Objective: To analyze the epidemiological characteristics of category C intestinal infectious diseases among children and adolescents in Shenzhen from 2012 to 2024 and the association with meteorological factors, so as to provide a scientific basis for the targeted prevention and control of infectious diseases for children and adolescents. Methods: Using data from the "Infectious Disease Reporting Information Management System" of the "China Disease Prevention and Control Information System" covering the period from January 1, 2012 to December 31, 2024, the study analyzed clinical and confirmed cases of hand, foot, and mouth disease, other infectious diarrhea, and acute hemorrhagic conjunctivitis among individuals aged 6-19 years old to describe demographic and temporal characteristics. It used Joinpoint regression to calculate the average annual percent change (AAPC) and annual percent change (APC) to analyze incidence trends, and Spearman s correlation was combined to generalize linear models so as to assess the association between category C intestinal infectious diseases and meteorological factors. Results: From 2012 to 2024, a cumulative total of 61 019 cases of hand, foot, and mouth disease among children and adolescents, 58 498 cases of other infectious diarrhea, and 6 377 cases of acute hemorrhagic conjunctivitis were reported. The AAPC in the incidence rates of these three diseases was 19.19%, 31.03% and 31.48 %, respectively(all P <0.05). Notably, the incidence of hand, foot, and mouth disease increased significantly after 2022 (APC= 133.66 %, P <0.01). The temporal distribution showed that hand,foot,and mouth disease was most prevalent in May,June and July (seasonal index of 2.39,3.64,1.97), other infectious diarrhea was most prevalent in February,March and December (seasonal index of 1.22,1.25,1.47), and acute hemorrhagic conjunctivitis peaked in September and October (seasonal index of 4.22,2.16). Monthly average temperature could increase the risk of hand,foot,and mouth disease( β = 0.18 ,95% CI =0.11-0.25); as monthly average wind speed increased, the incidence of other infectious diarrhea ( β =-0.86, 95% CI = -1.50 to -0.22) and acute hemorrhagic conjunctivitis ( β =-1.32, 95% CI =-2.60 to -0.05) both decreased (all P < 0.05 ). Conclusions Among children and adolescents in Shenzhen, category C intestinal infectious diseases remain prevalent throughout the year；the number of reported hand, foot, and mouth disease cases has shown an upward trend in recent years.Temperature and wind speed significantly affect the number of reported cases of three types with category C intestinal infectious diseases.

ObjectiveMicrotube associated protein-2 （MAP-2）， alpha-tubulin （α-tubulin）， and synaptophysin （SYP） are important proteins in neuronal signal communication. This paper observed the effects of modified Zhigancao Tang on the expression of serum α-Synuclein （α-Syn） and its oligomers， MAP-2， α-tubulin， and SYP of patients with liver and kidney deficiency of Parkinson's disease （PD）， analyzed their correlation， and evaluated the therapeutic effect of modified Zhigancao Tang in patients with liver and kidney deficiency of PD based on α-Syn transmission pathway mediated by neuronal communication in vivo. MethodsA total of 60 patients with PD who met the inclusion criteria were randomly divided into a treatment group （30 cases） and a control group （30 cases）. Both groups were treated on the basis of PD medicine， and the treatment group was treated with modified Zhigancao Tang. Both groups were treated for 12 weeks. The changes in UPDRS score， TCM syndrome score， and expression of serum α-Syn and its oligomers， MAP-2， α-tubulin， and SYP were observed before and after 12 weeks of treatment in each group. The correlation between the above-mentioned serum biological indexes and the levels of serum α-Syn and its oligomers was analyzed. ResultsAfter treatment， the TCM syndrome score， UPDRS score， UPDRS-Ⅱ score， and UPDRS-Ⅲ score of the treatment group were significantly decreased （P<0.05， P<0.01）. The UPDRS score， UPDRS-Ⅱ score， and UPDRS-Ⅲ scores in the treatment group were significantly decreased compared with those in the control group after treatment （P<0.05）. After treatment， the total effective rate of the control group was 63.3% （19/30）， and that of the treatment group was 86.7% （26/30）. The clinical effect of the observation group was better than the control group （Z=-2.03， P<0.05）. The total effective rate of the observation group was better than that of the control group， and the difference was statistically significant （χ²=5.136， P<0.05）. After treatment， the oligomer level of serum α-Syn and MAP-2 level in the treatment group were significantly decreased （P<0.05， P<0.01）. The levels of serum α-Syn and its oligomers， as well as α-tubulin in the treatment group， were significantly decreased compared with those in the control group after treatment （P<0.05， P<0.01）. Serum α-Syn was correlated with serum MAP-2 and α-Syn oligomer in patients with PD （P<0.05， P<0.01） but not correlated with serum SYP . Serum α-Syn oligomers of patients with PD were correlated with serum MAP-2 and α-tubulin （P<0.05， P<0.01） but not correlated with serum SYP level. Serum SYP of patients with PD was correlated with serum MAP-2 （P<0.05）. ConclusionModified Zhigancao Tang has a therapeutic effect on patients with liver and kidney deficiency of PD by inhibiting the production of α-Syn oligomers and intervening α-Syn microtubule transport pathway in vivo.

Objective:To observe and analyze the short-term effects of intravitreal injection of Conbercept (IVC) on the expression levels of matrix metalloproteinase (MMP)-2 and MMP inhibitor-2 (TIMP-2) in the aqueous humor of eyes with proliferative diabetic retinopathy (PDR).Methods:A prospective clinical study. From March 2024 to June 2024, 30 consecutive patients with 30 eyes with PDR (PDR group) undergoing IVC combined with pars plana vitrectomy (PPV) at Department of Ophthalmology of The First Affiliated Hospital of University of Science and Technology were included in the study, along with 20 patients with 20 eyes undergoing cataract surgery (control group) during the same period. In the PDR group, IVC treatment was performed 3 to 7 days before PPV, and 0.05-0.10 ml aqueous humor was collected before IVC and before PPV. In the control group, 0.05-0.10 ml aqueous humor was collected before cataract surgery. The levels of vascular endothelial growth factor (VEGF), MMP-2, and TIMP-2 in the aqueous humor were measured using enzyme-linked immunosorbent assay. For normally distributed data, independent samples t-test were used for comparison between two groups; for non-normally distributed data, the Mann-Whitney U test was used. The correlation analysis of VEGF, MMP-2, TIMP-2 concentrations in aqueous humor of PDR patients was performed using Pearson's correlation coefficient. Results:There were no statistically significant differences in age ( Z=-1.810) and gender composition ( χ2=3.450) between the PDR group and the control group ( P>0.05). Before IVC, VEGF and MMP-2 expression levels were (0.23±0.10), (2.11±1.32) ng/ml and (0.12±0.03), (0.53±0.26) ng/ml in patients' aqueous fluid in PDR group and control group, respectively. The expression level of TIMP-2 and the ratio of MMP-2/TIMP-2 were (0.99±0.26), (1.76±0.11) ng/ml and 2.04 (1.19, 2.98), 0.36 (0.15, 0.39), respectively. Compared with the control group, the expression levels of VEGF and MMP-2 in aqueous humor in PDR group ( t=-5.030, -5.260) and the ratio of MMP-2/TIMP-2 ( Z=-5.740) were significantly increased, with statistical significance ( P<0.01). The expression level of TIMP-2 was significantly lower than that of control group, the difference was statistically significant ( t=12.120, P<0.01). After IVC, the expression levels of VEGF and MMP-2 in aqueous humor of PDR patients were (0.13±0.03) and (2.11±1.32) ng/ml, respectively. The expression level of TIMP-2 and the ratio of MMP-2/TIMP-2 were (0.95±0.28) ng/ml and 1.57 (1.02, 3.13), respectively. Compared with before IVC, the expression level of VEGF in aqueous humor in PDR group after IVC was significantly decreased, and the difference was statistically significant ( t=6.080, P<0.01). The expression levels of MMP-2 ( t=1.220), TIMP-2 ( t=0.290) and the ratio of MMP-2/TIMP-2 ( Z=-0.260) were not significantly different ( P=0.270, 0.780, 0.800). After IVC, there was no significant difference in VEGF expression level between PDR group and control group ( t=-1.200, P=0.240). The expression level of MMP-2 was still significantly increased ( t=-5.880), the expression level of TIMP-2 was still significantly decreased ( t=11.520), and the ratio of MMP-2/TIMP-2 was still significantly increased ( Z=-5.780), with statistical significance ( P<0.01). Correlation analysis showed that VEGF was positively correlated with MMP-2 in aqueous humor of PDR patients before IVC ( r=0.590, P<0.01). Conclusions:IVC can effectively reduce the level of VEGF in the aqueous humor of eyes with PDR in the short term, but it has no significant effect on the levels of MMP-2 and TIMP-2.

Objective:To observe and analyze the clinical phenotype and genetic characteristics of COL2A1 and COL11A1 de novo mutation (DNM) related Stickler syndrome type Ⅰ and Ⅱ patients. Methods:A family-based cohort study. From December 2023 to November 2024, 4 patients (all probands) with Stickler syndrome diagnosed by clinical and genetic testing in Department of Ophthalmology of People's Hospital of Ningxia Hui Autonomous Region and their parents (8 cases) were included in the study. The patients came from 4 unrelated families. A detailed medical history was taken, and the patients underwent best-corrected visual acuity (BCVA), refraction, and fundus color photography examinations. Systemic examinations included the oral and facial regions, skeletal, joints, and hearing. Peripheral venous blood samples were collected from the patients and their parents, and genomic DNA was extracted. Whole-exome sequencing was used to screen for pathogenic genes and their loci, which were then validated by Sanger sequencing and combined with segregation analysis in the families to identify candidate gene mutation sites. The candidate variants were assessed for pathogenicity according to the American College of Medical Genetics and Genomics (ACMG) criteria and guidelines for the classification of genetic variants. Additionally, cross-species conservation analysis was performed to determine the evolutionary conservation of wild-type amino acids, and protein three-dimensional modeling techniques were used to characterize the spatial conformational changes of the variant proteins and the alterations in their local hydrogen bond networks.Results:Among the 4 patients, there were 2 males and 2 females; their ages ranged from 3 to 12 years. There were 2 cases of Stickler syndrome type Ⅰ (proband of families 1 and 2) and 2 cases of type Ⅱ (proband of families 3 and 4). The diopters ranged from -8.00 to-18.00 D. BCVA ranged from no light perception to 0.6 -. There were 2 cases each of vitreous membrane-like and "bead-like" opacity. Three cases showed peripapillary atrophy arcs and leopard pattern changes in the retina; one case had bilateral retinal detachment with a large macular hole in the left eye, which had previously been treated with vitrectomy surgery. One case had bilateral sensorineural hearing loss. There were 3 cases of simple micrognathia; one case had a flat nasal bridge, short nose, midface depression, and micrognathia. Two cases had excessive elbow joint extension. The phenotypes of the parents of the 4 patients were normal. Genetic testing results revealed that the probands of families 1 and 2 carried COL2A1 gene c.85+1G>C (M1) splice site variant and c.3950_3951insA (p.M1317Ifs*48) (M2) frameshift variant, respectively; the probands of families 3 and 4 carried COL11A1 gene (NM_001854.4) c.2549 G>T (p.G850V) (M3) missense variant and c.3816+6T>C (M4) splice site variant, respectively. The parents did not carry the related gene variants. Among them, M2, M3, and M4 are newly reported DNM. According to the ACMG guidelines, they were all considered likely pathogenic. The cross-species conservation analysis results showed that the wild-type amino acid of the COL11A1 gene M3 missense variant was highly conserved across multiple different species. Protein local structure modeling analysis revealed that the COL2A1 gene M2 frameshift variant and the COL11A1 gene M3 missense variant significantly altered the tertiary structure conformation of the protein, leading to abnormal spatial arrangement and hydrogen bond network in the key functional domains Conclusion:The COL2A1 gene M1 splice site variant, M2 frameshift variant, and the COL11A1 gene M3 missense variant, M4 splice site variant are respectively the potential pathogenic genes for families 1, 2, and families 3, 4; leading to the onset of Stickler syndrome type Ⅰ in families 1 and 2, and type Ⅱ in families 3 and 4.

Aim To investigate the protective effect of Shengmai Yin on myocardial ischemia/reperfusion in-jury(MI/RI)in vitro and in vivo and to unravel the underlying mechanism.Methods SD rats were divid-ed into the sham group,model group,and Shengmai Yin group(SM).Rat MI/RI model was established.Cardiac function,infarct area,pathological changes,cardiomyocyte apoptosis,macrophage infiltration,and serum cTnT and CK-MB levels were measured.The mRNA and protein expressions of Calpain-1 and Cal-pain-2 were assessed.The hypoxia/reoxygenation(H/R)model was constructed in H9c2 cells.The active ingredients of Shengmai Yin were screened using net-work pharmacology and verified by CCK-8.In the car-diomyocytes H/R model,Fluo-4 AM staining was used to detect the changes of Ca2+levels.Results Com-pared with model group,LVEF and LVFS of Shengmai Yin-treated rats increased,myocardial infarction area was reduced,while myocardial tissue injury was allevi-ated.Myocardial apoptosis rate and the number of macrophages were reduced.Similarly,cTnT and CK-MB levels decreased.In addition,the expression lev-els of Calpain-1 and Calpain-2 mRNA and protein de-creased in the SM treatment group.Under the H/R model,all the active ingredients of Shengmai decoction had protective effects on cardiomyocytes,and the treat-ment could reduce the level of Ca2+in cardiomyocytes.Conclusions Shengmai Yin has protective effects on MI/RI in rats.This effect may be related to the de-crease in Ca2+levels,as well as Calpain-1 and Calap-in-2 mRNA and protein expression.

Objective To evaluate the pharmacokinetics(PK)and pharmacodynamics(PD)of propofol injectable emulsion,and to assess the bioequivalence of test and reference formulations in healthy Chinese adult volunteers.Methods Thirty-two healthy Chinese adult volunteers were recruited and randomly assigned to a fasting.single-dose,two-period and double-crossover study.Propofol was given to eligible subjects at a speed of 30 μg·kg-1·min-1 for 30 min.The concentration of propofol in plasma was determined by avalidated high performance liquid chromatography-tandem mass spectrometery(HPLC-MS/MS)method.The PK parameters of the two preparations were calculated.Bispectral index(BIS)was measured to calculate the PD parameters of two formulations.Adverse events during the trial were recorded.Results Thirty-one volunteers were included in the pharmacokinetic parameter set.The mean values of PK parameters of test andreference formulations were as follows:Cmax were(660.87±110.25)and(683.13±125.75)ng·mL-1;AUC0-t were(473.50±86.03)and(478.40±80.25)h·ng·mL-1;AUC0-∞ were(500.45±96.49)and(507.84±88.00)h·ng·mL-1;tmax were 0.47(0.25,0.53)and 0.50(0.40,0.54)h;t1/2 were(2.97±1.74)and(3.08±1.82)h.Thirty-one volunteers were included in the bioequivalence set.The 90％confidence intervals(CI)for the geometric mean ratios of Cmax,AUC0-t,AUC0-∞ were 92.64％-101.39％,96.43％-101.00％,95.67％-100.70％,respectively.The mean values of PD parameters of test and reference formulations were as follows:BISmin were(75.94±13.66)and(74.39±12.32);BISAUC0-60minwere 5 569.85±182.78 and 5 575.68±166.19;T-BISmin were 23.00 and 29.00 min,respectively.There were no serious adverse events.Conclusion Two formulations of propofol injectable emulsion were bioequivalent and both of them exhibited good safety.

Sepsis is a life-threatening organ dysfunction disease caused by a dysregulated host response to infection.It has com-plex pathophysiological changes,and in severe cases,it can rap-idly develop into septic shock and multiple organ dysfunction or multiple organ failure.At present,the pathological mechanism of sepsis and its induced organ dysfunction is complex and the in-fluencing factors are numerous.So far,there is still a lack of specific and effective treatment strategies.RNA modify-N6-methyladenosine(m6 A)is one of the most common post-tran-scriptional modifications on eukaryotic RNAs.It is involved in the regulation of the occurrence and development of a variety of inflammatory diseases,including sepsis,and even multiple organ dysfunction induced by sepsis by affecting the metabolism of RNAs.It includes cardiac dysfunction,acute lung injury(ALI)and acute kidney injury(AKI).Therefore,this article will dis-cuss the effect of m6A modification on the function of immune cells,and its important role in sepsis and its induced multiple or-gan dysfunction diseases by regulating inflammatory signals,py-roptosis,mitochondrial damage and ferroptosis.This will provide new therapeutic targets and strategies for the clinical prevention and treatment of sepsis and its induced multiple organ dysfunc-tion diseases.

Objective To mine the risk signals of adverse drug events(ADEs)related to lecanemab through the U.S.Food and Drug Adminstration Adverse Event Reporting System(FAERS)database,to provide a reference for the safe clinical use of lecanemab.Methods Data on adverse events related to lecanemab from the fourth quarter,2010 to the second quarter 2024 in the FAERS were collected.Potential ADE signals were mined using the reporting odds ratio(ROR)method,Medicines and Healthcare Products Regulatory Agency(MHRA)method,Bayesian confidence propagation neural network(BCPNN)method and multi-item gamma Poisson shrinker(MGPS)method.The top 30 ADEs in terms of report frequency and signal strength,as well as ADEs categorized by system organ class(SOC),were statistically analyzed.Results A total of 868 adverse event reports related to lecanemab were collected,involving 1,986 instances of ADEs with 38 related ADE identified,the proportion of serious ADEs was 23.39％,and 87.15％of ADEs occurred in the first 3 months after the initiation of the drug.The top 30 PT signals in reported cases were headache,chills,fatigue,effusion type amyloid-related imaging abnormalities(ARIA-E),hemorrhage-type amyloid-related imaging abnormalities(ARIA-H),and so on.The top 30 signals in terms of signal intensity mainly included ARIA-E,ARIA-H,brain fog,infusion-related reactions.ADEs related to nervous system diseases were the most common.Fifteen new suspected or serious ADEs not recorded in the instructions were discovered,such as brain fog,formication,status epilepticus.Conclusion Risk assessment of patients'medication should be conducted before clinical use of lecanemab,especially in the first 3 months of the medication period,focus should be placed on monitoring common ADEs,such as ARIA-E,ARIA-H,infusion-related reactions.Attention also needs to be paid to the newly discovered suspected ADEs,to ensure the patients'medication safety.

Objective To observe the value of automated fiber quantification(AFQ)for analyzing relationships of abnormal white matter microstructures and executive dysfunction in children with attention deficit hyperactivity disorder(ADHD).Methods Brain diffusion tensor imaging(DTI)and white matter structure AFQ analysis were prospectively performed on 83 children with ADHD(ADHD group)and 52 healthy children(healthy control[HC]group).The axial diffusivity(AD),radial diffusivity(RD),mean diffusivity(MD),and fractional anisotropy(FA)of complete fiber bundles and respective segments were obtained and compared between groups.Partial correlation analysis was conducted of fiber bundle diffusion parameters and the scores of Swanson Nolan and Pelham-Ⅳ(SNAP-Ⅳ)and behavior rating inventory of executive function(BRIEF)in ADHD group.Receiver operating characteristic curves were applied to assess the efficacy of each diffusion parameter for evaluating ADHD.Results AD and MD of right anterior thalamic radiation(ATR),and AD of right cingulum bundle(CB)in ADHD group were all higher than those in HC group(FWE corrected,all P＜0.000 7).Significant differences of AD of the 54-78 segments of right ATR,MD of the 13-24 and 53-77 segments of right ATR,AD of the 24-26,53-56 and 93-97 segments of right CB,as well as MD of the 72-85 segments of left inferior longitudinal fasciculus(ILF)were found between groups(FWE corrected,all P＜0.001).In ADHD group,AD of 54-78 segments of right ATR were negatively correlated with the attention deficit scores,while of 24-26 segments of right CB were negatively correlated with the emotional control scores.MD of right ATR and some segments,AD of right CB and some segments in ADHD group were positively correlated with the scores of task initiation,planning,organization,monitoring and metacognitive index(all P＜0.05).The area under the curve(AUC)of segmental fiber bundle diffusion parameter and intact fiber bundle diffusion parameter for evaluating ADHD was 0.881 and 0.808,respectively,the former was higher than the latter(Z=2.435,P＜0.05).Conclusion AFQ could be used to analyze relationships of abnormal white matter microstructures and executive dysfunction in ADHD,which could be effectively evaluated based on specific fiber bundle segments.

[Objective] To explore the key factors affecting the efficiency and safety of hematopoietic stem cell apheresis. [Methods] The clinical data of 59 healthy donors who underwent allogeneic hematopoietic stem cell donation in the First Affiliated Hospital of Anhui Medical University from January 2021 to June 2024 were retrospectively analyzed. The number of CD34⁺ cells was used to evaluate the eligibility of stem cell collection. The effects of donor gender, age, patient weight, as well as the number of WBC, MNC, RBC, Hb, HCT, PLT, CD34⁺ cells, CD34⁺ percentage and instrument operating parameters on collection efficiency were analyzed. [Results] A total of 59 donors were enrolled, and 68 occasions of stem cell apheresis were performed, with a qualified collection rate of 56%. Donor gender, age, patient weight, total blood circulation volume, anticoagulant dosage, collection time, calcium gluconate dosage and RBC, Hb, HCT levels were not significantly correlated with the collection effect (P>0.05). Multivariate logistic regression analysis showed that the number of MNC cells, CD34⁺ cells and stem cell product volume were the key factors affecting the efficiency and safety. A total of 12 donors had mild adverse reactions during the collection process, and all of them were improved after treatment. [Conclusion] Optimizing apheresis strategy based on the three factors of MNC, WBC count and stem cell product volume on the day of collection will help to achieve high-quality collection and improve the success rate of transplantation.