Objective To develop an ultra-performance liquid chromatography-mass spectrometry(UPLC-MS/MS)method for the simultaneous quantification of dolutegravir,raltegravir,efavirenz,lamivudine and tenofovir in human plasma and to apply it to the therapeutic monitoring.Methods Dolutegravir-D5,raltegravir-D4,efavirenz-D5,lamivudine-13 C-15 N2 and tenofovir-D7 were used as internal standard,respectively.All samples were extracted using the protein precipitation method with acetonitrile and then diluted for analysis.Chromatographic separation was performed on Shim-pack XR-ODS Ⅲ(2.0 mmx50 mm,1.6 μm)column.Mobile phases A and B consisted of 0.1％formic acid in water and acetonitrile respectively.A programmed mobile phase gradient was used at a flow rate of 0.3 mL·min-1 and column temperature of 40 ℃.The tandem mass spectrometer was equipped with an electrospray ionization(ESI)source operating in multiple reaction monitoring(MRM)modes.After methodological validation,it can be used for therapeutic drug monitoring in HIV patients.Results There was good linearity in the validated concentration ranges of 62.5-3 000 ng·mL-1 for dolutegravir,10-500 ng·mL-1 for raltegravir,125-6 000 ng·mL-1for efavirenz,10-500 ng·mL-1 for lamivudine and 10-500 ng·mL-1 for tenofovir with the linear correlation coeffificients of determination(R2)of all higher than 0.998.The accuracy of both intra-day and inter-day studies ranged from 94.0％-109.3％,and the relative standard deviations were less than 7％.The IS-normalized matrix factor and extraction recoveries of all analytes were 95.7％-106.0％and 98.7％-104.5％at all concentrations.All analytes were stable in plasma at a certain storage environment.The trough blood concentrations of dolutegravir,efavirenz,lamivudine and tenofovir were 107.7-2 366.0,740.0-3 410.0,38.5-1 229.3,31.6-224.4ng·mL-1 in HIV patients,respectively.Conclusion The method is highly aceurate,easy to perform,low-cost,and suitable for therapeutic drug monitoring of dolutegravir,raltegravir,efavirenz,lamivudine and tenofovir in HIV patients.

The timely treatment of dental caries and pulp disease in primary teeth holds significant importance for maintaining children's oral health. Direct pulp capping (DPC) is a vital pulp treatment that involves covering the exposed pulp with bioactive materials to promote dentin bridge formation. DPC is commonly used in primary teeth with vital pulp and mechanical pulp exposure not exceeding 1 mm. DPC offers advantages such as minimal invasiveness, comfort, simplicity of operation and short chair-side time, making it suitable for pediatric dental clinical practice. Early studies suggested negative treatment outcomes for DPC in primary teeth with carious pulp exposure. Over the years, there have been advancements in materials and technology demonstrating positive outcomes in the clinical research of primary teeth with deep caries. However, due to the limited quality of related studies, DPC has not been widely recommended for the treatment of primary teeth with carious pulp exposure, and its widespread use needs further support by more high-quality evidence-based medical research. The success rate of DPC in primary teeth is influenced by factors including pulp status, clinical operations (such as isolation and caries removal), pulp capping material, cavity type, tooth position, coronal sealing, and dental fear. In clinical operation, dentists should accurately assess pulp status and minimize bacterial contamination. Mineral trioxide aggregate (MTA) is a DPC agent with relatively sufficient evidence and good therapeutic effects, and the crown should be tightly sealed after pulp capping. Additionally, the effects of novel biocompatible materials such as iRoot BP Plus used in DPC of primary teeth, and the influence of other factors like hemostatic methods on the prognosis of affected teeth, need further exploration.

OBJECTIVE To study the improvement effects of arbutin on myocardial fibrosis （MF） model rats and its mechanism. METHODS The network pharmacology was used to predict the potential target of arbutin in improving MF and molecular docking was used to validated. Totally 50 SD rats were given isoprenaline subcutaneously （5 mg/kg， once a day， for 14 consecutive days） to induce the MF model. Modeled rats were randomly divided into model group， captopril group （9 mg/kg）， arbutin low-dose， medium-dose and high-dose groups （50， 100， 200 mg/kg）， with 10 rats in each group. Another 10 healthy rats were included as normal group. Each group was given the corresponding drugs， once a day， for 28 consecutive days. Twenty-four hours after the final administration， electrocardiograms and heart-related indexes [heart weight index （HWI）， left ventricular weight index （LVWI）] of rats were detected； the levels of creatine kinase （CK）， lactate dehydrogenase （LDH）， N-terminal pro-brain natriuretic peptide （NT-proBNP） and type Ⅰ collagen （Col Ⅰ） and Col Ⅲ were detected in myocardial tissue of rats； the pathological changes of myocardial tissue were observed， and protein and mRNA expressions of adenosine deaminase （ADA） and adenosine kinase （ADK） were detected in the myocardial tissue of rats. RESULTS The results of network pharmacology showed that the main targets of arbutin improving MF were ADA and ADK. The results of molecular docking showed that arbutin bind stably with ADA and ADK. The results of experimental verification showed that compared with model group， the amplitude of ST and T waves in electrocardiogram were improved in administration groups， and the symptoms of atrial flutter were alleviated； HWI （except for arbutin medium-dose group）， LVWI， the levels of CK， LDH， NT-proBNP， Col Ⅰ and Col Ⅲ in the myocardial tissue of rats were decreased significantly （P＜0.05）； the degree of myocardial fibrosis in rats decreased； protein and mRNA expressions of ADA and ADK in the myocardial tissue were significantly increased （P＜0.05）. CONCLUSIONS Arbutin can improve cardiac fibrosis and cardiac function of MF model rats， the mechanism of which may be associated with up-regulating protein and mRNA expressions of ADA and ADK，influencing the nucleotide metabolism and collagen generation. zhangminghao@hactcm.edu.cn

Objective To analyze micronutrient levels in three types of female patients with diffuse hair loss.Methods The clinical data of 299 female patients with diffuse alopecia from January 2018 to June 2021 in the Department of Dermatology of Daping Hospital were analyzed retrospectively.Results The level of serum 25-hydroxyvitamin D in patients with diffuse alopecia was significantly lower than that in the control group,and had no impact to the type of diffuse alopecia.The concentration of serum zinc in patients with diffuse alopecia areata was also significantly lower than that in the control group.When ferritin≤50 ng/mol was taken as the threshold of iron deficiency and 25-hydroxyvitamin D≤20 ng/mol,as the indicator level of serum 25-hydroxyvitamin D deficiency,the proportion of serum 25-hydroxyvitamin D and serum ferritin deficiency in all the three types of diffuse hair loss patients was higher than that in the control group(P＜0.05).So,lack of iron and serum 25-hydroxyvitamin D were belived to be related to the occurrence of diffuse alopecia of women.Conclusions Iron metabolism disorder and se-rum 25-hydroxyvitamin D level play a key role in female diffuse alopecia,while the effects of copper and zinc on hair growth and hair loss cycle are not well identified yet.

Objective:To compare the application effect of domestic and imported intravenous radiofrequency closure system in the treatment of primary varicose veins of lower extremities.Methods:This single-center prospective, non-inferiority randomized controlled trial was performed in the Department of Vascular Surgery, the Fourth Affiliated Hospital, Zhejiang University School of Medicine from January 2021 to January 2022. Patients with primary varicose veins of lower extremities who met the ataxation criteria were randomly assigned to the experimental group(domestic novel venous radiofrequency closure system) or the control group(imported venous radiofrequency closure system) in a ratio of 1∶1. The two groups of subjects were compared in terms of target vein closure rate, technical success rate, system operation performance, incidence of adverse events and incidence of serious adverse events(SAE) within 6 months after surgery. Quantitative data were compared by Mann-Whitney U test, and categorical data were compared by χ2 test and non-inferiority test. Results:A total of 80 subjects were included in the trial (41 in the experimental group and 39 in the control group), including 27 males and 53 females, aged ( M(IQR)) 55(23) years (range:40 to 78 years). There were 48 cases of left lower limb and 32 cases of right lower limb. The technical success rate and system control performance between the groups were 100%.The incidence of adverse events (58.5% (24/41) vs. 61.5% (24/39), χ2=0.075, P=0.784), and the incidence of SAE (7.3% (3/41) vs. 5.1% (2/39), χ2=0.163, P=0.686) within 6 months after surgery in experimental group and control group had no statistical significance. There was one device-related adverse event in each of the two groups. In the experimental group, one patient developed endovenous heat-induced thrombosis after surgery and recovered after taking rivaroxaban tablets. One patient in the control group had pain in the upper right thigh for more than 1 day after operation, which was cured after using analgesic cream. No device-related SAE occurred. The venous closure rate of the experimental group was 100% (38/38) at 6 months after surgery, and that of the control group was 97.4% (37/38). The difference between the two groups was 2.63% (95% CI:-3.19 to 8.45, Z=4.865, P<0.01), and the 95% CI lower limit of the difference in target venous closure rate between two groups was greater than the non-inferiority threshold of -10.00%. Conclusion:The early application effect of the new domestic intravenous radiofrequency closure system in patients with primary varicose veins of lower extremities is in line with expectations, it is not inferior to the imported system.

Objective: To compare the effectiveness of qualitative and quantitative fecal immunochemical tests (FIT) in identifying colorectal cancer, so as to provide insights into perfecting screening strategies for colorectal cancer. Methods: Participants in the Colorectal Cancer Screening Program for Key Populations in Zhejiang Province from May 2020 to December 2021 were recruited, and their demographic information, lifestyle and disease history were collected through a questionnaire survey. Qualitative or quantitative FIT along with a questionnaire-based risk assessment were employed as the initial screening tests. Individuals who were positive in any FIT or had high-risk assessment results were required to attend a subsequent colonoscopy examination. The positive rate, detection rate of colorectal cancer, positive predictive value and number of colonoscopies required were compared between qualitative and quantitative FITs, and stratified analyses by gender and age were conducted. Results: Totally 4 099 769 participants were included. The qualitative FIT group included 3 574 917 individuals, yielding a positive rate of 11.35%, a detection rate of 1.19%, a positive predictive value of 0.48% and 83.84 colonoscopies required to detect one cancer case. The quantitative FIT group involved 524 852 individuals, yielding a positive rate of 6.70%, a detection rate of 2.31%, a positive predictive value of 1.01% and 43.23 colonoscopies required to detect one cancer case. The quantitative FIT group showed significantly higher detection rate of colorectal cancer, higher positive predictive value and less number of colonoscopies required compared to the qualitative FIT group (all P<0.05). The same results were obtained after stratification by gender and age. Conclusion Compared to qualitative FIT, quantitative FIT improves the detection of colorectal cancer and reduces the workload of colonoscopy examinations, making it more suitable for colorectal cancer screening in large-scale populations.

Small for gestational age (SGA) infants are more likely to experience neurocognitive impairments compared to appropriate for gestational age (AGA) infants. This paper reviews recent research on the neurocognitive development of SGA children. SGA can lead to a "brain-sparing effect" due to growth restriction, which may affect cerebral blood flow and brain structure. However, this does not guarantee normal brain development. Restrictive blood flow can result in changes in brain structure, such as reduced total white matter and gray matter volume in various brain regions, including the cerebral cortex, hippocampus and cerebellum, ultimately leading to decreased head circumference. SGA children also exhibit lower scores in all neurocognitive domains, including intelligence, attention, memory, and executive function. This may result in poor academic performance and an increased risk of social, behavioral, and neurological problems, such as cerebral palsy, epilepsy, visual and hearing impairments, as well as comorbidities like attention deficit hyperactivity disorder(ADHD), autism spectrum disorder(ASD), anxiety, depression, and schizophrenia. Several risk factors for SGA-related neurocognitive impairments have been identified, including gestational hypertension, abnormal gestational weight, smoking, and catch-up growth. Studies have shown that the best interventions to improve cognitive dysplasia include nutrient supplementation, continued breastfeeding, high-quality education, and appropriate early intervention (responsive parenting) are effective in improving cognitive outcomes for SGA children.

The timely treatment of dental caries and pulp disease in primary teeth holds significant importance for maintaining children's oral health.Direct pulp capping(DPC)is a vital pulp treatment that involves covering the ex-posed pulp with bioactive materials to promote dentin bridge formation.DPC is commonly used in primary teeth with vi-tal pulp and mechanical pulp exposure not exceeding 1 mm.DPC offers advantages such as minimal invasiveness,com-fort,simplicity of operation and short chair-side time,making it suitable for pediatric dental clinical practice.Early stud-ies suggested negative treatment outcomes for DPC in primary teeth with carious pulp exposure.Over the years,there have been advancements in materials and technology demonstrating positive outcomes in the clinical research of prima-ry teeth with deep caries.However,due to the limited quality of related studies,DPC has not been widely recommended for the treatment of primary teeth with carious pulp exposure,and its widespread use needs further support by more high-quality evidence-based medical research.The success rate of DPC in primary teeth is influenced by factors including pulp status,clinical operations(such as isolation and caries removal),pulp capping material,cavity type,tooth position,coronal sealing,and dental fear.In clinical operation,dentists should accurately assess pulp status and minimize bacte-rial contamination.Mineral trioxide aggregate(MTA)is a DPC agent with relatively sufficient evidence and good thera-peutic effects,and the crown should be tightly sealed after pulp capping.Additionally,the effects of novel biocompati-ble materials such as iRoot BP Plus used in DPC of primary teeth,and the influence of other factors like hemostatic methods on the prognosis of affected teeth,need further exploration.

The operating room was the core department of a hospital,and its operational efficiency had a significant impact on the high-quality development of a hospital.An analysis has revealed that low efficiency and irrational allocation in the operating room were mainly due to the lack of operational regulations and norms,the unreasonable arrangement of surgical specialties,and the unbalanced allocation of supporting resources.To address these issues,the First Affiliated Hospital of Zhengzhou University has taken into account the overall allocation of resources for the central operating room and the central operating room,and formulated strategies to improve operational efficiency,including adjusting the operational mechanism,optimizing the structure of surgical specialties,and providing corresponding supporting resources.Based on the adjustment of surgical structure,the implementation effect of the program was measured and evaluated,which provided practical strategies for optimizing operating room efficiency in hospitals.

The increasing operating pressure of large public hospitals has forced hospitals to focus on opening up income sources and reducing expenditure.The purchase and maintenance of medical equipment is one of the important economic activities of hospi-tals.However,there are problems in large public hospitals,such as the argumentation for equipment acquisition ignoring evaluation of operational efficiency,the costing model that leads to a lack of willingness of departments to purchase equipment,and the lack of standard processes and systems for renting medical equipment among departments.Based on this,it explores the establishment of a medical equipment sharing operation mechanism in large public hospitals,promotes the improvement of the efficiency of medical equipment use in large public hospitals by establishing a medical equipment sharing center,standardizing the purchase of shared equipment,entering shared equipment information,setting up shared equipment leasing specifications,and clarifying the equipment return process and maintenance,so as to effectively control hospital operating costs,and help the high-quality development of public hospitals.