Autosomal dominant polycystic kidney disease （ADPKD） is a systemic hereditary renal disorder and can affect multiple organs， and congenital hepatic fibrosis is one of the manifestations of liver involvement and is an important complication of ADPKD. Symptomatic management is currently the main treatment method for this disease， and disease-specific drugs such as tolvaptan have limited indications and cannot correct the underlying genetic defect. This article reports a case of ADPKD with congenital hepatic fibrosis， and sirolimus was identified as the individualized treatment regimen based on peripheral blood functional genomic analysis and drug sensitivity prediction platform. The patient achieved significant improvements in symptoms and quality of life after treatment， with a stable kidney volume. This case shows that functional genomics has a potential value in guiding individualized treatment of rare genetic disorders， which provides new treatment ideas and practice paths for similar patients.

Objective:To retrospectively analyze the short-term curative effects of various treatment methods for displaced femoral neck fractures in young and healthy elderly individuals aged 65 to 74 years, while also exploring the surgical treatment options available for this population.Methods:A retrospective analysis was conducted on 159 patients with displaced femoral neck fractures(Garden types Ⅲ and Ⅳ)who were treated at Zhengzhou Orthopedic Hospital from July 2019 to June 2021.Among these patients, 75 were male and 84 were female, with ages ranging from 65 to 74 years, and an average age of 69.1±2.9 years.Patients were categorized based on the treatment method received: the total hip arthroplasty(THA)group comprised 77 cases, the hemiarthroplasty(HA)group included 42 cases, and the internal fixation(IF)group contained 40 cases.We compared intraoperative blood loss, operation time, Harris hip joint function scores one-year post-operation, and the incidence of secondary surgeries across the groups.Results:All 159 patients were followed up for a duration of 36 to 60 months(mean 45.1 months)postoperatively.Intraoperative blood loss was recorded as follows: IF group(19.3±7.0 ml), HA group(303.7±33.8 ml, P<0.001), and THA group(453.6±75.6 ml), with statistically significant differences in pairwise comparisons among the three groups(all P<0.001).The operation times were: IF group(40.7±13.1 min), HA group(53.2±7.5 min), and THA group(96.8±23.6 min), again showing statistically significant differences between each pair of groups(all P<0.001).The Harris hip score at one year postoperatively was(82.1±8.0)points, with an excellent and good rate of 82.4%.Specifically, the THA group scored(82.1±8.1)points with an excellent and good rate of 83.1%; the HA group scored(82.3±7.5)points with an excellent and good rate of 83.3%; and the IF group scored(81.8±8.0)points with an excellent and good rate of 80.0%.No statistically significant differences were observed in the excellent and good rates among the three groups(all P>0.05).A chi-square test performed on the overall postoperative complications among the three groups revealed no statistically significant differences( P=0.115). Conclusions:For relatively healthy elderly patients aged 65 to 74 with femoral neck fractures, hip replacement is not the sole treatment option.Treatment plans should be individualized based on patients' health conditions, transcending age limitations, to effectively address the growing challenges posed by femoral neck fractures in an aging society.

Objective:To investigate clinical characteristics, treatment approaches, and prognosis of drug-induced hypersensitivity syndrome (DIHS) in children.Methods:A retrospective analysis was performed on clinical data from pediatric inpatients with DIHS in Department of Dermatology, Beijing Children's Hospital from 2009 to 2023. The clinical data included demographic characteristics, clinical manifestations, laboratory findings, treatment regimens, and outcomes.Results:A total of 103 children with DIHS were included, comprising 54 males (52.4%) and 49 females (47.6%), with ages ( M [ Q1, Q3]) of 2.3 (1.2, 4.5) years. Primary causative drugs were antibiotics (52 cases, 45.2%), antiepileptic drugs (41 cases, 35.7%), and nonsteroidal anti-inflammatory drugs (19 cases, 16.5%), with a median latency period of 12 days. All patients presented with rashes, including 72 (69.9%) with maculopapular rashes, 69 (67.0%) with edema (including 46 with facial edema). Lip involvement occurred in 25 cases (24.3%), and mucosal involvement was noted in 11 cases (10.7%). Additionally, 102 (99.0%) patients had fever, and 79 (76.7%) presented with lymphadenectasis. Eosinophilia was present in 64 cases (62.1%). Among 84 patients tested for atypical lymphocytes, 51 (60.7%) showed elevated percentages of atypical lymphocytes. Liver involvement was noted in 94 cases (91.3%), followed by pulmonary involvement in 31 (30.1%), gastrointestinal symptoms in 25 (24.3%), cardiac involvement in 14 (13.6%), renal involvement in 10 (9.7%), and pancreatic involvement in 7 cases (6.8%). Among 82 patients tested for blood immunocytes, 49 (59.8%) showed decreased percentages of B lymphocytes, and 69 (84.1%) showed decreased percentages of natural killer cells. Of 88 patients tested for serum immunoglobulins, 40 (45.5%) showed decreased IgA levels. Among 20 patients tested for serum cytokines, 15 (75.0%), 15 (75.0%), 13 (65.0%), and 12 (60.0%) showed elevated levels of interleukin (IL) -5, IL-6, IL-10, and interferon-γ, respectively. All patients received systemic glucocorticoid therapy, among whom 86 additionally received intravenous immunoglobulin therapy, 4 received Janus kinase inhibitors, and 3 received dupilumab. Five patients died, 9 developed hemophagocytic lymphohistiocytosis, 6 developed bronchiolitis obliterans, and 5 experienced long-term immune-related sequelae. Conclusions:Among these children with DIHS, antibiotics were the most common causative drugs, and the latency period could be shorter than 2 weeks. In addition to the common involvement of the liver and lungs, gastrointestinal and cardiac impairments were relatively frequent, while renal involvement was rare. Immunological features included decreased percentages of B lymphocytes and natural killer cells, reduced IgA levels, and elevated levels of cytokines such as IL-5, IL-6, IL-10, and interferon-γ.

Objective To analyze the relationship between different degrees of cerebral venous sinus stenosis and the trans-stenotic pressure gradient using a 3D-printed hemodynamic simulation system for cerebral venous sinuses.Methods Based on the double elastic cavity model,a complete morphological model of the superior sagittal sinus,transverse sinus,and sigmoid sinuses was constructed using 3D printing technology.An in vitro hemodynamic simulation system incorporating pulsatile blood flow was established to simulate the hemodynamic environment of cerebral venous sinus stenosis.Using this system,both unilateral dominant drainage and bilateral balanced drainage were simulated.The degree of stenosis and the pressure upstream and downstream of the stenosis were measured.The pressure difference and pressure ratio were calculated to analyze the correlation between stenosis degree and the trans-stenotic pressure gradient.Results In the unilateral dominant drainage model,as the stenosis severity increased,the upstream pressure increased,whereas the downstream pressure remained relatively stable,leading to an increased pressure gradient between the two ends.The regression equation for stenosis degree(X)and pressure gradient(pressure difference ΔP)was:YΔP=1.962X-1.417(R=0.867,R2=0.753,P<0.001).In the bilateral balanced drainage model of cerebral venous sinuses,when the stenosis degree on one side of the model increased,the pressure gradient between the two ends changed slightly and eventually reached a stable state.The regression equation between X and ΔP was:YΔP=0.62X+1.047(R=0.98,R2=0.96,P<0.001).Conclusions Stenosis in cerebral venous sinuses with unilateral dominant drainage has a more significant impact on the pressure gradient,while unilateral stenosis in bilateral cerebral venous sinuses with balanced drainage has a smaller impact on the pressure gradient.This result suggests that for bilateral venous sinus stenosis,stent implantation can be prioritized in one side of the cerebral venous sinuses.

Objective To evaluate the diagnostic efficacy of the Kaiser score for ultrasound(US)BI-RADS 4A lesions and the potential to avoid unnecessary biopsies.Methods Data of patients who underwent breast US and magnetic resonance imaging(MRI)between May 2019 and June 2023 were retrospectively collected,and all cases were confirmed by puncture biopsy or surgical pathology.The diagnostic efficacy of Kaiser score and MRI BI-RADS classification for US BI-RADS 4A lesions was calculated and compared using pathologic findings as the gold standard.Results A total of 119 lesions(74 benign and 45 malignant lesions)were found in the 119 patients.The diagnostic efficacy of the Kaiser score was significantly better than that of the MRI BI-RADS classification(AUC:0.88 vs.0.65,P＜0.000 1).The concordance of the Kaiser score results with the pathologic findings and the inter-observer concordance were better than that of the MRI BI-RADS classification.Unnecessary biopsies could be avoided in 87.8％(65/74)and 33.8％(25/74)of the cases when the Kaiser score and the MRI BI-RADS classification were applied for the diagnosis of US BI-RADS 4A lesions,respectively.Conclusion The Kaiser score can provide a diagnostic basis for risk stratification of US BI-RADS 4A lesions,and its diagnostic efficacy and inter-observer agreement are superior to those of MRI BI-RADS classification.

Objective To explore the association between plasma fibrinogen(FBG)levels and the risk of in-hospital mortality among patients with septic shock.Methods The clinical data of 563 patients diagnosed with septic shock in the Intensive Care Unit(ICU)of Shenzhen Second People's Hospital from August 1,2018,to December 31,2020,were collected.Patient demographic information,basic vital signs,and blood routine and biochemical indices upon admission were gathered.Moreover,the Acute Physiology and Chronic Health Evaluation Ⅱ(APACHEⅡ)scores were calculated.Binary logistic regression analysis was conducted to explore the correlation between plasma fibrinogen levels and in-hospital mortality in patients with septic shock.Additionally,a generalized additive model(GAM)and smoothed curve fitting were employed to investigate the nonlinear relationship between plasma fibrinogen and in-hospital mortality.Receiver operating characteristic(ROC)curves were constructed for FBG and APACHEⅡ scores to predict in-hospital mortality in septic shock patients.The area under the curve(AUC)was computed to compare the predictive efficacies of the two.Furthermore,a segmented linear regression model was utilized for quantification.Results Binary logistic regression analysis demonstrated a significant negative correlation between plasma fibrinogen levels and in-hospital mortality among patients with septic shock(P<0.05).GAM modeling and smoothed curve fitting disclosed a nonlinear association between plasma fibrinogen levels and in-hospital mortality,with an inflection point at 5.54 g/L.The segmented linear regression model indicated that,to the left of the inflection point(FBG≤5.54 g/L),for every 1 g/L decrease in plasma fibrinogen,the risk of death increased by 24.5%(OR=0.755,P=0.003).Conversely,to the right of the inflection point(FBG>5.54 g/L),the relationship was not statistically significant(OR=1.049,P=0.685).The findings of the subgroup analyses indicated that the characteristics of the subgroups did not alter the relationship between blood fibrinogen levels and in-hospital mortality.Conclusion There is a nonlinear relationship between FBG levels and in-hospital mortality in patients with septic shock,which has predictive value for evaluating the risk of in-hospital mortality in this patient cohort.

The xylitol dehydrogenase(XDH)is a crucial enzyme involved in the xylose utilization in pentose-catabolizing yeasts and fungi.In addition to producing xylulose,XDH can also be employed to develop a biosensor for monitoring xylitol concentration.In this study,the gene encoding the thermophilic fungus Talaromyces emersonii XDH(TeXDH)was heterologously expressed in Escherichia coli BL21(DE3)at 16 ℃ in the soluble form.Recombinant TeXDH with high purity was purified by using a Ni-NTA affinity column.Size-exclusion chromatography and SDS-PAGE analysis demonstrated that the puri-fied recombinant TeXDH exists as a native trimer with a molecular mass of approximately 116 kD,and is composed of three identical subunits,each with a molecular weight of around 39 kD.The TeXDH strictly preferred NAD+as a coenzyme to NADP+.The optimal temperature and pH of the TeXDH were 40 ℃and 10.0,respectively.After EDTA treatment,the enzyme activity of TeXDH decreased to 43.26％of the initial enzyme activity,while the divalent metal ions Mg2+or Ca2+could recover the enzyme activity of TeXDH,reaching 103.32％and 110.69％of the initial enzyme activity,respectively,making them the optimal divalent metal ion cofactors for TeXDH enzyme.However,the divalent metal ions of Mn2+,Ni2+,Cu2+,Zn2+,Co2+,and Cd2+significantly inhibited the activity of TeXDH.ICP-MS and molecular doc-king studies revealed that 1 mol/L of TeXDH bound 2 mol/L Zn2+ions and 1 mol/L Mg2+ion.Further-more,TeXDH exhibited a high specificity for xylitol,laying the foundation for the development of future xylitol biosensors.

Aim To predict and verify the potential mechanism of the compatibility of"ginseng-astragalus-pueraria"in protecting islet morphology and improving insulin resistance by using network pharmacology.Methods The active ingredients and targets of the horn medicine were obtained from three platforms:TC-MSP,TCMIP,and BATMAN.The targets of type 2 dia-betes mellitus(T2DM)were obtained from three plat-forms:TTD,OMIM,and disgeNET.The PPI network was constructed by using the STRING database and Cy-toscape 3.9.1;GO and KEGG analysis were per-formed;POCASA 1.1 was used to predict protein binding sites,and AutoDock Vina1.1.2 was used for docking and experimental verification.Results"Gin-seng-astragalus-pueraria"screened out 2 021 targets,of which 152 were closely related to T2DM,and 10 key genes and the AGE-RAGE signaling pathway were i-dentified.Molecular docking showed that quercetin had good binding to RAGE,INS,and PI3K.Experi-ments showed that the horn drug increased insulin binding rate and secretion index and reduced serum in-sulin level and insulin resistance index.These data benefited from"ginseng-astragalus-pueraria"reducing the expression of AGE-RAGE,activating PI3K-Akt,in-hibiting NF-κB,and reducing the expression of IL-6,IL-1β and TNF-α.Conclusion The study suggests that"ginseng-astragalus-pueraria"regulates the AGE-RAGE/PI3K-Akt/NF-κB signaling pathway,repairs damaged islet morphology,and improves insulin resist-ance.

Objective:To explore the relationship between peripheral blood microRNA-29b (miR-29b), fibroblast growth factor 23 (FGF23), adiponectin (ADP) and disease progression as well as bone metabolism disorders in patients with chronic kidney disease (CKD).Methods:A total of 106 CKD patients diagnosed in the Department of Nephrology, the First People′s Hospital of Hefei from February 2022 to February 2024 were selected as the CKD group, and 103 healthy subjects who underwent physical examination during the same period were selected as the control group. Differences in peripheral blood miR-29b, ADP, FGF23, serum calcium, serum phosphorus, alkaline phosphatase (ALP), 25-hydroxyvitamin D, and renal function levels between the two groups were compared. The CKD group was stratified according to CKD stages, and the above indicators were compared. Simple linear correlation analysis was used to analyze the correlation between miR-29b, ADP, FGF23 and bone metabolism indicators.Results:The levels of peripheral blood ADP and FGF23 in the CKD group were higher than those in the control group, while the level of miR-29b was lower, with statistically significant differences (all P<0.05). The levels of serum phosphorus, ALP, serum creatinine, and 24-hour urinary protein in the CKD group were higher than those in the control group, while the levels of serum calcium and 25-hydroxyvitamin D were lower, with statistically significant differences (all P<0.05). Among the 106 CKD patients, there were 8 cases in CKD stage 1, 22 in stage 2, 38 in stage 3, 32 in stage 4, and 6 in stage 5. The levels of peripheral blood ADP and FGF23 in patients with CKD stages 4-5 were higher than those in patients with CKD stages 1-3, while the level of miR-29b was lower, with statistically significant differences (all P<0.05). The levels of serum phosphorus, ALP, serum creatinine, and 24-hour urinary protein in patients with CKD stages 4-5 were higher than those in patients with CKD stages 1-3, while the levels of serum calcium and 25-hydroxyvitamin D were lower, with statistically significant differences (all P<0.05). In CKD patients, peripheral blood miR-29b was positively correlated with serum calcium and 25-hydroxyvitamin D (all P<0.05), and negatively correlated with ALP ( P<0.05). Peripheral blood ADP in CKD patients was negatively correlated with serum calcium ( P<0.05) and positively correlated with ALP ( P<0.05). Peripheral blood FGF23 in CKD patients was negatively correlated with serum calcium ( P<0.05) and positively correlated with ALP ( P<0.05). Conclusions:The levels of peripheral blood ADP and FGF23 in CKD patients are significantly increased, and the level of miR-29b is significantly decreased, which are related to disease progression and bone metabolism disorders in CKD patients.

Objective To investigate the correlation between PPARγ and female interstitial cystitis/bladder pain syndrome (IC/BPS) and to establish a predictive model. Methods Clinical data were collected from 89 female IC/BPS patients (observational group) admitted to the hospital from June 2022 to December 2023,and 90 healthy female volunteers undergoing physical examinations during the same period (control group). Plasma levels of inflammatory factors,total antioxidant capacity (TAC),total glutathione (GSH),malondialdehyde (MDA),and PPARγ levels were measured. Significant clinical features were identified using LASSO regression and fitted into a multivariate logistic regression model. The diagnostic efficacy was assessed through receiver operat-ing characteristic (ROC) curves. Results Compared to the control group,the observation group exhibited signifi-cantly elevated age,BMI,NLR,absolute neutrophil count,IFN-α,IL-1β,IL-6,IL-8,TNF-α and CD3+CD4+T expression levels,while absolute lymphocyte count,IL-10,TAC,GSH and plasma PPARγ expression levels were significantly decreased (all P<0.05). LASSO regression identified 8 variables,including NLR,IFN-α,absolute neutrophil count,IL-1β,IL-6,TNF-α,CD3+CD4+T and PPARγ,which were incorporated into the predictive model. Multivariate binary logistic regression analysis revealed that elevated levels of IL-1β,TNF-α and CD3+CD4+T cells,along with reduced PPARγ levels,were independent risk factors for IC/BPS. ROC curve analy-sis indicated that the diagnostic efficacy of the combined PPARγ and clinical parameters (age,IL-1β,TNF-α and CD3+CD4+T) (AUC=0.901) was superior to PPARγ alone (AUC=0.839). Conclusion Plasma PPARγ levels are significantly reduced in female IC/BPS patients and serve as a potential diagnostic marker,with combined clinical parameters enhancing diagnostic accuracy.