OBJECTIVE To investigate the in vitro antitumor activity and in vivo targeting of nanopolymers co-loaded with arse-nic trioxide(ATO),an active ingredient of traditional Chinese medicine arsenic,and photosensitizer(IR780)to activate the patient's own immune system in the treatment of brain glioma in synergistically with chemotherapy and phototherapy.METHODS PLGA/AI containing ATO and IR780 was prepared by volatilization with multiple emulsion solvent.The particle size,potential and polydispersity index(PDI)were determined by dynamic light scatterometer(DLS)at different feed ratios.Transmission electron microscopy(TEM)was used to detect the morphology of PLGA/AI.Fluorescence spectrophotometer was used to investigate the spectroscopic characteris-tics.UV-vis spectrophotometer was used to determine the drug loading and encapsulation rate of IR780.Under laser irradiation,the physiological release of ATO was measured by dialysis bag method.The uptake of PLGA/AI in GL261 cells was photographed by confo-cal microscopy(CLSM).The cell uptake mechanism of PLGA/AI was investigated by flow cytometry(FCM).3D tumor spheroid mod-el was constructed to simulate the deep penetration of PLGA/AI in solid tumors.The synergistic anti-tumor effects of PLGA/AI in vitro were studied by MTT assay and dying staining.DCFH-DA staining and FCM determination of the co-expression of CD80 CD86 co-stimulatory molecules verified the immune activation induced by PLGA/AI in vitro photochemotherapy.The in vivo targeting of PLGA/AI and the tissue distribution of the main organs were investigated by means of in vivo imaging of small animals after tail vein injection.RESULTS The optimal ratio of ATO to IR780 was 1∶10,its particle size was(134.11±2.19)nm,Zeta potential was(-7.02±0.649)mV,PDI was 0.254±0.059,and it was a uniform spherical shape under TEM.The fluorescence spectra showed that IR780 was successfully loaded onto PLGA,and the drug loading and encapsulation rate of IR780 in PLGA/AI were(2.53±0.02)%and(71.26±0.38)%respectively.The results of in vitro release experiments showed that ATO could be released in response to laser light by IR780-mediated photo-dynamics.Cell uptake experiments showed that the nano-polymer could effectively enter tumor cells under clathrin-mediated endocytosis.In vitro investigation of cell viability,ROS detection and dendritic cell maturation experiment showed that it could effectively kill tumor cells by inducing a large amount of ROS to generate and activate immune cells.In vivo targe-ting and biological distribution study confirmed that PLGA/AI could effectively penetrate BBB into tumor sites.CONCLUSION The active ingredients of traditional Chinese medicine arsenic,ATO and IR780,use PLGA as carriers to form nano-polymers through the volatilization of multiple emulsion solvents,which can cross the BBB and effectively accumulate at the tumor site.Based on"strengthe-ning the healthy qi and eliminating pathogenic factors"and combined with chemotherapy and photo-immune activation,it has the po-tential for long-term anti-glioblastoma treatment.

OBJECTIVE To investigate the in vitro antitumor activity and in vivo targeting of nanopolymers co-loaded with arse-nic trioxide(ATO),an active ingredient of traditional Chinese medicine arsenic,and photosensitizer(IR780)to activate the patient's own immune system in the treatment of brain glioma in synergistically with chemotherapy and phototherapy.METHODS PLGA/AI containing ATO and IR780 was prepared by volatilization with multiple emulsion solvent.The particle size,potential and polydispersity index(PDI)were determined by dynamic light scatterometer(DLS)at different feed ratios.Transmission electron microscopy(TEM)was used to detect the morphology of PLGA/AI.Fluorescence spectrophotometer was used to investigate the spectroscopic characteris-tics.UV-vis spectrophotometer was used to determine the drug loading and encapsulation rate of IR780.Under laser irradiation,the physiological release of ATO was measured by dialysis bag method.The uptake of PLGA/AI in GL261 cells was photographed by confo-cal microscopy(CLSM).The cell uptake mechanism of PLGA/AI was investigated by flow cytometry(FCM).3D tumor spheroid mod-el was constructed to simulate the deep penetration of PLGA/AI in solid tumors.The synergistic anti-tumor effects of PLGA/AI in vitro were studied by MTT assay and dying staining.DCFH-DA staining and FCM determination of the co-expression of CD80 CD86 co-stimulatory molecules verified the immune activation induced by PLGA/AI in vitro photochemotherapy.The in vivo targeting of PLGA/AI and the tissue distribution of the main organs were investigated by means of in vivo imaging of small animals after tail vein injection.RESULTS The optimal ratio of ATO to IR780 was 1∶10,its particle size was(134.11±2.19)nm,Zeta potential was(-7.02±0.649)mV,PDI was 0.254±0.059,and it was a uniform spherical shape under TEM.The fluorescence spectra showed that IR780 was successfully loaded onto PLGA,and the drug loading and encapsulation rate of IR780 in PLGA/AI were(2.53±0.02)%and(71.26±0.38)%respectively.The results of in vitro release experiments showed that ATO could be released in response to laser light by IR780-mediated photo-dynamics.Cell uptake experiments showed that the nano-polymer could effectively enter tumor cells under clathrin-mediated endocytosis.In vitro investigation of cell viability,ROS detection and dendritic cell maturation experiment showed that it could effectively kill tumor cells by inducing a large amount of ROS to generate and activate immune cells.In vivo targe-ting and biological distribution study confirmed that PLGA/AI could effectively penetrate BBB into tumor sites.CONCLUSION The active ingredients of traditional Chinese medicine arsenic,ATO and IR780,use PLGA as carriers to form nano-polymers through the volatilization of multiple emulsion solvents,which can cross the BBB and effectively accumulate at the tumor site.Based on"strengthe-ning the healthy qi and eliminating pathogenic factors"and combined with chemotherapy and photo-immune activation,it has the po-tential for long-term anti-glioblastoma treatment.

Objective:To investigate the value of systemic inflammatory response syndrome (SIRS), pediatric sequential organ failure assessment (pSOFA) and pediatric critical illness score (PCIS) in predicting mortality of pediatric sepsis in pediatric intensive care units (PICU) from Southwest China.Methods:This was a prospective multicenter observational study. A total of 447 children with sepsis admitted to 12 PICU in Southwest China from April 2022 to March 2023 were enrolled. Based on the prognosis, the patients were divided into survival group and non-survival group. The physiological parameters of SIRS, pSOFA and PCIS were recorded and scored within 24 h after PICU admission. The general clinical data and some laboratory results were recorded. The area under the curve (AUC) of the receiver operating characteristic curve was used to compare the predictive value of SIRS, pSOFA and PCIS in mortality of pediatric sepsis.Results:Amongst 447 children with sepsis, 260 patients were male and 187 patients were female, aged 2.5 (0.8, 7.0) years, 405 patients were in the survival group and 42 patients were in the non-survival group. 418 patients (93.5%) met the criteria of SIRS, and 440 patients (98.4%) met the criteria of pSOFA≥2. There was no significant difference in the number of items meeting the SIRS criteria between the survival group and the non-survival group (3(2, 4) vs. 3(3, 4) points, Z=1.30, P=0.192). The pSOFA score of the non-survival group was significantly higher than that of the survival group (9(6, 12) vs. 4(3, 7) points, Z=6.56, P<0.001), and the PCIS score was significantly lower than that of the survival group (72(68, 81) vs. 82(76, 88) points, Z=5.90, P<0.001). The predictive value of pSOFA (AUC=0.82) and PCIS (AUC=0.78) for sepsis mortality was significantly higher than that of SIRS (AUC=0.56) ( Z=6.59, 4.23, both P<0.001). There was no significant difference between pSOFA and PCIS ( Z=1.35, P=0.176). Platelet count, procalcitonin, lactic acid, albumin, creatinine, total bilirubin, activated partial thromboplastin time, prothrombin time and international normalized ratio were all able to predict mortality of sepsis to a certain degree (AUC=0.64, 0.68, 0.80, 0.64, 0.68, 0.60, 0.77, 0.75, 0.76, all P<0.05). Conclusion:Compared with SIRS, both pSOFA and PCIS had better predictive value in the mortality of pediatric sepsis in PICU.

BACKGROUND:Hypoxic exercise can promote the degradation of body fat,and changes in the external environment can affect the circadian rhythm of animals,but the mechanisms by which changes in circadian rhythm regulate adipose tissue browning and fat degradation are unclear. OBJECTIVE:To elucidate the mechanism of clock gene regulation on epididymal adipose tissue Browning in obese rats undergoing hypoxia exercise. METHODS:Forty obese rats were randomly selected and divided into four groups(n=10 per group):normoxic sedentary group,hypoxic sedentary group,normoxic exercise group,and hypoxic exercise group for 4 weeks of intervention.The rats in the sedentary groups were not intervened,while those in the hypoxic groups lived in a hypoxic chamber with an oxygen concentration of 13.6%for the whole day.In the exercise groups,adaptive training was performed in the 1st week,and the speed and length of training remained unchanged for the last 3 weeks.The body mass,body length and perirenal fat mass of obese rats were measured.Serum levels of triacylglycerol,total cholesterol,low-density lipoprotein cholesterol,and high-density lipoprotein cholesterol in obese rats were detected by a biochemical assay kit.Liver fat content was observed by oil red O staining.Hematoxylin-eosin staining was used to evaluate the browning of epididymal adipose tissue of rats in different groups.RNA sequencing combined with bioinformatics analysis was used to analyze transcriptome changes in adipose tissue.The mRNA expressions of PGC-1α,Beclin 1,KLF 2 and Perilipin 1 in epididymal adipose tissue were detected by RT-PCR. RESULTS AND CONCLUSION:Hypoxic exercise intervention significantly decreased body mass,body fat percentage,Lee's index,serum triacylglycerol,total cholesterol,and low-density lipoprotein cholesterol levels(P＜0.01),and significantly increased high-density lipoprotein cholesterol level(P＜0.01).Oil red O staining and hematoxylin-eosin staining results showed that hypoxic exercise was more effective in promoting fat mobilization in liver tissue and promoting the browning of parepididymal adipose tissue compared with normoxic sedentary group,hypoxic sedentary group,and normoxic exercise group.RNA-seq results showed that hypoxic exercise significantly upregulated the expression of clock genes Dbp,Nr1d1,Sik1 and adipose tissue browning gene Ppargc1a(PGC-1α)and downregulated the expression of Arntl(Bmal1),accompanied by the enhanced expression of genes related to substance metabolism.qRT-PCR indicated that hypoxic exercise significantly increased the mRNA expression levels of PGC-1α and Perilipin1(P＜0.01).Therefore,these findings indicate that clock genes play an important role in promoting adipose tissue browning during hypoxic exercise.

The increasing incidence of myopia has become a significant public health issue worldwide.Since its estab-lishment in 2015,the International Myopia Institute(IMI)has published a series of white papers on myopia prevention and control in 2019 and 2021,advancing the scientific management and clinical research of myopia prevention and control worldwide.In 2023,IMI released new white papers on myopia prevention and control.In this paper,the highlights of the third series of IMI white papers on children,young adults,and emerging research areas in myopia are interpreted,intend-ing to help related professionals understand the management and research focus of myopia patients of different ages.

Objective:To evaluate the nutritional status of patients with decompensated liver cirrhosis and explore the correlation with malnutrition and the risk factors of depressed mood.Methods:190 cirrhotic patients admitted to the Department of Gastroenterology of the First Hospital of Shanxi Medical University from June to September 2023 were selected according to the inclusion and exclusion criteria. Eligible patients were divided into subgroups based on the presence or absence of malnutrition as determined by subjective global assessment (SGA). The Center for Epidemiological Studies Depression (CES-D) scale was used to assess patients' propensity for depressed mood. Relevant clinical data were also collected and analyzed.Results:A total of 185 patients were included, of which 126 were in the non-malnutrition group and 59 malnutrition group. There were significant between-group differences in terms of CES-D results, age, body mass index, platelets, D-dimer, serum sodium, third lumbar skeletal muscle index, grip strength, triceps skinfold thickness, and upper arm muscle circumference (all P<0.05). Correlation analysis showed that grip strength, triceps skinfold thickness, upper arm muscle circumference, serum sodium, and depressed mood tendency status were correlated with the development of cirrhotic malnutrition ( P<0.05). The diagnostic model for malnutrition in cirrhosis using these five indicators showed the area under the curve of 81.9%. Conclusions:Depression is closely related to the development of malnutrition in patients with liver cirrhosis. Independent risk factors for malnutrition in cirrhosis include serum sodium≤135 mmol/L, grip strength, triceps skinfold thickness, lower-than-normal upper arm circumference , and the tendency of depression , which demonstrate the combined contribution to the diagnosis of malnutrition in cirrhosis.

Morita therapy has been bom for more than 100 years.Inpatient Morita therapy is highly oper-able and easy to master.It can improve many refractory neuroses through four-stage treatment.But more neuroses are treated in outpatient clinics,and Morita therapy cannot be used in hospitalized patients.Therefore,the formula-tion of expert opinions on outpatient operations is particularly important.This paper is based on domestic and for-eign references,and after many discussions by domestic Morita therapy experts,and then drew up the first version of the expert opinions on operation of outpatient Morita therapy.Meanwhile the operation rule of Morita therapy in three stages of outpatient treatment was formulated:in the etiological analysis stage,under the theoretical guidance of Morita therapy,analyze the pathogenic factors,to improve treatment compliance and reduce resistance;during the operating stage,guide patients to engage in constructive and meaningful actions,realizing the achievement of letting nature take its course principle;in the cultivating character and enriching life stage,pay attention to positive infor-mation,expanding the scope and content of actions,improving the ability to adapt to complex life,and preventing recurrence caused by insufficient abilities.It will lay a foundation for the promotion of Morita therapy in domestic outpatient clinics,so that more patients with neurosis and other psychological diseases could receive characteristic Morita therapy treatment in outpatient clinics.

Objective:To investigate the iodine nutritional status of pregnant women in Jilin Province and its correlation with the distribution characteristics of water iodine in external environment, providing a basis for scientific iodine supplementation and prevention of iodine deficiency disorders.Methods:A retrospective analysis was conducted on the iodine survey data of drinking water for residents in Jilin Province in 2017 and the monitoring data of iodine deficiency disorders in 2021. The water iodine, salt iodine, and urinary iodine level of pregnant women were analyzed.Results:In 8 866 water samples from 873 townships (streets, hereinafter referred to as townships) of 60 counties (cities, districts) in 9 cities (autonomous prefectures) throughout the province, the median of water iodine was 4.60 μg/L, ranging from 0.00 to 81.30 μg/L. Among them, there were 758 townships with a median water iodine < 10 μg/L, accounting for 86.83% (758/873); 107 townships with a water iodine of 10 - < 40 μg/L, accounting for 12.26% (107/873). The median salt iodine was 23.50 mg/kg in 6 000 household consumption salt samples. The iodized salt coverage rate, iodized salt qualified rate, and qualified iodized salt consumption rate were 99.50% (5 970/6 000), 97.30% (5 809/5 970), and 96.82% (5 809/6 000), respectively. The iodized salt coverage rate in 9 cities (autonomous prefectures) were > 95%, the iodized salt qualified rate and qualified iodized salt consumption rate were > 90%. The median urinary iodine in 6 000 pregnant women's urine samples was 169.05 μg/L. Except for Bayshan City, which was iodine-deficient, the other 8 cities (autonomous prefectures) were iodine-suitable. The results of correlation analysis showed that there was no correlation between the urinary iodine level of pregnant women and the distribution of water iodine in the external environmental at the municipal (autonomous prefecture) level ( r = 0.60, P = 0.089). Conclusions:Most townships in Jilin Province are iodine-deficient in the external environment, and there are no water-borne high iodine area. The iodized salt coverage rate, iodized salt qualified rate, and qualified iodized salt consumption rate all meet the national standards. The iodine nutrition of pregnant women is generally at a suitable level, but there are still some areas where pregnant women are iodine-deficient, and there is no correlation with the distribution of water iodine.

Objective:To investigate the role of serum hepatitis B virus RNA (HBV RNA) in predicting HBeAg serological conversion in children with chronic hepatitis B.Methods:175 children aged 1~17 years with chronic hepatitis B who received interferon α (IFNα) for 48 weeks were selected. Patients were divided into HBeAg seroconversion and non-conversion based on whether HBeAg seroconversion occurred at 48 weeks of treatment.T-test and Mann-Whitney U test were used to compare between groups; chisquare test or Fisher exact probability method was used to compare the frequency between groups of classified variables; and Pearson correlation was used to analyze the correlation between indicators. Univariate and multivariate logistic regression analyses were used to identify influencing factors associated with HBeAg serological conversion. The predictive effect of HBV RNA, HBV DNA, and HBsAg on HBeAg serological conversion was compared and analyzed by the receiver operating characteristic curve (ROC).Results:The seroconversion rate of HBeAg at 48 weeks was 36.0% (63/175). The reduction in HBVRNA levels from baseline to the 12th, 24th, 36th, and 48th weeks of antiviral therapy was significantly greater in the HBeAg serological conversion group than that in the non-conversion group, and the difference was statistically significant between the two groups (P < 0.05). Univariate and multivariate regression analyses showed that age and a decline in HBV RNA levels at week 12 were independent predictors of HBeAg serological conversion. The area under the ROC curve (AUROC) of HBV RNA decline at week 12 was 0.677(95% CI∶0.549-0.806, P = 0.012), which was significantly better than the same period of AUROC of HBV DNA (0.657, 95% CI∶0.527-0.788, P = 0.025) and HBsAg (0.660, 95% CI∶0.526-0.795, P = 0.023) decline. HBV RNA levels decreased (>1.385 log10 copies/ml) at week 12, with a positive predictive value of 53.2%, a negative predictive value of 72.2%, a sensitivity of 77.4%, and a specificity of 57.9% for HBeAg seroconversion. Conclusion:HBV RNA level lowering during the 12th week of antiviral therapy can serve as an early predictor marker for HBeAg serological conversion in children with chronic hepatitis B.

As adult stem cells, human mesenchymal stem cells (hMSCs) have the potential for self-replication, renewal, and multidirection differentiation. Their unique biological function determines their wide clinical indications. Researchers can define the quality attributes of hMSCs according to clinical expectations. The quality study of hMSCs should consider microbiological safety, biological safety, cell biological properties, and biological effectiveness. Quality evaluation is a common physical, chemical, and biological evaluation method for hMSCs. Traditional product safety evaluation strategies cannot fully adapt to current technology and product usage characteristics. Researchers have developed new, effective evaluation methods based on current technology. In terms of product efficacy evaluation strategies, an efficacy evaluation system has been gradually established and standardized according to the intended clinical use and based on quality studies, which can enable researchers to evaluate hMSCs products more comprehensively at different stages and processes. In this paper, the progress of quality research and evaluation of human mesenchymal stem cells was reviewed to provide a reference for the utilization of stem cells in the field of regenerative medicine.