OBJECTIVES: To investigate the application value of thromboelastography (TEG) in assessing coagulation function in children with severe hemophilia A (HA) after emicizumab (EMI) therapy. METHODS: A retrospective analysis was performed on the activated partial thromboplastin time (APTT) and TEG testing results of 17 children with severe HA before and after EMI treatment at Shenzhen Children's Hospital from January 2023 to July 2024. Correlation analysis was conducted between coagulation factor VIII (FVIII) equivalent activity and reaction time (R value) measured by TEG. RESULTS: After EMI treatment, the mean bleeding rate for children with severe HA was 1.6 events per year, with 15 children (88%) without spontaneous bleeding or joint bleeding. The children with severe HA showed a significant reduction in APTT after EMI treatment (P<0.05), with a significantly shorter APTT than the normal control group (P<0.05). There was no correlation between APTT and FVIII equivalent activity after treatment (P>0.05). After EMI treatment, TEG parameters, including R value, kinetic time, alpha angle (α), maximum amplitude, clot strength, and coagulation index, shifted from a hypocoagulable state before treatment to a nearly normal state after treatment (P<0.05). The R value demonstrated a strong negative correlation with FVIII equivalent activity (r=-0.758, P<0.05). CONCLUSIONS The bleeding condition of children with severe HA can be effectively controlled after EMI treatment. Routine APTT testing cannot reflect true coagulation function, whereas TEG testing is clinically valuable in assessing the coagulation function of children with severe HA undergoing EMI treatment.
Humans ; Thrombelastography ; Hemophilia A/physiopathology* ; Male ; Child ; Antibodies, Bispecific/therapeutic use* ; Antibodies, Monoclonal, Humanized/therapeutic use* ; Blood Coagulation/drug effects* ; Child, Preschool ; Retrospective Studies ; Female ; Partial Thromboplastin Time ; Adolescent ; Infant

Objective:Analysis of subtype distribution characteristics of human papillomavirus (HPV) infection, pathological findings of HPV-positive patients operated colposcopy and cervical histopathological examination in Changsha from 2020 to 2022.Methods:Retrospective analysis of HPV infection status of 60 354 patients was treated in the First Affiliated Hospital of Hunan University of Chinese Medicine from Jan. 2020 to Oct. 2022. They were divided into<25 years old group (3 250 cases), 25-34 years old group (19 406 cases), 35-44 years old group (17 297 cases), 45-54 years old group (13 104 cases), 55-64 years old group (4 793 cases) and≥65 years old group (2 504 cases). Cervical exfoliated cells were collected from women and specimen of lesion site were collected from men. HPV genotyping detection used polymerase chain reaction (PCR) and flow fluorescence hybridization, which could detect 27 HPV genotypes. Analyze the distribution of HPV subtypes in patients of different age groups and different treatment departments. Analyze the relationship between the infection of HPV subtypes and the outcome of 224 patients with HPV positive who also underwent colposcopy and cervical histopathology. Pearson correlation test was used for correlation analysis, and two-tailed P<0.05 was statistically significant; Pearson chi-square test or continuous correction chi-square test was used to compare the rates between groups, and two-tailed P<0.05 was statistically significant; Chi-square split test was used to compare multiple sample rates. The standard test was corrected according to the number of groups and then compared. The difference was statistically significant when the two-tailed P value was less than the corrected standard test. Results:The overall positive rate of HPV was 16.4% (9 909/60 354). Among all HPV positive patients, affection of single type HPV accounted for 75.5% (7 479/9 909) and affection of multi-type HPV accounted for 24.5% (2 430/9 909). The top six HPV types with infection rates from high to low were: HPV52 22.8% (2 256/9 909), HPV58 11.1% (1 097/9 909), HPV53 10.5% (1 045/9 909), HPV16 9.0% (890/9 909), HPV61 7.8% (774/9 909) and HPV6 7.6% (750/9 909). The difference of overall infection rate between different age groups was statistically significant (χ 2=536.90, P<0.001). The HPV infection rate was the highest in the<25 years old group, 30.1% (978/3 250), and it is higher than the age groups of 25-34 years old, 15.6% (3 035/19 406), group of 35-44 years old, 14.2% (2 464/17 297), group of 45-54 years old, 16.1% (2 115/13 104), group of 55-64 years old, 19.1% (915/4 793) and group of≥65 years old, 16.1% (402/2 504), with statistical significance( P<0.001 respectively). The most common types of HPV infection were type 6, 16.7% (378/2 266) and type 11, 10.5% (239/2 266) in dermatology clinics. The positive rate of HPV16 accounted for 12/17 in cervical intraepithelial neoplasia (CIN) 3 and cervical cancer cases, it was significantly higher than that in the inflammatory cases, 25.0% (35/140) and CIN1 cases, 23.0% (11/48), the statistical values were χ 2=15.02, P<0.001 and χ 2=12.48, P<0.001, respectively, all of which were statistically significant. Conclusions:HPV infection rate is highest in young people under 25 years old. Low-risk HPV6 and 11 are the main types of skin and venereal diseases. Among the total cases, high-risk HPV52, 58 and 53 are the most common types of infection with women in Changsha. However, high-grade cervical intraepithelial neoplasia and cervical cancer are more closely related to HPV16 infection.

AIM: To explore the clinical efficacy of different anti-vascular endothelial growth factor(VEGF)drugs in the treatment of diabetic macular edema(DME), and analyze their relationship with optical coherence tomography(OCT)classification.METHODS: A total of 45 DME patients treated with ranibizumab(admitted to our hospital from February 2020 to February 2022)were selected as the ranibizumab group, and 45 DME patients treated with conbercept during the same period were selected as the conbercept group. The ranibizumab group was treated with retinal photocoagulation combined with ranibizumab, and the conbercept group was treated with retinal photocoagulation combined with conbercept. The improvement of symptoms(improvement time of macular edema, time of retinal thickness returning to normal, disappearance time of neovascularization and absorption time of fundus hemorrhage), levels of serum interleukin-6(IL-6)and VEGF, central macular thickness(CMT), best corrected visual acuity(BCVA), and complications were compared between the two groups, and the relationship between their clinical efficacy and different OCT types were analyzed.RESULTS: There was no significant difference in the improvement time of macular edema, time of retinal thickness returning to normal, disappearance time of neovascularization and absorption time of fundus hemorrhage between the two groups(P>0.05); After treatment, the values of IL-6, VEGF and BCVA in the two groups were significantly lower than those before treatment(P<0.01), but there was no significant difference between the two groups(P>0.05); compared with before treatment, CMT was significantly decreased in both groups after treatment(P<0.05), and compared with ranibizumab group, the CMT was significantly decreased in the conbercept group(P<0.01); there was no significant difference in the incidence of complications between two groups(P>0.05); there were significant differences in the total effective rate among patients with serous retinal detachment(SRD), cystoid macular edema(CME)and diffuse retinal thickening(DRT; P<0.05), among which DRT had the highest total effective rate and SRD had the lowest total effective rate.CONCLUSION: Both conbercept and ranibizumab in the treatment of DME can effectively improve the clinical symptoms of patients and reduce the inflammatory response, but conbercept can better reduce the level of CMT, and has better treatment effect on DRT-type DME patients.

AIM: To explore the relationship between the changes of serum circFTO and microRNA-141-3p(miR-141-3p)levels and the different disease stages of diabetes retinopathy.METHODS: A total of 198 patients with type 2 diabetes admitted to our hospital from October 2019 to November 2022 were collected as the study subjects, the patients were grouped into non diabetes retinopathy(NDR)group(70 cases), non proliferative diabetes retinopathy(NPDR)group(66 cases)and proliferative diabetes retinopathy(PDR)group(62 cases)according to different stages; meantime, 67 volunteers with normal physical examination results were collected as the control group. The levels of serum circFTO and miR-141-3p were detected by real-time fluorescent quantitative PCR(qRT-PCR); Pearson correlation analysis was used to examine the correlation between the serum circFTO, miR-141-3p and various indicators in patients with diabetes retinopathy; multivariate Logistic regression analysis was applied to explore the influencing factors of diabetes retinopathy.RESULTS: CircFTO, systolic blood pressure(SBP), and diastolic blood pressure(DBP)in PDR group were higher than those in control group, NDR group and NPDR group, while miR-141-3p and high-density lipoprotein cholesterol(HDL-C)were lower than those in control group, NDR group and NPDR group(P<0.05). Fasting blood glucose(FPG)and glycosylated hemoglobin(HbA1c)in NDR group, NPDR group and PDR group were higher than those in the control group(all P<0.05). The course of disease in PDR group was longer than that in NDR group and NPDR group(P<0.05). Serum circFTO in patients with diabetes retinopathy was positively correlated with SBP, DBP, FPG, HbA1c, and miR-141-3p was negatively correlated with SBP, DBP, FPG, HbA1c(all P<0.05). CircFTO was a risk factor for diabetes retinopathy, and miR-141-3p was a protective factor for diabetes retinopathy(P<0.05).CONCLUSION: Serum circFTO is obviously increased and miR-141-3p is obviously decreased in patients with diabetes retinopathy, both of them are closely related to disease stage, and are expected to become important indicators for evaluating disease progress.

The latest epidemiological data suggests that the situation of adult diabetes in China is severe, and metabolic diseases have become significant chronic illnesses that have a serious impact on public health and social development. After more than six years of practice, the National Metabolic Management Center(MMC) has developed distinctive approaches to manage metabolic patients and has achieved a series of positive outcomes, continuously advancing the standardized diagnosis and treatment model. In order to further improve the efficiency, based on the first edition, the second edition guideline was composed by incorporating experience of the past six years in conjunction with the latest international and domestic guidelines.

Aim To investigate the potential mechanism of Jiawei Duhuo Jisheng Mixture regulating intestinal flora in the treatment of knee osteoarthritis(KOA)by 16S rRNA sequencing.Methods Eight-week-old male C57 mice were randomly divided into three groups:sham group,DMM group,and model+Jiawei Duhuo Jisheng Mixture group(Mixture group),6 mice per group.KOA model was induced by destabilization of medial meniscus surgery.16.25 mL·kg-1 dose mixture was given daily to the mixture group,and normal saline was given to the sham and DMM group.After eight weeks,the knee joints and colons of mice were collected,and the knee joints were prepared into paraffin sections,and the cartilage changes were observed with Safranin O-Fast Green and immunohistochemistry staining.16S rRNA sequencing of intestinal contents was performed to observe the changes of intestinal flora.Results Compared with model group,Jiawei Duhuo Jisheng Mixture could significantly reduce cartilage wear and OARSI score(P=0.033 5,P=0.029 5).16S rRNA sequencing showed that Jiawei Duhuo Jisheng Mixtrue could change the intestinal flora richness of KOA model mice,and improve the Alpha diversity(Chao1,Simpson)and Beta diversity(PCoA,NMDS).LefSe analysis showed that there were species with significant difference in abundance among the three groups(P=0.001),mainly including Lactobacillus,Firmicutes,Proteobacteria and other species.MetaCyc analysis indicated that Jiawei Duhuo Jisheng Mixture had effects on various metabolic pathways such as fatty acid,sugar and amino acid of intestinal flora(P<0.05).Conclusions Jiawei Duhuo Jisheng Mixtrue can effectively protect the articular cartilage and delay the progression of KOA.The mechanism may be through regulating the intestinal flora structure,protecting the intestinal barrier and reducing the inflammatory response.

Malignant tumors seriously endanger human life and health, and their treatment has always been a research focus of scientists all over the world. Natural flavonoids and their derivatives have a variety of biological activities, especially regarding antitumor growth, with unique biological activities. They can interfere with the growth cycle of tumor cells, change the mitochondrial membrane potential, promote apoptosis, and can reduce the immune escape of tumor cells and prevent tumor metastasis by improving human immunity. In the human body, they regulate the biological signal transduction, leading to the up-regulation of pro-apoptotic protein expression. They inhibit the growth of solid tumors by regulating the growth of vascular epithelial cells and blocking the formation of blood vessels in tumor tissue. Recent studies have shown that these compounds can play an important role in the treatment of various human tumors and are expected to be developed into new antitumor drugs. This review summarizes the recent research results on the antitumor mechanism of flavonoids and their ability to inhibit tumor growth.

The mammalian target of rapamycin (mTOR)-sterol regulatory element-binding proteins (SREBPs) signaling promotes lipogenesis. However, mTOR inhibitors also displayed a significant side effect of hyperlipidemia. Thus, it is essential to develop mTOR-specific inhibitors to inhibit lipogenesis. Here, we screened the endogenous inhibitors of mTOR, and identified that FKBP38 as a vital regulator of lipid metabolism. FKBP38 decreased the lipid content

Objective:To detect serum levels of vitamin A (Vit A), vitamin D(Vit D)25-hydroxy vitamin D[25-(OH)D] and vitamin E(Vit E) in children aged 0-6 years in Tibetan Plateau of Garzi Prefecture, thus providing references for physical examinations and prevention of 4 key diseases (rickets, malnutrition anemia, pneumonia and diarrhea) in children in plateau areas by relevant government departments.Methods:A total of 2 122 children who participated in physical examination in 12 townships of Xiangcheng County and 14 townships of Daocheng County, Garzi Tibetan Autonomous Prefecture, Sichuan Province from April 2017 to April 2019 with 0-6 years old were recruited for surveying physical measurements and collection of venous blood.Serum Vit A and Vit E levels were detected by high performance liquid chromatography.Serum levels of 25-(OH)D were detected by high performance liquid chromatography tandem mass spectrometry.The relationship between Vit A, Vit E and 25-(OH)D levels with the gender, age, seasonal change and altitude was analyzed.Results:The serum Vit A level, subclinical Vit A deficiency rate and marginal vitamin A deficiency rate were(1.05±0.27) μmol/L, 8.15%(173/2 122 cases) and 45.99%(976/2 122 cases), respectively in 2 122 children with 0-6 years old.There were significant differences in the serum Vit A level, the subclinical Vit A deficiency rate and the marginal vitamin A deficiency rate in children with different ages, seasons and altitudes (all P<0.05). The serum level of 25-(OH)D and 25-(OH)D deficiency rate insufficient rate were (24.65±6.45) ng/L, 6.03%(128/2 122 cases) and 16.59%(352/2 122 cases), respectively.There were significant differences in the serum level of 25-(OH)D, 25-(OH)D deficiency rate and 25-(OH)D insufficient rate in children with different ages and seasons (all P<0.05). The mean serum Vit E level, Vit E deficiency rate and Vit E insufficient rate were (7.81±1.74) mg/L, 2.78%(59/2 122 cases) and 29.59%(628/2 122 cases), respectively.There were significant differences in serum Vit E level, Vit E deficiency rate and Vit E insufficient rate in children with different ages and seasons (all P<0.05). The mean serum levels of Vit A and Vit D remained the lowest before the age of 1 year, and their deficiencies at this age were the most significant.The mean serum level of Vit E remained the lowest in >1-2 years old, and its deficiency and insufficient at this age were the most significant.Vit A, D and E levels were significantly affected by seasonal changes, which were significantly higher in the summer than in the spring, autumn and winter.In addition, Vit A and 25-(OH)D were significantly affected by the altitude, which were the lowest above 4 km altitude. Conclusions:The overall serum levels of Vit A, 25-(OH) D and E in children with 0-6 years old in Tibetan Plateau areas of Ganzi Prefecture are lower than those in plain areas.Vit A, 25-(OH) D and Vit E levels significantly differed in the age, season and altitude, which are related to the lack of local resources, insufficient maternal nutrition during pregnancy and insufficient intake after birth, as well as temperature and light caused by changes in local seasons and altitude.Therefore, it is necessary to make reasonable supplements during pregnancy to prevent vitamin deficiency.

Herpes simplex virus type 1 (HSV-1) is a ubiquitous and widespread human pathogen, which gives rise to a range of diseases, including cold sores, corneal blindness, and encephalitis. Currently, the use of nucleoside analogs, such as acyclovir and penciclovir, in treating HSV-1 infection often presents limitation due to their side effects and low efficacy for drug-resistance strains. Therefore, new anti-herpetic drugs and strategies should be urgently developed. Here, we reported that baicalein, a naturally derived compound widely used in Asian countries, strongly inhibited HSV-1 replication in several models. Baicalein was effective against the replication of both HSV-1/F and HSV-1/Blue (an acyclovir-resistant strain)