKL Oral Prescription, including hyodeoxycholic acid, baicalin, chlorogenic acid, isochlorogenic acid C, epigoitrin, geniposide, cholic acid, isochlorogenic acid A, and γ-aminobutyric acid, may interfere with multiple biological processes related to inflammation, immune regulation, fever, and convulsion by acting on the key protein targets such as IL-6, TNF, prostaglandin-endoperoxide synthase 2(PTGS2), arachidonate 5-lipoxygenase(ALOX5), vascular cell adhesion molecule 1(VCAM1), nitric oxide synthase 2(NOS2), prostaglandin E2 receptor EP2 subtype(PTGER2), gamma-aminobutyric acid receptor subunit alpha(GABRA), gamma-aminobutyric acid type B receptor subunit 1(GABBR1), and 4-aminobutyrate aminotransferase(ABAT). This study reveals the effective components and mechanism of QKL Oral Prescription.
Chlorogenic Acid ; Drugs, Chinese Herbal/pharmacology* ; gamma-Aminobutyric Acid ; Interleukin-6 ; Medicine, Chinese Traditional ; Molecular Docking Simulation ; Tumor Necrosis Factor-alpha/genetics* ; Animals ; Mice ; RAW 264.7 Cells

Objective To understand the ability of the CDC to detect ammonia nitrogen in drinking water in Hubei Province. Methods The blind samples of two concentration levels were tested in the laboratories of the disease control institutions in the province, and the test results were evaluated by double-sample Z score. Results The satisfaction rate was 76.29% (74/97), the problem rate was 15.46% (15/97), and the dissatisfaction rate was 8.25% (8/97). Conclusion The detection ability of ammonia nitrogen in drinking water in laboratories of disease control institutions in Hubei Province is generally high，however，some laboratories need to be further improved.

Objective The purpose of this study was to produce cut-off values of fetal pulmonary artery stenosis (PS),allowing the application of Z-scores to evaluate fetal pulmonary artery.Methods A total of 214 normal singleton fetuses and 107 singleton fetuses with PS were included in this study.They were measured for standard biometry:biparietal diameter (BPD) and femoral diaphysis length (FL) and an assessment of gestation age (GA).The standardized fetal echocardiographic measurements included diameters of pulmonary valve annulus (PV),pulmonary artery (PA),ductus arteriosus (DA) and aorta (AO).Then we calculated the Z-scores from parameters of fetal size.The Z-scores differences of PV,PA,DA and AO in PS group were compared.The receiver operator characteristic (ROC) curves of PV and PA Z-scores were obtained by statistical analysis.Results Compared with the normal group,the Z-scores of PV,PA and DA decreased in the PS group,whereas the Z-scores of AO increased (P ＜0.01 for all).The critical values of Z-score for PV in diagnosing PS with BPD,FL and GA as variables were-1.13,-1.33,-1.28,with sensitivity 94.2％,90.3％,93.5％,specificity 60.0％,65.0％,62.5％,respectively.The critical values of Z-score for PA with BPD,FL and GA as variables were-1.01,-0.98,-1.01,with sensitivity 96.8％,96.8％,96.1％,specificity 65.0％,65.0％,62.5％,respectively.Conclusions In the fetus with pulmonary artery stenosis,PV,PA and DA Z-scores decreased,while AO Z-scores increased.The pulmonary artery Z-scores had important application value in quantitative evaluation and diagnosis of mild fetal pulmonary artery stenosis.

Objective To evaluate the short-term clinical effectiveness and feasibility of thoracic endovascular aortic repair(TEVAR) with in situ laser fenestration.Methods 24 patients who received TEVAR and in situ laser fenestration from January 2017 to March 2017 were retrospectively reviewed.Include 24 patients,19 males,5 females,with an average age of (54.00 ± 13.58) years old.The clinical data,including post-operative symptoms,hospitalization days,the success rate,postoperative complications,30-day fatality ratio,the patency rate of branch stents,endoleak,etc.Results The mean hospitalization time was(12.81 ±4.18) days.32 aortic arch branch vessels were treated using in situ laser fenestration,30 succeed in laser fenestration,surgical success rate was 93.8％.One case with postoperative paraplegia recovered after treatment,another one with the left common carotid incision hematoma recovered too.The incidence of operation-related complications was 8.3 ％.After the surgery 1 patient died,30-day fatality ratio of 4.2％.Imaging surveillance with computed tomography angiography(CTA) was performed one month later after the operation,the patency rate of branch stents was 100％,one case was found endoleak.Conclusion For revascularizating aortic arch branch vessels during TEVAR,in situ laser fenestration has an excellent successful rate and short-term curative effect,while the long-term surveillance is needed.

Objective To observe the effect of cefoperazone sulbactam on the efficacy inflammatory factors in patients with sepsis. Methods 80 cases of sepsis patients from January 2014 to April 2015, were double-blindly, randomized divided into control group(41 cases) and observation group(39 cases). The control group was treated with conventional treatment methods, the observation group was treated with cefoperazone sulbactam. After treatment, Leukocyte IL-6, IL-10, IL-1 and C- reactive protein (CRP) levels of interleukin and curative effect in the two groups were analyzed. Results After treatment, the levels of IL-6, IL-10, IL-1, CRP in the observation group were lower than those in the control group (t=15.555;t=11.122; t=9.379; t=34.782), the difference was statistically significant (P<0.05); The total effective rate in the observation group was 95.12%, which was significantly higher than that in the control group (76.93%), and the difference was statistically significant (P<0.05); The proportion of painless and severe pain in the observation group was significantly lower than that in the control group(76.93%), and the difference was statistically significant (P<0.05). Conclusion Cefoperazone sulbactam is effective in the treatment of sepsis, can improve the efficacy of treatment, it is a safe and effective treatment, should be promoted and used in clinical.

Objective·To evaluate the clinical value of two-dimensional ultrasound combined with four-dimensional color Doppler ultrasound in the diagnosis of uterine space-occupying lesion.Methods·A total of 75 patients with uterine space-occupying lesion were enrolled in this study from March 2015 to February 2016 at Hospital of Southwest Medical University.Patients received both two-dimensional ultrasound and four-dimensional color Doppler ultrasound to determine the location,number and nature of the lesions,as well as the clinical staging of malignant lesions,then the diagnostic accuracy was evaluated.Results·Among 75 patients,there were 26 cases with endometrial carcinoma,21 cases with hysteromyoma,16 cases with metropolypus,and 12 cases with uterine adenomyosis.The diagnostic accuracy of two-dimensional ultrasound combined with four-dimensional color Doppler ultrasound for the uterine space-occupying lesion was 88.0％,which was significantly higher than that of two-dimensional ultrasound (64.0％) (P＜0.05).What's more,the diagnostic accuracy of two-dimensional ultrasound combined with four-dimensional color Doppler ultrasound for the clinical staging of endometrial carcinoma was 88.5％,which was significantly higher than that of two-dimensional ultrasound (61.5％) (P＜0.05).Conclusion·Two-dimensional ultrasound combined with four-dimensional color Doppler ultrasound is more effective to improve the diagnostic accuracy of uterine space occupying lesion and clinical staging of endometrial carcinoma in comparison with two-dimensional ultrasound,which will favor the clinical strategy for the treatment of uterine space-occupying lesion.

Objective To investigate the characteristics of left and right ventricular volume and systolic function of tetralogy of Fallot(TOF)children by real-time three-dimensional echocardiography (RT-3DE).Methods Forty-five TOF children and 46 normal age-matched children were recruited in this study. Full volume imaging of left and right ventricle were obtained by RT-3DE and analyzed off-line by TomTec LV-Analysis and RV-Function.The measurements including:end-diastolic volume (LVEDV/RVEDV),end-systolic volume (LVESV/RVESV),ej ection fraction (LVEF/RVEF),peak systolic volume rate (LVPSVR/RVPSVR),stoke volume (LVSV/RVSV),cardiac output (LVCO/RVCO).And the volumetric parameters were indexed by BSA(indexed EDV,indexed SV,indexed CO).The measurements were compared between TOF group and normal group.The left and right ventricular measurements were also compared with each other within group.Results Compared with control group indexed LVEDV reduced in TOF group(P =0.000),while indexed RVEDV increased (P =0.002 ).For systolic function indexes:LVEF,RVEF, LVPSVR and RVPSVR in TOF group were both lower than that in normal group (P <0.05 ),indexed LVSV and indexed LVCO were also reduced (P <0.05 ),while indexed RVSV had no difference with normal(P >0.05)and indexed RVCO was increased (P =0.016).The volume and function comparision between left and right ventricle demonstrated:in normal group no difference were found in biventricular EDV,PSVR,SV,CO(P >0.05),except that LVEF was a litter higher than RVEF(P =0.000).In TOF group RVEDV,RVSV,RVCO were all greater than that of left ventricle(P <0.05),but RVEF was lower than LVEF(P =0.039).Conclusions In TOF group biventricular systolic function were both impaired and lost banlance between them.Under the volume and pressure overload the right ventricle improved pumping function by increasing heart rate.