ObjectiveThis study aims to investigate the effectiveness and potential mechanism of Erxian Decoction （二仙汤） for late-onset depression （LOD）. MethodsForty Wistar male rats of 7-8 weeks were divided into 20 each of normal group and youth depression group. Sixty Wistar male rats of 20 months were divided into 20 each of elder group， LOD group and Erxian Decoction group. The rats in youth depression group were modelled with chronic unpredictable mild stress （CUMS） for 6 weeks to build a depression model， and the elder rats in LOD group and Erxian Decoction group were modelled with CUMS for 6 weeks to build a LOD model， with no interventions in the normal group and the elder group. Gastric administration was carried out at the same time of modelling， rats in Erxian Decoction group were given 8 g/（kg·d） of Erxian Decoction by gavage， and rats in the normal group， youth depression group， elder group， and LOD group were given 4 ml/（kg·d） of pure water by gavage， for 6 weeks in each group. Sugar water preference experiment and forced swimming experiment were used to evaluate the depression-like behaviour of rats， absent field experiment was used to evaluate the spontaneous activity ability of rats， and T-maze experiment was used to evaluate the cognitive function of rats； Western blot assay was used to detect neuronal nuclei （NeuN）， nestin， doublecortin （DCX） in hippocampal tissue， and zonula occludens-l （ZO-1）， folate receptor α （FRα）， reduced folate carrier （RFC）， and protoncoupledfolate transporter （PCFT） protein expression in choroid plexus； immunofluorescence was used to detect the number of double-positive cells for Ki-67/nestin， the number of double-positive cells for 5-bromodeoxyuracil nucleoside （BrdU）/DCX in hippocampal dentate gyrus， and the protein expression of ZO-1， FRα， RFC， and PCFT in choroid plexus tissues； ELISA technique was used to detect plasma， cerebrospinal fluid， 5-methyltetrahydrofolate （5-MTHF） in hippocampal tissues； Pearson correlation analysis was used to correlate the 5-MTHF content in cerebrospinal fluid and hippocampal tissues and the expression of nestin， DCX， and NeuN proteins in hippocampal tissues of rats in youth depression group and LOD group. ResultsCompared with normal group， rats in youth depression group and LOD group showed reduced sugar water preference， reduced total distance travelled in the absent field， reduced number of times through the grid， prolonged forced swimming immobilisation， reduced hippocampal NeuN， nestin and DCX protein expression， reduced number of Ki-67/nestin double-positive cells in hippocampal dentate gyrus， reduced number of BrdU/DCX double-positive cells in hippocampal dentate gyrus， and reduced expression of ZO-1 and FRα proteins and fluorescence intensity （P＜0.05 or P＜0.01）； the correct rate of T-maze on days 3 and 4 in the rats of youth depression group and on days 2 to 4 in the rats of LOD group significantly decreased， and the content of 5-MTHF in the cerebrospinal fluid and hippocampal tissues of the rats of LOD group significantly decreased as well （P＜0.05 or P＜0.01）. Compared with youth depression group， rats in LOD group showed a decrease in total distance travelled in absenteeism， number of times through the grid， a significant decrease in the correct rate of the T-maze on day 1-4， a decrease in NeuN， nestin， DCX protein expression of hippocampal tissue and the number of Ki-67/nestin double-positive cells， BrdU/DCX double-positive cells of hippocampal dentate gyrus （P＜0.05 or P＜0.01）. Compared with LOD group， rats in Erxian Decoction group had elevated sugar-water preference and total distance travelled in absenteeism and number of times through the grid， shorter forced swimming immobility time， significantly higher correct rate of the T-maze on day 3-4， elevated expression of NeuN， nestin， and DCX proteins in hippocampal tissues， increased number of Ki-67/nestin double-positive cells and BrdU/DCX double-positive cells in hippocampal dentate gyrus， and increased 5-MTHF content in cerebrospinal fluid and hippocampal， and ZO-1， FRα， RFC， PCFT protein expression and fluorescence intensity increased in choroid plexus （P＜0.05 or P＜0.01）. Correlation analysis showed that there was a positive correlation between 5-MTHF content in cerebrospinal fluid （r = 0.466）， hippocampal tissue （r = 0.522） and nestin expression in hippocampal tissue （P＜0.05）. ConclusionErxian Decoction could improve depressive-like behaviour and cognitive impairment in LOD model rats， and its mechanism may promote hippocampal neurogenesis by alleviating structural damage to the choroid plexus of the brain tissue， and improving impaired choroid plexus folate transport.

Objective:To investigate the effects of SINC, a novel secreted protein of Chlamydia psittaci, on the apoptosis of host cells and the regulatory role of mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling pathway in it. Methods:HeLa cells were treated with recombinant SINC. The expression of Bax and Bcl-2 at protein level and the phosphorylation of ERK1/2 were analyzed by Western blot. Hoechst 33258 staining was used to detect the apoptosis of HeLa cells after SINC stimulation. Moreover, HeLa cells were pretreated with MEK1/2 inhibitor U0126 (50 μmol/L), and then stimulated with different concentrations of SINC for different time. Flow cytometry was used to detect the changes in cell apoptosis rates and Western blot was performed to detect the expression of Bax and Bcl-2 at protein level.Results:Treating HeLa cells with 10 μg/ml of SINC for 18 h resulted in down-regulated Bax and up-regulated Bcl-2 at protein level. Besides, the ratio of Bax/Bcl-2 was the lowest and a significant increase in the ratio of phosphorylated ERK1/2 (p-ERK1/2) to ERK1/2 was observed. Hoechst 33258 staining showed that the number of apoptotic bodies decreased significantly after stimulating HeLa cells with 5, 10 and 15 μg/ml of SINC. In the presence of MEK1/2 inhibitor U0126, the expression of Bcl-2 at protein level was down-regulated, while the expression of cleaved PARP was significantly up-regulated. Flow cytometry showed a significantly enhanced apoptosis of HeLa cells.Conclusions:SINC can inhibit the apoptosis of HeLa cells through activating the MAPK/ERK signaling pathway.

Objective:To construct a reliability management index system of cardiology medical equipment supply,to form a reliability evaluation strategy,and to improve the effectiveness of reliability management.Methods:13 supply management items were decomposed from the three links of spare parts before use,tracking during use and post-use processing of 126 medical equipment,and the probability of work error,probability of quality problems and risk expectation of diagnosis and treatment were evaluated in the whole process management,and the whole-process management countermeasures of grading and stratification,quality standardization and department cooperation was formed.2,000 pieces(sets)of medical equipment used in The People's Hospital of Longhua from 2021 to 2022 were selected by random sampling method,and the department cooperative management[referred to as collaborative management mode,1,000 pieces(sets)times]and reliability evaluation management[referred to as evaluation management mode,1,000 pieces(sets)times]were adopted respectively.The reliability and satisfaction of medical equipment under different management modes were compared.Results:The work error probabilities of pre-use spare parts,in-use tracking,post-use processing and supply of medical equipment adopting evaluation management mode were(4.74±2.19)%,(4.39±1.85)%,(5.75±1.88)%and(8.29±1.30)%,respectively,which were lower than the collaborative management mode,the difference was statistically significant(t=5.367,5.663,5.432,6.847;P<0.05);the probabilities of quality problems were(4.13±1.67)%,(3.89±1.25)%,(5.28±1.84)%and(7.64±1.18)%,respectively,which were lower than the collaborative management mode,the difference was statistically significant(t=6.504,6.229,5.123,6.166,P<0.05);the risk expectations of diagnosis and treatment were(2.74±0.89)%,(2.47±0.96)%,(3.42±0.95)%and(4.02±1.09)%,respectively,which were lower than the collaborative management mode,the difference was statistically significant(t=7.027,6.509,8.915,9.266,P<0.05).The satisfaction of the relevant staff on the performance quality,sterilization specifications,supply timeliness,level of collaboration and safety of the medical equipment adopting the evaluation management mode were(93.54±4.65)%,(91.67±4.11)%,(94.58±4.34)%,(92.39±3.82)%and(90.97±3.76)%,respectively,which were higher than the collaborative management mode,the difference was statistically significant(t=2.809,3.030,2.843,4.939,3.739,P<0.05).Conclusion:The reliability management model can reduce the work errors and security risks in medical equipment supply,improve the reliability of supply and improve the quality of supply service.

Objective:To explore the hematological phenotype and genotypic characteristics of five Chinese individuals with a rare thalassemia mutation HBB: c. 93-21G>A. Methods:A retrospective study was carried out on five individuals identified by the People′s Hospital of Yangjiang and Guangzhou Hybribio Co., Ltd. from May 2018 to September 2022. Routine blood test and hemoglobin electrophoresis were performed, and the genotypes of five subjects were determined by using PCR combined with reverse dot blotting (RDB), nested PCR, Gap-PCR and Sanger sequencing. This study was approved by Medical Ethics Cornmittee of the People′s Hospital of Yangjiang (Ethics No. 20240001).Results:Among the five individuals, hematological data of one was unavailable, and the remaining four had presented with microcytosis and hypochromia. The results of hemoglobin electrophoresis indicated that all of them had a HbA 2 level of ≥4.7%. Genetic analysis showed that one case had harbored compound heterozygous mutations of ααα anti3.7 triplet and HBB: c. 93-21G>A, one had compound heterozygous mutations of -α 3.7 and HBB: c. 93-21G>A, whilst the remaining three were heterozygous for the HBB: c. 93-21G>A mutation. Conclusion:The hematological phenotype of β-thalassemia carriers ( HBB: c. 93-21G>A) is similar to that of other β + thalassemia heterozygotes with mild β-thalassemia characteristics.

Objective Analyzing risk factors for prolonged ICU stay after cardiac surgery of Infective Endocarditis(IE)provides a basis for preventing extended ICU durations in postoperative IE cases.Methods From January 1,2019,to March 31,2021,a total of 223 patients with infective endocarditis who underwent cardiac surgery in the cardiac surgery department of Guangdong Provincial People's Hospital were included.Patients were divided into non-prolonged group(<3 days)and prolonged group(≥3 days)based on postoperative ICU stay duration.There were 156 cases in the non-prolonged group and 67 cases in the prolonged group.Single-factor analysis of risk factors for prolonged ICU stay was conducted using t-tests or rank-sum tests.Variables with P<0.05 in the single-factor analysis were further subjected to binary logistic regression for multivariate analysis.The accuracy of the model was evaluated using the ROC curve.Results Among the 223 patients,67 experienced prolonged ICU stay,with an incidence rate of 30%.Single-factor analysis results included gender,age,history of coronary heart disease,history of stroke,preoperative heart failure,aortic valve regurgitation area,left ventricular end-diastolic diameter,left ventricular ejection fraction(LVEF)<60%,extracorporeal circulation time,aortic cross-clamp time,use of Intra-Aortic Balloon Pump(IABP),endotracheal tube reintubation,pulmonary infection,use of Continuous Renal Replacement Therapy(CRRT),and prolonged mechanical ventilation time(>24 hours),among others.Multivariate analysis results revealed that preoperative LVEF<60%(OR=3.004,P=0.041),postopera-tive use of IABP(OR=31.686,P=0.008),and mechanical ventilation time>24 hours(OR=8.135,P<0.001)were independent risk factors for prolonged ICU stay after cardiac surgery.The model's AUC value for predicting risk factors for prolonged ICU stay was 0.858(95%CI:0.806～0.901,P<0.001).Conclusion Preoperative left ventricular ejection fraction(LVEF)<60%,the use of IABP,and mechanical ventilation time>24 hours were identified as independent risk factors for prolonged ICU stay after infective endocarditis(IE)surgery.In clinical practice,it is important to comprehensively address and manage various risk factors with the aim of reducing ICU stay duration and improving the overall success rate of the surgery.

Diabetic nephropathy (DN) is one of the complications of diabetes mellitus,which is accom-panied by severe microvascular lesions.and is also the most common inducing factor of end-stage chronic kid-ney disease.The traditional treatment of DN cannot fundamentally cure diabetes and its complications,and new treatment methods need to be explored urgently.At present,the diagnosis and treatment strategy of using mesenchymal stem cells-derived exosomes (MSCs-exo) has become a research hotspot in the early diagnosis and clinical treatment of DN.A number of studies have confirmed that MSCs-exo has high efficacy and safety in the treatment of DN,and MSCs-exo plays a renoprotective role in diabetic nephropathy models by transfer-ring its own contents to the damaged tissue.This article focuses on the research progress and therapeutic po-tential of mesenchymal stem cell-derived exosomes in regulating autophagy in diabetic nephropathy,in order to provide new ideas and methods for the treatment of DN.

Objective:To further improve the understanding of paroxysmal nocturnal hemoglobinuria (PNH), we retrospectively analyzed and summarized the clinical characteristics, treatment status, and survival status of patients with PNH in Zhejiang Province.Methods:This study included 289 patients with PNH who visited 20 hospitals in Zhejiang Province. Their clinical characteristics, comorbidity, laboratory test results, and medications were analyzed and summarized.Results:Among the 289 patients with PNH, 148 males and 141 females, with a median onset age of 45 (16-87) years and a peak onset age of 20-49 years (57.8% ). The median lactic dehydrogenase (LDH) level was 1 142 (604-1 925) U/L. Classified by type, 70.9% (166/234) were classical, 24.4% (57/234) were PNH/bone marrow failure (BMF), and 4.7% (11/234) were subclinical. The main clinical manifestations included fatigue or weakness (80.8%, 235/289), dizziness (73.4%, 212/289), darkened urine color (66.2%, 179/272), and jaundice (46.2%, 126/270). Common comorbidities were hemoglobinuria (58.7% ), renal dysfunction (17.6% ), and thrombosis (15.0% ). Moreover, 82.3% of the patients received glucocorticoid therapy, 70.9% required blood transfusion, 30.7% used immunosuppressive agents, 13.8% received anticoagulant therapy, and 6.3% received allogeneic hematopoietic stem cell transplantation. The 10-year overall survival (OS) rate was 84.4% (95% CI 78.0% -91.3% ) . Conclusion:Patients with PNH are more common in young and middle-aged people, with a similar incidence rate between men and women. Common clinical manifestations include fatigue, hemoglobinuria, jaundice, renal dysfunction, and recurrent thrombosis. The 10-year OS of this group is similar to reports from other centers in China.

Objective:To establish an epidemiological cut-off value (ECV) for antifungal drugs against Cryptococcus neoformans in East China through a multicenter in vitro drug susceptibility test. Methods:A retrospective collection of 479 clinical isolates of Cryptococcus neoformans was conducted by the East China Invasive Fungal Infection Group (ECIFIG) from January 1, 2017 to December 31, 2022. Mass spectrometry and gene sequencing were used for identification. A unified drug susceptibility testing system was established in the fungal laboratories across three sub centers in Shanghai, Jiangxi, and Jiangsu provinces. Drug susceptibility testings of Cryptococcus neoformans were independently completed in each center after passing consistency evaluation. Epidemiological breakpoints were established against fluconazole, voriconazole, amphotericin B, 5-fluorocytosine, isaconazole, posaconazole and itraconazole following the principles and procedures of the Clinical and Laboratory Standards Institute (CLSI) M57. Results:External consistency evaluation revealed that the minimum inhibitory concentration values ??for all drugs in each center did not differ by more than one dilution gradient. A new ECV type of Cryptococcus neoformans in East China was established, including fluconazole 16 mg/L, voriconazole 0.12 mg/L, amphotericin B 1 mg/L, 5-fluorocytosine 8 mg/L, isavuconazole 0.12 mg/L, posaconazole 0.5 mg/L, and itraconazole 0.5 mg/L. Conclusion:This study preliminarily revealed the drug susceptibility characteristics of clinical Cryptococcus neoformans in East China and established the ECVs for antifungal drugs against Cryptococcus neoformans in the region.

Objective:To compare and analyze the efficacy and safety of intraoperative radiotherapy (IORT) combined with conventional therapy (surgery combined with radiochemotherapy) and conventional therapy alone for pancreatic cancer.Methods:Literature review was conducted from PubMed, Cochrane Library, Web of Science, Embase, Chongqing VIP, CNKI, Wanfang Data and China Biomedical Literature Service System (SinoMed). The literatures that met the inclusion criteria were screened and the data were extracted. Meta-analysis was carried out by RevMan 5.4 software.Results:A total of 11 studies consisting of 813 patients were included. According to the combined results, compared with conventional therapy, IORT combined with conventional therapy could improve the overall survival rate of pancreatic cancer ( HR=0.66, 95% CI=0.54-0.81, Z=4.03, P<0.001), and did not increase the treatment-related side effects ( OR=1.00, 95% CI=0.69-1.46, Z=0.01, P=0.99), but failed to bring benefit to the local control rate ( HR=0.56, 95% CI=0.31-1.01, Z=1.93, P=0.05). Conclusions:The overall survival rate in the IORT combined with conventional therapy group is significantly better than that in the conventional therapy group. No significant difference is found in the treatment-related adverse reactions between two groups. IORT combined with conventional therapy is worthy of clinical application.

Klotho gene was originally discovered as an anti-aging gene, Klotho protein encoded by Klotho gene is expressed in multiple human tissues, and its most prominent function is the regulation of phosphate homeostasis. Klotho protein possesses various activities, including inhibition of multiple signaling pathways, reducing oxidative stress and suppressing inflammation, and these activities are associated with cancer. Klotho protein is discovered as a universal tumor suppressor, and its expression is associated with tumorigenesis and prognosis of patients. Lung cancer is the most common malignancy tumor, and it is the leading cause of cancer deaths worldwide because of its high incidence and mortality. This article summarizes the research progress of the role of Klotho on pathogenesis, therapeutic effect and prognosis in lung cancer, in order to provide new biomarker and target for diagnosis, treatment and prognosis of lung cancer.
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Humans ; Lung Neoplasms ; Carcinogenesis ; Inflammation