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*

Psoriasis is an incurable chronic inflammatory disease that requires new interventions. Here, we found that fibroblasts exacerbate psoriasis progression by promoting macrophage recruitment via CCL2 secretion by single-cell multi-omics analysis. The natural small molecule celastrol was screened to interfere with the secretion of CCL2 by fibroblasts and improve the psoriasis-like symptoms in both murine and cynomolgus monkey models. Mechanistically, celastrol directly bound to the low-density lipoprotein receptor-related protein 1 (LRP1) β-chain and abolished its binding to the transcription factor c-Jun in the nucleus, which in turn inhibited CCL2 production by skin fibroblasts, blocked fibroblast-macrophage crosstalk, and ameliorated psoriasis progression. Notably, fibroblast-specific LRP1 knockout mice exhibited a significant reduction in psoriasis like inflammation. Taken together, from clinical samples and combined with various mouse models, we revealed the pathogenesis of psoriasis from the perspective of fibroblast-macrophage crosstalk, and provided a foundation for LRP1 as a novel potential target for psoriasis treatment.

Antimicrobial resistance (AMR) is a growing public health crisis that requires innovative solutions. Emerging multidrug resistant (MDR) Salmonella typhimurium has raised concern for its effect on pathogenic infection and mortality in humans caused by enteric diseases. To combat these MDR Salmonella typhimurium pathogens, highly effective and broad-spectrum antibiotics such as flufenicol (FFC) need to be evaluated for their potent antibacterial activity against Salmonella typhimurium. However, the low solubility and low oral bioavailability of flufenicol need to be addressed to better combat AMR. In this work, we develop a novel nano-formulation, flufenicol nano-micelles (FTPPM), which are based on d-α-tocopherol polyethylene glycol 1,000 succinate (TPGS)/poloxamer 188 (P188), for the targeted treatment of biofilms formed by drug-resistant Salmonella typhimurium in the intestine. Herein, FTPPM were prepared via a thin film hydration method. The preparation process for the mixed micelles is simple and convenient compared with other existing nanodrug delivery systems, which can further decrease production costs. The optimized FTPPM demonstrated outstanding stability and sustained release. An evaluation of the in vivo anti-drug-resistant Salmonella typhimurium efficacy demonstrated that FTPPM showed a stronger efficacy (68.17 %) than did florfenicol-loaded TPGS polymer micelles (FTPM), flufenicol active pharmaceutical ingredients (FFC-API), and flufenicol commercially available medicine (FFC-CAM), and also exhibited outstanding biocompatibility. Notably, FTPPM also inhibited drug-resistant Salmonella typhimurium from forming biofilms. More importantly, FTPPM effectively restored intestinal flora disorders induced by drug-resistant Salmonella typhimurium in mice. In summary, FTPPM significantly improved the solubility and oral bioavailability of florfenicol, enhancing its efficacy against drug-resistant Salmonella typhimurium both in vitro and in vivo. FTPPM represent a promising drug-resistant Salmonella typhimurium treatment for curbing bacterial resistance via oral administration.

Objective To standardize the management of clinical trials in our hospital,reduce the incidence of protocol deviations,and provide a reference for improving the quality of clinical trials.Methods The healthcare failure mode and effect analysis(HFMEA)method was used to determine the potential failure modes of the current protocol deviation.The frequency,severity and detectability of failure modes were quantified and evaluated.The risk priority number(RPN)was calculated and the corresponding improvement measures were proposed.The RPN values before and after the implementation of HFMEA were statistically analyzed to evaluate the improvement effect.Results After the implementation of HFMEA activities,the RPN values of 14 potential failure modes decreased significantly(P<0.05);The risk level of 12 potential failure modes decreased.The HFMEA team members'ability in finding and solving problems,communication and cooperation were significantly improved.Conclusions The implementation of HFMEA activities contributes to the management of protocol deviation in clinical trials,can effectively reduce the occurrence of protocol deviation,and provides experience for improving the quality of drug clinical trials.

Objective To observe the value of subregional non-contrast CT(NCCT)radiomics features based on habitat imaging technology for predicting hematoma expansion(HE)in patients with spontaneous intracranial hemorrhage(sICH).Methods Data of 228 sICH patients with negative conventional imaging signs were retrospectively analyzed and divided into HE group(n=99)or non HE(NHE)group(n=129)based on the occurrence of HE nor not.also divided into training set(n=182)or test set(n=46)at a ratio of 8:2.Clinical data,NCCT data and laboratory examination results were compared between groups.Logistic regressive analysis was performed to screen the impact factors of HE.ROI of whole hematoma(ROIwhole)was sketched and clustered into 3 sub-regions(ROIsub1,ROIsub2 and ROIsub3,the latter located in the critical area between hematoma and brain tissue)with habitat imaging technology,and radiomics features of ROI were extracted and screened.Then 4 prediction models were constructed based on the above 4 ROI,and the efficacy of each model for predicting HE was analyzed.Results The fasting blood glucose in HE group was higher than that in NHE group(t=2.047,P=0.041),which was not independent impact factor for predicting HE in sICH patients(P=0.070)according to logistic regression analysis.The area under the curve of ROIsub3 radiomics model for predicting sICH HE in training and test set was 0.945 and 0.863,respectively,not significantly different with that of ROIwhole(0.921,0.813),ROIsub1(0.925,0.807)nor ROIsub2(0.909,0.720)(all P＞0.05).Decision curve analysis showed that ROIsub3 radiomics model could bring greater benefits than the other 3 models.Conclusion NCCT radiomics features of the critical area between hematoma and brain tissue based on habitat imaging technology had high value for predicting HE in sICH patients.

Objective:To investigate the therapeutic effects of internal fixation via the posterolateral combined posteromedial approach in the treatment of posterior pilon fracture (Klammer type Ⅲ).Methods:A retrospective study was performed to analyze the 69 posterior pilon fractures (Klammer type Ⅲ) which had been treated by internal fixation with hollow screws or a buttress plate at Department of Orthopaedic Trauma, Yantai Shan Hospital from January 2015 to January 2020. There were 36 males and 33 females with an age of (45.3±10.0) years and duration from injury to surgery of (6.0±1.5) d. They were assigned into 2 groups according to different surgical approaches. The observation group (41 cases) was treated through the posterolateral combined posteromedial approach while the control group (28 cases) through the posterolateral approach alone. The therapeutic effects were evaluated by comparing the 2 groups in terms of incision length, intraoperative bleeding, operation time, fracture union time, fracture reduction (evaluated by the Burrwell-Charnley radiological score), the ankle-hindfoot score of American Orthopaedic Foot and Ankle Society (AOFAS) and complications.Results:There was no significant difference in the preoperative general data between the 2 groups, showing comparability ( P>0.05). All the 69 cases were followed up for (16.9±4.0) months, revealing primary healing of all the incisions and no vascular injury or wound infection. The incision length [(11.2±1.8) cm] and operation time [(76.0±6.6) min] in the observation group were significantly shorter than those in the control group [(12.4±1.9) cm and (79.7±6.8) min], the excellent and good rate of reduction in the observation group (97.6%, 40/41) was significantly higher than that in the control group (89.3%, 25/28), and the ankle-hindfoot scores of AOFAS at 1, 3 and 12 months after operation in the observation group [(78.4±5.6), (79.5±2.8) and (86.9±2.1)] were significantly higher than those in the control group [(75.2±5.5), (78.0±3.2) and (85.8±2.3)] (all P<0.05). There was no significant difference in the intraoperative bleeding between the 2 groups ( P>0.05). In the control group, 2 patients developed numbness in the dorsum of foot, which gradually disappeared after 3 months of treatment, but no other complications like persistent pain or flexor contracture within 1 year after operation. Conclusion:In the treatment of Klammer type Ⅲ posterior pilon fracture, the posterolateral combined posteromedial approach can result in satisfactory therapeutic effects, because the surgical approach can fully expose the fracture and facilitate better reduction.

Serine/arginine-rich splicing factor 7 (SRSF7), a known splicing factor, has been revealed to play oncogenic roles in multiple cancers. However, the mechanisms underlying its oncogenic roles have not been well addressed. Here, based on N⁶-methyladenosine (m⁶A) co-methylation network analysis across diverse cell lines, we find that the gene expression of SRSF7 is positively correlated with glioblastoma (GBM) cell-specific m⁶A methylation. We then indicate that SRSF7 is a novel m⁶A regulator, which specifically facilitates the m⁶A methylation near its binding sites on the mRNAs involved in cell proliferation and migration, through recruiting the methyltransferase complex. Moreover, SRSF7 promotes the proliferation and migration of GBM cells largely dependent on the presence of the m⁶A methyltransferase. The two m⁶A sites on the mRNA for PDZ-binding kinase (PBK) are regulated by SRSF7 and partially mediate the effects of SRSF7 in GBM cells through recognition by insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2). Together, our discovery reveals a novel role of SRSF7 in regulating m⁶A and validates the presence and functional importance of temporal- and spatial-specific regulation of m⁶A mediated by RNA-binding proteins (RBPs).
Humans ; Cell Line, Tumor ; Cell Proliferation ; Gene Expression Regulation, Neoplastic ; Glioblastoma/genetics* ; Methyltransferases/metabolism* ; RNA Splicing Factors/metabolism* ; RNA, Messenger/genetics* ; RNA-Binding Proteins/metabolism* ; Serine-Arginine Splicing Factors/metabolism* ; RNA Methylation/genetics*

Objective:To study the effect of glucosamine combined with sodium hyaluronate on serum interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) levels in patients with Kashin-Beck disease (KBD).Methods:In a prospective design, patients with KBD admitted to South Hospital of Yantaishan Hospital from January 2017 to January 2019 were selected and divided into control, observation, and replacement groups. The control group was treated with glucosamine sulfate, the observation group was treated with intra-articular injection of sodium hyaluronate on the basis of the control group, and the replacement group was treated with artificial knee arthroplasty. The clinical efficacy, visual analogue scale (VAS) and Western Ontario and McMaster University Osteoarthritis Index (WOMAC) of the three groups were compared before treatment, 6 weeks and 6 months after treatment. Blood samples were collected from the patients, and the serum levels of IL-1β and TNF-α were measured by enzyme-linked immunosorbent assay (ELISA) to compare the serum levels of IL-1β and TNF-α in the three groups before treatment, 6 weeks and 6 months after treatment.Results:The age of patients in the control group was (53.76 ± 7.33) years old, including 19 males and 23 females. The age of patients in the observation group was (54.18 ± 7.06) years old, including 20 males and 22 females. The age of the replacement group was (55.17 ± 6.43) years old, including 17 males and 13 females. The total effective rate in observation group (92.86%, 39/42) was significantly higher than that of the control group (76.19%, 32/42, χ 2 = 4.459, P < 0.05). At 6 weeks and 6 months after treatment, the VAS scores in the observation group [(4.10 ± 1.21), (3.16 ± 0.95) points] were significantly lower than those in the control group [(5.48 ± 1.17), (4.06 ± 0.74) points, P < 0.05]; at 6 weeks after treatment, the VAS score in the replacement group [(3.28 ± 0.89) points] was significantly lower than that in the observation group ( P < 0.05). At 6 weeks and 6 months after treatment, the WOMAC scores in the observation group [(40.72 ± 4.19, 25.86 ± 3.02) points] were significantly lower than those in the control group [(48.29 ± 2.16), (36.81 ± 3.13) points, P < 0.05]; the WOMAC scores in the replacement group [(29.68 ± 4.22), (23.57 ± 3.86) points] were significantly lower than those of the observation group ( P < 0.05). The serum levels of IL-1β [(9.28 ± 2.74), (6.85 ± 2.27) pg/ml] and TNF-α [(12.66 ± 4.54), (10.34 ± 3.48) pg/ml] in the observation group were significantly lower than those in the control group [(12.78 ± 2.79), (10.36 ± 2.63), (15.51 ± 4.63), (14.64 ± 4.27) pg/ml, P < 0.05], the serum levels of IL-1β [(6.12 ± 3.55), (5.39 ± 2.23) pg/ml], TNF-α [(10.42 ± 3.13) , (8.19 ± 3.15) pg/ml] in the replacement group were significantly lower than those in the observation group at 6 weeks and 6 months after treatment ( P < 0.05). Conclusion:Glucosamine combined with intra-articular injection of sodium hyaluronate can relieve inflammation, improve pain and promote joint function recovery in patients with KBD, but there is still a certain gap compared with knee arthroplasty.

Objective:To investigate the clinical significance of fluid-attenuated inversion recovery (FLAIR) vascular hyperintensities (FVHs) in patients with chronic atherosclerotic middle cerebral artery occlusion.Methods:From July 2016 to November 2020, patients admitted to the Department of Neurology, Jiangdu People's Hospital of Yangzhou and first found chronic atherosclerotic middle cerebral artery occlusion were enrolled. The demographic, clinical and MRI imaging data were collected. According to the presence or absence of acute cerebral infarction, they were divided into the non-acute cerebral infarction group and the acute cerebral infarction group. According to the modified Rankin Scale score at 3 months after the onset, patients with acute cerebral infarction were further divided into the good outcome group (≤2) and the poor outcome group (>2). A multivariate logistic regression model was used to analyze the independent correlation between FVHs and the risk of cerebral infarction in patients with chronic atherosclerotic middle cerebral artery occlusion and the outcome in patients with cerebral infarction. Results:A total of 94 patients with chronic atherosclerotic middle cerebral artery occlusion were enrolled, including 38 with non-acute cerebral infarction (40.4%) and 56 with acute cerebral infarction (59.6%). In patients with acute cerebral infarction, 13 (23.2%) had a poor outcome, and 43 (76.8%) had a good outcome. The fibrinogen level, the proportion of patients with FVHs and the FVHs score in the cerebral infarction group were significantly higher than those in the non-cerebral infarction group (all P<0.05). Multivariate logistic regression analysis showed that the FVHs score was significantly, independently, and positively correlated with the risk of acute cerebral infarction (odds ratio 2.524, 95% confidence interval 1.400-4.552; P=0.002). The National Institutes of Health Stroke Scale score at admission, the modified Rankin Scale score at admission, and FVHs score in the poor outcome group were significantly higher than those in the good outcome group (all P<0.05). Multivariate logistic regression analysis showed that there was a significant independent negative correlation between the FVHs score and the outcome of patients with cerebral infarction (odds ratio 0.144, 95% confidence interval 0.045-0.459; P=0.001). Conclusions:FVHs suggest that the blood supply is in a state of decompensation. When FVHs are present, the risk of cerebral infarction in patients with chronic middle cerebral artery occlusion is significantly increased; the wider the range of FVHs, the higher the risk of poor outcome after cerebral infarction.

Objective:To compare the efficacy of the combination of abidol, lopinavir/ritonavir plus recombinant interferon α-2b (rIFNα-2b) and the combination of lopinavir/ritonavir plus rIFNα-2b for patients with COVID-19 in Zhejiang province.Methods:A multicenter prospective study was carried out to compare the efficacy of triple combination antiviral therapy and dual combination antiviral therapy in 15 medical institutions of Zhejiang province during January 22 to February 16, 2020. All patients were treated with rIFNα-2b (5 million U, 2 times/d) aerosol inhalation, in addition 196 patients were treated with abidol (200 mg, 3 times/d) + lopinavir/ritonavir (2 tablets, 1 time/12 h) (triple combination group) and 41 patients were treated with lopinavir/ritonavir (2 tablets, 1 time/12 h) (dual combination group). The patients who received triple combination antiviral therapy were further divided into three subgroups: <48 h, 3-5 d and >5 d according the time from the symptom onset to medication starting. The therapeutic efficacy was compared between triple combination group and dual combination group, and compared among 3 subgroups of patients receiving triple combination antiviral therapy. SPSS 17.0 software was used to analyze the data.Results:The virus nucleic acid-negative conversion time in respiratory tract specimens was (12.2±4.7) d in the triple combination group, which was shorter than that in the dual combination group [(15.0±5.0) d] ( t=6.159, P<0.01). The length of hospital stay in the triple combination group [12.0 (9.0, 17.0) d] was also shorter than that in the dual combination group [15.0 (10.0, 18.0) d] ( H=2.073, P<0.05). Compared with the antiviral treatment which was started within after the symptom onset of in the triple combination group, the time from the symptom onset to the viral negative conversion was 13.0 (10.0, 17.0), 17.0 (13.0, 22.0) and 21.0 (18.0, 24.0) d in subgroups of 48 h, 3-5 d and >5 d, respectively ( Z=32.983, P<0.01), while the time from antiviral therapy to viral negative conversion was (11.8±3.9), (13.5±5.1) and (11.2±4.3) d, respectively( Z=6.722, P<0.05). Conclusions:The triple combination antiviral therapy of abidol, lopinavir/litonavir and rIFNα-2b shows shorter viral shedding time and shorter hospitalization time, compared with the dual combination antiviral therapy; and the earlier starting triple combination antiviral therapy will result in better antiviral efficacy.