Objective To investigate the gray matter volume(GMV)changes and molecular basis underlying antipsychotic-induced weight gain(AIWG).Methods One hundred twenty-nine first-episode schizophrenia patients from October 2019 to December 2021 were enrolled in this study.Patients with≥7%weight gain(weight gain,WG)and patients with<3%weight changes(weight stable,WS)were studied.All patients underwent T1-weighted MRI scanning at baseline and after 8 week treatment.Transcriptome-neuroimaging correlations were used to investigate brain gene profiles from the Allen Human Brain Atlas and GMV changes induced by AIWG.Results Thirty-three patients with WG and 27 with WS completed the GMV measures.Compared with baseline,the WG group showed reduced GMV in right hippocampus,left basal ganglia,and right inferior parietal lobule,etc.and increased GMV in bilateral thalamus(P<0.05).The WS group showed reduced GMV in bilateral orbital gyrus,bilateral inferior frontal gyrus and bilateral hippocampus(P<0.05).These GMV changes in WG group were spatially correlated with expression levels of 354 genes,which were exclusively enriched in Cushing syndrome,neuroinflammation and glutamatergic signaling,and Pnoc+.Conclusion The study has demonstrated increased GMV in thalamus in schizophrenia patients with AIWG which may be associated with Cushing syndrome and Pnoc+.These findings may provide important insights into the molecular mechanisms of AIWG.

AIM: To evaluate the effect of remimazolam on early postoperative cognitive function in elderly patients with hip fracture based on a randomized controlled trial. METHODS: A total of 106 elderly patients, aged 65-90 years, ASA grade Ⅱ or III, who underwent hip fracture surgery under combined spinal-epidural anesthesia in the Sixth Affiliated Hospital of Wenzhou Medical University from December 2022 to June 2023 and met the inclusion criteria, were selected and randomized into remimazolam group (group R) and propofol group (group P) according to the random number table, with 53 cases in each group. Patients in group P received a slow intravenous injection of propofol at a dose of 0.3-0.5 mg / kg (injection time of 1min), followed by a pump infusion at 0.5-3 mg · kg

An effective therapeutic regimen for hepatic fibrosis requires a deep understanding of the pathogenesis mechanism. Hepatic fibrosis is characterized by activated hepatic stellate cells (aHSCs) with an excessive production of extracellular matrix. Although promoted activation of HSCs by M2 macrophages has been demonstrated, the molecular mechanism involved remains ambiguous. Herein, we propose that the vitamin D receptor (VDR) involved in macrophage polarization may regulate the communication between macrophages and HSCs by changing the functions of exosomes. We confirm that activating the VDR can inhibit the effect of M2 macrophages on HSC activation. The exosomes derived from M2 macrophages can promote HSC activation, while stimulating VDR alters the protein profiles and reverses their roles in M2 macrophage exosomes. Smooth muscle cell-associated protein 5 (SMAP-5) was found to be the key effector protein in promoting HSC activation by regulating autophagy flux. Building on these results, we show that a combined treatment of a VDR agonist and a macrophage-targeted exosomal secretion inhibitor achieves an excellent anti-hepatic fibrosis effect. In this study, we aim to elucidate the association between VDR and macrophages in HSC activation. The results contribute to our understanding of the pathogenesis mechanism of hepatic fibrosis, and provide potential therapeutic targets for its treatment.
Humans ; Hepatic Stellate Cells/pathology* ; Receptors, Calcitriol ; Liver Cirrhosis/pathology* ; Macrophages/metabolism*

Rheumatoid arthritis (RA) is an autoimmune disease characterized by severe synovial inflammation and cartilage damage. Despite great progress in RA therapy, there still lacks the drugs to completely cure RA patients. Herein, we propose a reprogrammed neutrophil cytopharmaceuticals loading with TNFα-targeting-siRNA (siTNFα) as an alternative anti-inflammatory approach for RA treatment. The loaded siTNFα act as not only the gene therapeutics to inhibit TNFα production by macrophages in inflamed synovium, but also the editors to reprogram neutrophils to anti-inflammatory phenotypes. Leveraging the active tendency of neutrophils to inflammation, the reprogrammed siTNFα/neutrophil cytopharmaceuticals (siTNFα/TP/NEs) can rapidly migrate to the inflamed synovium, transfer the loaded siTNFα to macrophages followed by the significant reduction of TNFα expression, and circumvent the pro-inflammatory activity of neutrophils, thus leading to the alleviated synovial inflammation and improved cartilage protection. Our work provides a promising cytopharmaceutical for RA treatment, and puts forward a living neutrophil-based gene delivery platform.

Background and Objectives: Mesenchymal stem cells (MSCs) have immunomodulatory function and participate in the pathogenesis of many immunoregulation-related diseases, including psoriasis. Previously, we found that MSCs from psoriatic lesions overexpress the proinflammatory microRNA, miR-155 and exhibit a decreased immunosuppressive capacity. But the origin of these aberrant characteristics is still not clear. To investigate whether inflammatory cytokines in serum and peripheral blood mononuclear cells (PBMCs) from psoriatic patients can regulate the expression patterns of immunoregulation-related cytokines and the immunoregulation function of MSCs. Methods: and Results: Normal dermal mesenchymal stem cells (nDMSCs) were treated with serum or PBMCs derived from patients with psoriasis or healthy donors. Expression of miR-155 and immunoregulation-related genes in each MSCs were measured using real-time PCR or western-blot. Meanwhile, the immunosuppressive capacity of DMSCs was evaluated by its inhibitory ability on proliferation of activated PBMCs. Compared to control serum, psoriatic serum significantly increased the expression levels of miR-155 (27.19±2.40 vs. 3.51±1.19, p<0.001), while decreased TAB2 expression (0.28±0.04 vs. 0.72±0.20, p<0.01) in DMSCs. Expression levels of immunoregulation-related genes such as PGE2, IL-10, and TLR4 were also markedly down-regulated following the psoriatic serum treatment. Those DMSCs treated with healthy serum could inhibit PBMC proliferation, while those psoriatic serum-treated DMSCs could not inhibit PBMC proliferation effectively. Conclusions Psoriatic serum up-regulate the expression of miR-155, down-regulate the expression of immunoregulation- related genes (PGE2, IL-10, and TLR4) in DMSCs, and along with the inhibition of the immunosuppressive function of MSCs.

AIM: To observe the effects of single-dose of fentanyl on sedation and agitation during recovery after pediatric adenotonsillectomy day surgery during anesthesia induction. METHODS: A total of 157 children undergoing elective adenotonsillectomy, with ASA physical status I or II, aged 3-10 years were selected during January and March in 2022 in the Second Affiliated Hospital of Wenzhou Medical University. The children were divided into two groups according to random number table method: remifentanil combined with fentanyl group (group RF, n = 78) and remifentanil group (group R, n = 79). Children in group RF received a single-dose injection of 1 μg/kg of fentanyl and 2.5 μg/kg of remifentanil during induction, children in group R received an equal volume of normal saline and 2.5 μg/kg of remifentanil injection. Children in both groups were intubated after propofol induction and anesthetized with combination of sevoflurane-remifentanil. The incidence and severity of emergence agitation (EA), Ramsay sedation score and FLACC pain score in post-anesthesia care unit (PACU), extubation time, recovery time, PACU stay time, discharge time were recorded. RESULTS: Compared with group R, the incidence of EA was significantly lower (38.0% vs. 18.0%, P = 0.005), the maximum PAED score during recovery was significantly lower (7.7 ±3.3 vs. 8.9 ± 3.4, P = 0.027), and the Ramsay sedation score was significantly higher at 15 min after admission of PACU (4.4 ± 1.1 vs. 3.8 ± 1.4, P = 0.01), as well as discharge of PACU (2.0 ± 0.3 vs. 1.8 ±0.4, P = 0.03) in RF group . There was no significant difference in extubation time, recovery time, PACU stay time, discharge time, pain score (discharge of PACU and 2 h after operation) between two groups (P > 0.05). CONCLUSION: A single-dose injection of fentanyl (1 μg/kg) during anesthesia induction can increase the degree of sedation and reduce the incidence of EA in PACU after pediatric daytime adenotonsillectomy.

Objective:To observe the peripapillary atrophy (PPA) and peripapillary choroidal vascularity index (CVI) in patients with different degrees of myopia and to analyze their correlations.Methods:A cross-sectional clinical study. From September 2021 to December 2021, 281 mypoic patients of 281 eyes treated in Eye Hospital of Wenzhou Medical University at Hangzhou were included in this study, and the right eye was used as the treated eye. There were 135 eyes in 135 males and 146 eyes in 146 females. The age was 28.18±5.78 years. The spherical equivalent refraction (SE) was -5.13±2.33 D. The patients were divided into three groups: low myopia group (group A, -3.00 D

Background and Objectives: Psoriasis is a chronic inflammatory skin disease, which the mechanisms behind its initiation and development are related to many factors. DMSCs (dermal mesenchymal stem cells) represent an important member of the skin microenvironment and play an important role in the surrounding environment and in neighbouring cells, but they are also affected by the microenvironment. We studied the glucose metabolism of DMSCs in psoriasis patients and a control group to reveal the relationship among glucose metabolism, cell proliferation activity，and VEC (vascular endothelial cell) differentiation in vitro, we demonstrated the biological activity and molecular mechanisms of DMSCs in psoriasis. Methods: and Results: We found that the OCR of DMSCs in psoriatic lesions was higher than that in the control group, and mRNA of GLUT1 and HK2 were up-regulated compared with the control group. The proliferative activity of DMSCs in psoriasis was reduced at an early stage, and mRNA involved in proliferation, JUNB and FOS were expressed at lower levels than those in the control group. The number of blood vessels in psoriatic lesions was significantly higher than that in the control group (p＜0.05), which the mRNA of VEC differentiation, CXCL12, CXCR7, HEYL and RGS5 tended to be increased in psoriatic lesions compared to the control group, in addition to Notch3. Conclusions We speculated that DMSCs affected local psoriatic blood vessels through glucose metabolism, and the differentiation of VECs, which resulted in the pathophysiological process of psoriasis.

Objective:To establish a prediction model of postoperative 1-year mortality risk in elderly patients undergoing hip fracture surgery and verify its efficacy.Methods:Patients of both sexes, aged ≥65 yr, of American Society of Anesthesiologists physical status Ⅰ-Ⅳ, who underwent an operation for traumatic hip fracture in the Second Affiliated Hospital of Wenzhou Medical University from January 2017 to December 2018, were enrolled and randomly assigned to model group and verification group in a ratio of 3∶1.The demographic characteristics, clinical data and results such as laboratory examinations were collected.In model group, the logistic regression analysis was used to recognize the independent risk factors for 1-year mortality after procedure, and the prediction model was established.In verification group, the prediction efficacy was analyzed using the receiver operating characteristic curve, and the degree of fitting was evaluated by Hosmer-Lemeshow goodness-of-fit test.Results:Multivariate logistic analysis indicated that age ≥84 yr, Charlson comorbidity index ≥2 points, Braden score on admission to hospital ≤16 points, preoperative urea nitrogen ≥8.8 mmol/L and postoperative albumin ≤ 29.6 g/L were the independent risk factors for 1-year mortality after hip fracture surgery in elderly patients ( P<0.05). The prediction model was established based on the risk factors mentioned above.The area under receiver operating characteristic curve was 0.870, and the sensitivity and specificity were 82.8% and 80.0%, respectively.The prediction model showed good fitting ( χ2=4.672, P=0.700). Conclusion:Age ≥84 yr, Charlson comorbidity index ≥2 points, Braden score on admission to hospital≤16 points, preoperative urea nitrogen ≥8.8 mmol/L and postoperative albumin ≤ 29.6 g/L are the independent risk factors for 1-year mortality after hip fracture surgery in elderly patients, and the prediction model established based on the above indicators has good efficacy.

Objective To investigate the effect of comprehensive management mode intervention in elderly patients with moderate/severe chronic obstructive pulmonary disease at stable stage. Methods A total of 150 elderly patients with stable-stage COPD were randomly divided into two groups, 75 in each group. The control group received routine medication, while the observation group was given comprehensive management mode intervention, including health education,rational medication, pulmonary rehabilitation training and psychological guidance. Both groups were treated for 12 months. Differences in lung function parameters, modified Medical Research Council (mMRC) dyspnea scale, COPD assessment test (CAT), 6-minute walk test (6MWT), and frequency of acute exacerbation of COPD (AECOPD) were compared between the two groups. Results: After treatment, FEV1/FVC and FEV1%pred of observation group（57.65±11.62%、61.83±13.50%）were higher than control group（52.38±13.24%、53.42±13.93%）(P<0.05), the mMRC and CAT scores of the observation group were decreased (P<0.05), and the 6MWT was increased (P<0.05), but no significant differences in the control group (P>0.05). Within 12 months of treatment, the frequency of AECOPD in the observation group was less than that in the control group (P<0.05). Conclusions: In the treatment of elderly patients with moderate/severe chronic obstructive pulmonary disease, comprehensive management mode intervention can help delay the deterioration of lung function, correct the difficulty of breathing, improve the quality of life, and reduce the number of AECOPD.