Background With the progression of industrialization, an increasing number of emerging contaminants are entering aquatic environments, posing significant threats to the safety of drinking water. Therefore, establishing a system for identifying unknown hazardous factors and implementing safety warning mechanisms for drinking water is of paramount importance. Among these efforts, non-target screening plays a critical role, but its effectiveness is largely constrained by the scope of coverage of sample pre-treatment methods. Objective To integrate modern chromatography/mass spectrometry techniques with advanced data mining methods to develop a non-discriminatory sample pre-treatment method for comprehensive enrichment of unknown contaminants in drinking water, laying a technical foundation for the discovery and identification of unknown organic hazardous factors in drinking water. Methods A non-discriminatory pre-treatment method based on supramolecular and solid-phase extraction was developed. The final target compounds including 333 pesticides, 194 pharmaceuticals and personal care products (PPCPs), and 59 per- and polyfluoroalkyl substances (PFASs) were used for optimizing the pre-treatment method, confirming its coverage. The impacts of different eluents on the absolute recovery rates of target compounds were compared to select the conditions with the highest recovery for sample pre-treatment. The effects of different supramolecular solvents and salt concentrations on target compound recovery were also evaluated to determine the most suitable solvent and salt concentration. Results The solid-phase extraction elution solvents, supramolecular extraction solvents, and salt concentrations were optimized based on the target compound recovery rates. The optimal recovery conditions were achieved using 2 mL methanol, 2 mL methanol (containing 1% formic acid), 2 mL ethyl acetate, 2 mL dichloromethane, hexanediol supramolecular solvent, and 426 mg salt. The detection method developed based on these conditions showed a good linear relationship for all target compounds in the range of 0.1-100.0 ng·mL⁻¹, with R² > 0.99. The method’s limit of detection ranged from 0.01 ng⁻¹ to 0.95 ng⁻¹, and 95% of target compounds were recovered in the range of 20%-120%, with relative standard deviation (RSD) less than 30%, indicating good precision. Conclusion The combined pre-treatment method of solid-phase extraction and supramolecular solvent extraction can effectively enrich contaminants in drinking water across low, medium, and high polarities, enabling broad-spectrum enrichment of diverse trace contaminants in drinking water. It provides technical support for broad-spectrum, high-throughput screening and identification of organic pollutants in drinking water, and also serves as a reference for establishing urban drinking water public safety warning systems.

The inherent complexity of Alzheimer's disease (AD) and failed clinical trials have spiked the interest in multifunctional ligands that target at least two key disease-associated macromolecules in AD pathology. Here we present a focused series of pleiotropic N-carbamoylazole prodrugs with dual mechanism of action. Pseudo-irreversible inhibition of the first therapeutic target, human butyrylcholinesterase (hBChE), enhances cholinergic transmission, and thereby provides symptomatic treatment, same as the standard therapeutics in use for AD. Simultaneously, this step also functions as a metabolic activation that liberates a nanomolar selective α ₂-adrenergic antagonist atipamezole, which blocks pathological amyloid β (Aβ)-induced and noradrenaline-dependent activation of GSK3β that ultimately leads to hyperphosphorylation of tau, thus achieving a disease-modifying effect. Lead compound 8 demonstrated long-term pseudo-irreversible hBChE inhibition, metabolic activation in human plasma, blood-brain barrier permeability, and p.o. bioavailability in mice. Multi-day in vivo treatment with 8 in an Aβ-induced AD murine model revealed a significant alleviation of cognitive deficit that was comparable to rivastigmine, the current drug of choice for AD therapy. Furthermore, decreased GSK3β activation and lowered tau phosphorylation were observed in APP/PS1 mice. This surpasses the symptomatic-only treatment with cholinesterase inhibitors, as it directly blocks an essential pathological cascade in AD. Therefore, these multifunctional α ₂-adrenergic antagonists-butyrylcholinesterase inhibitors, exemplified by lead compound 8, present an innovative, small molecule-based, disease-modifying approach to treatment of AD.

[Objective] To explore the clinical application of cutaneous ureterostomy-flap embedding in radical cystectomy plus urinary diversion. [Methods] The clinical data of 10 patients with bladder cancer treated with this method in our hospital during Feb.and May 2023 were involved.Cutaneous ureterostomy-flap embedding was used in urinary diversion.The stoma-free rate and stenosis rate of stomas within 1 year postoperatively, differences in renal function indicators 1 day before operation and 1 year after operation, urinary diversion-related complications within 6 months postoperatively, including hydronephrosis, urinary tract infections, renal stones were analyzed. [Results] All surgeries were successfully completed.At 1 year postoperatively, renal function indicators showed no significant difference compared to preoperative levels (P>0.05). At 6 months postoperatively, 1 patient developed renal stones, successfully treated with surgery; 2 had urinary tract infection, recovered after antibiotic treatment; 2 had mild unilateral hydronephrosis, alleviated with conservative management.At 1 year postoperatively, the catheter-free rate was 80%(8/10), with no worsening of hydronephrosis or occurrence of ureteral obstruction, and the stent placement duration ranged from 97 to 211 days, average (151.63±42.47) days.The ureteral stent was not removed in 2 patients within 1 year, so the stoma stenosis rate was 20%(2/10). [Conclusion] The application of flap embedding in urinary diversion following radical cystectomy is a simple and safe procedure, with few postoperative complications, high success rate of stent removal, and overall favorable outcomes.

The gene encoding regulatory subunit 15 A of protein phosphatase 1 produces a protein that is a universally present protein phosphatase in eukaryotic cells.In this study,genomic DNAs were extracted from the blood of 89 Chinese Holstein cows and were used as templates for PCR amplification of the target fragment of the PPP1R15A gene.The product was tested and a polymor-phic site,E3-250T＞A was found.The polymorphism of this side and its correlation with milk pro-duction traits in Chinese Holstein cattle were statistically analyzed using SPSS 23.0 software.The findings revealed three genotypes at this site:AA,AT and TT.Cows possessing the AT and TT genotypes exhibited significant differences(P＜0.01)in milk fat and solid non-fat content com-pared to those with the AA genotype.While no significant differences were noted for other milk production traits,including milk yield,protein,lactose,somatic cell count,blood urea nitrogen,and corrected milk.The identification of functional SNPs in the PPP1R15A gene provides a theoretical basis for further research and identification of causal variations in the cow PPP1R15A gene.

The basic concept and related background of multivariate statistical process control(MSPC)were intro-duced.The basic process of MSPC implementation and the common statistics and control charts were described.The important role of MSPC in the pharmaceutical production process was emphasized,especially in the field of tra-ditional Chinese medicine,providing reference for the selection of quality control methods in drug production process.The advantages and disadvantages of MSPC were summarized,and the development trend of MSPC in drug production and quality control was prospected.

Following the principles of evidence-based medicine,in accordance with the structure and drafting rules of standardized documents,based on literature research,according to the characteristics of chronic cough in children and issues that need to form a consensus,the TCM Guidelines for Diagnosis and Treatment of Chronic Cough in Children was formulated based on the Delphi method,expert discussion meetings,and public solicitation of opinions.The guideline includes scope of application,terms and definitions,eti-ology and diagnosis,auxiliary examination,treatment,prevention and care.The aim is to clarify the optimal treatment plan of Chinese medicine in the diagnosis and treatment of this disease,and to provide guidance for improving the clinical diagnosis and treatment of chronic cough in children with Chinese medicine.

Objective To analyze the sequence of LysinB protein in bacteriophage TM4,express LysinB protein in E.coli and evaluate its bactericidal activity in vitro.Methods Bacteriophage TM4 LysinB gene was synthesized and the recombinant prokaryotic expression plasmid was constructed.The soluble protein was induced and purified.The biological characteristics of bacteriophage TM4 LysinB protein were analyzed by online software program.Mycobacterium smegmatis was cultured in 7H9 medium,and its bactericidal effect and stability were detected.Results The theoretical isoelectric point was 6.66,the instability index was 28.71,which was a stable and amphiphilic protein.In the secondary structure,The random coil,α-helix,β-fold and turn Angle accounted for 42.00％,40.25％,12.00％and 5.75％;In the tertiary structure,the content of random coil was high.The peptide composed of AA at positions 11 to 73 constituted the peptidoglycan binding domain.The regions of B cell epitopes and the strong binding peptides of T cell epitopes were predicted.LysinB protein has a significant ability to kill Mycobacterium smegmatis in vitro.PBST protein buffer with pH8.0 was beneficial to maintain the bactericidal effect of LysinB proteins during the experimental cycle.Conclusion This study expands the comprehensive understanding of the LysinB protein of mycobacterial phage TM4 lyase,and also provides reference for the development of stable storage of phage enzyme preparation and its clinical application.

Objective:To investigate regulatory effect and mechanism of protein kinase C(PKC)δ/θ-dual functional oxidase 1(Duox1)-reactive oxygen species(ROS)signaling pathway on human airway mucin(MUC)5AC,to provide a new target for treatment of high secretion of airway mucus.Methods:Human airway epithelial cells 16HBE were pretreated with PKC and its subunit PKCδ/θ inhibitor,Duox1 inhibitor or free radical scavenger DMTU,respectively,and then human neutrophil elastase(HNE)stimulation to establish an in vitro airway inflammatory cell model.Generation level of ROS in each group of cells was determined by kit,mRNA levels of Duox1 and MUC5AC were detected by real-time fluorescent quantitative PCR,influence of interfering factors of each group of cells on Duox1 protein level was determined by Western blot,and protein expression of MUC5AC in each group of cells was detected by ELISA and immunofluorescence.Results:Compared with control group,ROS production in HNE group was increased significantly,expressions of Duox1 and MUC5AC mRNA and protein were also increased(P<0.05).After administration of Duox1 inhibitors,free radical scavengers or PKC inhibitors and PKCδ/θ inhibitors,ROS production was significantly inhibited,Duox1 and MUC5AC mRNA and protein expressions were decreased(P<0.05),while after giving PKCα/β,ROS generation,Duox1 and MUC5AC mRNA and pro-tein expressions were not significantly changed compared with HNE group(P>0.05).Conclusion:HNE can mediate high expression of MUC5AC through PKCδ/θ-Duox1-ROS,which plays an important role in development of high secretion of airway mucus in vitro cell model experiment.

Objective To compare and analyze the results of hysterosalpingography(HSG)in primary infertility patients who received ultra-liquefied ethiodized poppyseed oil-based contrast medium or iodized oil-based contrast medium.Methods A total of 212 patients with primary infertility who received HSG examination were enrolled,of which 96 patients were in the ultra-liquefied ethiodized pop-pyseed oil-based contrast medium group,while 116 patients were in the iodized oil-based contrast medium group.The visual analogue scale(VAS)score of pain during HSG,adverse reactions(allergic reaction of contrast medium,contrast medium reflux,etc.),24 h-peri-toneal distribution and natural pregnancy rate within 1 year after HSG were analyzed between the two groups.Results The VAS score[(1.62±0.92)points]and the incidence of contrast medium reflux(5.2％)in the ultra-liquefied ethiodized poppyseed oil-based con-trast medium group were lower than those in the iodized oil-based contrast medium group[(3.2±1.42)points and 13.8％],respectively and the differences between the two groups were statistically significant(P＜0.05).In the 24 h-peritoneal distribution,the diagnosis rate of mild pelvic adhesion in the ultra-liquefied ethiodized poppyseed oil-based contrast medium group(26％)was lower than that in the iodized oil-based contrast medium group(39.7％),and the difference was statistically significant(P=0.041).The natural pregnancy rate of the two groups within 1 year was significantly improved,but there was no significant difference between the two groups(P＞0.05).Conclusion Ultra-liquefied ethiodized poppyseed oil-based contrast medium has less pain,lower incidence adverse reactions and better peritoneal distribution,and improve the natural pregnancy rate in primary infertility patients undergoing HSG.It is a high priority contrast medium for HSG.

Objective:To determine the expression and diagnostic value of peripheral blood lymphocytes and functional activation status in non-Hodgkin lymphoma with hemophagocytic lymphohistiocytosis (NHL-HLH) .Methods:We retrospectively analyzed clinical data from 30 newly diagnosed NHL-HLH patients admitted to Jiangsu Province Hospital from September 2022 to September 2023. We assessed peripheral blood lymphocytes and activation status by flow cytometry. Forty newly diagnosed patients with NHL who received treatment at our hospital during the same period and had lymphocyte and functional activation indexes were selected as the control group. The differences in relative and absolute lymphocyte counts and functional activation indexes between the two groups were compared. The optimal cutoff values for continuous variables were calculated from the receiver operating characteristic curve and logistic regression analysis was used to evaluate the risk factors in NHL patients with HLH.Results:A total of 30 NHL-HLH patients were evaluated, including 12 T-cell lymphoma and 18 B-cell lymphoma patients. Forty individuals were in the control group, which included 19 T-cell lymphoma and 21 B-cell lymphoma patients. The absolute counts of CD3 + T, CD4 + T, CD8 + T, and NK cells, along with the relative count of NK cells, were significantly lower in the HLH group compared with that in the control group (all P values<0.01) . The expression of CD38 and HLA-DR on CD8 + T-cell activated subgroups was significantly higher in the NHL-HLH group compared with that in the control group (CD8 +CD38 +/CD8 + T expression median: 57.4% vs 21.5%, P<0.001; CD8 +CD38 +/CD8 + T expression median: 49.7% vs 33.5%, P=0.028, respectively) . In addition, CD28 expression on CD4 + and CD8 + T cells was significantly higher in NHL-HLH patients ( P<0.01) . ROC curve and multivariate logistic regression analyses revealed that absolute NK cell count ≤72.0 cells/μl, CD4 +CD28 +/CD4 + T >94.2%, and CD8 +CD28 +/CD8 + T >38.4% were risk factors for predicting the occurrence of NHL-HLH patients. The sensitivity and specificity of the regression model were 86.7% and 86.1%, respectively, with an area under the curve of 0.94 ( P<0.001) . Conclusions:In NHL patients with HLH, there was a significant reduction in the absolute number of peripheral blood lymphocyte subpopulations, whereas T-cell function was notably activated. Specifically, absolute counts of NK cells ≤72.0 cells/μl, CD4 +CD28 +/CD4 + T >94.2%, and CD8 +CD28 +/CD8 + T >38.4% were identified as risk factors for predicting the development of NHL-HLH patients. This will assist in early clinical diagnosis and treatment.