OBJECTIVE To systematically analyze the compatibility stability of commonly used intravenous antibiotics in the intensive care unit （ICU）， and to provide evidence-based support for rational clinical drug use. METHODS Medication data from the ICU of Hebei General Hospital between January and December 2024 were extracted from the Prescription Automatic Screening System. Commonly used intravenous antibiotics and other intravenous drugs in the ICU were selected through consultations with critical care and pharmacy experts in Hebei province， drug package inserts and compatibility information retrieved from Micromedex， Trissel’s Injectable Drug Handbook and PubMed. The physicochemical stability of drug combinations was analyzed. In addition， Cytoscape 3.10.2 software was used to construct a drug compatibility network for identifying high-risk drugs. RESULTS &CONCLUSIONS A total of 904 pairwise drug combinations involving 16 antibacterial agents and 65 intravenous drugs were collected. Among them， 549 combinations （60.7%） were compatible， 88 combinations （9.7%） were incompatible， 82 combinations （9.1%） had conflicting evidence， and 185 combinations （20.5%） lacked valid data support. High-risk combination drugs primarily involved Amphotericin B for injection， Ceftazidime for injection， Imipenem-cilastatin for injection， Ceftriaxone sodium for injection， Vancomycin hydrochloride for injection， etc. The main risk factors for drug-drug incompatibility included drug concentration， temperature， mixing rate， pH， and chemical structure. In clinical practice， drugs and diluents should be selected rationally based on specific compatibility data， and research and monitoring of drug compatibility should be further strengthened.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Objective:To investigate the protective effects of resveratrol (RSV) on human sperm cryopreservation and explore its underlying protective mechanisms.Methods:A total of 165 normal fresh semen samples were collected from the Reproductive Medicine Center, Department of Obstetrics and Gynecology and Human Sperm Bank of the First Affiliated Hospital of Anhui Medical University between December 2022 and December 2024. Among them, 65 samples were used to obtain semen parameters before and after conventional freezing. Each sample of the other 104 samples was mixed at a 2∶1 volume ratio with cryoprotectant containing 0, 10 -?, 10 -?, or 10 -? mol/L RSV, followed by cryopreservation in liquid nitrogen for 24 h. Post-thaw assessments included routine sperm parameters, sperm DNA fragmentation index (DFI) evaluated by sperm chromatin dispersion assay, reactive oxygen species (ROS) levels measured via flow cytometry, RSV and nuclear factor erythroid 2-related factor 2 (NRF2) interactions examined by molecular docking and cellular thermal shift assay (CETSA), NRF2 protein contents analyzed by immunofluorescence and Western blotting, mRNA levels of NRF2 and downstream antioxidant proteins Heme Oxygenase-1 (HO-1) and NAD(P)H: quinone oxidoreductase 1 (NQO1) quantified by qRT-PCR and effects of NRF2 inhibitor ML385 on sperm parameters. Results:Compared with fresh samples, conventional cryopreservation significantly reduced sperm motility (all P<0.001). The addition of 10 -? mol/L RSV significantly improved the percentage of forward motile sperm after freezing (26.98%±8.98% vs. 19.61%±8.03%, P<0.001) while reducing DFI (9.84%±3.81% vs. 15.06%±4.22%, P<0.001) and ROS levels ( P<0.001) compared with the post-freezing group without the addition of RSV. Both molecular docking analysis and CETSA confirmed that RSV interacted with NRF2. Notably, sperm cryopreserved with 10 -? mol/L RSV exhibited significantly higher contents of NRF2 and its downstream effectors HO-1 and NQO1 compared with the post-freezing group without the addition of RSV (all P<0.001). This protective effect was markedly attenuated by co-treatment with the NRF2 inhibitor ML385, as evidenced by a significant decline in sperm motility ( P<0.001). Conclusion:RSV exerts cryoprotective effects likely through NRF2-mediated antioxidant pathways, reducing oxidative stress and enhancing post-thaw sperm quality.

This article reported the clinical pharmacist's involvement in the treatment of a high-risk neuroblastoma pediatric patient with naxitamab and the implementation of individualized medication monitoring.Upon admission,the clinical pharmacist collaborated with the physician to develop a dosing regimen and an allergy-prevention plan for naxitamab.On the day of administration,the pediatric patient experienced an infusion-related reaction.After evaluating by the physician and clinical pharmacist,the pediatric patient was administed albumin for volume expansion,electrolyte supplementation,vasopressor support,and mechanical ventilation,while temporarily suspending naxitamab infusion.Concurrent anti-inflammatory and infection-prevention therapies led to the pediatric patient's improvement,allowing the completion of the remaining three naxitamab infusions.The clinical pharmacist provided pharmaceutical recommendations for infusion-related pain,rash,and hypotension,which were adopted by the physician.As one of the earliest cases of naxitamab use in China,this case highlighted the role of clinical pharmacists in pharmaceutical care for patient with complex conditions,particularly in optimizing treatment plans and ensuring medication safety,offering practical experience and reference for the rational use of naxitamab in pediatric patients.

Through molecular docking and experimental validation,24 SPF male KM mice were ran-domly divided into four groups:the control group(CON),model group(LPS),high-dose Yang Shuhua group(YSH-H),which was gavaged with drug solution containing 1 g/mL crude Yang Shuhua,and the low-dose Yang Shuhua group(YSH-L),which was gavaged with drug solution containing 0.5 g/mL crude Yang Shuhua for a 17-day experimental period.Mouse body weight was recorded during the experiment,and fecal scoring was done 1 h after intraperitoneal injection of LPS.At the end of the experiment,histopathological changes in the jejunum tissue were examined,and the expression of tight junction protein-related genes was detected.Compared to the CON group,mice in the LPS group showed significant decreases in villus height,villus height/crypt depth(V/C)ratio(P＜0.01),and significant increase in crypt depth(P＜0.01).The mRNA ex-pression levels of ZO-1 and claudin-1 were significantly decreased(P＜0.01).Compared to the LPS group,mice in the YSH-H group showed significant decrease in crypt depth(P＜0.05),significant increase in villus height(P＜0.05),and significant increase in V/C ratio(P＜0.01).The YSH-L group showed a significant increase in V/C ratio(P＜0.05),a trend of decreased crypt depth,and an increasing trend of villus height.The mRNA expression of ZO-1 in the YSH-H group showed a significant increase(P＜0.05)and claudin-1 showed an increasing trend.Luteolin,quercetin,kaempferol,eriodictyol,and the top 5 potential key targets TP53,IL-1β,TNF,AKT1,and IL-10 exhibited molecular docking scores less than-20.95 kJ/mol,indicating strong activity.GO and KEGG enrichment analysis suggested that Yang Shuhua compounds might act on enteritis through the TNF signaling pathway,IL-17 signaling pathway,and PI3K-Akt signaling pathway.The qPCR results showed an upward trend in the mRNA expression levels of TLR4 and AKT1,significant in-crease in Caspase-1 and ASC(P＜0.05),and significantly increased expression of NF-κB and NL-RP3(P＜0.01).The mRNA expression level of AKT1,TLR4,NLRP3,ASC,Caspase-1,and NF-κB decreased compared to the LPS group,with significant differences in Caspase-1 and NF-κB(P＜0.05).This study suggests that Yang Shuhua exerts anti-enteritis effects through multiple compo-nents and pathways,with blockade of the TLR4-AKT-NF-κB pathway possibly being a key thera-peutic mechanism for treating enteritis.

Objective To investigate the clinical features of chronic hepatitis C(CHC)patients with hepatitis C virus genotype 3(HCV GT3)infection and the risk factors for disease progression.Methods A multicenter retrospective cohort study was conducted among 1 002 CHC patients from 11 clinical centers in Northwest China from December 2017 to November 2023,and according to their genotype,they were divided into GT1,GT2,GT3,and GT6 groups.Clinical features were compared between the patients with different genotypes.The one-way analysis of variance was used for comparison of normally distributed continuous data between groups,and the Scheffe test was used for further comparison between two groups.The Kruskal-Wallis H test was used for comparison of data with skewed distribution between groups;the chi-square test or Fisher test was used for comparison of categorical data between groups.The multivariate logistic regression analysis was used to explore the influencing factors for the progression of CHC to liver cirrhosis.Results In terms of the genotype,there were 427 patients with GT1 infection,242 with GT2 infection,299 with GT3 infection(210 patients with GT3a infection,87 with GT3b infection,and 2 with unclassified genotype),and 34 with GT6 infection.The patients with GT3 infection had a significantly younger age than those with GT1 infection(51.3±0.5 years vs 53.2±0.6 years,P<0.05)or GT2 infection(51.3±0.5 years vs 53.7±0.8 years,P<0.05),and for the patients with liver cirrhosis,the patients with GT3 infection had a significantly younger age than those with GT1 infection(52.1±0.5 years vs 59.4±0.9 years,P<0.001)or GT2 infection(52.1±0.5 years vs 58.1±1.1 years,P<0.001).Among the patients with GT3 infection,male patients accounted for 77.9%and the patients with liver cirrhosis accounted for 46.2%,which were significantly higher than those among the patients with GT1,GT2 or GT6 infection(all P<0.001).At baseline,the patients with GT3 infection had significantly higher levels of alanine aminotransferase(ALT)and aspartate aminotransferase(AST)than those with GT1 or GT2 infection,significantly higher aspartate aminotransferase-to-platelet ratio index(APRI)and fibrosis-4(FIB4)than those with GT1,GT2 or GT6 infection,a significantly lower platelet count(PLT)than those with GT2 or GT6 infection,a significantly higher level of alpha-fetoprotein than those with GT2 or GT6 infection,and a significantly lower level of albumin(Alb)than those with GT6 infection(all P<0.05).There were no significant differences between the patients with GT3a infection and those with GT3b infection in age,sex,the proportion of patients with liver cirrhosis,comorbidities,HCV RNA quantification,PLT,ALT,AST,alkaline phosphatase,Alb,APRI,and FIB-4(all P>0.05).The multivariate logistic regression analysis showed that PLT≤150×109/L(odds ratio[OR]=10.72,95%confidence interval[CI]:5.76-35.86,P<0.001)and Alb≤35 g/L(OR=3.74,95%CI:1.22-11.45,P=0.021)were risk factors for liver cirrhosis.Conclusion Most CHC patients with GT3 infection are male in Northwest China,and compared with the patients with other genotypes,such patients tend to have a younger age of onset and higher degrees of liver inflammation activity and fibrosis.Low PLT and a low level of Alb are risk factors for progression to liver cirrhosis in CHC patients with GT3 infection.

Objective:To investigate the protective effects of resveratrol (RSV) on human sperm cryopreservation and explore its underlying protective mechanisms.Methods:A total of 165 normal fresh semen samples were collected from the Reproductive Medicine Center, Department of Obstetrics and Gynecology and Human Sperm Bank of the First Affiliated Hospital of Anhui Medical University between December 2022 and December 2024. Among them, 65 samples were used to obtain semen parameters before and after conventional freezing. Each sample of the other 104 samples was mixed at a 2∶1 volume ratio with cryoprotectant containing 0, 10 -?, 10 -?, or 10 -? mol/L RSV, followed by cryopreservation in liquid nitrogen for 24 h. Post-thaw assessments included routine sperm parameters, sperm DNA fragmentation index (DFI) evaluated by sperm chromatin dispersion assay, reactive oxygen species (ROS) levels measured via flow cytometry, RSV and nuclear factor erythroid 2-related factor 2 (NRF2) interactions examined by molecular docking and cellular thermal shift assay (CETSA), NRF2 protein contents analyzed by immunofluorescence and Western blotting, mRNA levels of NRF2 and downstream antioxidant proteins Heme Oxygenase-1 (HO-1) and NAD(P)H: quinone oxidoreductase 1 (NQO1) quantified by qRT-PCR and effects of NRF2 inhibitor ML385 on sperm parameters. Results:Compared with fresh samples, conventional cryopreservation significantly reduced sperm motility (all P<0.001). The addition of 10 -? mol/L RSV significantly improved the percentage of forward motile sperm after freezing (26.98%±8.98% vs. 19.61%±8.03%, P<0.001) while reducing DFI (9.84%±3.81% vs. 15.06%±4.22%, P<0.001) and ROS levels ( P<0.001) compared with the post-freezing group without the addition of RSV. Both molecular docking analysis and CETSA confirmed that RSV interacted with NRF2. Notably, sperm cryopreserved with 10 -? mol/L RSV exhibited significantly higher contents of NRF2 and its downstream effectors HO-1 and NQO1 compared with the post-freezing group without the addition of RSV (all P<0.001). This protective effect was markedly attenuated by co-treatment with the NRF2 inhibitor ML385, as evidenced by a significant decline in sperm motility ( P<0.001). Conclusion:RSV exerts cryoprotective effects likely through NRF2-mediated antioxidant pathways, reducing oxidative stress and enhancing post-thaw sperm quality.

Objective:To explore the formulation patterns and potential targets of traditional Chinese medicine (TCM) in the treatment of pneumoconiosis using data mining, network pharmacology, and Mendelian randomization (MR) .Methods:In November 2023, prescription data for TCM compound treatments of pneumoconiosis from the past five years were retrieved from the China National Knowledge Infrastructure (CNKI), Wanfang, and VIP databases. The formulation patterns of TCM for pneumoconiosis were analyzed based on drug frequency, association rules, and cluster analysis, followed by the identification of core drugs. Network pharmacology and MR analysis were then applied to determine the potential targets for pneumoconiosis treatment.Results:A total of 100 TCM prescriptions were included, involving 182 herbs, with 15 high-frequency herbs. A total of 24 strong association rules were identified, including 16 herbs. Cluster analysis identified three groups of drug combinations. The core drug combination, "Astragalus Root-Codonopsis Root-Tangkuei-Chinese Magnolia Vine Fruit-Danshen Root-Prepared Rehmannia Root" was determined, which interacted with 47 common targets associated with pneumoconiosis. Further protein-protein interaction (PPI) analysis identified 18 core targets, and MR analysis confirmed that Caspase-3 (CASP3) and Cathepsin B (CTSB) were risk factors for pneumoconiosis ( OR=1.35, 1.44; P=0.038, 0.038) . Conclusion:The core drug combination for the treatment of pneumoconiosis with TCM is "Astragalus Root-Codonopsis Root-Tangkuei-Chinese Magnolia Vine Fruit-Danshen Root-Prepared Rehmannia Root". The medication mainly focuses on tonifying lung qi, moistening dryness and stopping coughing, circulating blood and transforming stasis, which are supplemented with herbs for nourishing yin and moistening dryness, warming yang and dissipating cold. Finally, the key targets for treating pneumoconiosis are screened out, providing an important basis for the development of therapeutic drugs for it.

Objective To investigate the clinical features of chronic hepatitis C(CHC)patients with hepatitis C virus genotype 3(HCV GT3)infection and the risk factors for disease progression.Methods A multicenter retrospective cohort study was conducted among 1 002 CHC patients from 11 clinical centers in Northwest China from December 2017 to November 2023,and according to their genotype,they were divided into GT1,GT2,GT3,and GT6 groups.Clinical features were compared between the patients with different genotypes.The one-way analysis of variance was used for comparison of normally distributed continuous data between groups,and the Scheffe test was used for further comparison between two groups.The Kruskal-Wallis H test was used for comparison of data with skewed distribution between groups;the chi-square test or Fisher test was used for comparison of categorical data between groups.The multivariate logistic regression analysis was used to explore the influencing factors for the progression of CHC to liver cirrhosis.Results In terms of the genotype,there were 427 patients with GT1 infection,242 with GT2 infection,299 with GT3 infection(210 patients with GT3a infection,87 with GT3b infection,and 2 with unclassified genotype),and 34 with GT6 infection.The patients with GT3 infection had a significantly younger age than those with GT1 infection(51.3±0.5 years vs 53.2±0.6 years,P<0.05)or GT2 infection(51.3±0.5 years vs 53.7±0.8 years,P<0.05),and for the patients with liver cirrhosis,the patients with GT3 infection had a significantly younger age than those with GT1 infection(52.1±0.5 years vs 59.4±0.9 years,P<0.001)or GT2 infection(52.1±0.5 years vs 58.1±1.1 years,P<0.001).Among the patients with GT3 infection,male patients accounted for 77.9%and the patients with liver cirrhosis accounted for 46.2%,which were significantly higher than those among the patients with GT1,GT2 or GT6 infection(all P<0.001).At baseline,the patients with GT3 infection had significantly higher levels of alanine aminotransferase(ALT)and aspartate aminotransferase(AST)than those with GT1 or GT2 infection,significantly higher aspartate aminotransferase-to-platelet ratio index(APRI)and fibrosis-4(FIB4)than those with GT1,GT2 or GT6 infection,a significantly lower platelet count(PLT)than those with GT2 or GT6 infection,a significantly higher level of alpha-fetoprotein than those with GT2 or GT6 infection,and a significantly lower level of albumin(Alb)than those with GT6 infection(all P<0.05).There were no significant differences between the patients with GT3a infection and those with GT3b infection in age,sex,the proportion of patients with liver cirrhosis,comorbidities,HCV RNA quantification,PLT,ALT,AST,alkaline phosphatase,Alb,APRI,and FIB-4(all P>0.05).The multivariate logistic regression analysis showed that PLT≤150×109/L(odds ratio[OR]=10.72,95%confidence interval[CI]:5.76-35.86,P<0.001)and Alb≤35 g/L(OR=3.74,95%CI:1.22-11.45,P=0.021)were risk factors for liver cirrhosis.Conclusion Most CHC patients with GT3 infection are male in Northwest China,and compared with the patients with other genotypes,such patients tend to have a younger age of onset and higher degrees of liver inflammation activity and fibrosis.Low PLT and a low level of Alb are risk factors for progression to liver cirrhosis in CHC patients with GT3 infection.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.