Prescription optimization is a crucial aspect in the study of traditional Chinese medicine （TCM） compounds. In recent years， the introduction of mathematical methods， data mining techniques， and artificial neural networks has provided new tools for elucidating the compatibility rules of TCM compounds. The study of TCM compounds involves numerous variables， including the proportions of different herbs， the specific extraction parts of each ingredient， and the interactions among multiple components. These factors together create a complex nonlinear dose-effect relationship. In this context， it is essential to identify methods that suit the characteristics of TCM compounds and can leverage their advantages for effective application in new drug development. This paper provided a comprehensive review of the cutting-edge optimization experimental design methods applied in recent studies of TCM compound compatibilities. The key technical issues， such as the optimization of source material selection， dosage optimization of compatible herbs， and multi-objective optimization indicators， were discussed. Furthermore， the evaluation methods for component effects were summarized during the optimization process， so as to provide scientific and practical foundations for innovative research in TCM and the development of new drugs based on TCM compounds.

Background Although current evidence suggests a link between outdoor air pollution and depressive symptoms, the effect of solid fuel use (a significant indoor air pollutant) on depressive symptoms in China's rural middle-aged and elderly population remains poorly understood. Objective To explore the association between solid fuel use for cooking and depressive symptoms among middle-aged and elderly people in rural areas of China, and to provide a basis for the prevention and control of depressive symptoms among residents in rural areas. Methods Data were obtained from the 2020 China Family Panel Studies (CFPS), depressive symptoms were assessed using 8-item Center for Epidemiologic Studies Depression Scale (CES-D), and cooking fuel type was self-reported. Subsequently, two-level binary unconditional logistic regression models were fitted to assess the impact of solid fuel use for cooking on depressive symptoms. Results A total of 7991 participants aged 45 years and older [mean age (58.52±9.18) years] were included in the study, with a mean CES-D score of 6.07±4.48 and a mean positive depressive symptoms rate of 34% (40.54% in the solid fuel group and 30.81% in the clean fuel group, χ²=74.40, P<0.001). After controlling for potential confounding covariates, rural middle-aged and elderly residents in the solid fuel group had a higher risk of reporting depressive symptoms than those in the clean fuel group (OR=1.36, 95%CI: 1.20-1.54), an association that was unaffected by participant characteristics and was positive across age and gender groups. Conclusion There is a positive association between solid fuel use for cooking and depressive symptoms in middle-aged and elderly people in rural areas of China. It is recommended that rural areas promote the upgrading of stoves through the installation of ventilation equipment or the switch from solid cooking fuel to clean fuel. This approach is directed toward reducing exposure to household air pollution, alleviating the prevalence of depression among middle-aged and elderly residents in vast rural areas, and enhancing their mental health.

Objective To evaluate the economic value of fluticasone furoate/umeclidinium/vilanterol(FF/UMEC/VI)powder for inhalation in the treatment of symptomatic chronic obstructive pulmonary disease patients with acute exacerbation risk from the perspective of the Chinese health system.Methods Based on subgroup analysis of the China cohort in the IMPACT trial,a four-state lifetime Markov model was established with a 3-month cycle.The model simulation period was 11 years.Clinical efficacy,health benefits,and cost data were obtained through published literature.The health outcomes included quality adjusted life year(QALY).Using 3 times Chinas per capita gross domestic product(GDP)in 2023 as the willingness-to-pay threshold,the cost-utility analysis method was used for analysis the economic viability of FF/UMEC/VI.The scenario analysis,one-way sensitivity analysis and probability sensitivity analysis were used to verify the robustness of the results.Results Compared with fluticasone furoate/vilanterol(FF/VI),FF/UMEC/VI in the treatment of symptomatic chronic obstructive pulmonary disease patients with acute exacerbation risk saved costs 8 118.66 yuan and obtained an additional 0.000 06 QALYs,giving it an economic advantage.Compared with umeclidinium/vilanterol(UMEC/VI),FF/UMEC/VI treatment paid 2 784.41 yuan more and received 0.000 45 QALYs less,making UMEC/VI more cost-utility.The scenario analysis results further confirmed the robustness of the model.The sensitivity analysis results showed that when the drug cost of FF/UMEC/VI per cycle decreases to 637.29 yuan,FF/UMEC/VI had economic benefits under a willingness-to-pay threshold of 3 times China's per capita GDP in 2023.Conclusion For patients with symptomatic chronic obstructive pulmonary disease at risk of acute exacerbation,FF/UMEC/VI is more cost-utility than FF/VI.Compared with UMEC/VI,FF/UMEC/VI has economic viability after price reducing.

Objective:A gas chromatography analysis system for fatty acid compositions of hydrogenated palm glycerides was established to provide a reference for quality standards of hydrogenated palm glycerides.Methods:In this test,a DB-WAX(30 m ×0.53 mm,1.0 μm)strong polarity gas chromatographic column was employed with an injection volume of 1 μL and a split ratio of 120∶1.The initial column temperature was 70℃,sustained for 2 min,ramped up to 230 ℃ at a rate of 5 ℃ per minute,and maintained for 10 min,with the inlet temperature of 250 ℃ and the detector temperature of 250 ℃.Results:In this experiment,the gas chromatograph-ic method was established successfully to determine fatty acid compositions of hydrogenated palm glycerides.The validated results indicated that the method exhibited well-suited system applicability,specificity and precision,and the RSD(％)fulfilled the requirements.The limit of detection(LOD)and limit of quantification(LOQ)values of nine fatty acid methyl esters were defined,and fatty acid compositions of seven batches of samples were checked successfully.Conclusion:The GC methodology developed in this study is suitable for the analysis and determina-tion of fatty acid compositions in hydrogenated palm glycerides,which can serve as a reference for the quality control of this pharmaceutical excipient and the establishment of quality standards.

AIM:Clopidogrel and aspirin are com-monly used drugs for the secondary prevention of cerebrovascular disease.Due to drug resistance,their preventive effect is often affected.This article explores the clinical value of clopidogrel and aspirin pharmacogenetic genetic testing in the secondary prevention of ischemic stroke.METHODS:220 pa-tients with mild ischemic stroke or TIA admitted to our hospital from 2021.7 to 2022.9 were included and randomly divided into individualized treatment group and clopidogrel conventional treatment group(control group).The patients were followed up for one year to observe stroke recurrence and hemorrhagic events.RESULTS:(1)Compared with the control group,the recurrence rate of ischemic stroke in the individualized treatment group after 1-year follow-up was slightly lower(5.82％vs.7.92％,P＞0.05),the risk of cerebral hemorrhage was simi-lar,but the risk of other occurrences was increased(6.79％vs.0.99％,P＜0.05).(2)COX regression analy-sis showed that ESRS(HR 2.576,95％CI 1.226-5.413,P=0.013)and history of hypertension(HR 5.517,95％CI 1.624-18.737,P=0.006)were associated with recurrence of ischemic stroke,independent of anti-thrombotic regimen(HR 0.918,95％CI 0.291-2.894,P=0.883).CONCLUSION:Aspirin GPIBA,PTGS1,and ITGB3 gene polymorphisms have limited signifi-cance in guiding antiplatelet medication.Selecting aspirin maintenance therapy for clopidogrel CYP2C19*2*3 allele carriers cannot significantly re-duce the risk of recurrence of minor ischemic stroke and may increase other bleeding risks.COX regression analysis shows that ESRS and history of hypertension are independent risk factors for stroke recurrence.

To investigate the effects of Pithecellobium clypearia extract on the tissue structure,in-flammatory lesions as well as microbial diversity in the intestinal of yellow-feathered broilers.2401-day-old yellow-feathered broilers were randomly divided into four groups(groups A,B,C and D),groups A,B and C were supplemented with Pithecellobium clypearia extract in basal diets with concentrations of 0.5,1.0 and 2.0 g/kg,respectively.Group D served as the control group without adding Pithecellobium clypearia extract in diets,and the full trial period lasted for 70 d.Duodenum and jejunum samples were collected on the 20th,40th and 70th days of the test,the vil-lous/crypt ratio of duodenum and jejunum were calculated,and the mRNA expression level of in-flammatory cytokine as well as related pathways were detected in each group,respectively.In addition,the contents of cecum were collected at 70 th day of the experiment and the microbial di-versity in cecum were also analysed by 16S rDNA sequencing.The results showed that adding 0.5 and 1.0 g/kg of Pithecellobium clypearia extract in the diet could significantly increase the veloci-ty height/crypt depth ratio of duodenum and jejunum(P＜0.05)compared to control group,as well as the mRNA expression level of tight junction protein(CLDN1 and CLDN5)in jejunum,which further improved the structure of mucous of intestinal.Pithecellobium clypearia extract could significantly(P＜0.05)decrease the mRNA expression level of inflammatory cytokine inclu-ding IL-1β,IL-8 and TNF-α,as well as the related pathway genes such as TLR4,MyD88 and NF-κB in jejunum,thus reduced the inflammatory lesions in intestinal.Pithecellobium clypearia ex-tract also could significantly increase the abundance of beneficial microbial such as Parabacteroide and Prevotellaceae,while significantly decrease the abundance of pathogenic microbial such as Proteobacteria in cecum(P＜0.05)and improve the microbial diversity in intestinal.In summary,Pithecellobium clypearia extract could improve the structure of intestinal tissue and the gut barri-er function,as well as the microbial diversity in cecum,and also decrease the inflammatory lesions in jejunum,which is helpful to the intestinal health for yellow-feathered broilers.The present study provides scientific basis for the development of Pithecellobium clypearia as a safe feed additive in the future.

Objective: To compare the clinical outcomes and biomechanical characteristics of 1-, 2-, and 3-level pedicle subtraction osteotomy (PSO), and establish selection criteria based on preoperative radiographic parameters. Methods: Patients undergone PSO to treat ankylosing spondylitis from February 2009 to May 2019 in Sun Yat-sen Memorial Hospital of Sun Yat-sen University were enrolled. According to the quantity of osteotomy performed, the participants were divided into group A (1-level PSO, n = 24), group B (2-level PSO, n = 19), and group C (3-level PSO, n = 11). Clinical outcomes were assessed before surgery and at the final follow-up. Comparisons of the radiographic parameters and quality-of-life indicators were performed among and within these groups, and the selection criteria were established by regression. Finite element analysis was conducted to compare the biomechanical characteristics of the spine treated with different quantity of osteotomies under different working conditions. Results: Three-level PSO improved the sagittal parameters more significantly, but resulted in longer operative time and greater blood loss (p < 0.05). Greater stress was found in the proximal screws and proximal junction area of the vertebra in the model simulating 1-level PSO. Larger stress of screws and vertebra was observed at the distal end in the model simulating 3-level PSO. Conclusion Multilevel PSO works better for larger deformity correction than single-level PSO by allowing greater sagittal parameter correction and obtaining a better distribution of stress in the hardware construct, although with longer operation time and greater blood loss. Three-level osteotomy is recommended for the patients with preoperative of global kyphosis > 85.95°, T1 pelvic angle > 62.3°, sagittal vertical alignment > 299.55 mm, and pelvic tilt+ chin-brow vertical angle > 109.6°.

Objective:To investigate the feasibility and safety of a treatment system for stentless discharge after flexible ureteroscopic lithotripsy assisted by flexible negative pressure sheath.Methods:The clinical data of 72 patients with upper urinary calculi admitted to the Second Hospital of Tianjin Medical University from November 2022 to February 2023 were retrospectively analyzed. All patients achieved stentless discharge after flexible ureteroscopic lithotripsy assisted by flexible negative pressure sheath. There were 50 males and 22 females. The average age was (54.7±12.1) years. Preoperative urine culture was positive in 14 cases, negative in 3 cases (4.2%)with nitrite positive, and 11 cases were negative for urine culture and nitrites but positive of white blood cells (+ + + ). There were 29 cases of renal calculi, 33 cases of upper ureteral calculi, and 10 cases of upper ureteral calculi combined with renal calculi.The mean stone diameter was 17.0(14.0, 24.0)mm. CT value was (1 049.3±258.6)HU. Twenty-four patients carried ureteral stents before operation. A total of 42 cases used ureteral sheaths with diameters of F11/13, and 30 cases used sheaths with diameters of F12/14.During the operation, an infusion pump was used to provide sufficient irrigation pressure. The negative pressure suction was attached to the distal end of the sheath. The flexible head of the sheath was guided to the target renal calyx, to completely aspirate stone fragments. Stone baskets was used in 11 cases during the procedure. The level of ureteral injury was assessed according to the Traxer grading system at the end of the operation. A ureteral stent with extraction string was retained.On the first day postoperatively, CT scanning was performed to evaluate the residual stone fragments. Patients were discharged on postoperative day 2-3 after the removal of the ureteral stent and catheter. Follow-up was conducted for 30 days postoperatively, during which the Ureteral Stent Symptom Questionnaire (USSQ) was used to assess voiding symptoms and pain. Painkiller usage and emergency revisit situations were recorded. CT scans were performed to evaluate the stone-free rate on postoperative day 30.Results:The average operation time was 30.0 (20.0, 44.5) minutes. A total of 70 cases had no ureteral injuries, and 2 cases had Grade 1 ureteral injuries (minor mucosal damage). Three cases developed fever within 72 hours postoperatively, with no cases of septic shock or fever after stent removal. Eight patients reported waist and abdominal discomfort after discharge and took oral pain medication. Among them, one patient returned to the emergency department for pain treatment. Five patients reported moderate or severe genitourinary symptoms (including voiding frequency, nocturia, urgency/incontinence, dysuria, hematuria, and incomplete emptying) based on subjective evaluation. All patients could work and recovered a normal daily life after discharge and there was no readmission or additional surgical procedures. There were 61 patients achieved immediate stone-free status on the first day after surgery, and 66 patients achieved stone-free status during follow-up at 30 days postoperatively.Conclusions:Stentless discharge after flexible ureteroscopic lithotripsy assisted by flexible negative pressure sheath is safe and feasible.

Objective:To explore the relationship between hemoglobin variability (Hb-var) and risk of all-cause death and cardiovascular death in patients with peritoneal dialysis (PD), and to provide basis for reducing the risk of death in PD patients.Methods:It was a multicenter retrospective cohort study. The clinical data of regular PD patients from Nanfang Hospital of Southern Medical University, Shunde Hospital of Southern Medical University, Foshan First People's Hospital and Ganzhou People's Hospital from July 1, 2008 to December 31, 2019 were collected. Hb-var was calculated based on hemoglobin at baseline before PD and in the first year after PD. The patients were divided into low Hb-var group, moderate Hb-var group and high Hb-var group according to the tertiles of first year Hb-var, and the differences of baseline clinical data among three groups were compared. Follow-up endpoints included death, transfer to hemodialysis, transfer to kidney transplantation, transfer to other centers, loss of follow-up, or on December 31, 2021. Cox regression analysis model was used to analyze the association of the first-year Hb-var with all-cause death and cardiovascular death. Fine-Gray competitive risk regression model was used to evaluate the impact of competitive events on mortality risk.Results:A total of 1 562 patients with PD were included in the study, aged (47.6±13.8) years old, with 821 males (52.6%) and baseline hemoglobin of 81 (69, 94) g/L. Hb-var in the first year of PD was 26.6 (16.7, 40.3) g/L. There were statistically significant differences in age, body mass index, serum albumin, hemoglobin, serum creatinine, serum calcium, serum phosphorus, intact parathyroid hormone and the proportion of renin-angiotensin system inhibitors among low Hb-var group (<20.0 g/L), moderate Hb-var group (20.0-35.5 g/L) and high Hb-var group (≥35.5 g/L, all P<0.05). The follow-up time was 33 (19, 51) months, and 208 patients (13.3%) died, among which 111 patients (53.4%) died of cardiovascular death. Multivariate Cox regression analysis showed that the higher Hb-var in the first year, the lower the risk of all-cause death ( HR=0.98, 95% CI 0.97-0.99, P=0.018) and cardiovascular death ( HR=0.98, 95% CI 0.97-0.99, P=0.041) in PD patients. Compared with low Hb-var group, the risk of all-cause death ( HR=0.56, 95% CI 0.37-0.82, P=0.003) and cardiovascular death ( HR=0.54, 95% CI 0.31-0.95, P=0.032) was lowest in the high Hb-var group. The competitive risk regression model analysis showed that Hb-var in the first year was still negatively correlated with the risk of all-cause death ( HR=0.98, 95% CI 0.97-0.99, P=0.041) and cardiovascular death ( HR=0.98, 95% CI 0.97-0.99, P=0.039). Conclusion:High Hb-var in the first year is associated with low risk of all-cause death and cardiovascular death in PD patients with severe anemia at baseline.

Objective:To investigate the early clinical characteristics of elderly patients with severe burns and the risk factors on prognosis.Methods:This study was a retrospective case series study. Clinical data of 124 elderly patients with severe burns who met the inclusion criteria and were admitted to the 12 hospitals from January 2015 to December 2020 were collected, including 4 patients from the Fourth People's Hospital of Dalian, 5 patients from Fujian Medical University Union Hospital, 22 patients from Guangzhou Red Cross Hospital of Jinan University, 5 patients from Heilongjiang Provincial Hospital, 27 patients from the First Affiliated Hospital of Naval Medical University, 9 patients from the First Affiliated Hospital of Nanchang University, 10 patients from Affiliated Hospital of Nantong University, 9 patients from Tongren Hospital of Wuhan University & Wuhan Third Hospital, 12 patients from the 924 th Hospital of PLA, 6 patients from Zhangjiagang First People's Hospital, 4 patients from Taizhou Hospital of Zhejiang Province, and 11 patients from Zhengzhou First People's Hospital. The patients' overall clinical characteristics, such as gender, age, body mass index, total burn area, full-thickness burn area, inhalation injury, causative factors, whether combined with underlying medical diseases, and admission time after injury were recorded. According to the survival outcome within 28 days after injury, the patients were divided into survival group (89 cases) and death group (35 cases). The following data of patients were compared between the two groups, including the basic data and injuries (the same as the overall clinical characteristics ahead); the coagulation indexes within the first 24 hours of injury such as prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time, D-dimer, fibrinogen degradation product (FDP), international normalized ratio (INR), and fibrinogen; the blood routine indexes within the first 24 hours of injury such as white blood cell count, platelet count, neutrophil-to-lymphocyte ratio, monocyte count, red blood cell count, hemoglobin, and hematocrit; the organ function indexes within the first 24 hours of injury such as direct bilirubin, total bilirubin, urea, serum creatinine, aspartate aminotransferase, alanine aminotransferase, total protein, albumin, globulin, blood glucose, triglyceride, total cholesterol, alkaline phosphatase, creatine kinase, electrolyte indexes (potassium, sodium, chlorine, calcium, magnesium, and phosphorus in blood), uric acid, myoglobin, and brain natriuretic peptide; the infection and blood gas indexes within the first 24 hours of injury such as procalcitonin, C-reactive protein, pH value, oxygenation index, base excess, and lactate; treatment such as whether conducted with mechanical ventilation, whether conducted with continuous renal replacement therapy, whether conducted with anticoagulation therapy, whether applied with vasoactive drugs, and fluid resuscitation. The analysis was conducted to screen the independent risk factors for the mortality within 28 days after injury in elderly patients with severe burns. Results:Among 124 patients, there were 82 males and 42 females, aged 60-97 years, with body mass index of 23.44 (21.09, 25.95) kg/m 2, total burn area of 54.00% (42.00%, 75.00%) total body surface area (TBSA), and full-thickness burn area of 25.00% (10.00%, 40.00%) TBSA. The patients were mainly combined with moderate to severe inhalation injury and caused by flame burns. There were 43 cases with underlying medical diseases. The majority of patients were admitted to the hospital within 8 hours after injury. There were statistically significant differences between patients in the 2 groups in terms of age, total burn area, full-thickness burn area, and inhalation injury, and PT, APTT, D-dimer, FDP, INR, white blood cell count, platelet count, urea, serum creatinine, blood glucose, blood sodium, uric acid, myoglobin, and urine volume within the first 24 hours of injury (with Z values of 2.37, 5.49, 5.26, 5.97, 2.18, 1.95, 2.68, 2.68, 2.51, 2.82, 2.14, 3.40, 5.31, 3.41, 2.35, 3.81, 2.16, and -3.82, respectively, P<0.05); there were statistically significant differences between two groups of patients in whether conducted with mechanical ventilation and whether applied with vasoactive drugs (with χ2 values of 9.44 and 28.50, respectively, P<0.05). Age, total burn area, full-thickness burn area, serum creatinine within the first 24 hours of injury, and APTT within the first 24 hours of injury were the independent risk factors for the mortality within 28 days after injury in elderly patients with severe burns (with odds ratios of 1.17, 1.10, 1.10, 1.09, and 1.27, 95% confidence intervals of 1.03-1.40, 1.04-1.21, 1.05-1.19, 1.05-1.17, and 1.07-1.69, respectively, P<0.05). Conclusions:The elderly patients with severe burns had the injuries mainly from flame burns, often accompanied by moderate to severe inhalation injury and enhanced inflammatory response, elevated blood glucose levels, activated fibrinolysis, and impaired organ function in the early stage, which are associated with their prognosis. Age, total burn area, full-thickness burn area, and serum creatinine and APTT within the first 24 hours of injury are the independent risk factors for death within 28 days after injury in this population.