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*

This study aims to investigate the mechanism of Qingrun Decoction in alleviating hepatic insulin resistance in type 2 diabetes mellitus(T2DM) rats through the reprogramming of amino acid metabolism. A T2DM rat model was established by inducing insulin resistance through a high-fat diet combined with intraperitoneal injection of streptozotocin. The model rats were randomly divided into five groups: model group, high-, medium-, and low-dose Qingrun Decoction groups, and metformin group. A normal control group was also established. The rats in the normal and model groups received 10 mL·kg~(-1) distilled water daily by gavage. The metformin group received 150 mg·kg~(-1) metformin suspension by gavage, and the Qingrun Decoction groups received 11.2, 5.6, and 2.8 g·kg~(-1) Qingrun Decoction by gavage for 8 weeks. Blood lipid levels were measured in different groups of rats. Pathological damage in rat liver tissue was assessed by hematoxylin-eosin(HE) staining and oil red O staining. Transcriptome sequencing and untargeted metabolomics were performed on rat liver and serum samples, integrated with bioinformatics analyses. Key metabolites(branched-chain amino acids, BCAAs), amino acid transporters, amino acid metabolites, critical enzymes for amino acid metabolism, resistin, adiponectin(ADPN), and mammalian target of rapamycin(mTOR) pathway-related molecules were quantified using quantitative real-time polymerase chain reaction(qRT-PCR), Western blot, and enzyme-linked immunosorbent assay(ELISA). The results showed that compared with the normal group, the model group had significantly increased serum levels of total cholesterol(TC), triglycerides(TG), low-density lipoprotein cholesterol(LDL-C), and resistin and significantly decreased ADPN levels. Hepatocytes in the model group exhibited loose arrangement, significant lipid accumulation, fatty degeneration, and pronounced inflammatory cell infiltration. In liver tissue, the mRNA transcriptional levels of solute carrier family 7 member 2(Slc7a2), solute carrier family 38 member 2(Slc38a2), solute carrier family 38 member 4(Slc38a4), and arginase(ARG) were significantly downregulated, while the mRNA transcriptional levels of solute carrier family 1 member 4(Slc1a4), solute carrier family 16 member 1(Slc16a1), and methionine adenosyltransferase(MAT) were upregulated. Furthermore, the mRNA transcription and protein expression levels of branched-chain α-keto acid dehydrogenase E1α(BCKDHA) and DEP domain-containing mTOR-interacting protein(DEPTOR) were downregulated, while mRNA transcription and protein expression levels of mTOR, as well as ribosomal protein S6 kinase 1(S6K1), were upregulated. The levels of BCAAs and S-adenosyl-L-methionine(SAM) were elevated. The serum level of 6-hydroxymelatonin was significantly reduced, while imidazole-4-one-5-propionic acid and N-(5-phospho-D-ribosyl)anthranilic acid levels were significantly increased. Compared with the model group, Qingrun Decoction significantly reduced blood lipid and resistin levels while increasing ADPN levels. Hepatocytes had improved morphology with reduced inflammatory cells, and fatty degeneration and lipid deposition were alleviated. Differentially expressed genes and differential metabolites were mainly enriched in amino acid metabolic pathways. The expression levels of Slc7a2, Slc38a2, Slc38a4, and ARG in the liver tissue were significantly upregulated, while Slc1a4, Slc16a1, and MAT expression levels were significantly downregulated. BCKDHA and DEPTOR expression levels were upregulated, while mTOR and S6K1 expression levels were downregulated. Additionally, the levels of BCAAs and SAM were significantly decreased. The serum level of 6-hydroxymelatonin was increased, while those of imidazole-4-one-5-propionic acid and N-(5-phospho-D-ribosyl)anthranilic acid were decreased. In summary, Qingrun Decoction may improve amino acid metabolism reprogramming, inhibit mTOR pathway activation, alleviate insulin resistance in the liver, and mitigate pathological damage of liver tissue in T2DM rats by downregulating hepatic BCAAs and SAM and regulating key enzymes involved in amino acid metabolism, such as BCKDHA, ARG, and MAT, as well as amino acid metabolites and transporters.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Rats ; Insulin Resistance ; Diabetes Mellitus, Type 2/genetics* ; Male ; Liver/drug effects* ; Amino Acids/metabolism* ; Rats, Sprague-Dawley ; Humans ; Metabolic Reprogramming

Neuropathic pain, often featuring allodynia, imposes significant physical and psychological burdens on patients, with limited treatments due to unclear central mechanisms. Addressing this challenge remains a crucial unsolved issue in pain medicine. Our previous study, using protein kinase C gamma (PKCγ)-tdTomato mice, highlights the spinal feedforward inhibitory circuit involving PKCγ neurons in gating neuropathic allodynia. However, the regulatory mechanisms governing this circuit necessitate further elucidation. We used diverse transgenic mice and advanced techniques to uncover the regulatory role of the descending serotonin (5-HT) facilitation system on spinal PKCγ neurons. Our findings revealed that 5-HT neurons from the rostral ventromedial medulla hyperpolarize spinal inhibitory interneurons via 5-HT_2C receptors, disinhibiting the feedforward inhibitory circuit involving PKCγ neurons and exacerbating allodynia. Inhibiting spinal 5-HT_2C receptors restored the feedforward inhibitory circuit, effectively preventing neuropathic allodynia. These insights offer promising therapeutic targets for neuropathic allodynia management, emphasizing the potential of spinal 5-HT_2C receptors as a novel avenue for intervention.
Animals ; Neuralgia/physiopathology* ; Protein Kinase C/metabolism* ; Receptor, Serotonin, 5-HT2C/metabolism* ; Hyperalgesia/physiopathology* ; Mice, Transgenic ; Mice ; Spinal Cord/metabolism* ; Serotonin/metabolism* ; Male ; Neurons/metabolism* ; Mice, Inbred C57BL

AIM To investigate the effects of Modified Baitouweng Decoction and Lizhong Decoction on mouse ulcerative colitis(UC).METHODS The mouse model of UC was established by 3％dextran sulfate sodium(DSS)induction.The C57BL/6 mice were randomly divided into the blank group,the model group,the low,medium and high dose Modified Baitouweng Decoction and Lizhong Decoction groups(3,6,12 g/kg),and sulfasalazine group(300 mg/kg),for 7 days gavage of the appropriate drugs,with 10 mice in each group.The mice had their disease activity index(DAI)and colonic mucosal damage index(CMDI)calculated;their colonic length and unit colonic weight measured;their histopathologic changes of colon observed by HE;their colonic ROS,MDA levels and GSH-Px,SOD activities detected by superoxide anion fluorescent probes and kits;their colonic levels of TNF-α,IL-6 and IL-1β detected by ELISA;their colonic LC3 expression detected by immunofluorescence method;and their colonic AMPK,mTOR and p70S6K protein expressions detected by Western blot method.RESULTS Compared with the blank group,the model group displayed significantly higher DAI score,CMDI score,unit colon weight,pathology score,ROS and MDA content,TNF-α,IL-6,and IL-1β levels,and mTOR and p70S6K protein expression(P＜0.01);and significantly lower colon length,GSH-Px and SOD activity,LC3 level,and phosphorylated AMPK protein expression(P＜0.01).Compared with the model group,the groups intervened with Modified Baitouweng Decoction and Lizhong Decoction or sulfasalazine shared decreased DAI score,CMDI score,unit colon mass,pathology score,ROS,MDA,TNF-α,IL-6,IL-1β levels,mTOR,p70S6K protein expressions(P＜0.01);and significantly improved symptomsin terms of the elevated colonic length,GSH-Px,SOD activities,LC3 level,AMPK protein expression(P＜0.01).CONCLUSION Modified Baitouweng Decoction and Lizhong Decoction may attenuate inflammatory response and oxidative damage in UC mouse models via AMPK/mTOR/p70S6K signaling pathway.

Objective:To investigate the relationship between work fit, work stress, and occupational fatigue among medical staff, and to analyze the independent and interactive effects of work fit and work stress on occupational fatigue.Methods:A stratified random sampling method was employed to select 1162 employees from two top-tier hospitals as the research subjects. A questionnaire survey was conducted to collect information on basic demographics, work stress, work fit, and occupational fatigue. Chi-square test, analysis of variance, and logistic regression equations were used to evaluate the interactive effects of work fit and work stress on occupational fatigue.Results:This study included 1162 medical Homo sapiens personnel, among whom 884 were job-adapted and 362 were in a stressful state. Univariate logistic regression analysis showed that the risk of occupational fatigue significantly increased in the 40-49 age group ( OR=1.89) and the bachelor's degree group ( OR=2.52, P<0.01). Smoking and alcohol consumption were also associated with a significantly higher risk of occupational fatigue ( P<0.01). In terms of occupational characteristics, compared to clinical doctors, nurses and pharmaceutical/technical Homo sapiens personnel had lower risks ( OR=0.57, 0.43, P<0.05). Compared to high-ranking Homo sapiens personnel, those with no title or junior titles exhibited lower risks ( OR=0.51, 0.43, P<0.05). Working hours exceeding 55 hours per week and night shifts 3-4 times per week significantly increased fatigue risk ( OR=1.94, 1.90, P<0.05). Occupational stress and job discomfort were identified as risk factors for occupational fatigue ( OR=11.94, 3.26, P<0.05). Job adaptation and occupational stress exhibited a multiplicative interaction on physical fatigue after adjusting for confounders[ OR (95% CI) =0.43 (0.22, 0.84) ]. Additionally, job adaptation and occupational stress demonstrated an additive interaction on mental fatigue, with RERI (95% CI) =2.64 (0.11, 5.59), API (95% CI) =0.38 (0.08, 0.67), and SI (95% CI) =1.78 (1.01, 3.14). Medical Homo sapiens personnel in a stressful state had a 7.25-fold higher risk of fatigue compared to those not in a stressful state, while those with job discomfort had a 2.01-fold higher risk compared to those in an adapted state. Conclusion:Occupational stress and job fit have interactive effects on physical fatigue and mental fatigue in medical Homo sapiens personnel. A stressful state combined with job discomfort increases the risk of fatigue occurrence, providing a basis for developing intervention strategies for occupational fatigue among medical Homo sapiens personnel.

Objectives:To investigate the enhancement of tumor penetration and photodynamic therapy (PDT) efficacy in triple-negative breast cancer by hyaluronidase (HAase) using a novel pH-responsive IR780-loaded photosensitive micelle.Methods:The pH-responsive IR780-loaded photosensitive micelles were prepared using the nanoprecipitation method, and their morphology, size, and encapsulation efficiency were characterized. The in vitro stability and pH-responsive drug release of the micelles were also evaluated. The cytotoxicity of the micelles on triple-negative breast cancer cells (MDA-MB-231) was assessed using a cell counting kit. A nude mouse breast cancer model was established, and HAase was injected intratumorally 24 hours before intravenous injection of the photosensitive micelles. The effect of HAase on the biodistribution and tumor uptake of the micelles was detected using small animal in vivo imaging. CD31 and HIF-1α immunofluorescence staining were performed to investigate the mechanism of HAase-enhanced tumor penetration. The body weight and tumor volume of the mice were measured, and necrosis and apoptosis of tumor tissues were assessed using HE staining and TUNEL staining, respectively. Results:Transmission electron microscopy showed that the micelles had a uniform particle size of approximately 60-70 nm, with a hydrated particle size of (98.03±0.22) nm. The IR780 encapsulation efficiency was 74.15%, with a drug loading content of 2.07%. After 7 days at 4 ℃, there was no significant change in hydrated particle size ( P=0.062). The 24-hour release rates of the micelles in PBS at pH 7.4 and 6.5 were (2.41±0.21)% and (43.69±2.09)%, respectively, showing a significant difference ( P＜0.000 1). The cytotoxicity assay revealed that the cell viability in the micelles group without light exposure was significantly higer than that in the micelles group under light exposure [(97.00±5.38)% vs. (53.27±9.00)%, P=0.000 2]. The micelles were able to target and accumulate in the tumor tissue, and this accumulation increased significantly with HAase treatment. CD31 and HIF-1α immunofluorescence staining indicated that the CD31 signal was enhanced [(0.27±0.05)% vs. (4.57±0.27)%, P＜0.000 1] and the HIF-1α signal was reduced [(5.14±0.38)% vs. (0.08±0.04)%, P＜0.000 1] in the HAase-treated group compared to that in the micelle-only group. After 11 days of treatment with HAase combined with photosensitive micelles, there was no statistically significant difference in mouse body weight ( P＞0.05). However, the tumor volume inhibition rate in the HAase-micelle-mediated PDT group was significantly higher than that in the micelle-mediated PDT group [(87.66±6.37)% vs. (25.34±12.63)%, P=0.002]. Histological staining showed a significant increase in tumor cell necrosis and apoptosis in the HAase-micelle-mediated PDT group. Conclusion:HAase enhances the deep tumor penetration and targeted accumulation of pH-responsive IR780-loaded photosensitive micelles, significantly improves the efficacy of photodynamic therapy in triple-negative breast cancer.

In this work,a fluorescent probe PIN was synthesized using indole-3-carbohydrazide and pyrenecarboxaldehyde as raw materials.PIN showed weak fluorescence emission in aqueous solution with acetonitrile volume fraction of 70％.However,when Cu2+was added to this aqueous solution of PIN,a new fluorescence emission peak appeared at 495 nm,and the intensity of this peak gradually increased with the increase of concentration of Cu2+,and also caused a significant change in the fluorescence color of the solution.In contrast,the addition of 15 kinds of other common metal ions did not cause such change.The detection limit of PIN for Cu2+was 78.7 nmol/L,which was much lower than the maximum permitting level of Cu2+in drinking water in hygienic standard for drinking water in China.Therefore,PIN was a highly selective and sensitive fluorescence-enhanced probe for Cu2+.Meanwhile,the addition of Cu2+could also cause a new absorption peak at 440 nm in the ultraviolet-visible absorption spectrum of the aqueous solution of PIN,and meanwhile the colorless PIN solution changed into yellow,exhibiting the performance of PIN as a colorimetric probe for Cu2+.By fitting with the Levenberg-Marquardt algorithm equation,the binding ratio of PIN to Cu2+was 2:1,and the binding constant was 3.42×1012 L2/mol2.In addition,the binding mode of PIN with Cu2+was explored by using proton nuclear magnetic resonance(1H NMR)titration experiments and density functional theory simulations.The results showed that the addition of Cu2+could cause the aggregation of PIN molecules to form excimers,thus showing highly selective recognition.Finally,PIN was made into a simple test strip,which could achieve rapid and convenient fluorescence detection of Cu2+in actual water samples.

Objective:To investigate whether the rs612529 C/T and rs11669663 G/A in VSTM1 gene are associated with leukocyte signaling inhibitory receptor-1(SIRL-1)expression and an increased risk for systemic lupus erythematosus(SLE)in a Han Chinese cohort.Methods:A total of 200 patients with SLE and 218 healthy controls(HC)were enrolled.Relevant laboratory characteris-tics of patients with SLE were also collected.Genotyping of rs612529 C/T and rs11669663 G/A were performed by Sanger sequencing technology.SIRL-1 expression was assessed in peripheral blood neutrophils and monocytes was detected by flow cytometry.Levels of autoantibodies associated with SLE were detected by ELISA.Results:In both SLE group and HC,the C allele of rs612529 was asso-ciated with a decreased expression level of SIRL-1 on monocytes,with a gradual increased in SIRL-1 protein level from the CC over the CT to the TT genotype.C allele of rs612529 was associated with higher serum anti-dsDNA antibody titers in patients with SLE(P<0.05).In the case of rs11669663 G/A,no significant association of genotypes with SLE susceptibility was detected.Conclusion:VSTM1 rs612529 C/T may contribute to SLE disease activity and regulate SIRL-1 expression on monocytes in the Han Chinese cohort.

The CDH23 gene is a pathogenic mutant gene of the USH1D subtype in Usher syndrome.In this study,two wild-type Cdh23 full-length plasmids(～16 kb)with different promoters were construc-ted,and fluorinated polyethylene imine(FPEI)was used as a delivery vector to transfect the house ear institute-organ of corti 1(HEI-OC1)and the optimal expression plasmid was obtained by evaluating the transfection efficiency in vitro.Firstly,the results of the synthesis of FPEI were analyzed using Fourier transform infrared absorption spectroscopy to prove the successful synthesis of FPEI.After that,the plas-mid encapsulation ability of FPEI and the surface potential and hydration diameter of the formed comple-xes were characterized by agarose gel blocking assay,Zeta potential assay,and dynamic light scattering assay.It was found that FPEI had good plasmid encapsulation ability,and the FPEI plasmid complexes were all positively charged at high mass ratio,with the distribution of particle sizes in the range of 100-300 nm.The low cytotoxicity and high transfection efficiency of FPEI in HEI-OC1 cells were verified by Cell Counting Kit-8(CCK-8)and flow cytometry.Comparing FPEI with Lipofectamine 3000 and differ-ent quality PEI(25K,40K)transfection reagents,the transfection efficiency of FPEI was found to be significantly better than that of the traditional transfection reagents.Quantitative real-time polymerase chain reaction(qRT-PCR)and Western blot results showed that the CAG promoter was better than the CMV promoter,which could be used as the optimal expression plasmid for the subsequent in vivo experi-ments.In addition,it was verified by cellular immunofluorescence that CDH23 was mainly distributed in the cytoplasm after overexpression.The above results demonstrated that FPEI can be used as an efficient delivery vector for in vitro overexpression of large genes represented by Cdh23,which provides an impor-tant experimental basis for subsequent in vivo gene therapy of USH1D syndrome.

Objective To analyze the prevalence of latent tuberculosis infection(LTBI)among relevant healthcare workers(HCWs)in designated tuberculosis medical institutions(MIs)in Yantai City,and explore its influencing factors.Methods The cluster random sampling method was adopted to select two county-and district-level desig-nated tuberculosis MIs.All HCWs underwent questionnaire survey and creation tuberculin skin test(C-TST)at the same time,and the influencing factors for LTBI were analyzed.Results A total of 215 HCWs from designated tu-berculosis MIs were included for analysis,37 were diagnosed with LTBI,with an infection rate of 17.21％(95％CI:12.42％-22.93％).Multivariate logistic regression analysis showed that clinicians(OR=3.19,95％CI:1.05-9.69),laboratory technician(OR=5.90,95％CI:1.21-28.77),working years≥10 years(OR=3.31,95％CI:1.39-7.90),and tuberculosis history of family members(OR=6.49,95％CI:1.01-41.46)were independent risk factors for LTBI.Conclusion The infection risk of clinicians and laboratory technicians who directly contact with tuberculosis patients or Mycobacterium tuberculosis is higher than that of other HCWs,and is related to the length of working years.It is suggested that healthcare-associated infection control measures should be streng-thened,and tuberculosis active screening should be carried out regularly for HCWs in key departments.