Umbilical cord mesenchymal stem cells (UC-MSCs) have been widely used in regenerative medicine, but there is limited research on the stability of UC-MSCs formulation during production. This study aims to assess the stability of the cell stock solution and intermediate product throughout the production process, as well as the final product following reconstitution, in order to offer guidance for the manufacturing process and serve as a reference for formulation reconstitution methods. Three batches of cell formulation were produced and stored under low temperature (2-8 ℃) and room temperature (20-26 ℃) during cell stock solution and intermediate product stages. The storage time intervals for cell stock solution were 0, 2, 4, and 6 h, while for intermediate products, the intervals were 0, 1, 2, and 3 h. The evaluation items included visual inspection, viable cell concentration, cell viability, cell surface markers, lymphocyte proliferation inhibition rate, and sterility. Additionally, dilution and culture stability studies were performed after reconstitution of the cell product. The reconstitution diluents included 0.9% sodium chloride injection, 0.9% sodium chloride injection + 1% human serum albumin, and 0.9% sodium chloride injection + 2% human serum albumin, with dilution ratios of 10-fold and 40-fold. The storage time intervals after dilution were 0, 1, 2, 3, and 4 h. The reconstitution culture media included DMEM medium, DMEM + 2% platelet lysate, 0.9% sodium chloride injection, and 0.9% sodium chloride injection + 1% human serum albumin, and the culture duration was 24 h. The evaluation items were viable cell concentration and cell viability. The results showed that the cell stock solution remained stable for up to 6 h under both low temperature (2-8 ℃) and room temperature (20-26 ℃) conditions, while the intermediate product remained stable for up to 3 h under the same conditions. After formulation reconstitution, using sodium chloride injection diluted with 1% or 2% human serum albumin maintained a viability of over 80% within 4 h. It was observed that different dilution factors had an impact on cell viability. After formulation reconstitution, cultivation in medium with 2% platelet lysate resulted in a cell viability of over 80% after 24 h. In conclusion, the stability of cell stock solution within 6 h and intermediate product within 3 h meets the requirements. The addition of 1% or 2% human serum albumin in the reconstitution diluent can better protect the post-reconstitution cell viability.

In this article,the mechanism of Shanxian Granule in inhibiting liver cancer,lung cancer,sarcoma,melanoma and other tumors was reviewed,with a view to providing a theoretical basis for the clinical research of Shanxian Granules in the treatment of malignant tumors.Shanxian Granule are the pure Chinese medicine preparation for counteracting malignant tumor developed by the Oncology Research Team of Shaanxi University of Chinese Medicine on the basis of the theory of traditional Chinese medicine syndrome differentiation and treatment combined with decades of clinical experience as well as the achievements of modern pharmacological research.Shanxian Granule are mainly composed of Crataegi Fructus,Agrimoniae Herba,Panacis Quinquefolii Radix,Curcumae Rhizoma,Testudinis Carapax et Plastrum,Trionycis Carapax,Corydalis Rhizoma,and Polyporus,and have the actions of benefiting qi and nourishing yin,supporting healthy-qi and cultivating the essence,activating blood and removing stasis,and eliminating swelling and counteracting cancer.The compatibility of Shanxian Granule embodies the principle of supporting healthy-qi but avoiding maintaining pathogens,and eliminating pathogens but avoiding injuring healthy-qi.The granules can effectively inhibit the growth and metastasis of liver cancer,lung cancer,sarcoma,melanoma and other tumors both in vivo and in vitro,alleviate the clinical symptoms of tumor patients,and improve their prognosis.The anti-tumor mechanism of Shanxian Granules is related to the enhancement of body immune function,inhibition of tumor cell proliferation,enhancement of tumor cell apoptosis,inhibition of tumor cell invasion and metastasis as well as the tumor angiogenesis.

Objective To investigate the predictive value of new simplified insulin resistance(IR)assessment indexes in identifying subclinical left ventricular systolic function impairment in patients with type 2 diabetes mellitus(T2DM).Methods A total of 150 T2DM patients with preserved left ventricular ejection fraction(LVEF≥50%)who were admitted to Department of Endocrinology of the First Affiliated Hospital of Air Force Medical University from June 2021 to December 2021 were retrospectively analyzed.All patients underwent two-dimensional speckle tracking echocardiography to measure left ventricular global longitudinal strain(GLS).According to GLS value,the subjects were divided into the normal group(GLS≥18%group,n=80)and the impaired group(GLS<18%group,n=70).Some new simplified IR assessment indicators were calculated and compared between the two groups,including body mass index(BMI),TG/HDL-C ratio,triglyceride-glucose(TyG)index,TyG-BMI index,TyG-WHR and metabolic score for IR(METS-IR).Correlation between the GLS and the new simplified IR assessment indexes was analyzed.The receiver operating characteristic(ROC)curve was used to analyze the diagnostic efficacy of different simplified IR assessment indexes,with the area under the curve(AUC)calculated.Furthermore,according to whether the subjects were complicated with hypertension,binary logistics regression analysis was performed to explore the independent correlation between the simplified IR assessment index and GLS<18%.Results Total 150 were included with aged(54.5±13.7)years with 96(64.0%)men and 54(36.0%)women.Compared with the GLS≥18%group,the TG/HDL-C ratio,TyG index,TyG-BMI,and METS-IR of subjects in the GLS<18%group were significantly increased(P<0.05).Pearson correlation analysis showed that TG/HDL-C ratio,TyG index,TyG-BMI,TyG-WHR,and METS-IR were negatively correlated with GLS(P<0.05).ROC analysis showed that TyG index had a certain predictive value for the evaluation of GLS<18%(AUC=0.678,95%CI 0.591-0.765,P<0.001).Stratification based on hypertension and further adjusting for confounding factors,TyG index remains significantly associated with GLS<18%(OR=3.249,95%CI 1.045-10.103,P=0.042).Conclusions The novel simplified insulin resistance evaluation indexes are closely associated with left ventricular subclinical systolic dysfunction in T2DM patients with preserved ejection fraction.TyG index is an effective index to identify left ventricular subclinical dysfunction in these populations.

Objective To analyze the risk factors for severe illness caused by coronavirus disease 2019 in Fuzhou city.Methods The data of 4081 confirmed cases with current address in Fuzhou was collected from China Information System for Disease Control and Prevention from January 1 to June 30,2023.The epidemiological data of those cases was investigated such as the demographic characteristics,clinical manifestations and past medical history,etc.The risk factors of severe cases were analyzed by using the logistic regression.Results 4081 confirmed cases had been reported including 671 severe cases and 3410 non-severe cases.The demographic characteristics of severe cases,such as the proportion of male,age and current address in community were higher than that of non-severe cases,vaccination rate was lower than non-severe cases(59.02%vs.80.12%),the differences are statistically significant(P＜0.001).The clinical manifestations such as interval time between onset and visit(P=0.001),fever(P=0.002),difficulty in breathing/shortness of breath(P=0.001)were the factors related to severe illness.The past medical histories such as history of chronic lung disease,history of heart cerebrovascular disease of severe cases,were higher than that of non-severe cases(P＜0.001).Multivariate logistic regression showed that the male,the higher age,current address in community,no vaccination,the longer interval time between onset and visit,fever,difficulty in breathing/shortness of breath,the history of chronic lung disease,the history of heart cerebrovascular disease raised the risk of becoming severe cases.The healing time for severe cases was longer than that for non-severe cases(P＜0.001).Conclusion Sex,age,current address,vaccination,interval time between onset and visit,fever,difficulty in breathing/shortness of breath,history of chronic lung disease,and history of heart cerebrovascular disease are the influencing factors for severe illness.

Objective To evaluate the patient-reported outcome(PRO)of patients with breast cancer who underwent autologous breast reconstruction and implant breast reconstruction.Methods Patients who underwent breast reconstruction in Shanghai Cancer Center,Fudan University from Jan 2020 to Jun 2021 were selected,including 111 patients who underwent autologous breast reconstruction and 108 patients who underwent implant breast reconstruction.Chinese version Breast-Q2.0 scale,breast cancer specificity scale QLQ-BR23 and EORTC quality of life scale QLQ-C30 were used to investigate the PRO of the two groups 18 months after operation.Results The rate of stage Ⅲ breast cancer in the self-weight construction group was higher than that in the implant reconstruction group(64.9%vs.44.4%,P<0.001).The preoperative neoadjuvant therapy and postoperative radiotherapy in the autologous reconstruction group were higher than those in the implant reconstruction group(P<0.001).Postoperative chemotherapy and endocrine therapy in the autologous reconstruction group were lower than those in the implant reconstruction group(P<0.001).The study based on Breast-Q scale showed that the breast satisfaction of autologous reconstruction group was higher than that of implant reconstruction(59.28±17.20 vs.54.94±14.48,P<0.05).The study based on QLQ-BR23 showed that the self-weight construction group was higher than the implant reconstruction group in the field of arm symptoms(20.02±20.80 vs.12.65±16.18,P<0.05).The study based on QLQ-C30 scale showed that there was no significant difference in all functional areas and symptom areas of patients.There was no significant difference in the number and time of social regression between the two groups.Conclusion Breast reconstruction can improve the PRO of breast cancer patients,and oncology factors will affect the choice of breast reconstruction.Patients with autologous breast reconstruction are more satisfied with breast appearance,but upper limb symptoms such as swelling and pain are more obvious than implant reconstruction,which is related to the higher proportion of axillary lymph node dissection in patients with autologous reconstruction.There is no significant difference in quality of life and social regression between the two groups.

ObjectiveTo investigate the effects of maltol aluminum exposure on miR-193a-3p, demethylase AlkB homolog 5 (ALKBH5), phosphatase and tensin homolog deleted on chromosome ten (PTEN) and protein kinase B (AKT), and whether miR-193a-3p is involved in aluminum-induced cognitive impairment by regulating ALKBH5/PTEN/AKT signaling pathway. Methods Specific pathogen-free male SD rats were randomly divided into control group and low-, medium- and high- dose groups according to their body weight, with eight rats in each group. Rats in the low-, medium-, and high- dose groups were intraperitoneally injected with maltol aluminum solution at concentrations of 10.00, 20.00, and 40.00 μmol/kg body weight, respectively, while the rats in control group were given an equal volume of 0.9% sodium chloride solution. Rats were injected for five days every week for three months. After injection, the novel object recognized test was used to assess the learning and memory ability of the rats. The relative expression of miR-193a-3p and B-cell lymphocytoma-2 (Bcl-2), Bcl-2 associated X protein (Bax) and cysteine aspartate protease-3 (Caspase-3) mRNA in rat hippocampus was detected using the real-time quantitative polymerase chain reaction. The relative protein expression of ALKBH5, PTEN, and AKT2 in the rat hippocampus was detected using Western blot. Results The discrimination index and the preference index of the new object recognition test of the rats in high-dose group were lower than those in control group and low-dose group (all P<0.05). The relative expression of miR-193a-3p and Bcl-2 mRNA in the hippocampus of the rats in high-dose group was lower than those in control group and low-dose group (all P<0.05). The relative mRNA expression of Bax in the high-dose group was higher than those in the control group and low-dose group (both P<0.05). The relative mRNA expression of Caspase-3 of the rats in the high-dose group was higher than that in the other three groups (both P<0.05). The relative protein expression of ALKBH5 in the hippocampus of the rats in the high-dose group was lower than that in the control group (P<0.05). The relative expression of PTEN protein was higher than those in the control group and low-dose group (both P<0.05). The relative protein expression of AKT2 was lower than those in the control group and low-dose group (both P<0.05). Conclusion Sub-chronic aluminum exposure can inhibit the expression of miR-193a-3p in the hippocampus of rats, which may disrupt the ALKBH5/PTEN/AKT pathway and affect normal neuronal homeostasis and cellular function. This pathway may play an important role in aluminum-induced cognitive impairment.

Objective:To investigate the clinical value of left ventricular shape index (SI) and eccentricity index (EI) in evaluating left ventricular remodeling.Methods:A retrospective analysis was performed on 324 patients (264 males, 60 females, age (62.5±11.8) years) diagnosed with myocardial infarction (MI) and 113 healthy controls (HC; 47 males, 66 females, age (57.8±10.7) years) who received gated myocardial perfusion imaging (GMPI) in First Hospital of Shanxi Medical University from January 2016 to September 2020. SI (end-diastolic SI (EDSI), end-systolic SI (ESSI)), EI and left ventricular function parameters (end-diastolic volume (EDV), end-systolic volume (ESV), left ventricular ejection fraction (LVEF), summed motion score (SMS), summed thickening score (STS), peak ejection rate (PER) and peak filling rate (PFR)) were obtained by quantitative gated SPECT (QGS) software. Propensity score (PS) inverse probability of treatment weighting (IPTW) was used to balance the intergroup covariates. The differences and correlations of EDSI, ESSI, EI and left ventricular function parameters between patients in MI group and HC group were analyzed. ROC curve analysis was used to evaluate the values of EDV, EDSI, ESSI and EI alone and in combination in the assessment of left ventricular systolic function impairment. Data were analyzed by independent-sample t test, Pearson correlation and Spearman rank correlation analyses, and Delong test. Results:After IPTW, EDSI and ESSI in MI group ( n=319) were higher than those in HC group ( n=133; EDSI: 0.66±0.09 vs 0.60±0.06; ESSI: 0.59±0.11 vs 0.47±0.07; t values: 8.05, 14.67, both P<0.001), and EI was lower than that in HC group (0.81±0.06 vs 0.85±0.03; t=-8.93, P<0.001). In both groups, there were significant correlations between EDSI and ESSI ( r values: 0.928, 0.873), between EDSI, ESSI and EI ( r values: from -0.831 to -0.641), between EDSI, ESSI and LVEF ( r values: from -0.627 to -0.201), between ESSI and EDV, ESV and SMS ( rs values: 0.336-0.584), between ESSI and -PER, PFR ( rs values: from -0.406 to -0.402, r values: from -0.352 to -0.325) (all P<0.01). ROC curve analysis showed that EDV (AUC: 0.895) and ESSI (AUC: 0.839) had the highest efficacy in evaluating left ventricular systolic function impairment in MI group and HC group, respectively. EDV-EDSI-ESSI-(1-EI) had higher efficacy in the assessment of impaired left ventricular systolic function in MI group (AUC: 0.956), which was higher than that of EDV or EDV-EDSI or EDV-ESSI or EDV-(1-EI) ( z values: from -2.64 to -2.18, P values: 0.008-0.029); EDV-EDSI-ESSI-(1-EI) also had high efficacy in HC group (AUC: 0.911), which was higher than that of EDV or EDV-EDSI or EDV-(1-EI) ( z values: from -2.60 to -2.43, P values: 0.009-0.015). Conclusions:In MI patients, the increase of SI and the decrease of EI indicate the increase of left ventricular sphericity and the aggravation of left ventricular remodeling. SI and EI have certain clinical application values in evaluating left ventricular morphology, predicting left ventricular remodeling and left ventricular systolic function impairment.

Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical Gram-negative bacteria isolates from bloodstream infections in China in 2022.Methods:The clinical isolates of Gram-negative bacteria from blood cultures in member hospitals of national bloodstream infection Bacterial Resistant Investigation Collaborative System（BRICS）were collected during January 2022 to December 2022. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 software were used to analyze the data.Results:During the study period，9 035 strains of Gram-negative bacteria were collected from 51 hospitals，of which 7 895（87.4%）were Enterobacteriaceae and 1 140（12.6%）were non-fermenting bacteria. The top 5 bacterial species were Escherichia coli（ n=4 510，49.9%）， Klebsiella pneumoniae（ n=2 340，25.9%）， Pseudomonas aeruginosa（ n=534，5.9%）， Acinetobacter baumannii complex（ n=405，4.5%）and Enterobacter cloacae（ n=327，3.6%）. The ESBLs-producing rates in Escherichia coli， Klebsiella pneumoniae and Proteus spp. were 47.1%（2 095/4 452），21.0%（427/2 033）and 41.1%（58/141），respectively. The prevalence of carbapenem-resistant Escherichia coli（CREC）and carbapenem-resistant Klebsiella pneumoniae（CRKP）were 1.3%（58/4 510）and 13.1%（307/2 340）；62.1%（36/58）and 9.8%（30/307）of CREC and CRKP were resistant to ceftazidime/avibactam combination，respectively. The prevalence of carbapenem-resistant Acinetobacter baumannii（CRAB）complex was 59.5%（241/405），while less than 5% of Acinetobacter baumannii complex was resistant to tigecycline and polymyxin B. The prevalence of carbapenem-resistant Pseudomonas aeruginosa（CRPA）was 18.4%（98/534）. There were differences in the composition ratio of Gram-negative bacteria in bloodstream infections and the prevalence of main Gram-negative bacteria resistance among different regions，with statistically significant differences in the prevalence of CRKP and CRPA（ χ2=20.489 and 20.252， P<0.001）. The prevalence of CREC，CRKP，CRPA，CRAB，ESBLs-producing Escherichia coli and Klebsiella pneumoniae were higher in provinicial hospitals than those in municipal hospitals（ χ2=11.953，81.183，10.404，5.915，12.415 and 6.459， P<0.01 or <0.05），while the prevalence of CRPA was higher in economically developed regions（per capita GDP ≥ 92 059 Yuan）than that in economically less-developed regions（per capita GDP <92 059 Yuan）（ χ2=6.240， P=0.012）. Conclusions:The proportion of Gram-negative bacteria in bloodstream infections shows an increasing trend，and Escherichia coli is ranked in the top，while the trend of CRKP decreases continuously with time. Decreasing trends are noted in ESBLs-producing Escherichia coli and Klebsiella pneumoniae. Low prevalence of carbapenem resistance in Escherichia coli and high prevalence in CRAB complex have been observed. The composition ratio and antibacterial spectrum of bloodstream infections in different regions of China are slightly different，and the proportion of main drug resistant bacteria in provincial hospitals is higher than those in municipal hospitals.

Cardiovascular diseases are a group of disorders of the heart and blood vessels, primarily including coronary heart disease, stroke, and other diseases. It is the world’s leading cause of death, and its incidence is increasing yearly. Hypertension is a major risk factor for cardiovascular disease. Wnt signaling comprises a series of highly conservative cascading events controlling fundamental biological processes. Wnt signaling pathways include the canonical Wnt pathway (or Wnt/β-catenin pathway), the non-canonical planar cell-polarity pathway, and the non-canonical calcium-dependent pathways. Abnormal Wnt signaling promotes cell proliferation and differentiation, cardiac malformations, various malignancies, so drugs targeting Wnt signaling play a great therapeutic potential. Wnt/β‑catenin pathway is involved in the occurrence and development of cardiovascular diseases such as atherosclerosis and stroke by regulating cell proliferation, migration, apoptosis, blood-brain barrier permeability, inflammation, oxidative stress, and immune response. Based on the latest research progress, this review summarizes the role of Wnt/β‑catenin signaling in cardiovascular diseases, in order to provide new ideas for the prevention and treatment of cardiovascular diseases.

Natural products are important sources of drug discovery. However, the traditional methods of extraction and isolation, as well as chemical synthesis for obtaining natural products are associated with issues such as operational complexity, high costs, low efficiency, and environmental pollution. Constructing microbial cell factories through synthetic biology methods to produce medicinal natural products has the advantages of high efficiency, low cost, and environmental protection. Nevertheless, the scope and yield improvement of the products are limited by the limitations of enzymes in microbial cell factories. Protein engineering is considered one of the most effective approaches to overcome these limitations. This article introduces commonly used methods of protein engineering technology and summarizes its specific applications in improving enzyme performance, modifying the enzymatic environment, and promoting the development of synthetic biology tools in the field of pharmaceutical natural product synthesis. Furthermore, it analyzes the current bottlenecks and challenges in protein engineering and looks forward to its future application prospects, offering insights for the development and practical use of protein engineering technology.