OBJECTIVE To explore the pharmacokinetic characteristics of 3 blood-absorbed components of Xiangshao sanjie oral liquid in rats with hyperplasia of mammary gland （HMG）. METHODS Female SD rats were divided into control group and HMG group according to body weight， with 6 rats in each group. The HMG group was given estrogen+progesterone to construct HMG model. After modeling， two groups were given 1.485 g/kg of Xiangshao sanjie oral liquid （calculated by crude drug） intragastrically， once a day， for 7 consecutive days. Blood samples were collected before the first administration （0 h）， and at 5， 15， 30 minutes and 1， 2， 4， 8， 12， 24 hours after the last administration， respectively. Using chlorzoxazone as the internal standard， the plasma concentrations of ferulic acid， paeoniflorin and rosmarinic acid in rats were detected by UPLC-Q/TOF-MS. The pharmacokinetic parameters [area under the drug time curve （AUC0－24 h， AUC0－∞）， mean residence time （MRT0－∞）， half-life （t1/2）， peak time （tmax）， peak concentration （cmax）] were calculated by the non-atrioventricular model using Phoenix WinNonlin 8.1 software. RESULTS Compared with the control group， the AUC0－24 h， AUC0－∞ and cmax of ferulic acid in the HMG group were significantly increased （P＜0.05）； the AUC0－24 h， AUC0－∞ ， MRT0－∞ ， t1/2 and cmax of paeoniflorin increased， but there was no significant difference between 2 groups （P＞0.05）； the AUC0－24 h and MRT0-∞ of rosmarinic acid were significantly increased or prolonged （P＜0.05）. C ONCLUSIONS In HMG model rats， the exposure of ferulic acid， paeoniflorin and rosmarinic acid in Xiangshao sanjie oral liquid all increase， and the retention time of rosmarinic acid is significantly prolonged.

Objective To investigate the effects of Toxoplasma gondii type Iand IIrhoptry protein 16 (ROP16) on the polarization and inflammatory response of mouse alveolar macrophages, so as to provide the scientific evidence for unveiling the immunoregulatory mechanisms following T. gondii infection in host cells and the clinical diagnosis and treatment of pulmonary toxoplasmosis. MethodsMouse alveolar macrophages served as blank controls, and mouse alveolar macrophages transfected with the empty lentiviral expression vector served as negative controls, and mouse alveolar macrophages transfected with lentiviral vectors overexpressing T. gondii type I and II ROP16 served as the type I and II ROP16 overexpression groups. Following puromycin selection, stably transfected cells that overexpressed type Iand IIROP16 were generated, observed for green fluorescence expression under a fluorescence microscope and verified using PCR, Western blotting and real-time quantitative reverse transcription PCR (RT-qPCR) assays. The expression of ROP16, inducible nitric oxide synthase (iNOS), arginase (Arg)-1, mannose receptor (CD206), cluster of differentiation 86 (CD86), NOD-like receptor thermal protein domain associated protein 3 (NLRP3), caspase-1, apoptosis-associated speck-like protein containing a CARD (ASC), and interleukin (IL)-1β proteins was determined in mouse alveolar macrophages using Western blotting assay, and the mRNA levels of ROP16, iNOS, IL-1β, IL-4, IL-12, IL-18, Arg-1, IL-10, IL-6, tumor necrosis factor (TNF)-α and transforming growth factor (TGF)-β were detected in mouse alveolar macrophages using RT-qPCR assay. Results Fluorescence microscopy showed 90% of mouse alveolar macrophages producing green fluorescent signals in the type Iand II ROP16 overexpression groups and the negative control group. The relative ROP16 protein expression was 1.000 ± 0.000, 1.003 ± 0.020, 1.349 ± 0.055, and 1.376 ± 0.080 in mouse alveolar macrophages in the blank control group, negative control group, and type Iand IIROP16 overexpression groups (F = 35.30, P < 0.01), and the relative ROP16 mRNA expression was 1.007 ± 0.172, 2.030 ± 0.356, 1 409.579 ± 75.960, and 1 413.581 ± 27.712 in the blank control group, negative control group, and type Iand II ROP16 overexpression groups (F = 811.00, P < 0.01). The ROP16 expression was significantly higher in the type Iand IIROP16 overexpression groups than in the blank control group at both protein and mRNA levels (all P value < 0.01). Western blotting assay detected significant differences among the four groups in terms of iNOS, Arg-1, CD86, CD206, NLRP3, caspase-1, ASC, and IL-1β protein expression (F = 124.70, 82.40, 79.82, 919.40, 84.74, 39.85, 2 354.00 and 65.96, all P values < 0.05), and the expression of Arg-1, CD206, NLRP3, caspase-1, ASC, and IL-1β proteins was significantly higher in the type I ROP16 overexpression group than in the blank control group (all P values < 0.001), while the expression of iNOS, CD86, NLRP3, caspase-1, ASC, and IL-1β proteins was significantly higher in the type II ROP16 overexpression group than in the blank control group (all P values < 0.01). RT-qPCR assay detected significant differences among the four groups in terms of iNOS, IL-1β, IL-4, IL-12, IL-18, Arg-1, IL-10, IL-6, TNF-α, and TGF-β mRNA expression (F = 407.00, 1 528.00, 833.10, 267.90, 989.80, 161.80, 461.10, 5 529.00, 849.60 and 8 836.00, all P values < 0.05), and the Arg-1, IL-4, IL-10, and TGF-β mRNA expression was significantly higher in the type I ROP16 overexpression group than in the blank control group (all P values < 0.001), while the iNOS, IL-1β, IL-12, IL-18, IL-6, and TNF-α mRNA expression was significantly higher in the type II ROP16 overexpression group than in the blank control group (all P values < 0.001). Conclusions T. gondii type IROP16 may induce M2-dominant phenotypes of mouse alveolar macrophages, and type II ROP16 may induce M1-dominant phenotypes of mouse alveolar macrophages. Both T. gondii type I and II ROP16 may activate NLRP3, and mediate the activation of ASC, caspase-1 and IL-1β to promote inflammatory responses.

ObjectiveTo explore the effects of the Tai Chi training on bone density， bone turnover markers， and heart rate variability for people with high-risk osteoporosis， and to provide evidence for the prevention of osteoporosis at early stage. MethodsSixty-six cases of people with high risk of osteoporosis were included， and they were divided into 33 cases each in the intervention group and the control group using the random number table method. The control group received osteoporosis health education three times a week， and the intervention group received Tai Chi training under the guidance of a trainer three times a week for 40 mins each time on the basis of the control group， and both groups were intervened for 12 weeks. Dual-energy X-ray absorptiometry was used to measure the bone density of L₁~L₄ vertebrae， bilateral femoral necks and bilateral total hips in the two groups before and after the intervention； enzyme-linked immunosorbent assay was used to determine bone turnover markers before and after the intervention， including pro-collagen type Ⅰ pro-amino-terminal prepropyl peptide （P1NP） and β-collagen type Ⅰ cross-linking carboxy-terminal peptide （β-CTX）. Seven cases with good compliance in the intervention group were selected. After wearing the heart rate sensor， they successively performed Tai Chi training and walking activities recommended by the guideline for 20 mins each， and the heart rate variability （HRV） during exercise was collected， including time-domain indexes such as standard deviation of normal sinus intervals （SDNN）， root-mean-square of the difference between adjacent RR intervals （RMSSD）， frequency-domain metrics such as low-frequency power （LF）， high-frequency power （HF）， and low-frequency/high-frequency power ratio （LF/HF）， as well as nonlinear metrics such as approximate entropy （ApEn）， sample entropy （SampEn）. ResultsFinally， 63 cases were included in the outcome analysis， including 30 cases in the intervention group and 33 cases in the control group. After the intervention， the differences of L₁~L₄ vertebrae， bone density of bilateral femoral neck and bilateral total hip in the intervention group were not statistically significant when compared with those before intervention （P＞0.05）， while the bone density of all parts of the control group decreased significantly compared with that before intervention （P＜0.05）， and the difference in the bone density of the L₁~L₄ vertebrae， bilateral femoral neck， and the right total hip before and after the intervention of the intervention group was smaller than that of the control group （P＜0.05）. The differences in P1NP and β-CTX between groups before and after intervention was not statistically significant （P＞0.05）. Compared with walking exercise， LF decreased， HF increased and LF/HF decreased during Tai Chi exercise （P＜0.05）； the time domain indexes and non-linear indexes between groups had no statistically significant difference （P＞0.05）. ConclusionTai Chi exercise can maintain lumbar， hip， and femoral bone density and improve sympathetic/parasympathetic balance in people at high risk for osteoporosis， but cannot significantly improve bone turnover markers.

OBJECTIVE To provide reference for the establishment and optimization of add-on payment policy in China. METHODS The two-party evolutionary game model was constructed， involving medical insurance and medical institutions，and simulation experiments were conducted. The effects of factors such as whether the establishment of add-on payment policy by the medical insurance department， the compensation ratio， and the cost and incremental utility of new technology on the adoption of innovative technologies by medical institutions were analyzed under the backdrop of the reform of the diagnosis-related groups （DRG） payment system. RESULTS & CONCLUSIONS The add-on payment policy can effectively incentivize the utilization of innovative technologies， but it also carries the risk of overuse or misuse of new technologies. The compensation ratio， unit price of new technology， and cost savings derived from the improved effectiveness of new technologies， as well as the incremental utility of new technology， will all affect the equilibrium state of the evolutionary game， potentially even reversing it. It is recommended to optimize the selection criteria for the scope of add-on payment， so as to incentivize the use of innovative technologies while controlling the risk of their misuse. Additionally， a reasonable approach should be taken to adopt either standalone payment or supplementary payment models based on the surplus level of medical insurance funds in the coordinated regions. Meanwhile， a regular adjustment mechanism should be established to ensure smooth integration between the add-on payment and the DRG payment system.

ObjectiveTo study the effect and mechanism of Yixintai on mitochondrial fission proteins in the rat model of chronic heart failure. MethodTen of 60 SD rats were randomly selected as the sham operation group， and the remaining 50 rats were subjected to ligation of the left anterior descending coronary artery for the modeling of heart failure post myocardial infarction. The successfully modeled rats were randomized into model， low-， medium-， and high-dose （1.4， 2.8， and 5.6 g·kg^-1， respectively） Yixintai， and trimetazidine （10 mg·kg^-1） groups. The rats were administrated with corresponding doses of drugs by gavage， and the rats in the model group and sham operation group were given an equal volume of normal saline by gavage for 28 consecutive days. Enzyme-linked immunosorbent assay （ELISA） was then employed to measure the levels of amino-terminal pro-B-type natriuretic peptide （NT-pro BNP）， B-type natriuretic peptide （BNP）， and adenosine triphosphate （ATP） in the serum. Color Doppler ultrasound imaging was conducted to examine the cardiac function indicators. Hematoxylin-eosin staining and Masson staining were conducted to observe the pathological changes in the heart， and Image J was used to calculate collagen volume fraction （CVF）. Transmission electron microscopy was employed to observe the ultrastructural changes of myocardial cells. Terminal-deoxynucleoitidyl transferase-mediated nick-end labeling （TUNEL） was employed to measure the apoptosis rate of myocardial cells. Western blot was employed to determine the protein levels of mitochondrial fission protein 1 （Fis1） and mitochondrial fission factor （Mff） in the outer mitochondrial membrane of the myocardial tissue. ResultCompared with the sham operation group， the model group showed elevated levels of NT-pro BNP and BNP in the serum， decreased ATP content， left ventricular ejection fraction （LVEF）， and left ventricular fraction shortening （LVFS）， increased left ventricular end-diastolic diameter （LVIDd） and left ventricular end-systolic diameter （LVIDs）， disarrangement of myocardial cells， inflammatory cell infiltration， increased collagen fibers and CVF， damaged myocardium and mitochondria， and increased apoptosis rate of myocardial cells， and up-regulated expression of Fis1 and Mff in the cardiac tissue （P<0.01）. Compared with the model group， different doses of Yixintai and trimetazidine lowered the serum levels of NT-pro BNP and BNP （P<0.05）， increased the ATP content （P<0.05）， increased LVEF and LVFS （P<0.01）， decreased LVIDd and LVIDs （P<0.01）. Moreover， the drugs alleviated the myocardial inflammatory damage and fibrosis， reduced CVF （P<0.01）， repaired the myocardial mitochondrial structure， and decreased the apoptosis rate of myocardial cells （P<0.01）. Medium- and high-dose Yixintai and trimetazidine down-regulated the expression of Fis1 and Mff in the myocardial tissue （P<0.05）. ConclusionYixintai can improve mitochondrial structure， reduce myocardial cell apoptosis， and improve cardiac function by inhibiting the expression of Fis1 and Mff in the myocardial tissue.

The precise localization of pulmonary nodules has become an important technical key point in the treatment of pulmonary nodules by thoracoscopic surgery, which is a guarantee for safe margin and avoiding removal of too much normal lung parenchyma. With the development of medical technology and equipment, the methods of locating pulmonary nodules are also becoming less trauma and convenience. There are currently a number of methods applied to the preoperative or intraoperative localization of pulmonary nodules, including preoperative percutaneous puncture localization, preoperative transbronchial localization, intraoperative palpation localization, intraoperative ultrasound localization, and localization according to anatomy. The most appropriate localization method should be selected according to the location of the nodule, available equipment, and surgeon鈥檚 experience. According to the published literatures, we have sorted out a variety of different theories and methods of localization of pulmonary nodules in this article, summarizing their advantages and disadvantages for references.

Objective To investigate the mechanism of matrix metalloproteinase(MMP)-9 involved in epithelial mesenchymal transformation(EMT)in chronic sinusitis(CRS).Methods The expression of MMP-9 from polypoid middle turbinate tissue was detected by immunohistochemical staining qPCR and Western blot assay in 42 patients with CRS and 8 patients underwent septoplasty.Primary human nasal epithelial cells HNEpc were cultured in vitro and divided into the control group,the TGF-β1 group(5 μg/L TGF-β1 intervention)and the TGF-β1+si-MMP-9 group(transfected with si-MMP-9 and 5 μg/L TGF-β1 intervention).The expression of MMP-9 was detected by cell immunofluorescence staining.Expression levels of TGF-β1,MMP-9 and EMT-related proteins E-cadherin,vimentin and α-SMA were detected by Western blot assay.Results(1)The positive expression rate of MMP-9 was significantly higher in the nasal mucosa of CRS with nasal polyps(CRSwNP)group(54.5%,12/22)than that of the CRS without polyps(25.0%,5/20)group and the control group(12.8%,1/8).The relative expression levels of MMP-9 mRNA and protein in nasal mucosa were higher in the CRSwNP group than those in the CRSsNP group and the control group(P＜0.05).(2)Compared with the control group,the expressions levels of TGF-β1,MMP-9,vimentin and α-SMA were increased in the TGF-β1 group,while the expression of E-cadherin was decreased(P＜0.05).Compared with the TGF-β1 group,expression levels of TGF-β1,MMP-9,vimentin and α-SMA were decreased in the TGF-β1+si-MMP-9 group,and the expression of E-cadherin was increased(P＜0.05).Conclusion The expression of MMP-9 is increased in CRS patients,which may be involved in the development of CRS through the regulation of EMT.

ObjectiveTo investigate the differences in clinical efficacy of different medication regimens of Wangbi Tablets （尪痹片） for knee osteoarthritis （KOA） in a real-world setting， providing a basis for rational clinical use of Wangbi Tablets. MethodsA prospective registry study was conducted， involving 2，999 KOA patients registered in 30 hospitals nationwide from January 26th， 2019， to December 17th， 2021. Based on the use of Wangbi Tablets during the observation period， patients were divided into a monotherapy group （1，507 cases） and a combination therapy group （1，492 cases）， and the combination group can be further divided into Wangbi Tablets plus Chinese medicine （CM）， Wangbi Tablets plus western medicine （WM）， and Wangbi Tablets plus Chinese and western medicine （CM+WM） subgroups. The baseline data of patients in the monotherapy group and the combination group were compared， including age， gender， body weight， medication time， clinical stage， K-L grade， and others. Efficacy indicators included the Visual Analog Scale （VAS） score， Western Ontario and McMaster Universities Osteoarthritis Index （WOMAC） score， and EuroQol five-dimensional （EQ-5D） health index， which were evaluated before and after 4-， 8- and 12-week treatment， and the difference before and after treatment was calculated after 4， 8 and 12 weeks of treatment. The difference between the baseline and 12 weeks of treatment of all the above indicators was used as the dependent variables， and gender， age， body mass index （BMI）， course of disease， K-L grade， and clinical stage were used as independent variables， when multiple linear regression was taken to explore the influencing factors of the efficacy. At the same time， the occurrence of major symptoms （including morning stiffness， joint swelling， soreness of waist and knees， fear of wind， and fear of cold） was counted， and the disappearance of symptoms at each time point was counted after 4， 8， and 12 weeks of treatment. ResultsAt baseline， there were no statistically significant differences in gender and age distribution between the monotherapy and combination therapy groups （P＞0.05）； the proportion of patients in the acute stage and recovery stage was higher in the monotherapy group than in the combination therapy group， while the proportion in the remission stage was lower （P＜0.05）； the VAS score was higher in the monotherapy group， and the EQ-5D index was lower （P＜0.01）， with no statistically significant difference in total WOMAC score between the two groups （P＞0.05）. Compared to those measured before treatment and at previous timepoint， the VAS score and WOMAC total score significantly decreased in both groups， while EQ-5D value increased （P＜0.05）. The difference in VAS score between baseline and after 12-week treatment was higher in the monotherapy group than the combination group， while the differences in WOMAC total score and EQ-5D value between baseline and after 4-， 8- and 12-week treatment were higher in the combination group （P＜0.05）. Multiple linear regression showed that VAS score before treatment had greatest impact on pain improvement （P＜0.01）， and compared to Wangbi Tablets monotherapy， the combination of Wangbi tablets with WM or CM had larger associations with pain improvement （P＜0.05）； and Wangbi Tablets had better efficacy when the course of treatment was ＞28 days （P＜0.01）. Wangbi Tablets plus WM had a better effect on improving the overall function of the knee joint than Wangbi Tablets alone （P＜0.01）； and the efficacy of Wangbi Tablets with a course of treatment ＞28 days was better （P＜0.05）. The improvement of quality of life of patients in the attack and remission stages was more obvious than that in the recovery stage （P＜0.01）； Wangbi Tablets plus WM or CM had a better effect on improving quality of life than Wangbi Tablets alone （P＜0.05）. Before treatment， the proportion of patients with morning stiffness， soreness of waist and knees， fear of wind and chills in the monotherapy group was higher than that in the combination group （P＜0.01）. The proportion of main symptoms in both groups decreased after 4， 8 and 12 weeks of treatment （P＜0.05）. After 4 weeks of treatment， the disappearance rate of each main symptom in the combination group was higher than that in the monotherapy group， and after 12 weeks of treatment， the disappearance rate of fear of wind in the monotherapy group was higher than that in the combination group， while the disappearance rate of joint swelling and soreness of waist and knees was lower （P＜0.05）. ConclusionWangbi Tablets， whether used alone or in combination with other medications， is effective throughout the course of KOA， with greater benefits in improving joint function and quality of life during the acute and remission stages compared to the recovery stage. Combination therapy had a faster onset of effect， but began to converge with monotherapy after 8 weeks. The best efficacy was observed with the combination of Wangbi Tablets with WM， followed by combination with CM.

Objective To compare the discrepancies among results of three commonly used laboratory direct test methods for maximal oxygen uptake(VO2max),explore their linear regression relationships,mutual predictability and comparability.Methods Using a quasi-experimental design of cluster sampling and within-group interaction design,20 male cross-country skiers were tested for VO2max using the Bruce protocol(Method 1),90-second incremental load exercise on power bicycle(Method 2),and 1-minute incremental load exercise on treadmill(Method 3),with an interval of one week.The indepen-dent and dependent variable were the three VO2max test methods and the VO2max,respectively.Results Significant differences were found in the average VO2max of the three test results,with the value mea-sured by Method 1 ranking the first,followed by that assessed by Method 3 and Method 2(P<0.05).Moreover,the frequency of individual differences in the results of the three methods showed that the VO2max of Method 1 was about 6 and 3 ml/min·kg higher than that measured by Method 2 and 3.However,at the same treadmill speed,the average blood lactate evaluated using Method 3 was higher than Method 1,and the speed reached aerobic and anaerobic thresholds about one speed unit(1 km/h)lower than Method 1.Meanwhile,linear regression analyses of the test results between Method 1 and 2,as well as Method 1 and 3 showed that both the regression models and coefficients were statis-tically significant(P<0.001),with the R-squared values of 9.25 and 9.05,respectively.Conclusion The Bruce protocol performs best in assessing the maximum value of the athlete's VO2max phase,whose results have linear regression relationships with the other two methods,and can be used for pre-dicting their results.Moreover,athletes of different events and levels can choose different VO2max test methods accordingly.Lastly,the speed and heart rate ranges corresponding to the aerobic and anaero-bic thresholds can serve as an effective and convenient method to control the training intensity.

Heart failure is a group of complex clinical syndromes in the middle and late stages of cardiovascular diseases.Mitochondrial homeostasis imbalance is one of the pathological mechanisms in the occurrence and development of heart failure.This article revolved around the"yin-yang theory"in TCM and explained the pathological mechanism of heart failure through mitochondrial homeostasis.Heart failure is the syndrome of deficiency in nature and excess in superficiality fundamental.Its basic pathogenesis is"yang deficiency and yin excess".Based on the deficiency of heart yang qi and the stagnation of yin pathogens,the combination of deficiency and excess runs through the entire disease.Mitochondrial homeostasis imbalance is a manifestation of yin-yang imbalance at the cellular micro level,mainly manifested as inhibition of mitochondrial biosynthesis,mitochondrial dynamics imbalance,mitophagy disorder,etc.,which affects mitochondrial structure and function and leads to abnormal myocardial energy metabolism.Therefore,based on the"yin-yang theory",the basic treatment method is to"tonify deficiency and damage excess"to regulate mitochondrial biosynthesis,mitochondrial dynamics,and mitophagy,thereby maintaining mitochondrial homeostasis and improving myocardial energy metabolism,which is of great significance for the prevention and treatment of heart failure.