Based on the different medical systems and textual contexts within Inner Canon of Yellow Emperor （《黄帝内经》）， this paper argues that "opening， closing， and pivot" in the three yin and three yang theory encompasses both spatial and temporal dimensions. From the spatial perspective， the concepts of opening， closing and pivot are used to describe the dynamic movement of qi within the meridian system. In The Spiritual Pivot·Root and Knot （《灵枢·根结》）， the theory primarily explains the superficial-deep and exterior-interior hierarchy of the meridians， emphasizing the movement of channel qi and the transmission of disease. By contrast， Basic Questions·Treatise on the Separation and Union of Yin and Yang （《素问·阴阳离合论篇》） primarily explains the relationships of separation and union between yin and yang among different regions and orientations on the same body-surface level. From the temporal perspective， the theory also explains the waxing and waning of yin and yang according to seasonal changes throughout the year， and has been applied to clinical practice within the theory of the five circuits and six qi. Therefore， opening， closing， and pivot in the three yin and three yang theory encompasses multiple connotations， including meridian structure， spatial distribution， seasonal qi transformation， and the annual circulation of climatic qi. Clarifying these different levels and their respective scopes of application is essential for accurately understanding the rich connotations of the opening， closing and pivot theory.

OBJECTIVE：To study the effects of rat intestinal flora on the pharmacokinetic parameters of pyrazinamide and its active metabolite pyrazinoic acid. METHODS ：Totally 16 SD rats were randomly divided into trial group and control group ，with 8 rats in each group. Trial group was given mixed antibiotics （streptomycin sulfate+neomycin sulfate ）intragastrically to construct pseudoaseptic rat model. After modeling ，both groups were given pyrazinamide intragastrically （150 mg/kg）. Before and 0.167， 0.333，0.667，1，1.5，2，3，4，6，9 h after administration ，0.1 mL blood sample was collected from orbital venous plexus ，and 0.3 mL blood sample was collected from orbital venous plexus 12，24 h after administration. Using phenacetin as internal standard ， LC-MS/MS method was adopted to determine the plasma concentration of pyrazinamide and pyrazinoic acid. The determination was performed on Agilent ZORBAX SB-Aq column with mobile phase consisted of 0.2％ formic acid （containing 8 mmol/L ammonium acetate）-methanol（gradient elution ）at the flow rate of 1 mL/min. The column temperature was set at 30 ℃，and sample size was 10 μL. The ion source was ESI and the temperature of ion source was 500 ℃. The collision gas was nitrogen and the pressure was 10 psi. The temperature of mass transfer interface was 100 ℃. The mass spectrum monitoring mode was multi reaction monitoring ， and the collection mode was positive ion mode. The monitoring transition ion-pairs were m/z 124.0→79.0（pyrazinamide），m/z 125.1→79.1（pyrazinic acid ）and m/z 180.0→110.2（internal standard ）. The de-clustering potential and collision voltage were 55， 26 and 85 V，24，23 and 28 V，respectively. The pharmacokinetic parameters were calculated and compared by using DAS 2.1.1 software. RESULTS ：The linear ranges of pyrazinamide and pyrazinoic acid were 25-5 000 ng/mL（r＝0.997 6）and 100-12 500 ng/mL（r＝0.999 0）. The lower limits of quantification were 25 and 100 ng/mL，respectively. Intra-batch and inter-batch accuracy were 92.93％-100.50％，and RSDs of intra-batch and inter-batch precision and matrix effect tests were all lower than or equal to 8.42％（n＝6 or n＝3）. Compared with control group ，tmax of pyrazinamide in trial group was prolonged significantly （P＜0.01）； there was no statistical significance in other pharmacokinetic parameters between 2 groups（P＞0.05）. CONCLUSIONS ：The absorption of single dose pyrazinamide is delayed with the change of intestinal flora in rats.

OBJECTIVE:To study risk factors for carbapenem-resistant Acinetobacter baumannii(CRAB)infection,and to provide reference for its clinical prevention. METHODS:In retrospective study,302 A. baumannii(AB)infection patients were collected from our hospital during Dec. 2012 to Jun. 2017. According to the results of drug sensitivity test,those patients were divided into CRAB group(116 cases)and non-CRAB group(186 cases). Risk factors for CRAB infection were analyzed by using univariate analysis. Multivariate Logistic regression analysis was performed for variables with significant difference between 2 groups. RESULTS:Univariate analysis showed that the factors of significant difference in 2 groups including patients suffering from septic shock(P=0.003),sepsis(P=0.000),combined with other infection(P=0.006),diabetes(P=0.029),malignant tumors(P=0.036),patients suffering from infection of other site except for pulmonary infection,intraabdominal infection and skin infection(P=0.009)before AB isolation,patients given carbapenems(P=0.002)and antifungal drugs 28 d before AB isolation(P=0.002). Multivariate Logistic regression analysis showed that the factors of significant difference in 2 groups including patients suffering from sepsis(P=0.033)or diabetes(P=0.011)before AB isolation. CONCLUSIONS:Independent risk factors for CRAB infection include patients suffer from sepsis or diabetes before AB isolation.

Objective: To investigate the clinical effect and safety of long-acting pegylated interferon-α-2b (Peg-IFN-α-2b) (Y shape, 40 kD) injection (180 μg/week) in the treatment of HBeAg-positive chronic hepatitis B (CHB) patients, with standard-dose Peg-IFN-α-2a as positive control. Methods: This study was a multicenter, randomized, open-label, and positive-controlled phase III clinical trial. Eligible HBeAg-positive CHB patients were screened out and randomized to Peg-IFN-α-2b (Y shape, 40 kD) trial group and Peg-IFN-α-2a control group at a ratio of 2:1. The course of treatment was 48 weeks and the patients were followed up for 24 weeks after drug withdrawal. Plasma samples were collected at screening, baseline, and 12, 24, 36, 48, 60, and 72 weeks for centralized detection. COBAS® Ampliprep/COBAS® TaqMan® HBV Test was used to measure HBV DNA level by quantitative real-time PCR. Electrochemiluminescence immunoassay with Elecsys kit was used to measure HBV markers (HBsAg, anti-HBs, HBeAg, anti-HBe). Adverse events were recorded in detail. The primary outcome measure was HBeAg seroconversion rate after the 24-week follow-up, and non-inferiority was also tested. The difference in HBeAg seroconversion rate after treatment between the trial group and the control group and two-sided confidence interval (CI) were calculated, and non-inferiority was demonstrated if the lower limit of 95% CI was > -10%. The t-test, chi-square test, or rank sum test was used according to the types and features of data. Results: A total of 855 HBeAg-positive CHB patients were enrolled and 820 of them received treatment (538 in the trial group and 282 in the control group). The data of the full analysis set showed that HBeAg seroconversion rate at week 72 was 27.32% in the trial group and 22.70% in the control group with a rate difference of 4.63% (95% CI -1.54% to 10.80%, P = 0.1493). The data of the per-protocol set showed that HBeAg seroconversion rate at week 72 was 30.75% in the trial group and 27.14% in the control group with a rate difference of 3.61% (95% CI -3.87% to 11.09%, P = 0.3436). 95% CI met the non-inferiority criteria, and the trial group was non-inferior to the control group. The two groups had similar incidence rates of adverse events, serious adverse events, and common adverse events. Conclusion In Peg-IFN-α regimen for HBeAg-positive CHB patients, the new drug Peg-IFN-α-2b (Y shape, 40 kD) has comparable effect and safety to the control drug Peg-IFN-α-2a.

OBJECTIVE: To investigate the expression and clinical significance of Muc1, p63 protein in diffuse sclerosing variant of papillary thyroid carcinoma and conventional papillary thyroid carcinoma. METHOD: Immunohistochemistry (SP) was used to detect the expressions of Muc1, p63 protein in 30 samples of DSVPTC (experiment group) and 30 samples of CPTC (control group). Patients in two groups were matched in age, gender, tumor side, tumor size and date of diagnosis. RESULT: (1) The positive rate of Muc1 in DSVPTC and CPTC was 76.67% (23/30) and 53.33% (16/30) respectively, immunohistochemical staining expressed as brown or tan particles in the membrane or the cytoplasm,with a significant difference between the two groups (P < 0.05). The positive rate of p63 in DSVPTC and CPTC was 80% (24/30) and 43.33% (13/30) respectively, immunohistochemical staining expressed as a brown or tan particles in the muclei,with a significant difference between the two groups (P < 0.05). (2) Cervical lymph node metastasis rate in DSVPTC and CPTC was 50% (15/30) and 20% (6/30) respectively, with a significant difference between the two groups (P < 0.05). (3) In All cases,the positive rate of Muc1 in cervical lymph node metastasis group (21 cases) and without metastasis group (39 cases) was 85.71% (18/21) and 53.85% (21/39) respectively,with a significant difference between the two groups (P < 0.05); the positive rate of p63 was 95.24% (20/21) and 43.59% (17/39) respectively,with a significant difference between the two groups (P < 0.01). (4) Spearman rank correlation analysis showed that expression of Muc1 and p63 were positively correlated in both groups(r = 0.530,0. 386, P < 0.05). CONCLUSION (1) There are high expression of Muc1 and p63 protein in DSVPTC, and relatively low expression in CPTC, DSVPTC have a higher rate of cervical lymph node metastasis at the time of being diagnosed, compared to the CPTC. These results show that DSVPTC is a more biologically aggressive variant of the PTC. (2) Abnormal expression of Muc1 and p63 may be important to promote the progression and metastasis of PTC, thus they can be used as predictors of malignant behavior in PTC. (3) Muc1 and p63 may be synergistically promote proliferation and invasion metastasis of the PTC malignant cell.
Adolescent ; Adult ; Aged ; Carcinoma ; classification ; metabolism ; pathology ; Carcinoma, Papillary ; Female ; Humans ; Lymphatic Metastasis ; Male ; Membrane Proteins ; metabolism ; Middle Aged ; Mucin-1 ; metabolism ; Thyroid Cancer, Papillary ; Thyroid Neoplasms ; classification ; metabolism ; pathology ; Young Adult