Based on LI Gao's Academic Thought， focusing on the process of qi transformation and taking the regulation and restoration of metabolism and immunity as the entry point， a "source-pivot-convergence" diagnostic and therapeutic model for malignant tumors is constructed. In this model， spleen and stomach internal injury is the source of malignant tumor occurrence， while the disorder of ascending and descending is the pivot of the disease development， and the generation of yin fire is the convergence of malignant tumor progression. Based on this， the three major therapeutic methods of clearing the source， harmonizing the pivot， and resolving the convergence are established. To fortify spleen and boost qi， consolidate the root and clear the source， modified Buzhong Yiqi Decoction（补中益气汤）can be used. To raise the clear and direct the turbid downward， regulate qi and harmonize the pivot， modified Shengyang Yiwei Decoction （升阳益胃汤） is suggested. To restore balance and promote circulation， disperse accumulation and resolve convergence， modified Shengyang Sanhuo Decoction （升阳散火汤） is selected. In clinical practice， these formulas can be used in combination according to the complexity of the pathogenesis， and further adapted with prescriptions for promoting dispersion and penetrating pathogenic factors， resolving phlegm and promoting circulation， activating blood and eliminating concretions， which can provide a reference for the prevention and treatment of tumor diseases.

Based on LI Gao's Academic Thought， focusing on the process of qi transformation and taking the regulation and restoration of metabolism and immunity as the entry point， a "source-pivot-convergence" diagnostic and therapeutic model for malignant tumors is constructed. In this model， spleen and stomach internal injury is the source of malignant tumor occurrence， while the disorder of ascending and descending is the pivot of the disease development， and the generation of yin fire is the convergence of malignant tumor progression. Based on this， the three major therapeutic methods of clearing the source， harmonizing the pivot， and resolving the convergence are established. To fortify spleen and boost qi， consolidate the root and clear the source， modified Buzhong Yiqi Decoction（补中益气汤）can be used. To raise the clear and direct the turbid downward， regulate qi and harmonize the pivot， modified Shengyang Yiwei Decoction （升阳益胃汤） is suggested. To restore balance and promote circulation， disperse accumulation and resolve convergence， modified Shengyang Sanhuo Decoction （升阳散火汤） is selected. In clinical practice， these formulas can be used in combination according to the complexity of the pathogenesis， and further adapted with prescriptions for promoting dispersion and penetrating pathogenic factors， resolving phlegm and promoting circulation， activating blood and eliminating concretions， which can provide a reference for the prevention and treatment of tumor diseases.

Chronic stress triggers the imbalance of the homeostasis of the tumor immune microenvironment(TIME),which is a key factor driving the development of lung cancer.Based on the mapping relationship between the concept of"spirit"in traditional Chinese medicine and chronic stress,and between"qi"and"immunity",it is believed that the cross-linking mechanism of"chronic stress-TIME-lung cancer"aligns with the understanding of traditional Chinese medicine of disease as involving the interplay between the"body,qi and spirit".The disorganization of"spirit"and"qi"is not only the root of the change of the"form",but also the key to prevent and control it.The treatment principle of synergizing to improve the chronic stress of"regulating the spirit"and remodeling the TIME of"invigorating the qi"is further proposed,which emphasizes on grasping the core pathogenesis of lung cancer at each stage of its evolution in order to administer medicines,drawing on the clinical experience and pharmacological research results in order to accurately hit the target,and combining special therapies like acupuncture,Chinese kungfu,sound therapy to treat the change of"shape"by modulating neuro-endocrine-immune network homeostasis,so as to provide new ideas and accessible solutions for the comprehensive prevention and treatment system of lung cancer.

Objective To establish a rapid analysis method for cyanide based on a ratiometric fluores-cent probe,providing a quantitative strategy for on-site visual and rapid detection of cyanide.Methods A dual-emission ratiometric fluorescent probe(AuNCs-FL)was constructed by using bovine serum al-bumin(BSA)-stabilized gold nanoclusters(AuNCs,fluorescence emission at 660 nm)as the responsive signal unit and fluorescein(FL,emission at 515 nm)as the internal reference.Results The etching effect of cyanide on AuNCs resulted in fluorescence quenching at 660 nm,while the fluorescence inten-sity of FL at 515 nm remained unchanged,enabling a rapid response analysis of cyanide shift from red to green fluorescence.The developed probe enabled rapid analysis of cyanide within 3 min,with a limit of detection(LOD)of 3.4 mg/L and a visual detection range of 10-100 mg/L.Conclusion The AuNCs-FL fluorescent probe is structurally simple,low-cost,and easy to operate,delivering rapid and accurate results.It also avoids the interference from sulfides encountered in commercial cyanide test kits,making it suitable for the on-site rapid detection of suspected powder samples in cyanide poisoning cases.

OBJECTIVE: To investigate the relationship between physical activity and genetic risk and their combined effects on the risk of developing chronic obstructive pulmonary disease. METHODS: This prospective cohort study included 318,085 biobank participants from the UK. Physical activity was assessed using the short form of the International Physical Activity Questionnaire. The participants were stratified into low-, intermediate-, and high-genetic-risk groups based on their polygenic risk scores. Multivariate Cox regression models and multiplicative interaction analyses were used. RESULTS: During a median follow-up period of 13 years, 9,209 participants were diagnosed with chronic obstructive pulmonary disease. For low genetic risk, compared to low physical activity, the hazard ratios ( HRs) for moderate and high physical activity were 0.853 (95% confidence interval [ CI]: 0.748-0.972) and 0.831 (95% CI: 0.727-0.950), respectively. For intermediate genetic risk, the HRs were 0.829 (95% CI: 0.758-0.905) and 0.835 (95% CI: 0.764-0.914), respectively. For participants with high genetic risk, the HRs were 0.809 (95% CI: 0.746-0.877) and 0.818 (95% CI: 0.754-0.888), respectively. A significant interaction was observed between genetic risk and physical activity. CONCLUSION Moderate or high levels of physical activity were associated with a lower risk of developing chronic obstructive pulmonary disease across all genetic risk groups, highlighting the need to tailor activity interventions for genetically susceptible individuals.
Humans ; Pulmonary Disease, Chronic Obstructive/epidemiology* ; Exercise ; Male ; Female ; Middle Aged ; Prospective Studies ; Aged ; Genetic Predisposition to Disease ; Risk Factors ; United Kingdom/epidemiology* ; Incidence ; Adult

Chronic stress triggers the imbalance of the homeostasis of the tumor immune microenvironment(TIME),which is a key factor driving the development of lung cancer.Based on the mapping relationship between the concept of"spirit"in traditional Chinese medicine and chronic stress,and between"qi"and"immunity",it is believed that the cross-linking mechanism of"chronic stress-TIME-lung cancer"aligns with the understanding of traditional Chinese medicine of disease as involving the interplay between the"body,qi and spirit".The disorganization of"spirit"and"qi"is not only the root of the change of the"form",but also the key to prevent and control it.The treatment principle of synergizing to improve the chronic stress of"regulating the spirit"and remodeling the TIME of"invigorating the qi"is further proposed,which emphasizes on grasping the core pathogenesis of lung cancer at each stage of its evolution in order to administer medicines,drawing on the clinical experience and pharmacological research results in order to accurately hit the target,and combining special therapies like acupuncture,Chinese kungfu,sound therapy to treat the change of"shape"by modulating neuro-endocrine-immune network homeostasis,so as to provide new ideas and accessible solutions for the comprehensive prevention and treatment system of lung cancer.

Pharmacokinetics of traditional Chinese medicine(TCM)is a discipline that adopts pharmacokinetic research methods and techniques under the guidance of TCM theories to elucidate the dynamic changes in the absorption,distribution,metabolism and excretion of active ingredients,active sites,single-flavour Chinese medicinal and compounded formulas of TCM in vivo.However,the sources and components of TCM are complex,and the pharmacodynamic substances and mechanisms of action of the majority of TCM are not yet clear,so the pharmacokinetic study of TCM is later than that of chemical medicines,and is far more complex than that of chemical medicines,and its development also confronts with challenges.The pharmacokinetic study of TCM originated in the 1950s and has experienced more than 70 years of development from the initial in vivo study of a single active ingredient,to the pharmacokinetic and pharmacodynamic study of active ingredients,to the pharmacokinetic study of compound and multi-component of Chinese medicine.In recent years,with the help of advanced extraction,separation and analysis technologies,gene-editing animals and cell models,multi-omics technologies,protein purification and structure analysis technologies,and artificial intelligence,etc.,the pharmacokinetics of TCM has been substantially applied in revealing and elucidating the pharmacodynamic substances and mechanisms of action of Chinese medicines,research and development of new drugs of TCM,scientific and technological upgrading of large varieties of Chinese patent medicines,as well as guiding the rational use of medicines in clinics.Pharmacokinetic studies of TCM have made remarkable breakthroughs and significant development in theory,methodology,technology and application.In this paper,the history of the development of pharmacokinetics of TCM and the progress of cutting-edge research was reviewed,with the aim of providing ideas and references for the pharmacokinetics of TCM and related research.

Objective To study the pharmacokinetic(PK)characteristics,bioequivalence and safety of two kinds of vildagliptin tablets in Chinese healthy subjects in postprandial state.Methods A single-center,open,balanced,randomized,single-dose,two-period,two-sequence,crossover design was adopted.Each period,subjects orally took 50 mg of the test formulation or reference formulation after a high-fat meal.Blood samples were collected at preset time points and the plasma concentration of vildagliptin was measured by liquid chromatography/mass spectrometry(LC-MS/MS).The PK parameters were calculated using Phoenix WinNonlin 8.2 software;and the bioequivalence of the two formulations was evaluated.Demographic and baseline characteristics,as well as safety analysis of the subjects,were performed using SAS 9.4 software.Results Out of 24 subjects,one subject withdrew from the trial before administration in the first period,and another withdrew before administration in the second period.Under postprandial conditions,the main pharmacokinetic parameters of vildagliptin tablets for the test and reference formulations were Cmax were(230±73.9)and(203±44.0)ng·mL-1,AUC0-t were(1 065.93±215.46)and(1 029.30±185.78)ng·h·mL-1,AUC0-∞ were(1 078.74±217.93)and(1 041.59±190.66)ng·h·mL-1.The 90％confidence intervals for the geometric mean ratios of Cmax,AUC0-t and AUC0-∞ were within the requirements of the equivalent range of bioequivalence(80.00％-125.00％).During the trial,five subjects experienced mild adverse events,with no serious adverse events occurring.Conclusion Two kinds of vildagliptin tablets have bioequivalence in postprandial state,and have good safety and tolerability in healthy subjects.

Objective To explore the clinical efficacy of high hip center technique total hip arthroplasty(THA)for CroweⅡ and Ⅲ developmental dysplasia of hip(DDH)and severe hip osteoarthritis(HOA).Methods From January 2018 to Jan-uary 2020,74 patients with Crowe type Ⅱ and Ⅲ DDH and severe HOA were admitted,and 37 cases of anatomical hip center reconstruction were taken as control group,including 7 males and 30 females,aged from 42 to 65 years old with an average of(58.40±4.98)years old,body mass index(BMI)ranged from 18 to 29 kg·m-2 with an average of(23.02±2.21)kg·m-2.Thirty-seven routine high hip center technical reconstruction were performed as study group,including 5 males and 32 females,aged from 41 to 65 years old with an average of(57.31±5.42)years old,BMI ranged from 18 to 29 kg·m-2 with an average of(23.14±2.07)kg·m-2.The patients presented with hip pain,limited function and range of motion,and gait instability before surgery.All patients underwent THA,the control group underwent intraoperative anatomical hip center reconstruction,and the study group underwent intraoperative high hip joint reconstruction.The perioperative indicators of the two groups were com-pared.The hip joint function,balance function and gait of the patients were evaluated before surgery,3 months,6 months,and 12 months after surgery.The length difference of both lower limbs,horizontal distance of rotation center,vertical distance of ro-tation center and femoral eccentricity were measured before operation and 1 year after operation.The incidence of complica-tions in the two groups during the operation and postoperative follow-up was counted.Results The operation time of the study group was shorter than that of the control group,and the intraoperative blood loss was less than that of the control group(P＜0.05).After 12-months follow-up,1 was lost to followvup in study group and 2 were lost to follow-up in control group.The Har-ris scores and Berg balance scale(BBS),pace,stride frequency and single step length in the study group were higher than those in the control group at 3 months and 6 months after operation(P＜0.05);there was no statistically significant difference between the two groups in the indexes 12 months after operation(P＞0.05).The vertical distance of the center of rotation of the study group was greater than that of the control group 12 months after operation(P＜0.05),and there was no significant difference in the length difference of the lower limbs,the horizontal distance of the center of rotation,and the femoral eccentricity between two groups(P＞0.05).There were no complications in either group.Conclusion The long-term effects of TH A in patients with DDH and severe HO A were similar between the two central hip reconstruction methods,and the safety was good,and the high hip central reconstruction technique could shorten the operation time and reduce the amount of intraoperative blood loss.At the same time,it has certain advantages in early recovery of hip joint function,balance function and walking function of patients.

Objective To study the pharmacokinetic(PK)characteristics,bioequivalence and safety of two kinds of vildagliptin tablets in Chinese healthy subjects in postprandial state.Methods A single-center,open,balanced,randomized,single-dose,two-period,two-sequence,crossover design was adopted.Each period,subjects orally took 50 mg of the test formulation or reference formulation after a high-fat meal.Blood samples were collected at preset time points and the plasma concentration of vildagliptin was measured by liquid chromatography/mass spectrometry(LC-MS/MS).The PK parameters were calculated using Phoenix WinNonlin 8.2 software;and the bioequivalence of the two formulations was evaluated.Demographic and baseline characteristics,as well as safety analysis of the subjects,were performed using SAS 9.4 software.Results Out of 24 subjects,one subject withdrew from the trial before administration in the first period,and another withdrew before administration in the second period.Under postprandial conditions,the main pharmacokinetic parameters of vildagliptin tablets for the test and reference formulations were Cmax were(230±73.9)and(203±44.0)ng·mL-1,AUC0-t were(1 065.93±215.46)and(1 029.30±185.78)ng·h·mL-1,AUC0-∞ were(1 078.74±217.93)and(1 041.59±190.66)ng·h·mL-1.The 90％confidence intervals for the geometric mean ratios of Cmax,AUC0-t and AUC0-∞ were within the requirements of the equivalent range of bioequivalence(80.00％-125.00％).During the trial,five subjects experienced mild adverse events,with no serious adverse events occurring.Conclusion Two kinds of vildagliptin tablets have bioequivalence in postprandial state,and have good safety and tolerability in healthy subjects.