OBJECTIVE To evaluate the efficacy， safety and economics of the centrally procured generic versus original esomeprazole in the treatment of acute non-variceal upper gastrointestinal bleeding （ANVUGIB）. METHODS A retrospective collection of real-world clinical data was conducted for ANVUGIB patients who received treatment at Shenzhen People’s Hospital and University of Hong Kong-Shenzhen Hospital from January 2018 to March 2024. Patients were divided into imported original drug group （original drug group， 221 cases） and centrally procured generic drug group （generic drug group， 75 cases） according to the types of drug used. Propensity score matching （PSM） was performed at a ratio of 3∶1 to compare the clinical efficacy， safety and economics between the two groups. RESULTS Totally 241 patients were included after PSM， with 170 in the original drug group and 71 in the generic drug group. There were no significant differences between the two groups in terms of rebleeding rate， rate of second endoscopic intervention， blood transfusion rate， length of hospital stay， mortality due to gastrointestinal bleeding， 30-day readmission due to rebleeding， and overall survival rate （P＞0.05）. The incidence of adverse events among all patients in both groups also showed no statistically significant difference （P＞0.05）； furthermore， the adverse events reported by the respective hospitals to the National Center for ADR Monitoring were comparable between the two groups. After PSM， the median total drug cost and high-dose esomeprazole cost in the generic drug group were significantly lower than those in the original drug group， while the median nursing fee and bed fee were significantly higher than those in the original drug group （P＜0.05）. There was no statistically significant difference between the two groups in terms of median total hospitalization expenses， total treatment costs， laboratory fees， examination fees， material costs， or consultation fees （P＞0.05）. CONCLUSIONS The clinical efficacy and safety of centrally procured generic esomeprazole in the treatment of ANVUGIB are comparable to those of the original drug， and it is more economical.

Tumor cells use glycolysis to provide material and energy under hypoxic conditions to meet the energy requirements for rapid growth and proliferation， namely the Warburg effect. Even under aerobic conditions， tumor cells mainly rely on glycolysis to provide energy. Therefore， glucose transporter protein 1（GLUT1）， which is involved in the process of glucose metabolism， plays an important role in tumorigenesis， development and drug resistance， and is considered to be one of the important targets in the treatment of malignant tumors. In recent years， research on tumor glucose metabolism has gradually become a hot spot. It has been shown that various factors are involved in the regulation of tumor energy metabolism， among which the role of GLUT1 is the most critical. In this paper， the authors reviewed the latest research progress of GLUT1-targeted traditional Chinese medicine（TCM） active ingredient nano-delivery system in tumor therapy， aiming to reveal the feasibility and effectiveness of this system in the delivery of chemotherapeutic drugs. The GLUT1-targeted TCM active ingredient nano-delivery system can overcome the bottleneck of the traditional targeting strategy as well as the high-permeability long retention（EPR） effect. In summary， the authors believe that the GLUT1-targeted TCM active ingredient nano-delivery system provides a new strategy for targeted treatment of tumors and has a broad application prospect in tumor prevention and treatment.

Corneal refractive surgery and intraocular collamer lens(ICL)implantation are the mainstream refractive surgery methods at present. Many studies have proved that ICL implantation can effectively improve the postoperative visual acuity of patients. ICL implantation has gained favor among refractive doctors and patients because of its multiple advantages. Excellent postoperative visual acuity and visual quality are the key factors to improve patients' satisfaction. In order to evaluate the subjective and objective visual quality of patients after operation and avoid complications, this article reviews the visual quality and postoperative complications after ICL implantation.

Objective: To analyze the prevalence and the risk factors of fungal sepsis in 25 neonatal intensive care units (NICU) among preterm infants in China, and to provide a basis for preventive strategies of fungal sepsis. Methods: This was a second-analysis of the data from the "reduction of infection in neonatal intensive care units using the evidence-based practice for improving quality" study. The current status of fungal sepsis of the 24 731 preterm infants with the gestational age of <34⁺⁰ weeks, who were admitted to 25 participating NICU within 7 days of birth between May 2015 and April 2018 were retrospectively analyzed. These preterm infants were divided into the fungal sepsis group and the without fungal sepsis group according to whether they developed fungal sepsis to analyze the incidences and the microbiology of fungal sepsis. Chi-square test was used to compare the incidences of fungal sepsis in preterm infants with different gestational ages and birth weights and in different NICU. Multivariate Logistic regression analysis was used to study the outcomes of preterm infants with fungal sepsis, which were further compared with those of preterm infants without fungal sepsis. The 144 preterm infants in the fungal sepsis group were matched with 288 preterm infants in the non-fungal sepsis group by propensity score-matched method. Univariate and multivariate Logistic regression analysis were used to analyze the risk factors of fungal sepsis. Results: In all, 166 (0.7%) of the 24 731 preterm infants developed fungal sepsis, with the gestational age of (29.7±2.0) weeks and the birth weight of (1 300±293) g. The incidence of fungal sepsis increased with decreasing gestational age and birth weight (both P<0.001). The preterm infants with gestational age of <32 weeks accounted for 87.3% (145/166). The incidence of fungal sepsis was 1.0% (117/11 438) in very preterm infants and 2.0% (28/1 401) in extremely preterm infants, and was 1.3% (103/8 060) in very low birth weight infants and 1.7% (21/1 211) in extremely low birth weight infants, respectively. There was no fungal sepsis in 3 NICU, and the incidences in the other 22 NICU ranged from 0.7% (10/1 397) to 2.9% (21/724), with significant statistical difference (P<0.001). The pathogens were mainly Candida (150/166, 90.4%), including 59 cases of Candida albicans and 91 cases of non-Candida albicans, of which Candida parapsilosis was the most common (41 cases). Fungal sepsis was independently associated with increased risk of moderate to severe bronchopulmonary dysplasia (BPD) (adjusted OR 1.52, 95%CI 1.04-2.22, P=0.030) and severe retinopathy of prematurity (ROP) (adjusted OR 2.55, 95%CI 1.12-5.80, P=0.025). Previous broad spectrum antibiotics exposure (adjusted OR=2.50, 95%CI 1.50-4.17, P<0.001), prolonged use of central line (adjusted OR=1.05, 95%CI 1.03-1.08, P<0.001) and previous total parenteral nutrition (TPN) duration (adjusted OR=1.04, 95%CI 1.02-1.06, P<0.001) were all independently associated with increasing risk of fungal sepsis. Conclusions: Candida albicans and Candida parapsilosis are the main pathogens of fungal sepsis among preterm infants in Chinese NICU. Preterm infants with fungal sepsis are at increased risk of moderate to severe BPD and severe ROP. Previous broad spectrum antibiotics exposure, prolonged use of central line and prolonged duration of TPN will increase the risk of fungal sepsis. Ongoing initiatives are needed to reduce fungal sepsis based on these risk factors.
Infant ; Infant, Newborn ; Humans ; Birth Weight ; Intensive Care Units, Neonatal ; Retrospective Studies ; Tertiary Care Centers ; Infant, Extremely Low Birth Weight ; Gestational Age ; Infant, Extremely Premature ; Sepsis/epidemiology* ; Retinopathy of Prematurity/epidemiology* ; Bronchopulmonary Dysplasia/epidemiology*

OBJECTIVES: To investigate the difference in intestinal microbiota between preterm infants with neurodevelopmental impairment (NDI) and those without NDI. METHODS: In this prospective cohort study, the preterm infants who were admitted to the neonatal intensive care unit of Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region from September 1, 2019 to September 30, 2021 were enrolled as subjects. According to the assessment results of Gesell Developmental Scale at the corrected gestational age of 1.5-2 years, they were divided into two groups: normal (n=115) and NDI (n=100). Fecal samples were collected one day before discharge, one day before introducing solid food, and at the corrected gestational age of 1 year. High-throughput sequencing was used to compare the composition of intestinal microbiota between groups. RESULTS: Compared with the normal group, the NDI group had a significantly higher Shannon diversity index at the corrected gestational age of 1 year (P<0.05). The principal coordinate analysis showed a significant difference in the composition of intestinal microbiota between the two groups one day before introducing solid food and at the corrected gestational age of 1 year (P<0.05). Compared with the normal group, the NDI group had a significantly higher abundance of Bifidobacterium in the intestine at all three time points, a significantly higher abundance of Enterococcus one day before introducing solid food and at the corrected gestational age of 1 year, and a significantly lower abundance of Akkermansia one day before introducing solid food (P<0.05). CONCLUSIONS There are significant differences in the composition of intestinal microbiota between preterm infants with NDI and those without NDI. This study enriches the data on the characteristics of intestinal microbiota in preterm infants with NDI and provides reference for the microbiota therapy and intervention for NDI in preterm infants.
Infant ; Child ; Infant, Newborn ; Humans ; Child, Preschool ; Infant, Premature ; Prospective Studies ; Gastrointestinal Microbiome ; China ; Infant, Premature, Diseases ; Gestational Age

ObjectiveTo study the effect and underlying mechanism of Stemona tuberosa alkaloids on the proliferation and apoptosis of human non-small cell lung cancer NCI-H460 cells. MethodNon-small cell lung cancer NCI-H460 cells were divided into a blank group and S. tuberosa alkaloids groups （50， 100， 150， 200， and 250 mg·L^-1）. The effect of S. tuberosa alkaloids on the proliferation of human NCI-H460 cells was observed by thiazolyl blue tetrazolium bromide （MTT） assay and colony formation assay. Cell apoptosis was observed by Hoechst 33258 staining and flow cytometry. Real-time fluorescence-based polymerase chain reaction （Real-time PCR） was used to detect the effect of S. tuberosa alkaloids on the mRNA expression of cysteinyl aspartate-specific protease 3 （Caspase-3）， B-cell lymphoma-2 （Bcl-2）， Bcl-2-associated X protein （Bax）， and epidermal growth factor receptor （EGFR）. The protein expression levels of Caspase-3， Bax， Bcl-2， protein kinase B （Akt）， phosphorylated （p-）Akt， EGFR， c-Jun N-terminal kinase （JNK）， p-JNK， p38 mitogen-activated protein kinase （p38 MAPK）， and p-p38 MAPK were measured by Western blot. ResultCompared with the blank group， the S. tuberosa alkaloids groups showed increased inhibition rate on cell proliferation （P<0.01）， reduced number of cell clones formed and the rate of cell clonal formation （P<0.05， P<0.01）， and increased karyopyknosis， cytoplasmic aggregation， and cell apoptosis rate （P<0.01）. The S. tuberosa alkaloids groups at 100， 150， 200， and 250 mg·L^-1 showed increased Caspase-3 mRNA expression （P<0.05）， decreased EGFR mRNA expression （P<0.05， P<0.01）， up-regulated protein expression of Caspase-3 and p-JNK （P<0.01）， and down-regulated protein expression of EGFR and p-Akt （P<0.05， P<0.01）. Additionally， compared with the blank group， the S. tuberosa alkaloids groups showed increased expression of Bax mRNA （P<0.01）， decreased expression of Bcl-2 mRNA （P<0.01）， up-regulated protein expression of Bax and p-p38 MAPK （P<0.01）， and down-regulated protein expression of Bcl-2 （P<0.01）. ConclusionsS. tuberosa alkaloids can inhibit proliferation and induce apoptosis of human non-small cell lung cancer NCI-H460 cells， and the mechanism may be related to the inhibition of EGFR protein expression and phosphorylation of Akt protein， as well as the activation of the JNK/p38 MAPK signaling pathway.

OBJECTIVE: To investigate a family with congenital dysfibrinogenemia, and analyze the risk of hemorrhage and thrombosis and blood transfusion strategies. METHODS: Prothrombin time (PT), activated partial thromboplastin time (APTT) and thrombin time (TT) of the proband and her family members were detected by automatic coagulometer, fibrinogen (Fg) activity and antigen were detected by Clauss method and PT algorithm respectively. Meanwhile, thromboelastometry was analyzed for proband and her family members. Then, peripheral blood samples of the proband and her family members were collected, and all exons of FGA, FGB and FGG and their flanks were amplified by PCR and sequenced to search for gene mutations. RESULTS: The proband had normal APTT and PT, slightly prolonged TT, reduced level of Fg activity (Clauss method). The Fg of the proband's aunt, son and daughter all decreased to varying degrees. The results of thromboelastogram indicated that Fg function of the proband and her family members (except her son) was basically normal. Gene analysis showed that there were 6233 G/A (p.AαArg35His) heterozygous mutations in exon 2 of FGA gene in the proband, her children and aunt. In addition, 2 polymorphic loci were found in the family, they were FGA gene g.9308A/G (p.AαThr331Ala) and FGB gene g.12628G/A (p.BβArg478Iys) polymorphism, respectively. The proband was injected with 10 units of cryoprecipitate 2 hours before delivery to prevent bleeding, and no obvious bleeding occurred during and after delivery. CONCLUSION Heterozygous mutation of 6233G/A (p.AαArg35His) of FGA gene is the biogenetic basis of the disease in this family with congenital dysfibrinogenemia.
Humans ; Child ; Female ; Fibrinogen/genetics* ; Pedigree ; Afibrinogenemia/genetics* ; Mutation ; Blood Transfusion

ObjectiveTo investigate the effect of Stemona tuberosa alkaloids （STA） on apoptosis and phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） and c-Jun N-terminal kinase/p38 mitogen-activated protein kinase （JNK/p38 MAPK） signaling pathways in human lung cancer A549 cells. MethodA549 cells were classified into blank group and STA groups （100， 150， 200， 250， 300 mg⋅L^-1）. Thiazole blue （MTT） assay and colony formation assay were used to evaluate the proliferation of A549 cells. Apoptosis was observed based on Hoechst 33258 staining， flow cytometry， and Annexin V-FITC/PI staining. Western blot was employed to detect the expression of apoptosis-related proteins cysteine-aspartic acid protease-3 （Caspase-3）， B-cell lymphoma-2 （Bcl-2）-associated X protein （Bax）， and Bcl-2， and the expression of PI3K， phosphorylated （p）-PI3K， Akt， p-Akt， JNK， p-JNK， p38 MAPK， and p-p38 MAPK. ResultCompared with the blank group， STA groups （150， 200， 250， 300 mg⋅L^-1） demonstrated the increase in inhibition rate of cell proliferation （P<0.01） and cell clone inhibition rate， and decrease in cell clone formation rate （P<0.01）. In comparison with the blank group， STA groups showed typical characteristics of apoptosis， such as chromatin condensation and enhanced fluorescence reaction. The apoptosis rate of STA groups was significantly higher than that of the blank group （P<0.01）. Compared with the blank group， STA （150， 200， 250， 300 mg⋅L^-1） significantly up-regulated the protein expression of Caspase-3 and Bax （P<0.05， P<0.01） and down-regulated the expression of Bcl-2 protein （P<0.01）. Compared with the blank group， STA had no significant influence on the total protein expression of PI3K， Akt， JNK， and p38 MAPK. However， STA （150， 200， 250， 300 mg⋅L^-1） significantly decreased the levels of p-PI3K and p-Akt （P<0.05， P<0.01） and increased the level of p-p38 MAPK （P<0.05， P<0.01）. Compared with the blank group， STA （200， 250， 300 mg⋅L^-1） significantly raised the level of p-JNK （P<0.05， P<0.01）. ConclusionSTA can inhibit the proliferation and induce the apoptosis of A549 cells by inhibiting PI3K/Akt signaling pathway and activating JNK/p38 MAPK signaling pathway.

Objective: To investigate the relationship between body mass index (BMI) and sexual development in Chinese children. Methods: A nationwide multicenter and population-based large cross-sectional study was conducted in 13 provinces, autonomous regions and municipalities of China from January 2017 to December 2018. Data on sex, age, height, weight were collected, BMI was calculated and sexual characteristics were analyzed. The subjects were divided into four groups based on age, including ages 3-<6 years, 6-<10 years, 10-<15 years and 15-<18 years. Multiple Logistic regression models were used for evaluating the associations of BMI with sexual development in children. Dichotomous Logistic regression was used to compare the differences in the distribution of early and non-early puberty among normal weight, overweight and obese groups. Curves were drawn to analyze the relationship between the percentage of early puberty and BMI distribution in girls and boys at different Tanner stages. Results: A total of 208 179 healthy children (96 471 girls and 111 708 boys) were enrolled in this study. The OR values of B2, B3 and B4+ in overweight girls were 1.72 (95%CI: 1.56-1.89), 3.19 (95%CI: 2.86-3.57), 7.14 (95%CI: 6.33-8.05) and in obese girls were 2.05 (95%CI: 1.88-2.24), 4.98 (95%CI: 4.49-5.53), 11.21 (95%CI: 9.98-12.59), respectively; while the OR values of G2, G3, G4+ in overweight boys were 1.27 (95%CI: 1.17-1.38), 1.52 (95%CI: 1.36-1.70), 1.88 (95%CI: 1.66-2.14) and in obese boys were 1.27 (95%CI: 1.17-1.37), 1.59 (95%CI: 1.43-1.78), and 1.93 (95%CI: 1.70-2.18) (compared with normal weight Tanner 1 group,all P<0.01). Analysis in different age groups found that OR values of obese girls at B2 stage and boys at G2 stage were 2.02 (95%CI: 1.06-3.86) and 2.32 (95%CI:1.05-5.12) in preschool children aged 3-<6 years, respectively (both P<0.05). And in the age group of 6-10 years, overweight girls had a 5.45-fold risk and obese girls had a 12.54-fold risk of B3 stage compared to girls with normal BMI. Compared with normal weight children, the risk of early puberty was 2.67 times higher in overweight girls, 3.63 times higher in obese girls, and 1.22 times higher in overweight boys, 1.35 times higher in obese boys (all P<0.01). Among the children at each Tanner stages, the percentage of early puberty increased with the increase of BMI, from 5.7% (80/1 397), 16.1% (48/299), 13.8% (27/195) to 25.7% (198/769), 65.1% (209/321), 65.4% (157/240) in girls aged 8-<9, 10-<11 and 11-<12 years, and 6.6% (34/513), 18.7% (51/273), 21.6% (57/264) to 13.3% (96/722), 46.4% (140/302), 47.5% (105/221) in boys aged 9-<10, 12-<13 and 13-<14 years, respectively. Conclusions: BMI is positively correlated with sexual development in both Chinese boys and girls, and the correlation is stronger in girls. Obesity is a risk factor for precocious puberty in preschool children aged 3-<6 years, and 6-<10 years of age is a high risk period for early development in obese girls.
Adolescent ; Body Mass Index ; Child ; Child, Preschool ; China/epidemiology* ; Cross-Sectional Studies ; Female ; Humans ; Male ; Obesity/epidemiology* ; Overweight/epidemiology* ; Puberty ; Puberty, Precocious ; Sexual Development

AIM:To observe the clinical effect of ranibizumab combined with 577nm micropulse laser in the treatment of severe diabetic macular edema(DME). METHODS:There were 52 eyes of 52 patients diagnosed with severe DME who admitted to the People's Hospital of Guangxi Zhuang Autonomous Region from June 2016 to September 2019. The patients were randomly divided into the observation group(26 patients with 26 eyes, treated with ranibizumab combined with 577nm micropulse laser)and the control group(26 patients with 26 eyes, treated with ranibizumab alone). Patients in both groups received intravitreal injection of ranibizumab with “3+PRN” regimen. Followed up at 9mo after treatment to observe the central macular thickness(CMT), the best corrected visual acuity(BCVA)and the times of intravitreal injection of ranibizumab in the two groups.RESULTS:Compared with before treatment, the CMT and BCVA of the two groups were significantly improved at each time point after treatment(all P<0.001), but there was no difference between the two groups(P>0.05). During the follow-up period, the times of vitreous injection of ranibizumabin the observation group was significantly less than that in the control group(5.88±1.24 times vs 7.12±1.24 times, P=0.001). CONCLUSION:Both ranibizumab combined with 577nm micropulse laser and ranibizumab alone are effective in reducing edema and improving vision in patients with severe DME, but the combination therapy reduces the times of injection.