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.

Objective To investigate the clinical characteristics and prognosis of pneumococcal meningitis(PM),and drug sensitivity of Streptococcus pneumoniae(SP)isolates in Chinese children.Methods A retrospective analysis was conducted on clinical information,laboratory data,and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country.Results Among the 160 children with PM,there were 103 males and 57 females.The age ranged from 15 days to 15 years,with 109 cases(68.1% )aged 3 months to under 3 years.SP strains were isolated from 95 cases(59.4% )in cerebrospinal fluid cultures and from 57 cases(35.6% )in blood cultures.The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87)and 27% (21/78),respectively.Fifty-five cases(34.4% )had one or more risk factors for purulent meningitis,113 cases(70.6% )had one or more extra-cranial infectious foci,and 18 cases(11.3% )had underlying diseases.The most common clinical symptoms were fever(147 cases,91.9% ),followed by lethargy(98 cases,61.3% )and vomiting(61 cases,38.1% ).Sixty-nine cases(43.1% )experienced intracranial complications during hospitalization,with subdural effusion and/or empyema being the most common complication[43 cases(26.9% )],followed by hydrocephalus in 24 cases(15.0% ),brain abscess in 23 cases(14.4% ),and cerebral hemorrhage in 8 cases(5.0% ).Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old,with rates of 91% (39/43)and 83% (20/24),respectively.SP strains exhibited complete sensitivity to vancomycin(100% ,75/75),linezolid(100% ,56/56),and meropenem(100% ,6/6).High sensitivity rates were also observed for levofloxacin(81% ,22/27),moxifloxacin(82% ,14/17),rifampicin(96% ,25/26),and chloramphenicol(91% ,21/23).However,low sensitivity rates were found for penicillin(16% ,11/68)and clindamycin(6% ,1/17),and SP strains were completely resistant to erythromycin(100% ,31/31).The rates of discharge with cure and improvement were 22.5% (36/160)and 66.2% (106/160),respectively,while 18 cases(11.3% )had adverse outcomes.Conclusions Pediatric PM is more common in children aged 3 months to under 3 years.Intracranial complications are more frequently observed in children under 1 year old.Fever is the most common clinical manifestation of PM,and subdural effusion/emphysema and hydrocephalus are the most frequent complications.Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates.Adverse outcomes can be noted in more than 10% of PM cases.SP strains are high sensitivity to vancomycin,linezolid,meropenem,levofloxacin,moxifloxacin,rifampicin,and chloramphenicol.[Chinese Journal of Contemporary Pediatrics,2024,26(2):131-138]

Background/Aims: Chronic hepatitis C (CHC) patients who failed antiviral therapy are at increased risk for hepatocellular carcinoma (HCC). This study assessed the potential role of metformin and statins, medications for diabetes mellitus (DM) and hyperlipidemia (HLP), in reducing HCC risk among these patients. Methods: We included CHC patients from the T-COACH study who failed antiviral therapy. We tracked the onset of HCC 1.5 years post-therapy by linking to Taiwan’s cancer registry data from 2003 to 2019. We accounted for death and liver transplantation as competing risks and employed Gray’s cumulative incidence and Cox subdistribution hazards models to analyze HCC development. Results: Out of 2,779 patients, 480 (17.3%) developed HCC post-therapy. DM patients not using metformin had a 51% increased risk of HCC compared to non-DM patients, while HLP patients on statins had a 50% reduced risk compared to those without HLP. The 5-year HCC incidence was significantly higher for metformin non-users (16.5%) versus non-DM patients (11.3%; adjusted sub-distribution hazard ratio [aSHR]=1.51; P=0.007) and metformin users (3.1%; aSHR=1.59; P=0.022). Statin use in HLP patients correlated with a lower HCC risk (3.8%) compared to non-HLP patients (12.5%; aSHR=0.50; P<0.001). Notably, the increased HCC risk associated with non-use of metformin was primarily seen in non-cirrhotic patients, whereas statins decreased HCC risk in both cirrhotic and non-cirrhotic patients. Conclusions Metformin and statins may have a chemopreventive effect against HCC in CHC patients who failed antiviral therapy. These results support the need for personalized preventive strategies in managing HCC risk.

The present article was aimed to compare the effectiveness of different induction methods for depression models. Kunming mice were randomly divided into chronic unpredictable mild stress (CUMS) group, corticosterone (CORT) group, and CUMS+CORT (CC) group. The CUMS group received CUMS stimulation for 4 weeks, and the CORT group received subcutaneous injection of 20 mg/kg CORT into the groin every day for 3 weeks. The CC group received both CUMS stimulation and CORT administration. Each group was assigned a control group. After modeling, forced swimming test (FST), tail suspension test (TST) and sucrose preference test (SPT) were used to detect the behavioral changes of mice, and the serum levels of brain-derived neurotrophic factor (BDNF), 5-hydroxytryptamine (5-HT) and CORT were detected with ELISA kits. Attenuated total refraction (ATR) spectra of mouse serum were collected and analyzed. HE staining was used to detect morphological changes in mouse brain tissue. The results showed that the weight of model mice from the CUMS and CC groups decreased significantly. There was no significant change in immobility time of model mice from the three groups in FST and TST, while the glucose preference of model mice from the CUMS and CC groups was significantly reduced (P < 0.05). The serum 5-HT levels of model mice from the CORT and CC groups were significantly reduced, while the serum BDNF and CORT levels of model mice from the CUMS, CORT, and CC groups showed no significant changes. Compared with their respective control groups, the three groups showed no significant difference in the one-dimensional spectrum of serum ATR. The difference spectrum analysis results of the first derivative of the spectrogram showed that the CORT group had the greatest difference from its respective control group, followed by the CUMS group. The structures of hippocampus in the model mice from the three groups were all destroyed. These results suggest that both CORT and CC treatments can successfully construct a depression model, and the CORT model is more effective than the CC model. Therefore, CORT induction can be used to establish a depression model in Kunming mice.
Mice ; Animals ; Depression/etiology* ; Antidepressive Agents/pharmacology* ; Brain-Derived Neurotrophic Factor ; Serotonin

Advanced radiotherapy technology enables the dose to more accurately conform to the tumor target area of the patient, providing accurate treatment for the patient, but the gradient of the patient's radiation dose at the tumor edge is getting larger, which putting forward higher requirements for radiotherapy dose verification. The dose verification system software KylinRay-Dose4D can verify the patient's pre-treatment plan and the in vivo/on-line dose during the patient's treatment, providing important reference for the physicist to modify the radiotherapy plan and ensuring that the patient receives accurate treatment. This study introduces the overall design and key technologies of KylinRay-Dose4D, and tests the pre-treatment plan dose checking calculation and 2D/3D dose verification through clinical cases. The test results showed that the 2D/3D gamma pass rate (3 mm/3%) of KylinRay-Dose4D reconstructed dose compared with TPS plan dose and measured dose is larger than 95%, which indicating that the reconstructed dose of KylinRay-Dose4D meets the requirement of clinical application.
Humans ; Radiotherapy Dosage ; Radiotherapy Planning, Computer-Assisted/methods* ; Radiotherapy, Intensity-Modulated/methods* ; Software ; Neoplasms ; Phantoms, Imaging ; Radiometry/methods*

Objective:To investigate the influencing factors of survival benefit of patients after radical cystectomy and its correlation with preoperative albumin-to-alkaline phosphatase ratio (AAPR).Methods:The clinical data of 116 patients after radical cystectomy were retrospectively analyzed from January 2011 to January 2020 in Handan First Hospital. The influencing factors of survival benefit of patients after radical cystectomy were analyzed and the correlation between preoperative AAPR and overall survival time were evaluated. Kaplan-Meier method was used for survival analysis, and Log-rank test was used for comparison between groups. Cox proportional regression model was used to analyze the influencing factors of survival and prognosis and the correlation with preoperative AAPR. Trend Chi-square test was used to evaluate the level of preoperative AAPR.Results:Univariate Cox regression analysis showed that age, tumor diameter, pT stage, pN stage, histopathological grade, hydronephrosis, postoperative adjuvant chemotherapy and preoperative AAPR level were related to the overall survival time of patients after radical cystectomy( P<0.05). Multivariate Cox regression analysis showed that in calibration model Ⅰ and Ⅱ, the risk of death in high AAPR group was 0.351 and 0.433 times higher than low AAPR group( P<0.05). The risk of death decreased to 85.9% and 84.6% for every one unit increase of preoperative AAPR. The overall survival time of patients with high AARP level were significantly longer than patients with low and medium AARP level( P<0.05). Conclusion:The survival benefit of patients after radical cystectomy was independently related to the preoperative AAPR level; the higher the preoperative AAPR level, the longer the overall survival time.

Uric acid (UA) is the final product of purine metabolism in human body,and its metabolic disorder will induce hyperuricemia (HUA).The occurrence and development of HUA are associated with a variety of pathological mechanisms such as oxidative stress injury,activation of inflammatory cytokines,and activation of renin-angiotensin-aldosterone system.These mechanisms directly or indirectly affect the bioavailability of endogenous nitric oxide (NO).The decrease in NO bioavailability is common in the diseases with high concentration of UA as an independent risk factor.In this review,we summarize the mechanisms by which high concentrations of UA affect the endogenous NO bioavailability,with a focus on the mechanisms of high-concentration UA in decreasing the synthesis and/or increasing the consumption of NO.This review aims to provide references for alleviating the multisystem symptoms and improving the prognosis of HUA,and lay a theoretical foundation for in-depth study of the correlations between HUA and other metabolic diseases.
Humans ; Nitric Oxide ; Uric Acid ; Hyperuricemia ; Biological Availability ; Cytokines

Objective: To analyze the mortality level and tendency of road traffic injury in Shandong province from 2012 to 2020. Methods: Based on the data of road traffic deaths from the cause of death registration system in Shandong province from 2012 to 2020, the mortality rates of road traffic injury were calculated by sex, age, area, and injury type. The mortality was standardized based on the age structure of the Chinese population in the sixth Population Census in 2010. The annual percent change (APC) and average annual percent change (AAPC) of the mortalities and the standarized mortalities were calculated by using Joinpoint regression model, and the trends were also examined. Results: In 2020, the crude mortality of road traffic injury in Shandong Province was 15.58/100 000, and the standardized mortality was 12.90/100 000. From 2012 to 2020, the standardized mortality of road traffic injury in Shandong province showed a downward trend with AAPC of -5.4%. The standardized mortality of middle-south mountain areas, male and children aged 0-14 years in Shandong showed a significantly decreasing trend with AAPC of -6.8%, -6.1% and -6.0%, respectively. The standardized mortality of people aged 65 years and over did not decrease significantly, but the number of deaths increased significantly by 50.96% in 2020 (5 780 cases), compared with those in 2012 (3 829 cases). The standardized mortality of pedestrian and motorcyclists decreased significantly with AAPC of -7.5% and -6.7%, respectively. There was no significant change in the standardized mortality among people who rode motor vehicles or bicycles. Conclusion: From 2012 to 2020, the standardized mortality of road traffic injury in Shandong Province showed an obvious downward trend, but the standardized mortality of people aged 65 years and over did not decrease significantly. In the future, it is still necessary to take government-led, multi-sectoral collaboration, with a focus on comprehensive preventive measures, to further reduce road traffic injury mortality.
Accidents, Traffic ; Asian People ; Child ; Government ; Humans ; Male ; Mortality ; Motor Vehicles

Objective: To describe the clinical characteristics of Mycoplasma pneumoniae infection and analyze the factors associated with co-infections with other pathogens in children, and provide evidence for improvement of community acquired pneumonia (CAP) prevention and control in children. Methods: Based on the surveillance of hospitalized acute respiratory infections cases conducted in Soochow University Affiliated Children's Hospital (SCH), the CAP cases aged <16 years hospitalized in SCH between 2018 and 2021 were screened. The pathogenic test results of the cases were obtained through the laboratory information system, and their basic information, underlying conditions, and clinical characteristics were collected using a standardized questionnaire. The differences in clinical characteristics between M. pneumoniae infection and bacterial or viral infection and the effect of the co-infection of M. pneumoniae with other pathogens on clinical severity in the cases were analyzed; logistic regression was used to analyze the factors associated with the co-infections with other pathogens. Results: A total of 8 274 hospitalized CAP cases met the inclusion criteria. Among them, 2 184 were positive for M. pneumoniae (26.4%). The M. pneumoniae positivity rate increased with age (P<0.001), and it was higher in girls (P<0.001) and in summer and autumn (P<0.001). There were statistically significant differences in the incidence of wheezing, shortness of breath, wheezing sounds and visible lamellar faint shadow on chest radiographs, as well as fever and hospitalization days among M. pneumoniae, bacterial, and viral infection cases (all P<0.05). In the cases aged <60 months years, co-infection cases had higher rates of wheezing, gurgling with sputum and stridor; and in the cases aged ≥60 months, co-infection cases had a higher rate of shortness of breath (all P<0.05). Multifactorial logistic regression analysis showed that being boys (aOR=1.38,95%CI:1.15-1.67), being aged <6 months (aOR=3.30,95%CI:2.25-4.89), 6-23 months (aOR=3.44,95%CI:2.63-4.51), 24-47 months (aOR=2.50,95%CI:1.90-3.30) and 48-71 months (aOR=1.77,95%CI:1.32-2.37), and history of respiratory infection within 3 months (aOR=1.28,95%CI:1.06-1.55) were factors associated with co-infections of M. pneumoniae with other pathogens. Conclusions: M. pneumoniae was the leading pathogen in children hospitalized due to CAP. M. pneumoniae infections could cause fever for longer days compared with bacterial or viral infections; M. pneumoniae was often co-detected with virus or bacteria. Being boys, being aged <72 months and history of respiratory infection within 3 months were associated factors for co-infections.
Bacteria ; Child ; Coinfection/epidemiology* ; Community-Acquired Infections/epidemiology* ; Dyspnea ; Female ; Humans ; Male ; Mycoplasma pneumoniae ; Pneumonia, Mycoplasma/microbiology* ; Respiratory Sounds ; Respiratory Tract Infections/epidemiology* ; Virus Diseases

Objective: To investigate the correlation between methylation in human papillomavirus 16 (HPV16) long control region (LCR) and cervical intraepithelial neoplasia grade ≥2 (CIN2+). Methods: The literature retrieval was conducted by using the databases of PubMed, Embase, Cochrane Library, Web of Science, CNKI, Wanfang data and Weipu according to the inclusion and exclusion criteria, and the retrieval period was from the establishment of the databases to February 27^th, 2022. Software RevMan 5.3 and Stata 15.1 were used for Meta-analysis. Results: A total of 17 literatures were included involving 1 421 subjects. Results of Meta-analysis showed that OR of the correlation between methylation of HPV16 LCR and CIN2+ was 1.56 (95%CI: 0.70-3.47). Subgroup analysis showed that methylation of the 5' terminal, enhancer and promoter regions were not associated with CIN2+, while in four E2 binding sites (E2BS), the methylation of E2BS1, E2BS3 and E2BS4 increased the risk of CIN2+, with the ORs of 3.92 (95%CI: 1.92-7.99), 10.50 (95%CI: 3.67-30.04) and 3.65 (95%CI: 1.58-8.41), respectively. However, subgroup analysis on E2BS2 was not performed due to the limitation of the number of literatures. According to the different sources of population, the risk of CIN2+ in Chinese population was associated with methylation of HPV16 LCR (OR=2.14, 95%CI: 1.31-3.50). There was a correlation between the risk of CIN2+ and HPV16 LCR methylation in the population with pyrosequencing of HPV16 LCR, and OR was 1.75 (95%CI: 1.03-2.98). Conclusion: The risk of CIN2+ is correlated with the methylation of E2BS in HPV16 LCR, which can be used as potential biomarkers.
Female ; Humans ; Methylation ; Human papillomavirus 16/genetics* ; Asian People ; Uterine Cervical Neoplasms ; Uterine Cervical Dysplasia