BACKGROUND: While emotional distress, encompassing anxiety and depression, has been associated with negative clinical outcomes, its impact across various clinical departments and general hospitals has been less explored. Previous studies with limited sample sizes have examined the effectiveness of specific treatments (e.g., antidepressants) rather than a systemic management strategy for outcome improvement in non-psychiatric inpatients. To enhance the understanding of the importance of addressing mental health care needs among non-psychiatric patients in general hospitals, this study retrospectively investigated the impacts of emotional distress and the effects of early detection and management of depression and anxiety on hospital length of stay (LOS) and rate of long LOS (LLOS, i.e., LOS >30 days) in a large sample of non-psychiatric inpatients. METHODS: This retrospective cohort study included 487,871 inpatients from 20 non-psychiatric departments of a general hospital. They were divided, according to whether they underwent a novel strategy to manage emotional distress which deployed the Huaxi Emotional Distress Index (HEI) for brief screening with grading psychological services (BS-GPS), into BS-GPS ( n = 178,883) and non-BS-GPS ( n = 308,988) cohorts. The LOS and rate of LLOS between the BS-GPS and non-BS-GPS cohorts and between subcohorts with and without clinically significant anxiety and/or depression (CSAD, i.e., HEI score ≥11 on admission to the hospital) in the BS-GPS cohort were compared using univariable analyses, multilevel analyses, and/or propensity score-matched analyses, respectively. RESULTS: The detection rate of CSAD in the BS-GPS cohort varied from 2.64% (95% confidence interval [CI]: 2.49%-2.81%) to 20.50% (95% CI: 19.43%-21.62%) across the 20 departments, with a average rate of 5.36%. Significant differences were observed in both the LOS and LLOS rates between the subcohorts with CSAD (12.7 days, 535/9590) and without CSAD (9.5 days, 3800/169,293) and between the BS-GPS (9.6 days, 4335/178,883) and non-BS-GPS (10.8 days, 11,483/308,988) cohorts. These differences remained significant after controlling for confounders using propensity score-matched comparisons. A multilevel analysis indicated that BS-GPS was negatively associated with both LOS and LLOS after controlling for sociodemographics and the departments of patient discharge and remained negatively associated with LLOS after controlling additionally for the year of patient discharge. CONCLUSION Emotional distress significantly prolonged the LOS and increased the LLOS of non-psychiatric inpatients across most departments and general hospitals. These impacts were moderated by the implementation of BS-GPS. Thus, BS-GPS has the potential as an effective, resource-saving strategy for enhancing mental health care and optimizing medical resources in general hospitals.
Humans ; Retrospective Studies ; Male ; Length of Stay/statistics & numerical data* ; Female ; Middle Aged ; Adult ; Psychological Distress ; Inpatients/psychology* ; Aged ; Anxiety/diagnosis* ; Depression/diagnosis*

Objective To evaluate the effectiveness,safety and economy of generic venlafaxine sustained-release capsules and the original drug in clinical practice based on real world clinical data.Methods This is a multicenter,retrospective real-world study.The information of outpatients who used venlafaxine sustained-release capsules in 7 hospitals from October 2021 to October 2022 was collected,including prescription data and laboratory data.They were divided into generic drug group and original drug group.After the baseline level was corrected by propensity score match method,the prescription daily dose,plasma concentration,medication possession ratio,the continuous medication rate for 3,6 and 9 months,dressing change rate,the incidence of adverse reactions,the frequency of drug use,the average daily cost,the annual cost per capita and the proportion of the average annual cost of drugs were compared between the two groups.Results After the baseline level was corrected by propensity score matching method,the prescription daily dose and medication possession ratio(MPR≥0.8)in the generic drug group were higher than that of the original drug group(P＜0.05).There was no statistically difference in plasma concentration between the two groups(P=0.294).The continuous medication rate for 3,6 and 9 months in the generic drug group were statistically higher than those in the original drug group(P＜0.01).The single dressing change rate of the generic drug group was lower than that of the original drug group(P=0.032).There was no significant difference in the rate of secondary dressing change between the two groups(P=1.000).There were no significant differences in the incidence of abnormal ALT,AST,TC,Na,APTT,and PLC between two groups(P＞0.05).The average daily cost of the generic drug group was lower than that of the original drug group.The per capita annual cost of drugs and the proportion of average annual cost of drugs in the generic drug group were significantly lower than those in the original drug group(P＜0.01).Conclusion In the actual clinical diagnosis and treatment,no clinically significant differences in effectiveness and safety were found between the generic venlafaxine sustained-release capsule and the original-patented,while the economic advantages of the generic drug were better than that of the original-patented drug.

Objective To investigate the effect of Biejiajian Pill(BJJP)on malignant biological behavior of hepatocellular carcinoma Hep3B cells and its regulatory mechanism.Methods A total of 72 healthy SD rats were randomly divided into blank control(BC)group,low(0.55 g/kg),medium(1.10 g/kg)and high(2.20 g/kg)BJJP experimental group,and drug-containing serum was prepared.Hep3B cells were divided into BC group,normal rat serum treatment(NC)group,low dose BJJP(LBJJP)group,medium dose BJJP(MBJJP)group and high dose BJJP(HBJJP)group,empty plasmid(pcDNA3.1)group,and CKLF-like MARVEL transmembrane domain containing 6(CMTM6)overexpression(pcDNA3.1-CMTM6)group,and the NC+pcDNA3.1 group,MBJJP+pcDNA3.1 group,NC+pcDNA3.1-CMTM6 group and MBJJP+pcDNA3.1-CMTM6 group.The proliferation of hepatoma Hep3B cells was detected by CCK-8.The migration and invasion of hepatoma Hep3B cells were detected by Transwell assay.The expression levels of proliferation-related proteins proliferating cell nuclear antigen(PCNA),epithelial-mesenchymal transition(EMT)related proteins(E-cadherin,N-cadherin and Vimentin),and CMTM6 proteins in hepatoma Hep3B cells were detected by Western blotting experiments.Results Compared with those in BC group,there were no significant differences in the proliferation,migration and invasion abilities of Hep3B cells,or the expression levels of PCNA,EMT related proteins(E-cadherin,N-cadherin and Vimentin)and CMTM6 protein in NC group(P＞0.05).Compared with NC group,LBJJP,MBJJP and HBJJP drug-containing serum inhibited the proliferation,migration and invasion of Hep3B cells,downregulated the protein expression of PCNA;MBJJP and HBJJP upregulated the protein expression of E-cadherin.The protein expressions of N-cadherin,Vimentin and CMTM6 were downregulated,with significant differences(P＜0.05).Compared with pcDNA3.1 group,the protein expression of CMTM6,cell proliferation,migration,invasion,PCNA protein expression,N-cadherin protein expression,and Vimentin protein expression in Hep3B cells in pcDNA3.1-CMTM6 group were significantly upregulated,while the protein expression of E-cadherin was significantly downregulated(P＜0.05).Compared with NC+pcDNA3.1 group,the proliferation,migration and invasion abilities of Hep3B cells in MBJJP+pcDNA3.1 group were decreased,the expression levels of PCNA,Vimentin and N-cadherin protein were decreased,while the expression level of E-cadherin protein was increased.Compared with NC+pcDNA3.1-CMTM6 group,MBJJP+pcDNA3.1-CMTM6 group had the same results in the proliferation,migration and invasion abilities of Hep3B cells and the protein expression levels of PCNA,Vimentin,N-cadherin and E-cadherin.The differences were statistically significant(all P＜0.05).Conclusion BJJP may inhibit the proliferation,migration,invasion and EMT of hepatoma Hep3B cells by regulating the expression of CMTM6.

Objective To investigate the effect of Biejiajian Pill(BJJP)on malignant biological behavior of hepatocellular carcinoma Hep3B cells and its regulatory mechanism.Methods A total of 72 healthy SD rats were randomly divided into blank control(BC)group,low(0.55 g/kg),medium(1.10 g/kg)and high(2.20 g/kg)BJJP experimental group,and drug-containing serum was prepared.Hep3B cells were divided into BC group,normal rat serum treatment(NC)group,low dose BJJP(LBJJP)group,medium dose BJJP(MBJJP)group and high dose BJJP(HBJJP)group,empty plasmid(pcDNA3.1)group,and CKLF-like MARVEL transmembrane domain containing 6(CMTM6)overexpression(pcDNA3.1-CMTM6)group,and the NC+pcDNA3.1 group,MBJJP+pcDNA3.1 group,NC+pcDNA3.1-CMTM6 group and MBJJP+pcDNA3.1-CMTM6 group.The proliferation of hepatoma Hep3B cells was detected by CCK-8.The migration and invasion of hepatoma Hep3B cells were detected by Transwell assay.The expression levels of proliferation-related proteins proliferating cell nuclear antigen(PCNA),epithelial-mesenchymal transition(EMT)related proteins(E-cadherin,N-cadherin and Vimentin),and CMTM6 proteins in hepatoma Hep3B cells were detected by Western blotting experiments.Results Compared with those in BC group,there were no significant differences in the proliferation,migration and invasion abilities of Hep3B cells,or the expression levels of PCNA,EMT related proteins(E-cadherin,N-cadherin and Vimentin)and CMTM6 protein in NC group(P＞0.05).Compared with NC group,LBJJP,MBJJP and HBJJP drug-containing serum inhibited the proliferation,migration and invasion of Hep3B cells,downregulated the protein expression of PCNA;MBJJP and HBJJP upregulated the protein expression of E-cadherin.The protein expressions of N-cadherin,Vimentin and CMTM6 were downregulated,with significant differences(P＜0.05).Compared with pcDNA3.1 group,the protein expression of CMTM6,cell proliferation,migration,invasion,PCNA protein expression,N-cadherin protein expression,and Vimentin protein expression in Hep3B cells in pcDNA3.1-CMTM6 group were significantly upregulated,while the protein expression of E-cadherin was significantly downregulated(P＜0.05).Compared with NC+pcDNA3.1 group,the proliferation,migration and invasion abilities of Hep3B cells in MBJJP+pcDNA3.1 group were decreased,the expression levels of PCNA,Vimentin and N-cadherin protein were decreased,while the expression level of E-cadherin protein was increased.Compared with NC+pcDNA3.1-CMTM6 group,MBJJP+pcDNA3.1-CMTM6 group had the same results in the proliferation,migration and invasion abilities of Hep3B cells and the protein expression levels of PCNA,Vimentin,N-cadherin and E-cadherin.The differences were statistically significant(all P＜0.05).Conclusion BJJP may inhibit the proliferation,migration,invasion and EMT of hepatoma Hep3B cells by regulating the expression of CMTM6.

Objective To evaluate the effectiveness,safety and economy of generic venlafaxine sustained-release capsules and the original drug in clinical practice based on real world clinical data.Methods This is a multicenter,retrospective real-world study.The information of outpatients who used venlafaxine sustained-release capsules in 7 hospitals from October 2021 to October 2022 was collected,including prescription data and laboratory data.They were divided into generic drug group and original drug group.After the baseline level was corrected by propensity score match method,the prescription daily dose,plasma concentration,medication possession ratio,the continuous medication rate for 3,6 and 9 months,dressing change rate,the incidence of adverse reactions,the frequency of drug use,the average daily cost,the annual cost per capita and the proportion of the average annual cost of drugs were compared between the two groups.Results After the baseline level was corrected by propensity score matching method,the prescription daily dose and medication possession ratio(MPR≥0.8)in the generic drug group were higher than that of the original drug group(P＜0.05).There was no statistically difference in plasma concentration between the two groups(P=0.294).The continuous medication rate for 3,6 and 9 months in the generic drug group were statistically higher than those in the original drug group(P＜0.01).The single dressing change rate of the generic drug group was lower than that of the original drug group(P=0.032).There was no significant difference in the rate of secondary dressing change between the two groups(P=1.000).There were no significant differences in the incidence of abnormal ALT,AST,TC,Na,APTT,and PLC between two groups(P＞0.05).The average daily cost of the generic drug group was lower than that of the original drug group.The per capita annual cost of drugs and the proportion of average annual cost of drugs in the generic drug group were significantly lower than those in the original drug group(P＜0.01).Conclusion In the actual clinical diagnosis and treatment,no clinically significant differences in effectiveness and safety were found between the generic venlafaxine sustained-release capsule and the original-patented,while the economic advantages of the generic drug were better than that of the original-patented drug.

Objectives:To assess the effectiveness and safety of ivabradine for the treatment of chronic heart failure in the context of the new quadruple combination. Methods:Clinical data of 656 chronic heart failure patients hospitalized in Nanjing Drum Tower Hospital from March 2021 to June 2022 were retrospectively collected,and the patients were divided into control group(n=361)and observation group(n=295)according to ivabradine use,and both groups were treated with the new quadruple drug therapy.Propensity score matching was performed,268 patients in the observation group and 268 patients in the control group were successfully matched.The effectiveness(primary endpoint was the composite endpoint of cardiovascular death and rehospitalisation for worsening heart failure within 1 year of discharge;secondary endpoints were rehospitalisation for worsening heart failure,all-cause rehospitalisation,cardiovascular death,and all-cause death)and safety outcome measures(including bradycardia,atrial fibrillation,blurred vision,renal impairment,and hypertension)were compared between the two groups at 1 year after treatment. Results:After matching,there were no statistically significant differences at baseline characteristics between the two groups.Kaplan-Meier survival curve showed that the occurrence rates of primary endpoints(P=0.031),readmission for worsening heart failure(P=0.020),and all-cause readmission(P=0.036)were lower in the observation group than in the control group.Multivariate Cox proportional hazard regression analysis showed that the occurrence rates of primary endpoint events(P=0.045)and readmission for heart failure worsening(P=0.028)were lower in the observation group than in the control group. Conclusions:The ivabradine use on top of the new quadruple therapy regimen in patients with chronic heart failure is beneficial to improve one-year prognosis with favorable safety profile.

OBJECTIVE To evaluate the effects of ivabradine on vascular endothelial function in patients with coronary artery disease. METHODS PubMed， Embase， the Cochrane Library， Web of Science， CNKI， Wanfang Data， VIP and CBM databases were retrieved to collect randomized controlled trials （RCTs） about ivabradine （intervention group） versus placebo or β-blocker （control group） from the inception to Mar. 20th 2023. The meta-analysis was performed by using RevMan 5.4 software after literature screening， data extraction and quality evaluation. RESULTS A total of 12 RCTs were included， involving 1 206 patients. The results of meta-analysis showed that the levels of flow-mediated dilation （FMD） [MD＝1.71， 95%CI （0.96， 2.46）， P＜0.000 01] and nitric oxide （NO） [MD＝5.80， 95%CI （5.02， 6.59）， P＜0.000 01] in the intervention group were significantly higher than control group， while endothelin-1（ET-1） level was significantly lower than control group [MD＝－7.45， 95%CI （－8.42， －6.47）， P＜0.000 01]. There was no statistical significance in nitroglycerin-mediated dilation （NMD） level between 2 groups [MD＝0.13， 95%CI（－0.74， 1.00）， P＝0.77]. Subgroup analyses based on the different medications and intervention time in the control group showed better improvement in FMD level of patients receiving ivabradine， compared with placebo （P＜0.05）； compared with placebo and β-blocker， the level of NO in patients receiving ivabradine was improved significantly （P＜0.05）， while ET-1 level was decreased significantly （P＜0.05）. Regardless of the duration of the intervention， the levels of FMD， NO， and ET-1 in the intervention group were significantly improved compared to the control group （P＜0.01）， while the difference in NMD was not statistically significant （P＞0.05）. CONCLUSIONS Ivabradine can improve vascular endothelial function in patients with coronary artery disease.

Objective : To explore whether the NLRP3 inflammasome is activated after Newcastle disease virus (NDV) exposure to esophageal cancer ECA109 cells , whether its activation is related to K + efflux , and the effect of ATP/P2X7 axis on the activation of NLRP3 inflammasome. Methods: The expression of NLRP3 and IL⁃1β was detected by Western blot; the content of IL⁃1β in the supernatant was detected by ELISA ; the formation of ASC spots was detected by fluorescence immunoassay; the change of intracellular K + concentration was detected by fluorescent probe technology; Interventions with ATPase , ATP and P2X7 receptor inhibitors were used to investigate their role in NLRP3 inflammasome activation. Results: Compared with the control group , the expression of NLRP3 , IL⁃1β and ASC protein in cells was up⁃regulated after NDV F3 infection ; the intracellular potassium concen tration decreased with the prolongation of infection time (P < 0. 05) . After the intervention of P2X7 receptor inhibitor, the efflux of intracellular K + was blocked. With the increase of inhibitor concentration , the efflux of K + was maximally inhibited at 10 μmol/L (P < 0. 05) . The results of ATPase and ATP intervention showed that ATPase inhibited K + efflux , while ATP promoted K + efflux. Western blot results showed that compared with the control group , P2X7 receptor was inhibited , and the expressions of NLRP3 and IL⁃1β were down⁃regulated ; after ATPase intervened cells , the expressions of NLRP3 and IL⁃1β decreased ; After ATP intervention in cells , the protein expressions of NLRP3 and IL⁃1β were up⁃regulated (P < 0. 05) . Conclusion NDV F3 infection of ECA109 cells can activate the NLRP3 inflammasome , the mechanism may be related to the ATP/P2X7 axis.

AIM: To establish a ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method to determination the plasma concentration of clozapine and compare the bioequivalence of a generic clozapine tablet with Clozaril

OBJECTIVE Alzheimer's disease(AD)is the most common neurodegenerative disease worldwide.Neuroinflammation is a potential target for the patients with AD.It is attributed to activated microglia and the release of various inflammatory mediators from infec-tion,ischemia and toxin accumulation.Accumulating evi-dence has indicated that the cGAS-STING pathway driven neuroinflammation in neurological disease.TSG is a main natural active ingredient that derived from polyg-onum multiflorum.Previous research from our group found that TSG has beneficial effects of anti-aging,anti-inflammatory action and improving memory function in APP/PS1 transgenic AD mice.Here,we investigated the effects of TSG on cognitive impairment and neuroinflam-mation in APP/PS1-AD mice and explore the underly-ing mechanism by which TSG ameliorates memory func-tion in the cGAS-STING-mediated inflammatory response.METHODS The Morris water mace test and the novel object recognition test were performed to test the effects of TSG on spatial learning and cognitive and memory abil-ity in APP/PS1 double transgenic AD mice model.In addi-tion,real-time quantitative PCR,Western blotting,ELISA analysis,and flow cytometry to examine gene and pro-tein expression of cGAS-STING related pro-inflammatory cytokines and chemokines.Statistical analyses were ana-lyzed using the SPSS 25.0 package by analysis of vari-ance(ANOVA).Neuman-Keuls or Tukey's multiple-com-parisons test were conducted as ANOVA justified post hoc comparisons between group means.RESULTS We demonstrated that AD transgenic mice exhibited cognitive deficits accompanied by the elevated serum and brain inflammation.The expressions of serum inflammatory cytokines and the activation of microglia in cerebral cor-tex and hippocampus were suppressed after TSG treat-ment,which was probably attributable to the decrease of cyclic GMP-AMP synthase(cGAS)and stimulator of interferon genes(STING)triggered immune response.Additionally,the data showed that TSG treatment reduced the expression level of inflammatory cytokines(IL-1β,TNF-α,IFN-β,IFN-α)in microglial cells BV2 primed with LPS and IFN-γ.CONCLUSION TSG implicated the health benefits in preventing cognitive disorders by inhib-iting neuroinflammation via cGAS-STING signalling path-way in AD.