Epidermal growth factor receptor-tyrosine kinase inhibitor （EGFR-TKI） represent a class of small-molecule targeted therapeutics for oncology treatment， and serve as first-line therapy for advanced non-small cell lung cancer （NSCLC） with EGFR- sensitive mutations， with representative agents including gefitinib， dacomitinib， and osimertinib. In clinical practice， dose adjustment of EGFR-TKI may be required for cancer patients under special circumstances such as drug combinations or hepatic/ renal impairment. Physiologically-based pharmacokinetic （PBPK） model， capable of predicting pharmacokinetic （PK） processes in humans， has emerged as a vital tool for clinical dose optimization. This article sorts the modeling methodologies， workflows， and commonly used software tools for PBPK model， and summarizes the current applications of PBPK model in EGFR-TKI precision therapy as of June 30， 2024. Findings demonstrate that PBPK modeling methods commonly employ the “bottom-up” approach and the middle-out approach. The process typically involves four steps： parameter collection， compartment selection， model validation， and model application. Commonly used software for modeling includes Simcyp， GastroPlus， and open-source software such as PK- Sim. PBPK model can be utilized for predicting drug-drug interactions of EGFR-TKI co-administered with metabolic enzyme inducers or inhibitors， acid-suppressive drugs， or traditional Chinese and Western medicines. It can also adjust dosages in conjunction with genomics， predict PK processes in special populations （such as patients with liver or kidney dysfunction， pediatric patients）， evaluate the efficacy and safety of drugs， and extrapolate PK predictions from animal models to humans.

Background Atherosclerotic cardiovascular disease (ASCVD) is a major contributor to the global burden of cardiovascular diseases. However, evidence from meta-analyses on the association between ambient ozone exposure and ASCVD risk remains relatively insufficient. Objective To explore the epidemiological association between ambient ozone exposure and ASCVD, providing scientific evidence for ASCVD prevention and control from the perspective of environmental risk factor management. Methods We systematically searched PubMed, Web of Science, Embase, the Cochrane Library, CNKI, Wanfang Database, CBM, and VIP for published epidemiological studies on the relationship between ambient ozone exposure and ASCVD from January 2007 to December 2023. We performed quality assessment and data extraction of the included studies, and utilized meta-analysis to evaluate the effects of short-term and long-term ozone exposure on different ASCVD outcomes, including mortality and incidence of ischemic heart disease (IHD) and ischemic stroke (IS). Results A total of 24 studies were included based on a set of predetermined eligibility criteria. The meta-analysis results indicated that short-term ozone exposure was associated with an increased risk of ASCVD mortality and incidence. Specifically, short-term ozone exposure was significantly associated with an elevated risk of IHD mortality (combined RR=1.011, 95%CI: 1.008, 1.015; P < 0.05). Additionally, short-term ozone exposure was significantly linked to increased IS mortality (combined RR=1.005, 95%CI: 1.003, 1.008; P < 0.05) and incidence (combined RR=1.015, 95%CI: 1.003, 1.027; P < 0.05). Conclusion Short-term exposure to ambient ozone significantly elevates acute cardiovascular disease risk. However, the epidemiological association between long-term ozone exposure and ASCVD remains inconclusive. Future high-quality cohort studies with refined exposure assessment methods are warranted to elucidate the chronic cardiovascular effects of ozone exposure.

Volatile organic compounds (VOCs) and semi-volatile organic compounds (SVOCs) are common organic compounds in indoor and outdoor air, and enter the human body primarily through the respiratory tract and directly damage the respiratory system. Previous studies have suggested that exposure to VOCs/SVOCs may associate with the prevalence, incidence, and progression of asthma, but the extent of the associations is still vague. Furthermore, biomarkers for efficient and simple asthma diagnosis, typing, and attack prediction remain unclear at this stage. From the perspective of the collection and detection methods of VOCs/SVOCs, this paper summarized the epidemiological associations and underlying biological mechanisms between VOCs/SVOCs exposure and the prevalence, incidence, and progression of asthma in children/adults. It also demonstrated the application of VOCs/SVOCs in recent years in assisting asthma diagnosis, such as distinguishing asthma patients from the healthy population, differentiating different asthma phenotypes, and predicting asthma acute exacerbations, aiming to provide a scientific basis for improving current asthma management.

OBJECTIVE To investigate the effects of CYP3A5 gene polymorphism and Wuzhi capsule （WZ） on early postoperative tacrolimus exposure and adverse reactions in renal transplant patients. METHODS A total of 132 patients who underwent renal transplantation and received tacrolimus + mycophenolic acids + prednisone after operation in our hospital from September 2021 to September 2023 were selected and divided into four groups according to genotypes （CYP3A5*1 or CYP3A5*3/*3） and with or without WZ （“ +WZ” meant drug combination， “ +NO WZ” meant without combination）. The blood trough concentration/daily dose （c0/D） values of the four groups were analyzed on the 14th day， 1 month and 3 months after renal transplantation. The incidence of acute rejection and the incidence of tacrolimus-related adverse reactions within 3 months after transplantation were compared among 4 groups. RESULTS On the 14th day， 1 month and 3 months after surgery （except for the CYP3A5*1+WZ group）， c0/D values of CYP3A5*1 genotype patients were significantly lower than those of CYP3A5*3/*3 genotype patients regardless of whether they were treated with WZ additionally （P＜0.05）. Within 3 months after surgery， although there was no significant difference in the incidence of acute rejection and tacrolimus-related adverse reactions among the four groups （P＞ 0.05）， the incidence of hyperglycemia in patients with CYP3A5*3/*3 was higher （41.67%）. CONCLUSIONS CYP3A5 gene polymorphism is significantly related to tacrolimus c0/D in kidney transplant patients. Under the premise of c0 monitoring of tacrolimus， patients with CYP3A5*1 genotype should be given WZ as soon as possible after surgery to accelerate tacrolimus to reach the therapeutic concentration range， while CYP3A5*3/*3 genotype is not recommended to be given WZ because of the higher risk of hyperglycemia.

Objective To explore the impact of pH value of the reaction system on the properties of bovine hemoglobin modified with aldehydeated polyethylene glycol(PEG-bHb).Methods PEG-bHb conjugates were synthesized under varying pH conditions(6.0,6.5,7.4 and 8.0)of the reaction system while consistent molar ratios,temperature,and reaction time were maintained.The structural and functional attributes of PEG-bHb were characterized.Results The proportion of methemoglobin decreased with an increase in pH.In a weakly acidic reaction environment,the PEG-bHb was found to be relatively highly modified.At pH 6.5,the average number of PEG chains attached to the bHb surface was 6.86±0.38.Selective PEG modification of the N-terminal α-NH2 groups was more pronounced under weakly acidic conditions.Specifically,at pH 6.5,the modification efficiency of the N-terminal α-NH2 groups of bHb by aldehyde-activated PEG reached 95.4％for the α-chains and 99.3％for the β-chains.The PEG modification influenced the heme region microenvi-ronment of bHb,with minimal structural impact observed at pH 6.5.After modification,the oxygen affinity of PEG-bHb was enhanced,the Hill coefficient was reduced,and there were significant increases in colloid osmotic pressure,viscosity,and particle size,all of which differed markedly from the unmodified bHb group(P＜0.001).Conclusion The synthesis of PEG-bHb under weakly acidic conditions can result in a high degree of selective modification of the N-terminal α-NH2 groups and an overall high degree of modification.

Effective referral management of health and clinical services in maternal and child health hospitals plays an important role in enhancing patients′ medical experience, improving the efficiency and quality of maternal and child health services. A tertiary grade A maternal and child health hospital has carried out a practice of health and clinical service referral management based on information technology construction. A referral information module embedded in the hospital information system has been designed and constructed, and started to be applied in outpatient clinics in July 2021. At the same time, corresponding system and process construction, as well as quality control management and continuous improvement, have been carried out. The outpatient referral rate from July to December 2021 was 2.8% (11 466/412 808), from January to June 2022 it was 5.6% (22 705/402 586), from July to December 2022 it was 5.5% (22 233/402 959), and from January to June 2023 it was 6.7% (23 373/347 898). The referral rate has continued to improve and can provide reference for the referral management of other maternal and child health institutions.

Objective:To investigate personal exposures to nitrogen oxides(NOX)and nitrogen di-oxide(NO2)and the influence of baseline personal characteristics,living environment and daily activity patterns of the participants on the exposures among adults over 35 in Tianjin and Shanghai.Methods:In this panel study,91 healthy nonsmoking adults aged over 35 from Tianjin and Shanghai participated in our study.The study was conducted in summer and winter.The participants were followed for three times with an interval of at least two weeks.Only participants in Shanghai were followed once in winter because of the COVID-19 pandemic.Twenty-seven participants completed follow-up visits in both seasons.We measured their 24 h personal exposures to NOX and NO2and collected their baseline and time-activity in-formation through questionnaire/diary.The linear mixed model was used to analyze the associations be-tween potential influencing factors and personal NOX and NO2 exposure levels.Results:There were 349 follow-up visits with valid 24 h personal NO2 and NOX exposure measurements in the two cities.The ave-rage 24 h personal exposures to NO2 and NOX(volume fraction)in Tianjin participants were 18.0 x 10-9 and 26.2 × 10-9 in summer,and 31.0 x 10-9 and 54.9 x 10-9in winter,respectively;and the average 24 h personal exposures to NO2 and NOX in Shanghai participants were 38.7 x 10-9and 100.0x10-9in summer,and 45.5 x10-9 and 139.2 x 10-9 in winter,respectively.The results of univariate regression analysis showed that their personal NOX exposure levels were significantly associated with city,season,gender,average daily cooking times,and ambient NO2 concentrations measured at fixed-site monitoring stations.In addition to the above factors,the personal NOX exposure levels were also significantly associ-ated with educational level and the personal NO2 exposure levels were also significantly associated with passive smoking,average daily home time,cooking energy type,residential distance from main traffic road,and use of kitchen ventilators.Multivariate regression analysis showed that the personal exposure levels of NO2 and NOX were significantly lower in Tianjin than that in Shanghai,were significantly lower in summer than that in winter,and were significantly and positively associated with ambient NO2 concen-trations measured at fixed-site monitoring stations.In addition,personal NOX exposure levels were signifi-cantly lower in females than in males,and personal NO2 exposure levels were significantly positively asso-ciated with average daily cooking times and significantly inversely associated with average daily home time.For every interquartile range(IQR)increase(12.7 × 10-9)in ambient NO2,the personal NO2 exposure levels increased by 27.5％(95％CI:17.0％-38.9％),and personal NOX exposure levels in-creased by 16.1％(95％CI:7.1％-25.8％).Conclusion:Season,city and ambient NO2 concentra-tions are significant influencing factors of personal exposure levels of NO2and NOX At the same time,the personal exposures levels of NO2 are also affected by lifestyle factors.Our study provides scientific evi-dence for making precise air pollution control decisions and reducing the exposure levels of NOX in the population.

Objective:To assess the impact of exposure to particulate matter with aerodynamic diameter ≤2.5 μm(PM2.5)on non-accidental mortality under different apparent temperature levels and to further explore the modification effect of apparent temperature.Methods:This study used time-series design.Tianjin and Ningbo from China,Bangkok and Chiang Mai from Thailand were selected as the re-search sites,and the apparent temperature was applied as the exposure index.Through the quantitative estimation of the threshold temperature,the corresponding pollutant concentration was divided into high and low levels,and the generalized Poisson additive model was used to evaluate the association between PM2.5 exposure and non-accidental death of residents at different temperature levels.Results:The ave-rage concentrations of PM2.5 in Tianjin,Ningbo,Bangkok,and Chiang Mai during the study period were(73.6±35.6),(48.0±32.1),(33.5±28.4)and(32.6±28.6)μg/m3,respectively;the average daily non-accidental death counts were 148,57,28,and 8.The analysis of the generalized Poisson addi-tive model showed that the daily non-accidental death counts increased by 0.43％(95％CI:0.33％-0.54％)per 10 μg/m3 increase of PM2.5 in lag 0 day in Tianjin of China;0.27％(95％CI:0.08％-0.46％)per 10 μg/m3 increase of PM2.5 in lag 2 days in Ningbo of China.The effect was magnified in high temperature levels in Tianjin and in low temperatures in Ningbo and Bangkok.The mortality effect of PM2 5 in various temperature levels stayed still in co-pollutant regression models.Conclusion:Exposure to fine particulate matter had an adverse effect on non-accidental mortality,which reminded us to give further attention to the pollution control.The findings also indicated that apparent temperature might modify mortality effects of PM2 .5 and the modification effect varied in different regions.Protective policies due to regional differences should be made and more scientific and social attention on mutual effect of air pollution and climate change needs to be appealed.

Objective:To discuss the effect of the force feedback perceptual rehabilitation training on finger motor function of the patients with finger motor dysfunction after stroke,and to provide the basis for the clinical application and promotion of the force feedback perceptual rehabilitation training.Methods:A total of 86 patients with hand dysfunction after stroke were randomly divided into experimental group(n=43)and control group(n=43),and 3 cases in each group fell off from the experiment,and 80 cases were ultimately completed.On this basis,the patients in two groups received the conventional rehabilitation training for 40 min.The patients in control group received the conventional hand function training for 20 min,while the patients in experimental group received the force feedback perception rehabilitation training for 20 min,once per day,5 days per week,for a total of 6 weeks.The hand function recovery of the patients were evaluated before and after treatment by Action Research Arm Test(ARAT),grip strength,modified Ashworth scale(MAS),total active motion(TAM),Fugl-Meyer motor function assessment-upper limb(FMA-UL)finger motor part score,and Barthel index(BI).Results:Before treatment,there were no statistically significant differences in ARAT total score,grip strength,MAS grade,TAM,FMA-UL finger motor part score,and BI score of the patients between two groups(P＞0.05).After treated for 6 weeks,the ARAT scores,grip strengths,TAM,FMA-UL finger motor part scores,and BI scores of the patients in two groups were all increased than those before treatment(P＜0.05),while the MAS grades of the patients had no significant differences(P＞0.05).After treated for 6 weeks,compared with control group,the grasp score and grip score in ARAT score,and the difference of total ARAT score of the patients in experimental group were increased(P＜0.05),the TAM after treatment and the differences of grip strength,TAM,and FMA-UL finger motor part score of the patients before and after treatment were increased(P＜0.05),while the pinch scores and gross movement scores in ARAT score,MAS grades,and the differences of BI score before and after treatment had no significant differences(P＞0.05).Conclusion:Force feedback perceptual rehabilitation training is helpful in improving the finger motor function of the patients with finger motor dysfunction after stroke.

Glaucoma is the leading cause of irreversible blindness worldwide. The coverage rate and treatment outcome of glaucoma surgery are crucial for the prevention and treatment of glaucoma-related visual function impairment. This article analyzes the problems and challenges for glaucoma microsurgery training in China and introduces the current status of glaucoma surgery training in China and globally, and based on the experience of cataract surgery training platform in Eye Hospital of Wenzhou Medical University, this article also elaborates on the feasibility of constructing a structured hierarchical comprehensive training system for glaucoma microsurgery, including multimedia theoretical training, Dry-lab, surgical simulator, and a combination of Wet-lab laboratory microsurgery practice and clinical practice, in order to provide a reference for the training of glaucoma sturgeons in China.