OBJECTIVE To explore the main factors influencing the blood concentration of duloxetine， and provide a scientific basis for the individualized use of duloxetine. METHODS Retrospective analysis was conducted on 434 inpatients with depressive disorders at the First Hospital of Hebei Medical University， who were treated with duloxetine and underwent blood concentration monitoring between January 2022 and April 2024. The study examined the impact of various factors， including gender， age， body mass index （BMI）， gene phenotypes， combined medication， drug type （original/generic）， and genotyping results of gene single nucleotide polymorphism loci， on blood concentration and the concentration-to-dose （C/D） after dose adjustment. RESULTS The blood concentration of duloxetine was 76.65 （45.57， 130.31） ng/mL， and C/D was 0.96 （0.63， 1.60） ng·d/（mL·mg）. The blood concentration of duloxetine was positively correlated with the daily dose of administration （R2＝0.253 7， P＜0.001）. Blood concentration of duloxetine in 38.94% of patients exceeded the recommended range specified in the guidelines. Gender， age， BMI， combined use of CYP2D6 enzyme inhibitors， and CYP2D6 and CYP1A2 phenotypes had significant effects on C/D of duloxetine （P＜0.05）. CONCLUSIONS The patient’s age， gender， BMI， combined medication， and genetic phenotypes are closely related to the blood concentration of duloxetine.

Objective To explore the research hotspots and development trends in the field of cancer treatment in the past decade. Methods The CNKI and Web of Science Core Collection databases were searched for Chinese and English articles related to cancer treatment published over the last 10 years. Bibliometric research methods were employed, including keyword cluster analysis of published literature. Results A total of 45 455 Chinese articles and 866 958 English articles were retrieved. Combining the visualization analysis results and the current research dilemma of tumor treatment revealed that the current research hotspots of tumor treatment domestically and internationally can primarily focus on four key areas. In the realm of targeted therapy, efforts are directed towards the discovery of new drug targets, overcoming resistance to targeted therapy, and the development of monoclonal antibodies and antibody–drug conjugates. In the field of immunotherapy, the emphasis lies in enhancing the response rate to immune checkpoint inhibitors, determining the mechanisms behind resistance to immunotherapy, and improving the safety of treatment. The research in traditional Chinese medicine (TCM) covers evidence-based evaluation studies on TCM treatment, the identification of populations that can gain the most benefit from TCM, and strategies for improving the quality of life. In the area of novel drug development, cutting-edge technologies, such as organoid-based screening for anticancer drugs, synthetic biology, and artificial intelligence, are under investigation. Conclusion New targeted drugs, immune efficacy improvement, multidisciplinary integration, nano-delivery, and TCM innovation are the key research directions in the field of tumor therapy in the future.

OBJECTIVE To establish the HPLC fingerprint of Xintong granules and the quantitative analysis of multi- components by single-marker method （QAMS） to determine the contents of 7 components， so as to provide a scientific basis for their quality control. METHODS HPLC method was used to establish the fingerprints for 10 batches of Xintong granules （No. S1- S10）， and similarity evaluation， cluster analysis （CA） and partial least squares-discriminant analysis （PLS-DA） were performed. At the same time， the contents of seven components， including puerarin， daidzin， calycosin-7-O- β -D-glucoside， stilbene glycoside， naringin， icariin and tanshinone ⅡA， were determined by QAMS method， and were compared with the results of external standard method. RESULTS A total of 18 common peaks were marked and 7 peaks were identified in the HPLC fingerprints for 10 batches of Xintong granules， namely puerarin （peak 4）， daidzin （peak 7）， calycosin-7-O-β-D-glucoside （peak 9）， stilbene glycoside （peak 10）， naringin （peak 12）， icariin （peak 17）， and tanshinone ⅡA （peak 18）； the similarities among them were more than 0.990， and CA and PLS-DA results showed that S4-S5，S8-S10，S1-S3 and S6-S7 were clustered into three categories， respectively. Using naringin as the internal standard， the contents of puerarin， daidzin， calycosin-7-O-β-D-glucoside， stilbene glycoside， icariin and tanshinone ⅡA were determined to be 7.868 1-10.181 2， 1.709 2-2.374 1， 0.285 2-0.326 3， 1.024 1- 1.523 9， 0.140 2-0.290 4， and 0.077 1-0.219 4 mg/g， respectively， by the QAMS. These results showed no significant differences compared to those obtained by the external standard method. CONCLUSIONS Established HPLC fingerprint and QAMS method are convenient， stable and accurate， which can provide a basis for the quality evaluation of Xintong granules.

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.

Background Bisphenol compounds are non-persistent environmental endocrine disruptors and frequently detected in drinking water systems, indicating potential human health risks through drinking water. Objective To establish and optimize a simultaneous determination method for 16 BPs in drinking water by online solid-phase extraction-ultra high-performance liquid chromatography-triple quadrupole mass spectrometry, in order to efficiently monitoring BPs in drinking water. Methods Candidate online solid-phase extraction conditions, chromatographic columns, mobile phase systems, mass spectrometry parameters, and other conditions were compared by chromatographic peaks of BPs, and processing conditions such as water sample preservation and pretreatment were optimized. The pH level of drinking water samples was adjusted and solid particles were removed. After extraction and purification by an online solid-phase extraction system, samples were detected by ultra-high performance liquid chromatography tandem mass spectrometry and quantified by isotope internal standard method. The proposed method was verified by pure water and terminal tap water, and evaluated by spiked recovery rate and relative standard deviation. Eighty-eight tap water samples from different regions of local pipeline network were collected for method application. Results For the 16 BPs, the calibration curves showed good linearity between 1.0 and 75 ng·L⁻¹ and the correlation coefficients were greater than 0.995. The detection limit of the method was less than 0.30 ng·L⁻¹, and the quantification limit of the method was less than 1.0 ng·L⁻¹. When the spiked concentrations for the 16 BPs were 5.0, 15, and 40 ng·L⁻¹, the average spiked recovery rates of the test substances were between (100 ± 10)%, and the relative standard deviations were all below 10%. In the method application to the local terminal water samples, the positive rates of bisphenol S (BPS), bisphenol A (BPA), and bisphenol AF (BPAF) were as high as 93.2%, 77.3%, and 29.5%, respectively. The concentrations of BPS were from not detected (N.D.) to 37.8 ng·L⁻¹, and the concentrations of BPA were from N.D. to 52.0 ng·L⁻¹. Conclusion The method using an online solid-phase extraction system is established, featuring simple pre-treatment, small sample volume, high degree of automation, low detection limit, and good accuracy and precision. This method can be applied to the quantitative monitoring of 16 BPs at ng·L⁻¹ level in drinking water.

Objective To study the effects of sodium cantharidinate (SC) on the proliferation and apoptosis of gastric cancer cells through JAK2/ STAT3 pathway. Methods Gastric cancer cell line SGC-7901 was cultured and treated with different concentrations of SC (0.25, 0.5, 1.0, 2.0, 4.0, 8.0, and 16.0 μmol/L) and then transfected with control plasmid or JAK2 plasmid. Cell survival rate, apoptosis rate, and the expression levels of p-JAK2, p-STAT3, p-p38, p-ERK, and p-JNK were detected after 48 h of treatment. Results The results indicated that 1.0, 2.0, 4.0, 8.0, and 16.0 μmol/L of SC inhibited cell proliferation, and the survival rate decreased with an increase in SC concentration (P<0.05). SC doses of 1.0, 2.0, and 4.0 μmol/L were selected for the subsequent experiments. Compared with the control group, the apoptosis rate of the 1.0 μmol/L SC group exhibited no significant difference (P>0.05), while those of the 2.0 and 4.0 μmol/L SC groups increased significantly (P<0.05). The expression levels of p-JAK2 and p-STAT3 significantly decreased (P<0.05), while no significant difference was noted in the expression levels of p-p38, p-ERK, and p-JNK (P>0.05) in the 1.0, 2.0, and 4.0 μmol/L SC groups. The JAK2 plasmid was transfected simultaneously with the 4.0 μmol/L SC treatment; the expression levels of p-JAK2 and p-STAT3 and the survival rate increased, whereas the apoptosis rate decreased (P<0.05). Conclusion SC inhibits the growth and promotes the apoptosis of gastric cancer cells, and its mechanism may be related to the inhibition of JAK2/STAT3 pathway activation.

Objective Based on the U.S.Food and Drug Administration Adverse Event Reporting System(FAERS)database,data mining was conducted on hematological adverse events related to antibody drug conjugates(ADC),providing reference for the safe use of ADC drugs in clinical practice.Methods The report data from the third quarter of 2011 to the fourth quarter of 2022 were retrieved from the FAERS database.After data cleaning such as deduplication and name standardization,extract hematological adverse events related to ADC,and use report odds ratio method and the information component method for signal detection.Results A total of 101 610 adverse event reports were extracted,with 8 ADC drugs as the primary suspected drugs,and 5 768 ADC related hematological adverse event reports.Among them,3 423 cases of agranulocytosis were involved,and the signal intensity from strong to weak were sacituzumab govitecan(SG),gemtuzumab ozogamicin(GO),brentuximab vedotin(BV),polatuzumab vedotin(PV),enfortumab vedotin(EV),trastuzumab deruxtecan(TD),inotuzumab ozogamicin(IO)and ado-trastuzumab emtansine(TDM-1).There were 2 327 cases hematopoietic cell deficiency,with signals ranging from strong to weak were IO,SG,BV,EV,PV,TD,TDM-1,and GO.Report with clinical outcome of death of ADC drug related hematological adverse events included BV 179(16.84％),TDM-1 102(13.01％),TD 88(27.08％),GO 12(16.90％),IO 8(11.59％),EV 54(24.32％),PV 22(27.16％),and SG 84(21.05％).Adverse event time analysis showed that the number of events on the first day of TD,IO,and SG medication accounts for ≥ 40％of the total number of cases.The median time of hematological adverse events in TD,GO,IO,EV,PV,and SG was within one treatment course(21 days).Conclusion Attention should be paid to the risk of ADC drug-related hematological adverse event,during the clinical medication process,blood cell count changes should be closely monitored,and any abnormalities should be promptly diagnosed and treated.

OBJECTIVE To observe the changes of cardiac function,local inflammation level and macrophage M2 polarization in mice with acute myocardial infarction(AMI after electroacupuncture preconditioning at the Neiguan point,and to explore the possible mechanisms from the perspective of regulating the DNA-PK/Rictor/Myc signaling pathway.METHODS Male C57BL/6J mice were randomly divided into sham group,model group and electroacupuncture group,with 10 mice in each group.The electroacupuncture group received bilateral electroacupuncture interventions at the Neiguan points,sparse-dense wave,2/15 Hz,1 mA,20 min/time,once a day for 3 consecutive days,and AMI models were performed 0.5 h after the electroacupuncture interventions.The myocardial ischemia model was prepared by ligating the left anterior descending branch.Echocardiography was used to detect cardiac ejection frac-tion(EF and fractional shortening(FS to evaluate cardiac function;HE and TUNEL staining were used to observe the pathological morphology of myocardium and apoptosis of cardiomyocytes,and immunohistochemistry and ELISA were used to detect IL-1β,TNF-α and NLRP3 in infarcted myocardium and peripheral blood to evaluate the level of inflammation;flow cytometry was used to detect cardiac macrophage polarization status,and Western blot method to detect the protein expression levels of DNA-PK,p-DNA-PK,Rictor and Myc in infarcted myocardium.RESULTS Compared with the sham group,the model group showed significantly lower EF and FS(P<0.000 1,significant inflammatory cell infiltration,significantly higher cardiomyocyte apoptotic index(P<0.001,up-regulated expression of IL-1β,NLRP3 and TNF-α in the myocardium and serum(P<0.01,P<0.001,a significant increase in the percentage of macrophages(P<0.001,a decrease in the percentage of cardiac M2-type macrophages(P<0.000 1,and a significant decrease in the expression levels of p-DNA-PK,Rictor and Myc proteins in myocardium(P<0.05,P<0.000 1.Compared with the model group,EF and FS were significantly higher in the electroacupuncture group(P<0.000 1,inflammatory cell infiltration was re-duced,cardiomyocyte apoptotic index was decreased(P<0.01,and the expression of IL-1β,NLRP3 and TNF-α was down-regula-ted in myocardium and serum(P<0.05,P<0.01,P<0.001;the macrophage percentage was decreased(P<0.05,cardiac M2-type macrophage percentage was increased(P<0.01,and p-DNA-PK,Rictor and Myc protein expression was enhanced in myocardium(P<0.05,P<0.01,P<0.000 1.CONCLUSION Electroacupuncture preconditioning may promote macrophage M2 polarization,attenuate local inflammation,and reduce cardiomyocyte apoptosis by modulating the DNA-PK/Rictor/Myc signaling pathway,thus im-proving cardiac function and achieving myocardial protective effects.

  Objective  To evaluate the severity and features of pelvic coronal plane tilt in individuals with adolescent idiopathic scoliosis (AIS) who had lumbar curvature during the gait cycle.  Methods  AIS patients with lumbar curvature and patients with microcurvature (Cobb Angle less than 10 degrees) treated in Peking Union Medical College Hospital from September 2020 to February 2023 were retrospectively included. According to PUMC conservative classification system and Spinal Full-length Standing X-ray, AIS patients with lumbar curvature were enrolled. The bilateral iliac crest was used as the bony marker of the pelvic coronal surface, and the bilateral iliac crest height and its changes were measured during the standing position and walking cycle, so as to evaluate the degree of pelvic coronal tilt in AIS patients with lumbar curvature.  Results  A total of 209 AIS patients with lumbar curvature and 36 patients with microcurvature who met the inclusion and exclusion criteria were enrolled. The proportion of AIS patients with lumbar curvature who had a "congruent" relationship between the higher iliac crest and the convex side of the spine in standing position (iliac crest lower on the convex side than on the concave side) was significantly higher in AIS patients with lumbar curvature than patients with microcurvature(58.9% vs. 30.6%, P=0.002). AIS patients with lumbar curvature had statistically different bilateral iliac crest height change values throughout the gait cycle (including minimum, maximum, swing phase minimum, and swing phase maximum) (all P < 0.001), and the iliac crest height change values on the convex side were significantly higher than those on the concave side (all P < 0.05), whereas the patients with microcurvature did not have any statistically significant bilateral iliac crest height change values throughout the gait cycle (all P > 0.05).  Conclusion  The height of the iliac crest on the convex side of the lumbar spine is lower than that on the concave side in the standing position of AIS patients with lumbar curvature, and the value of the change of the iliac crest on the convex side of the pelvis is greater than that on the concave side in walking to maintain the balance of the body, which may provide a new direction for the intervention in the clinical rehabilitation treatment of AIS patients with lumbar curvature.

Objective:To analyze the pregnancy outcomes in patients with positive anti-centromere antibodies(ACA)receiving in vitro fertilization(IVF)-embryo transfer(ET)and natural conception.Methods:A case-control study was used to retrospectively analyze the clinical data of 3955 patients who received IVF-ET therapy and had the results of antinuclear antibody(ANA)spectrum at Zhejiang Provincial People's Hospital from June 2016 to June 2023.Patients with positive ACA and negative ACA were matched at a ratio of 1∶3 using propensity score matching.Embryo outcomes of IVF were compared between the two groups,and the impact of different fertilization methods and the use of immunosuppressants on pregnancy outcomes were analyzed using self-matching.The natural conception and disease progress were followed up for ACA-positive patients after IVF failure.Results:The ACA-positive patients accounted for 0.86%of all IVF patients(34/3955)and 2.51%of total ANA-positive IVF patients.Regardless of whether patients received conventional IVF(c-IVF)or intracytoplasmic sperm injection(ICSI),the ACA-positive group exhibited significant differences in oocyte maturity and fertilization compared to the ACA-negative group(both P＜0.01).Moreover,the ACA-positive group had a decreased number of D3 suboptimal embryos and D3 optimal embryos(both P＜0.05).In 5 cases of ACA-positive patients who underwent ICSI cycles,the two pronucleus(2PN)rate did not increase compared to c-IVF cycles(P＞0.05),and there was a decrease in the number of D3 high-quality embryos and D3 suboptimal embryos(both P＜0.05).After 1-2 months of immuno-suppressant treatment,12 ACA-positive patients underwent c-IVF/ICSI again,and there were no changes in egg retrieval and fertilization before and after medication(both P＞0.05),but there was an improvement in the 2PN embryo cleavage rate(P＜0.05).The number of embryos transferred was similar between the ACA-positive and negative groups,but the ACA-positive group had significantly lower embryo implantation rate and clinical pregnancy rate compared to the ACA-negative group(both P＜0.05),with no significant differences in the miscarriage rate between the two groups(P＞0.05).Twenty-seven ACA-positive patients attempted natural conception or artificial insemination after IVF failure,resulting in a total of 7 cases of clinical pregnancy.Conclusions:Serum ACA positivity may disrupt oocyte maturation and normal fertilization processes,with no improvement observed with ICSI and immunosuppressant use.However,ACA-positive patients may still achieve natural pregnancy.