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 compare the early predictive value of different scoring systems for the severity,organ failure and complications of acute pancreatitis(AP)in elderly patients under the newly revised Atlanta criteria.Methods Patients with acute pancreatitis treated was collected.After admission,complete the computed tomography severity index(CTSI),the bedside index of severity in acute pancreatitis(BISAP),the pancreatis 3(PANC-3)and the harmlessness acute pancreatitis score(HAPS).The area under receiver operating characteristic(ROC)curve(AUC),sensitivity,specificity and Yordan's index of four scores for predicting SAP,local pancreatic complications and multiple organ failure were compared.Results The areas under the ROC curve predicted by the CTSI,BISAP,PANC-3 and HAPS scoring systems for SAP were 0.76,0.91,0.48 and 0.55;sensitivities of 75.87％,89.61％,61.18％and 78.38％;specificity of 80.29％,74.72％,67.48％and 69.69％;Yordan's index of 0.56,0.64,0.29 and 0.48,respectively.The AUC of CTSI,BISAP,PANC-3 and HAPS scoring systems for predicting local pancreatic complications were 0.94,0.82,0.59 and 0.64;sensitivity of 74.59％,68.23％,71.11％and 69.28％;specificity of 93.88％,83.01％,78.59％and 76.46％;Yordan's index were 0.68,0.51,0.50 and 0.46,respectively.The AUC of CTSI,BISAP,PANC-3 and HAPS scoring systems for predicting multiple organ failure were 0.60,0.84,0.64 and 0.80,sensitivities were 54.18％,74.82％,58.59％and 65.67％,specificity were 76.11％,77.20％,72.68％and 89.36％,Jordan's indices were 0.30,0.52,0.31 and 0.55,respectively.Conclusion BISAP score is higher than CTSI,HAPS and PANC-3 scoring system in predicting the accuracy of sap and the risk of multiple organ failure.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

ObjectiveTo investigate the clinical appropriateness and application value of the peroxidase （POD） method for the detection of unbound bilirubin （UB） in neonatal serum. MethodsHydrogen peroxide （0.33 mol/L） and three different final concentrations （0.019， 0.038， 0.075 μg/mL） of horseradish peroxidase （HRP） were added to standard bilirubin solution （1， 2， 3 μmol/L） to obtain a standardized HRP primary rate constant Kp. Then 25 μL of neonatal serum was diluted by 41.6 fold， and measured with 2.4 and 4.8 μg/mL HRP at 37 ℃ under the dark， to determine the UB concentration. The accuracy， precision， and stability of the methodology were validated. The clinical characteristics of 33 jaundiced neonates were collected， including total serum bilirubin （TSB）， indirect bilirubin （IDB）， albumin （ALB）， bilirubin to albumin molar ratio （BAMR）， etc. The experimental data were analyzed by Graphpad Prism 8.0. ResultsA standardized Kp of （7.20±1.08） mL·μg^-1·min^-1 was determined at pH 7.4±0.2， 37 ℃ in the dark. The HRP activity and UB concentrations remained stable at -20 ℃ for 3 weeks and a week， respectively. The mean intra-day and inter-day coefficients of variation of the serum samples with different UB concentrations were less than 10%. In this study， the UB concentrations in 33 jaundiced neonates （gestational age ≥35 weeks） were measured by the POD method in the range of （0.32～1.20） μg/dL， which was positively correlated with TSB， IDB and BAMR. Of the five infants whose UB concentrations measured more than 1 μg/dL， three received intensive phototherapy （60%）. ConclusionsThe POD method combined with a standard equipment spectrophotometer to detect serum UB concentrations in neonates is easy to operate， rapid to detect， and low cost. This method has good accuracy and precision， which is convenient for clinical implementation. Moreover， the measurement of serum UB may assist us in better management of neonatal jaundice in clinical practice.

Objective: To investigate the prognostic factors of children with congenital heart disease (CHD) who had undergone cardiopulmonary resuscitation (CPR) in pediatric intensive care unit (PICU) in China. Methods: From November 2017 to October 2018, this retrospective multi-center study was conducted in 11 hospitals in China. It contained data from 281 cases who had undergone CPR and all of the subjects were divided into CHD group and non-CHD group. The general condition, duration of CPR, epinephrine doses during resuscitation, recovery of spontaneous circulation (ROSC), discharge survival rate and pediatric cerebral performance category in viable children at discharge were compared. According to whether malignant arrhythmia is the direct cause of cardiopulmonary arrest or not, children in CHD and non-CHD groups were divided into 2 subgroups: arrhythmia and non-arrhythmia, and the ROSC and survival rate to discharge were compared. Data in both groups were analyzed by t-test, chi-square analysis or ANOVA, and logistic regression were used to analyze the prognostic factors for ROSC and survival to discharge after cardiac arrest (CA). Results: The incidence of CA in PICU was 3.2% (372/11 588), and the implementation rate of CPR was 75.5% (281/372). There were 144 males and 137 females with median age of 32.8 (5.6, 42.7) months in all 281 CPA cases who received CPR. CHD group had 56 cases while non-CHD had 225 cases, with the percentage of 19.9% (56/281) and 80.1% (225/281) respectively. The proportion of female in CHD group was 60.7% (34/56) which was higher than that in non-CHD group (45.8%, 103/225) (χ²=4.00, P=0.045). There were no differences in ROSC and rate of survival to discharge between the two groups (P>0.05). The ROSC rate of children with arthythmid in CHD group was 70.0% (28/40), higher than 6/16 for non-arrhythmic children (χ²=5.06, P=0.024). At discharge, the pediatric cerebral performance category scores (1-3 scores) of CHD and non-CHD child were 50.9% (26/51) and 44.9% (92/205) respectively. Logistic regression analysis indicated that the independent prognostic factors of ROSC and survival to discharge in children with CHD were CPR duration (odds ratio (OR)=0.95, 0.97; 95%CI: 0.92~0.97, 0.95~0.99; both P<0.05) and epinephrine dosage (OR=0.87 and 0.79, 95%CI: 0.76-1.00 and 0.69-0.89, respectively; both P<0.05). Conclusions: There is no difference between CHD and non-CHD children in ROSC and survival rate of survival to discharge was low. The epinephrine dosage and the duration of CPR are related to the ROSC and survival to discharge of children with CHD.
Cardiopulmonary Resuscitation ; Child ; Child, Preschool ; Female ; Heart Arrest/therapy* ; Heart Defects, Congenital/therapy* ; Humans ; Intensive Care Units, Pediatric ; Male ; Retrospective Studies

Breast cancer has become the most commonly diagnosed cancer type in the world. A combination of chemotherapy and photothermal therapy (PTT) has emerged as a promising strategy for breast cancer therapy. However, the intricacy of precise delivery and the ability to initiate drug release in specific tumor sites remains a challenging puzzle. Therefore, to ensure that the therapeutic agents are synchronously delivered to the tumor site for their synergistic effect, a multifunctional nanoparticle system (PCRHNs) is developed, which is grafted onto the prussian blue nanoparticles (PB NPs) by reduction-responsive camptothecin (CPT) prodrug copolymer, and then modified with tumor-targeting peptide cyclo(Asp-d-Phe-Lys-Arg-Gly) (cRGD) and hyaluronic acid (HA). PCRHNs exhibited nano-sized structure with good monodispersity, high load efficiency of CPT, triggered CPT release in response to reduction environment, and excellent photothermal conversion under laser irradiation. Furthermore, PCRHNs can act as a photoacoustic imaging contrast agent-guided PTT. In vivo studies indicate that PCRHNs exhibited excellent biocompatibility, prolonged blood circulation, enhanced tumor accumulation, allow tumor-specific chemo-photothermal therapy to achieve synergistic antitumor effects with reduced systemic toxicity. Moreover, hyperthermia-induced upregulation of heat shock protein 70 in the tumor cells could be inhibited by CPT. Collectively, PCRHNs may be a promising therapeutic way for breast cancer therapy.

Diabetic nephropathy (DN) is one of the most common complications of diabetes mellitus, which is characterized in renal tubulointerstitial fibrosis (TIF). The current study was designed to investigate the protective effect of Jujuboside A (Ju A) on TIF in type 2 diabetes (T2DM) mice, and explore its underlying anti-fibrosis mechanism. A mouse T2DM model was established using high fat diet (HFD) feeding combined with intraperitoneal injection of streptozotocin (STZ). Then, diabetic mice were treated with Ju A (10, 20 and 40 mg·kg^-1·d^-1, i.g.) for 12 weeks. Results showed that administration of Ju A not only down-regulated fasting blood glucose (FBG) levels, but also improved hyperlipidemia and renal function in diabetic mice. Moreover, the reduced ECM accumulation was observed in the renal cortex of Ju A treated diabetic mice, while the TIF progression was also attenuated by Ju A through blocking the epithelial-to-mesenchymal transition (EMT) of renal tubular epithelial cells (RTECs). Further mechanism studies showed that Ju A treatment effectively down-regulated the protein expression and subsequent nuclear translocation of Yin Yang 1 (YY1) in the renal cortex of diabetic mice, and reduced the levels of transforming growth factor-β1 (TGF-β1) in the serum and renal cortex of Ju A treated mice. According to invitro studies, the up-regulated YY1/TGF-β1 signaling pathway was restored by Ju A in high glucose (HG) cultured HK-2 cells. Taken together, these findings demonstrated that Ju A can ameliorate the TIF of DN through down-regulating the YY1/TGF-β1 signaling pathway.
Animals ; Blood Glucose ; Diabetes Mellitus, Experimental/metabolism* ; Diabetes Mellitus, Type 2/drug therapy* ; Diabetic Nephropathies/metabolism* ; Fibrosis ; Mice ; Saponins ; Signal Transduction ; Streptozocin ; Transforming Growth Factor beta1/metabolism*

Objective:To analyze the long-term trend of viral hepatitis mortality in Jing’an District of Shanghai， and to provide a reference for viral hepatitis prevention and control. Methods:Mortality rate， standard mortality rate， PYLL and potential years of life lost rate （PYLL‰） of viral hepatitis in Jing’an district of Shanghai from 1976 to 2015 were calculated. The annual percent change （APC） of the mortality and PYLL‰ were analyzed by Joinpoint regression analysis. Results:From 1976 to 2015， there were 1 342 viral hepatitis death cases， including 832 males and 510 females. The average crude mortality rate was 8.31/100 000， and the average age-standardized mortality rate was 5.45/100 000. Among the deaths of viral hepatitis， men had a higher mortality rate， age-standardized mortality rate and PYLL% than women （χ2_Pearson=107.34， 112.93， 39.15， all P<0.01）， men were mainly in the age group of 35-64 years （accounted for 62.62%）， while women were mainly in the age group of 65 years and above （accounted for 55.49 %）， and the average death age of men was earlier than that of women （by rank-sum test： Z=-8.879，P<0.01）. After 1990 （except in 2002）， hepatitis B was the main cause of deaths from viral hepatitis， accounting for 75.00%-100%， and the proportion of other and unclassified cases gradually decreased. Overall， the mortality rate of viral hepatitis declined significantly during 1976-2015 （APC=-2.0%，P<0.05）， with the turning point in 2002. The mortality rate of viral hepatitis declined significantly from 2002 to 2015 （APC=-8.1%，P<0.05）. The overall PYLL‰ of viral hepatitis declined significantly during 1976-2015 （APC=-3.7%，P<0.05）， with the turning point in 1992. After 1992， the PYLL‰ of viral hepatitis declined significantly during 1992-2015 （APC=-6.5%，P<0.05）. Conclusion:There has been a significant decline trend of viral hepatitis in the mortality rate in Jing’an District of Shanghai from 2002 to 2015， with hepatitis B as the main cause of death.