Population pharmacokinetics is a research technique based on computer simulation and data analysis, and it has been employed to investigate the dynamic behavior of drug metabolism in different populations. This approach could address practical challenges such as prolonged clinical trial durations, high costs, and increased difficulty in traditional clinical trials. By comprehensively analyzing differences in the internal drug metabolism processes across populations with varying physiological and pathological conditions, population pharmacokinetics has emerged as an effective method to optimize drug development and clinical applications. This article provides a preliminary overview of the essence of population pharmacokinetics, its application in clinical trials, and potential future trends. We hope to serve as a reference and guidance for the application of new technologies and methods in clinical trials.

OBJECTIVE To analyze the metabolites of Zhideke granules and speculate its metabolic pathway in rats in vivo. METHODS Male SD rats were randomly divided into blank group and administration group （Zhideke granules， 9.45 g/kg）； they were given ultrapure water or relevant medicine， twice a day， every 6-8 h， for 3 consecutive days. Serum， urine and feces samples of rats were collected， and their metabolites were identified by UPLC-Q-Exactive-MS technique after intragastric administration of Zhideke granules； their metabolic pathways were speculated. RESULTS After intragastric administration of Zhideke granules， 16 prototype components （i.g. irisflorentin， baicalin， chlorogenic acid） and 11 metabolites （i.g. hydration products of kaempferol or luteolin， methylation products of chlorogenic acid， and hydroxylation products of baicalin） were identified in serum， urine and feces of rats. Among them， 8 prototype components and 4 metabolites were identified in serum samples； 10 prototype components and 7 metabolites were identified in urine samples； 8 prototype components and 5 metabolites were identified in the fecal samples. CONCLUSIONS The metabolites of Zhideke granules in rats mainly include baicalin， irisflorentin，chlorogenic acid， and the main metabolic pathways included methylation， hydroxylation， glucuronidation.

Background::Carotid intima-media thickness (IMT) and diameter, stiffness, and wave reflections, are independent and important clinical biomarkers and risk predictors for cardiovascular diseases. The purpose of the present study was to establish nationwide reference values of carotid properties for healthy Chinese adults and to explore potential clinical determinants.Methods::A total of 3053 healthy Han Chinese adults (1922 women) aged 18-79 years were enrolled at 28 collaborating tertiary centers throughout China between April 2021 and July 2022. The real-time tracking of common carotid artery walls was achieved by the radio frequency (RF) ultrasound system. The IMT, diameter, compliance coefficient, β stiffness, local pulse wave velocity (PWV), local systolic blood pressure, augmented pressure (AP), and augmentation index (AIx) were then automatically measured and reported. Data were stratified by age groups and sex. The relationships between age and carotid property parameters were analyzed by Jonckheere-Terpstra test and simple linear regressions. The major clinical determinants of carotid properties were identified by Pearson’s correlation, multiple linear regression, and analyses of covariance.Results::All the parameters of carotid properties demonstrated significantly age-related trajectories. Women showed thinner IMT, smaller carotid diameter, larger AP, and AIx than men. The β stiffness and PWV were significantly higher in men than women before forties, but the differences reversed after that. The increase rate of carotid IMT (5.5 μm/year in women and 5.8 μm/year in men) and diameter (0.03 mm/year in both men and women) were similar between men and women. For the stiffness and wave reflections, women showed significantly larger age-related variations than men as demonstrated by steeper regression slopes (all P for age by sex interaction <0.05). The blood pressures, body mass index (BMI), and triglyceride levels were identified as major clinical determinants of carotid properties with adjustment of age and sex. Conclusions::The age- and sex-specific reference values of carotid properties measured by RF ultrasound for healthy Chinese adults were established. The blood pressures, BMI, and triglyceride levels should be considered for clinical application of corresponding reference values.

OBJECTIVE To explore the effect of changing lifestyle diet in the treatment of laryngeal reflux disease(LRPD).METHODS A total of 92 patients with LRPD who received outpatient treatment in the Second Affiliated Hospital of Fujian Medical University from January 2022 to June 2023 were selected as the study control,divided into control group(46 cases)and treatment group(46 cases).The control group was treated with conventional acid suppression and gastric motogenic therapy.The treatment group was treated on the basis of the control group with giving guidance on lifestyle and diet.The changes of reflux symptom index scale(RSI)and reflux sign score scale(RFS)and the clinical efficacy of the two groups were compared 8 weeks and 12 weeks after treatment.RESULTS RSI total score was improved 8 weeks after treatment compared with before treatment in both RSI control group and treatment group(P＜0.05).The total RSI score of 12 weeks after treatment was improved compared with that of 8 weeks after treatment in both control and treatment groups(P＜0.05).The total RFS score at 8 weeks after treatment was improved in both control group and treatment group compared with before treatment(P＜0.05).Compared with 8 weeks after treatment,the total RFS score in both control group and treatment group was improved(P＜0.05).After 8 weeks of treatment,the total effective rate of the control group(60.9%)was compared with that of the treatment group(71.7%),and there was no significant difference between the two groups(χ2=1.335,P=0.513).After 12 weeks of treatment,the total effective rate of the control group(73.9%)was compared with the total effective rate of the treatment group(91.3%),and the difference between the two groups was statistically significant(χ2=6.226,P=0.044).CONCLUSION The change of lifestyle and diet should become an important part of the treatment of LRPD.By adjusting the unhealthy lifestyle and diet,the symptoms of patients can be significantly reduced and better clinical efficacy can be obtained.

Objective:To observe the application effect of mind mapping combined with interactive communication mode in clinical teaching of neurosurgery.Methods:A total of 40 students who practiced in the Department of Neurosurgery in the Affiliated Hospital of Guizhou Medical University from September 2019 to September 2020 were included in the control group, and traditional teaching was adopted; another 40 students who practiced from October 2020 to October 2021 were included in the observation group, and mind mapping combined with interactive communication mode was adopted for teaching. The two groups of students were taught for 2 weeks, and after the teaching, the teaching effect was compared between the two groups. SPSS 25.0 software was used to conduct t-test and Chi-square test. Results:After 2 weeks of teaching, the scores of theoretical knowledge (90.38±4.03) and practical operation skills (93.37±3.48) in the two groups were higher than those before teaching [(85.52±5.26) and (87.25±4.48)], with statistically significant differences ( t=4.63, 6.83, P<0.001). The case analysis score of the two groups was higher than that before teaching, and that of the observation group (86.03±6.07) was higher than that of the control group (79.13±5.57), with statistically significant differences ( t=5.30, P<0.001). The scores of interpersonal communication ability and cooperation ability of the two groups were higher than those before teaching. The scores of interpersonal communication ability (82.53±4.74), cooperation ability (169.73±7.55) of the observation group were higher than those of the control group [(77.93±4.45) and (158.42±8.01)], with statistically significant differences ( t=4.48, 6.49, P<0.001). Conclusion:Mind mapping combined with interactive communication mode can effectively improve the clinical basic knowledge and clinical practice ability of interns in the Department of Neurosurgery, and improve their communication and cooperation ability.

Objective:To investigate the clinical application value of coiled tube of femoral anterolateral flap in the repair of circumferential defect after resection of advanced hypopharyngeal carcinoma.Methods:Clinical data of 42 patients with advanced hypopharyngeal cancer admitted to the Second Affiliated Hospital of Fujian Medical University from January 2016 to April 2022 were retrospectively analyzed, including 41 males and 1 female, aged from 33 to 82 years old. All patients received surgical treatment, including total laryngectomy plus total laryngopharyngectomy in 20 cases, total laryngectomy, total laryngopharyngectomy and resection of partial tongue base in 8 cases, total laryngectomy, total laryngopharyngectomy and resection of cervical esophagus in 9 cases, total laryngectomy, total laryngopharyngectomy, and resection of partial tongue base and cervical esophagus in 5 cases. The postoperative circumferential defects were repaired with the coil tube of anterolateral femoral skin flap in phase Ⅰ, and the healing status of the flap, wound healing and swallowing function were observed. All cases were followed up.Results:The lengths of the hypopharyngeal defects were 7-18 cm and the sizes of the harvested flaps were 6 cm×9.5 cm-10 cm×20 cm. Flaps survived in 41 cases, flap necrosis occurred in one case, and the survival rate of flaps was 97.6%. One artery and one vein were anastomosed in 40 cases, and one artery and two veins were anastomosed in 2 cases. Postoperative cervical wound infection occurred in 5 cases, and pharyngeal fistula occurred in 2 cases. Three months of follow-up after surgery, 31 cases had normal diet, 9 cases presented with semi-liquid diet and 2 cases with liquid diet. Following up for 6-65 months, recurrence and metastasis occurred in 14 patients (33.3%), including primary site recurrence in 4 cases (9.5%), cervical lymph node recurrence in 6 cases (14.3%), and distant metastasis in 4 cases (9.5%). The 1-year and 3-year overall survival rates were respectively 79.4% and 60.5%.Conclusion:Coiled tube of femoral anterolateral flap is an ideal skin flap for repair of circumferential defects after resection of advanced hypopharyngeal carcinoma.

Objective:To summarize the clinical, pathological and muscle magnetic resonance imaging (MRI) features of human immunodeficiency virus (HIV)-associated nemaline myopathy (NM; HIV-NM).Methods:The present patient was a 23-year-old man with HIV infection who developed progressive proximal weakness and atrophy for more than 10 months. He was admitted to the Department of Neurology of Beijing Ditan Hospital in early June 2021. Electromyography showed myogenic findings. The serum creatine kinase was 202.4 U/L. CD 4+ count was 585×10 6/L. Serum monoclonal immunoglobulin (M protein) was negative. The patient underwent MRI examination of bilateral thigh muscles, biopsy of left biceps brachii and gene detection. The clinical, pathological and muscle MRI changes of HIV-NM were summarized based on the literature review. Results:MRI examination of bilateral thigh muscles showed edema changes. Muscle biopsy showed nemaline structures in some muscle fibers, accompanied by fiber atrophy and regeneration. No gene mutation related to clinical phenotype was found by second-generation sequencing. After intravenous immunoglobulin combined with prednisone, the patient′s weakness symptoms were significantly improved. A total of 17 cases of HIV-NM (including the present case) were identified in the literature, who were aged (33.7±9.1) years. Fifteen were males and two were females. All patients developed proximal limb weakness. Creatine kinase was normal or slightly elevated. Serum monoclonal protein was positive in 3 cases (3/7). Immunosuppressive therapy was effective.Conclusions:The main clinical characteristics of HIV-NM are progressive proximal limb weakness and muscle atrophy. The muscle pathology shows a large number of nemaline structures in atrophic muscle fibers. Muscle edema can be seen on muscle MRI. This is the first report of HIV-NM in China, which may be a special subtype of immune myopathy.

Objective To explore the association between lipid profiles and left ventricular hypertrophy in a Chinese general population. Methods We conducted a retrospective observational study to investigate the relationship between lipid markers [including triglycerides, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein (HDL) cholesterol, non-HDL-cholesterol, apolipoprotein A-I, apolipoprotein B, lipoprotein[a], and composite lipid profiles] and left ventricular hypertrophy. A total of 309,400 participants of two populations (one from Beijing and another from nationwide) who underwent physical examinations at different health management centers between 2009 and 2018 in China were included in the cross-sectional study. 7,475 participants who had multiple physical examinations and initially did not have left ventricular hypertrophy constituted a longitudinal cohort to analyze the association between lipid markers and the new-onset of left ventricular hypertrophy. Left ventricular hypertrophy was measured by echocardiography and defined as an end-diastolic thickness of the interventricular septum or left ventricle posterior wall > 11 mm. The Logistic regression model was used in the cross-sectional study. Cox model and Cox model with restricted cubic splines were used in the longitudinal cohort. Results In the cross-sectional study, for participants in the highest tertile of each lipid marker compared to the respective lowest, triglycerides [odds ratio (OR): 1.250, 95％CI: 1.060 to 1.474], HDL-cholesterol (OR: 0.780, 95％CI: 0.662 to 0.918), and lipoprotein(a) (OR: 1.311, 95％CI: 1.115 to 1.541) had an association with left ventricular hypertrophy. In the longitudinal cohort, for participants in the highest tertile of each lipid marker at the baseline compared to the respective lowest, triglycerides [hazard ratio (HR): 3.277, 95％CI: 1.720 to 6.244], HDL-cholesterol (HR: 0.516, 95％CI: 0.283 to 0.940), non-HDL-cholesterol (HR: 2.309, 95％CI: 1.296 to 4.112), apolipoprotein B (HR: 2.244, 95％CI: 1.251 to 4.032) showed an association with new-onset left ventricular hypertrophy. In the Cox model with forward stepwise selection, triglycerides were the only lipid markers entered into the final model. Conclusion Lipids levels, especially triglycerides, are associated with left ventricular hypertrophy. Controlling triglycerides level potentiate to be a strategy in harnessing cardiac remodeling but deserve to be further investigated.

Objective    To compare the clinical effects of segmentectomy and lobectomy for ≤2 cm lung adenocarcinoma with micropapillary and solid subtype negative by intraoperative frozen sections. Methods    The patients with adenocarcinoma who received segmentectomy or lobectomy in multicenter from June 2020 to March 2021 were included. They were divided into two groups according to a random number table, including a segmentectomy group (n=119, 44 males and 75 females with an average age of 56.6±8.9 years) and a lobectomy group (n=115, 43 males and 72 females with an average of 56.2±9.5 years). The clinical data of the patients were analyzed. Results    There was no significant difference in the baseline data between the two groups (P>0.05). No perioperative death was found. There was no statistical difference in the operation time (111.2±30.0 min vs. 107.3±34.3 min), blood loss (54.2±83.5 mL vs. 40.0±16.4 mL), drainage duration (2.8±0.6 d vs. 2.6±0.6 d), hospital stay time (3.9±2.3 d vs. 3.7±1.1 d) or pathology staging (P>0.05) between the two groups. The postoperative pulmonary function analysis revealed that the mean decreased values of forced vital capacity and forced expiratory volume in one second percent predicted in the segmentectomy group were significantly better than those in the lobectomy group (0.2±0.3 L vs. 0.4±0.3 L, P=0.005; 0.3%±8.1% vs. 2.9%±7.4%, P=0.041). Conclusion    Segmentectomy is effective in protecting lungs function, which is expected to improve life quality of patients.

Objective:To investigate the clinical characteristics and prognosis of cytomegalovirus (CMV) reactivation in patients with liver failure.Methods:A total of 75 patients diagnosed with liver failure and tested for serum CMV DNA between January 2016 and June 2019 in Huashan Hospital, Fudan University were retrospectively analyzed. According to the CMV DNA test results, the patients were divided into CMV DNA positive group and CMV DNA negative group. The classification of liver failure, the use of glucocorticoids, the proportions of T lymphocyte subsets of the two groups were compared and the prognosis was evaluated. Mann-Whitney U test and chi-square test were used to analyze the data. Results:Of the 75 patients with liver failure, 17 were CMV DNA positive and 58 were CMV DNA negative. Among the 17 CMV DNA positive patients, nine were acute (subacute) liver failure, and 13 were treated with glucocorticoids, which were all significantly higher than those in the CMV negative group (20.7%(12/58) and 20.7%(12/58), respectively). The differences were both statistically significant ( χ2=6.70 and 18.40, respectively, both P<0.05). The proportions of CD3 + T lymphocytes and CD8 + T lymphocytes in the CMV DNA positive group were both higher than those in the CMV DNA negative group, and the proportions of CD4 + T lymphocytes, the ratio of CD4 + /CD8 + T lymphocytes and the proportion of B lymphocytes were all lower than those in the CMV DNA negative group. The differences were all statistically significant ( U=274.50, 165.50, 273.00, 185.00 and 189.00, respectively, all P<0.05). Acute (subacute) liver failure (odds ratio ( OR)=4.3, 95% confidence interval ( CI) 1.3-12.6) and glucocorticoid use ( OR=12.5, 95% CI 3.4-38.3) were risk factors for CMV reactivation in patients with liver failure. The disease improvement rate in the CMV DNA negative group was 56.9% (33/58), and five out of 17 patients improved in the CMV DNA positive group, with a statistically significant difference ( χ2=1.99, P=0.04). Conclusions:The use of glucocorticoids increases the risk of CMV reactivation in patients with liver failure, and CMV reactivation in patients with liver failure presents immune disorders which seriously affect their prognosis. Therefore, it is important to pay attention to CMV DNA monitoring in patients with liver failure using glucocorticoids.