Objective To investigate the effect of MALAT1 expressions on cell proliferation and apoptosis in astrocytes by regulating mitogen-activated protein kinase(MAPK)/extracellular signal-regulated kinase(ERK1,2)pathway.Methods The MALAT1 gene was knocked down and over-expressed in C8-D1A cells by lentiviral and plasmid vectors,respectively.The expressions of MALAT1,cell proliferation-related markers(Ki67,MCM2,PCNA)and apoptosis-related proteins(Caspase-3,Bax,Bcl-2)were detected by quantitative real-time polymerase chain reaction(qPCR).CCK-8 assay and flow cytometry were used for cell proliferation and apoptosis in C8-D1A cells.Immunofluorescence was adopted to detect the protein expressions of Caspase-3 and Ki67.Western blotting was used to detect the protein expressions of Caspase-3,Bax,Bcl-2,ERK1/2,p-ERK1/2,p38MAPK and p-p38MAPK.Results Compared with the control group,over-expressed MALAT1 inhibited cell proliferation and induced cell apoptosis in C8-D1A cells while the knockdown of MALAT1 significantly enhanced cell proliferation and anti-apoptotic ability in C8-D1A cells.The proportion of C8-D1A cells in G0/G1-phase and G2/M-phase was higher than in the control group as evidenced by flow cytometry,but was lower in S-phase.Meanwhile,data showed that Caspase-3 was increased while p-ERK1/2 was decreased in terms of protein levels.The mRNA expressions of Ki67 and PCNA were decreased.After knockdown of MALAT1,the proportion of C8-D1A cells in S-phase was higher,but was lower in G2/M-phase.The protein expressions of Caspase-3 and Bax decreased while those of p-ERK1/2 and p-p38MAPK increased.The mRNA expressions of Ki67,MCM2 and PCNA were increased.The differences were all statistically significant(P＜0.05).Conclusion MALAT1 promotes astrocyte apoptosis and inhibits proliferation by regulating the MAPK/ERK1,2 signaling pathway.

Objective: To investigate the proportion of physical examinations among patients with severe mental disorders and its influencing factors in Shaoxing City, Zhejiang Province, so as to provide the evidence for improving the proportion of physical examinations among patients with severe mental disorders. Methods : The epidemiological and clinical features of patients with severe mental disorders included in community management in Shaoxing City in 2022 were collected from Zhejiang Provincial Severe Mental Disorder Management Information System, including demographics, disease diagnosis and treatment, physical examination, and rescue and assistance. Factors affecting the physical examination were identified among patients with severe mental disorders using a multivariable logistic regression model. Results: A total of 25 468 patients with severe mental disorders were enrolled in Shaoxing City in 2022, including 12 151 males and 13 317 females, with a male to female ratio of 0.91∶1, and the participants had a mean age of (54.34±14.71) years. Schizophrenia was the predominant type of severe mental disorders (15 419 cases, 60.54%), and 21 374 subjects participating in the physical examinations in 2022 (83.92%). Multivariable logistic regression analysis showed that female (OR=0.901, 95%CI: 0.832-0.975), urban areas (OR=0.506, 95%CI: 0.468-0.547), mental disorders due to epilepsy (OR=1.779, 95%CI: 1.104-2.866), hospitalized treatment (6 to 10 times, OR=0.523, 95%CI: 0.401-0.681; 11 times and more, OR=0.177, 95%CI: 0.108-0.288), special diseases in outpatient (OR=1.738, 95%CI: 1.597-1.891), receiving medical assistance (OR=2.851, 95%CI: 2.616-3.107), targets of the community care and assistance groups (OR=1.653, 95%CI: 1.471-1.857) and guardian (spouse, OR=1.777, 95%CI: 1.513-2.086; children, OR=1.277, 95%CI: 1.069-1.526; parents, OR=1.342, 95%CI: 1.143-1.576) were statistically associated with the proportion of physical examinations. Conclusions The proportion of health examinations was 83.92% among patients with severe mental disorders in Shaoxing City in 2022. Gender, residence, guardian, disease diagnosis, times of hospitalized treatment, medical assistance, special diseases in outpatients and target of community care and assistance groups were factors affecting health examinations among patients with severe mental disorders.

Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disease. At present, no definite ALS biomarkers are available. In this study, exosomes from the plasma of patients with ALS and healthy controls were extracted, and differentially expressed exosomal proteins were compared. Among them, the expression of exosomal coronin-1a (CORO1A) was 5.3-fold higher than that in the controls. CORO1A increased with disease progression at a certain proportion in the plasma of patients with ALS and in the spinal cord of ALS mice. CORO1A was also overexpressed in NSC-34 motor neuron-like cells, and apoptosis, oxidative stress, and autophagic protein expression were evaluated. CORO1A overexpression resulted in increased apoptosis and oxidative stress, overactivated autophagy, and hindered the formation of autolysosomes. Moreover, CORO1A activated Ca²⁺-dependent phosphatase calcineurin, thereby blocking the fusion of autophagosomes and lysosomes. The inhibition of calcineurin activation by cyclosporin A reversed the damaged autolysosomes. In conclusion, the role of CORO1A in ALS pathogenesis was discovered, potentially affecting the disease onset and progression by blocking autophagic flux. Therefore, CORO1A might be a potential biomarker and therapeutic target for ALS.
Mice ; Animals ; Amyotrophic Lateral Sclerosis/pathology* ; Calcineurin/metabolism* ; Motor Neurons/pathology* ; Microfilament Proteins/metabolism* ; Cytoskeletal Proteins/metabolism*

Objective:To compare closed reduction and intramedullary nailing versus open reduction and locking plate fixation in the treatment of middle and upper humeral fractures.Methods:A retrospective case-control study was conducted to analyze the clinical data of 62 patients with middle and upper humeral fracture who had been treated at Department of Orthopaedics, The First People's Hospital of Jinmen and at Department of Orthopedics, General Hospital of PLA Central Theater from October 2017 to February 2021. There were 35 males and 27 females, aged from 27 to 86 years. The left side was affected in 24 cases and the right side in 38 cases. All fractures were fresh. According to the AO classification, 16 cases were type A, 32 type B, and 14 type C. Of the patients, 29 were treated with closed reduction and intramedullary nailing (intramedullary nail group) and 33 with open reduction and locking plate fixation (locking plate group). The length of incision, operation time, intraoperative blood loss, hospital stay, fracture healing and complications were recorded and compared between the 2 groups. The pain degree was evaluated by visual analogue scale (VAS) at one week and one month after operation, and the functional recovery of the shoulder was evaluated by Constant-Murley score at one month and 12 months after operation.Results:There was no significant difference in the preoperative general data between the 2 groups, showing comparability ( P>0.05). The intramedullary nail group was followed up for 12 to 29 months and the locking plate group for 15 to 50 months. In the intramedullary nail group, the length of incision [(4.1±0.7) cm], operation time [(58.3±7.7) min], intraoperative blood loss [(52.7±6.5) mL], and hospital stay [(7.3±1.5) d] were significantly less than those in the locking plate group [(21.7±2.3) cm, (95.8±11.7) min, (237.4±14.9) ml, and (12.3±1.7) d] ( P<0.05). The fracture healing time in the intramedullary nail group was (5.0±1.9) months, significantly longer than that in the locking plate group [(3.5±1.7) months] ( P<0.05). The VAS scores at one week and one month after operation in the intramedullary nail group [(2.8±0.3) points and (1.2±0.5) points] were significantly lower than those in the locking plate group [(4.3±0.4) points and (1.6±0.5) points], and the Constant-Murley score at one month after operation in the intramedullary nail group [(63.5±7.4) points] was significantly higher than that in the locking plate group [(54.3±6.9) points] ( P<0.05). However, at 12 months after operation, there was no significant difference in the Constant-Murley score between the 2 groups ( P>0.05). In both groups, the VAS score at one month after operation was significantly lower than that at one week after operation while the Constant-Murley score at 12 months after operation was significantly higher than that at one week after operation ( P<0.05). In the intramedullary nail group, intraoperative distal refracture happened in one case; in the locking plate group, incision infection occurred in one case and postoperative radial nerve injury in another. There was no significant difference in the incidence of complications between the 2 groups [3.4% (1/29) versus 6.1% (2/33)] ( P>0.05). Conclusion:In the treatment of middle and upper humeral fractures, compared with open reduction and locking plate fixation, closed reduction and intramedullary nailing shows advantages of a smaller surgical incision, shorter operation time, less intraoperative blood loss, shorter hospital stay and faster functional recovery.

Objective:To explore the effect of the new model of "5G cloud plus medicine" network and linkage in improving the therapeutic effect for patients with severe trauma.Methods:A retrospective cohort study was conducted to analyze the clinical data of 410 patients with severe trauma admitted to Qingzhou People′s Hospital affiliated to Shandong First Medical University from November 2016 to November 2020. There were 258 males and 152 females, aged 16-80 years [(45.7±16.1)years]. The injury severity score (ISS) ranged from 17 to 55 points [(28.1±7.6)points]. A total of 210 patients with severe trauma were rescued by using the new model of "5G cloud plus medicine" network and linkage from November 1, 2018 to November 30, 2020 (observation group), and another 200 patients with severe trauma were rescued by the traditional treatment mode from November 1, 2016 to October 31, 2018 were selected as the control group. Time to start rescue (time from admission to the start of rescue), CT examination time (time from consultation to completion of CT scan), time to receive blood transfusion (time from blood transfusion request to execution), residence time in emergency room, ISS at postoperative 28 days, proportion of patients with blood transfusion, success rate of rescue and mortality rate were compared between the two groups.Results:Time to start rescue [(2.4±1.1)minutes], CT examination time [(29.1±10.3)minutes], time to receive blood transfusion [(28.1±10.2)minutes] and residence time in emergency room [(3.0±1.1)hours] in observation group were significantly shorter than those in control group [(5.5±1.2)minutes, (42.8±10.1)minutes, (48.5±13.1)minutes, (5.0±1.4)hours] (all P<0.05 or 0.01). ISS was (18.7±2.8)points in observation group, significantly lower than (22.1±3.4)points in control group ( P<0.05). Proportion of patients with blood transfusion was 49.5% (104/210) in observation group, similar with 42.5% (85/200) in control group ( P>0.05). Success rate of rescue was 99.0% (208/210) in observation group, significantly higher than 93.0% (186/200) in control group ( P<0.05). The mortality rate was 4.3% (9/200) in observation group, significantly lower than 8.5% (17/200) in control group ( P<0.05). Conclusion:For patients with severe trauma, the new model of "5G cloud plus medicine" network and linkage can effectively shorten the time to start rescue, CT examination time, time to receive blood transfusion and residence time in emergency room, improve the success rate of rescue and reduce the mortality rate, which is worthy of further promotion.

Objective:To investigate the effect of the liquid resuscitation therapy strategy using intra-abdominal pressure (IAP) and oxygenation index (PaO 2/FiO 2) as the end point in patients with severe acute pancreatitis (SAP). Methods:A retrospective study was performed, including 84 patients with SAP in emergency intensive care unit of Qingzhou Hospital Affiliated to Shandong First Medical University from January 2018 to August 2021. According to the status of fluid balance at admission, all patients were divided into the positive fluid balance group (43 cases) and the negative fluid balance group (41 cases). The clinical data including gender, age, etiology, underlying disease, acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) and sequential organ failure assessment (SOFA) of all patients were collected. Fluid balance, PaO 2/FiO 2, IAP, compliance rate, new mechanical ventilation rate and overall hospital stay of 1 week after admission were recorded and compared between the two groups. Results:After 72 hours of treatment, the cumulative fluid balance was (5 219.5±1 038.4) mL in the positive fluid balance group; IAP was higher than that before treatment [mmHg (1 mmHg≈0.133 kPa): 11.9±2.0 vs. 11.7±2.1], but no significant difference was found ( P > 0.05); PaO 2/FiO 2 was significantly higher than that before treatment (mmHg: 299.8±51.4 vs. 220.5±50.4, P < 0.05). After 72 hours of treatment, the cumulative fluid balance in negative fluid balance group was (-3 542.4±1 310.6) mL; IAP was significantly lower than before treatment (mmHg: 11.4±1.8 vs. 15.2±1.9, P < 0.05); PaO 2/FiO 2 was significantly higher than that before treatment (mmHg: 309.9±50.9 vs. 215.4±49.7, P < 0.05). In the fluid resuscitation goals, after 72 hours of treatment, the compliance rate in the negative fluid balance group was significantly higher than that in the positive fluid balance group [82.93% (34/41) vs. 62.79% (27/43), P < 0.05]; 1 week after admission, the new mechanical ventilation rate in the negative fluid balance group was significantly lower than that in the positive fluid balance group [21.95% (9/41) vs. 41.86% (18/43), P < 0.05]; however, there was no significant difference in overall hospital stay between the two groups (days: 41.2±10.9 vs. 39.1±11.5, P > 0.05). After treatment, 70 patients survived and 14 patients died (including 9 cases in the positive fluid balance group and 5 cases in the negative fluid balance group). Conclusions:Using IAP and PaO 2/FiO 2 to guide liquid therapy could result in effective fluid resuscitation in SAP. The treatment strategy effectively improved prognosis of patients with SAP.

Objective: To study the clinical features, therapeutic effects, prognostic factors of 140 patents with mantle cell lymphoma (MCL). Methods: Clinical data of 140 MCL patients admitted from June 2009 to January 2016 in our hospital were retrospectively analyzed. Results: The median age of 140 patients was 59 years with a ratio of 6∶1 for men and women. There were 134 cases (95.7%) in Ann-Arbor stage Ⅲ-Ⅳ, 37 cases (26.4%) with B symptoms, 61 cases (43.6%) with bone marrow involvement and 38 cases (27.1%) with enlarged spleen. The overall response rate (ORR), 3-year survival rate and progression-free survival rate in the treatment group with rituximab were 87.1%, 68.1% and 59.5% respectively, which were significantly higher than those in the rituximab-free treatment group (66.6%, 51.5% and 31.7%, respectively). The difference was statistically significant (all P<0.05). Among patients treated with rituximab, the complete remission rates (70.8% and 77.8%) of R-HyperCVAD/MA and VcR-CAP regimens were higher than those of R-CHOP regimen (39.0%, both P<0.05). However, there was no significant difference in the overall response rate, overall survival rate and progression-free survival rate (all P>0.05). Univariate analysis showed that age, Ki-67 index, B symptoms, bone marrow invasion, platelet count, LDH, β₂-MG and MIPI scores were associated with overall survival (all P<0.05). Multivariate analysis showed that age (HR=4.940, 95% CI: 2.347 to 10.397), B symptom (HR=2.900, 95% CI: 1.517-5.544), β₂-MG (HR=2.945, 95% CI: 1.656-5.238), Ki-67 index (HR=4.915, 95% CI: 2.554-9.456) and treatment with rituximab-containing regimen (HR=2.450, 95% CI: 1.352-4.440) were independent factors for OS. Conclusions Most patients with MCL were older adults and usually had bone marrow involvement and spleen involvement. Rituximab combined with chemotherapy (especially R-HyprCVAD/MA and VcR-CAP) had better clinical efficacy than conventional chemotherapy.

Objective To investigate the application value of MR SWI and DWI in the diagnosis of liver lesions.Methods 1 300 patients underwent 1.5T MRI scan of liver,no pathology or follow-up examination results of patients with focal liver lesions were excluded,147 patients were included and underwent conventional magnetic resonance(MRI),DWI and SWI.By 2 senior radiologists with double blind method of conventional MRI and MRI combined with DWI and SWI image reading,the feature and enhancement pattern of signal intensity were evaluated.Kappa test was used to evaluate the consistency of the diagnosis of 2 physicians.The pathological examination and comprehensive follow-up results were used as the gold standard.The diagnostic accuracy of the two groups was compared.Results 2 doctors had good consistency in the image diagnosis of the two groups.The Kappa values of conventional MRI and conventional MRI combined with DWI and SWI images were 0.912 and 0.936,respectively.The conventional MRI diagnosed primary hepatocellular carcinoma(HCC) in 40 cases,bile duct cancer cells (ICC) in 13 cases,liver metastasis (HMs) in 14 cases,cavernous hemangioma of the liver (CHL) in 17 cases.The conventional MRI combined with DWI and SWI diagnosed HCC in 50 cases,ICC in 20 cases,HMs in 20 cases,CHL in 24 cases,the differences were statistically significant (x2 =5.660,5.250,5.560,6.640,all P ＜ 0.05).Conclusion Conventional MRI combined with DWI and SWI can provide additional valuable information and improve diagnostic performance for liver lesions.

Objective To explore the influence of different blood gas strategies on cerebral protection and blood gas analysis during moderate hypothermic cardiopulmonar.Methods Patients under cardiac valve replacement with extracorporeal circulation (ECC) were performed in this study.The cerebral blood flow (CBF) and regional cerebral oxygen saturation (rSO2) were monitored at 5 points:(1)Induction of anesthesia (T1),(2) after 10 min of the beginning of cardiopulmonary bypass (T2),(3) during the moderate hypothermic phase of CBP managed by the alpha-stat after calibrate blood gas 15 min (T3),(4) pH-stat followed,after calibrate blood gas 15 min (T4),and (5) 10 min after CBP (T5).pH and pCO2 in patients were recorded and analyzed at T3 and T4.Results The CBF of T2 and T3 was lower than that of T1,but the difference was not significant (t =2.841,2.711;P =0.062,0.080).The CBF of T4 and T5 was higher than that of T3,but the difference was not significant (t =1.793,2.135;P =0.119,0.066).The CBF of T5 resumed to before operation.The rSO2 of T2 and T3 was lower than that of T1,but the difference was not significant (t =1.821,2.032;P =0.132,0.267),the rSO2 ofT4 and T5 was higher than that ofT3,but the difference was not significant (t =1.879,2.021;P =0.312,0.075).The rSO2 of T5 resumed to before operation.However,the pH was much lower in pH-stat than alpha-stat (t =17.541,P =0.000) and the pCO2 was much higher than alpha-stat (t =13.914,P =0.000).Conclusions Both pH-stat and alpha-stat have cerebral protection effects.However,compared to pH-stat,alpha-stat could reduce the possibility of acidosis,and maintain the acid-base equilibrium.

Acidic environment of organelles of eukaryotic cells plays an important role in endocytosis, the secretion of lysoso-mal enzymes and other physiological activities.V-ATPase (vacuolar ATPases) and CLC (chloride channel) family are widely distribu-ted and present in virtually all eukaryotic cells in intracellular membranes and in the plasma membrane.They are responsible for the a-cidification of the vesicular interior.In this paper, the distribution, structure, mechanism of action and physiological and pathological significance of V-ATPase and CLC protein are discussed.