Objective To study the therapeutic effect of Xuefu Zhuyu Capsule combined with sacubitril valsartan on dilated cardiomyopathy.Methods A total of 70 patients with dilated cardiomyopathy who were hospitalized in the Hospital from January to December 2020 were selected as the research objects and random-ly divided into control group and experimental group,with 35 cases in each group.The control group was only treated with sacubitril valsartan,and the experimental group was treated with Xuefu Zhuyu Capsule combined with sacubitril valsartan.According to the patient's blood pressure and renal function,sacubitril valsartan was titrated from a small dose to the maximum dose.Xuefu Zhuyu Capsule was uesd 2.4 g each time,twice a day,and the treatment time was three months.The symptoms of heart failure,glycosylated hemoglobin(HbA1c),low density lipoprotein(LDL),total cholesterol(TC),triglyceride(TG),ALT,AST,N-terminal pro-brain natriuretic peptide(NT-proBNP),left ventricular end-systolic diameter(LVEDd),left ventricular end-dias-tolic diameter(LVEDs),ejection fraction(EF)and the incidence of arrhythmia were observed in the two groups after treatment.Results After treatment,the level of NT-proBNP in the experimental group was sig-nificantly lower than that in the control group(P＜0.05).There was no significant difference in LDL,TC,TG,LVEDd,LVEDs and EF between the two groups(P＞0.05).The incidence of atrial tachycardia and ven-tricular premature beat in the experimental group was higher than that in the control group(P＜0.05).Con-clusion Xuefu Zhuyu Capsule combined with sacubitril valsartan can significantly improve the symptoms of patients with heart failure and reduce the level of NT-proBNP,but it may increase the proportion of patients with atrial tachycardia and ventricular premature beats.

Developmental coordination disorder (DCD) is a neurodevelopmental disorder with high incidence, low diagnosis rate and early onset of symptoms, which hinders the development of physical and mental health in children.Early identification and intervention of DCD can help reduce the lifelong adverse effects of the disease.However, general public in China still lacks awareness of this condition,and healthcare workers do not pay enough attention to the early screening and intervention of DCD.This paper summarizes the clinical characteristics, early screening and diagnosis of DCD, and expounds the clinical treatment of DCD from the two aspects of western and Chinese medicine intervention, and proposes the intervention treatment of integrated Chinese and western medicine for the first time, hoping to promote the development of early screening work, provide a new method for the research and development of DCD intervention in China, and improve the effectiveness of treatment.

Objective:To investigate the relationship between NOD-like receptors 3 (NLRP3) inflammasomes mediated inflammatory response and the pathogenesis of depression, and to investigate the effect of fluoxetine on this process.Methods:120 male C57BL/6J (wild-type) mice were randomly divided into control group 1, control group 2, chronic unpredictable mild stress (CUMS) group, and CUMS plus fluoxetine group. Another 30 male C57BL/6J (NLRP3-/-) mice were selected as NLRP3-/- group. Control group 1 and control group 2 had No treatment; CUMS group, CUMS plus fluoxetine group, and NLRP3-/- group were given chronic unpredictable mild stimulation for six weeks. After modeling, mice in control group 2 and CUMS plus fluoxetine group were intraperitoneally injected with fluoxetine (10 mg/(kg·d)). In contrast, mice in the other three groups were injected with the same amount of normal saline every day for four weeks. Behavioral tests were performed once a week before and after stress stimulation. Tail venous blood was drawn immediately before stress stimulation, three weeks later and six weeks after stress stimulation and was centrifuged at 3000 r/min for 10 min. The supernatant was kept and frozen for future use. Serum levels of interleukin-1β(IL-1β) and interleukin-18 (IL-18) were detected by enzyme-linked immunosorbent assay. After drug intervention (10 mg/(kg·d) fluoxetine or the same volume of normal saline), the mice in each group underwent behavioral tests once a week. The results included the sugar water preference test, forced swimming test (FST), and tail suspension test (TST). Tail venous blood was drawn from mice in each group at 1, 3, and 4 weeks after fluoxetine administration, and the supernatant was centrifuged and stored for later use. Serum levels of IL-1β and IL-18 were detected by enzyme-linked immunosorbent assay. At the above time points, 5 mice in each group were sacrificed each time, and fresh hippocampal tissues were collected and stored at a low temperature. NLRP3, urinary winter peptidase (caspase-1), the induction of transcription factors-KB (nuclear factor-κB, NF-κB), IL-1β and the IL-18 in the hippocampus brain regions were detected by using Western Blot.Results:(1) Model establishment: After six weeks of CUMS, compared with control group 1 and control group 2, the sugar water consumption of mice in CUMS group and CUMS+fluoxetine group was significantly reduced, and the immobility time of FST and TST was significantly prolonged, which proved that the model establishment was successful. After CUMS, NLRP3-/- group mice did not show depression-like changes in FST, sugar water preference test, and TST, which indicated that the model failed to be established. (2) After intraperitoneal fluoxetine injection, there were no significant differences in sugar water consumption, FST and TST immobility time between control group 2 and control group 1 ( P>0.05), and the sugar water consumption of mice in CUMS plus fluoxetine group was significantly increased, compared with CUMS group ( P<0.05). The immobility time of FST and TST was significantly shortened ( P<0.05). (3) The results of the enzyme-linked immunosorbent assay showed that after stimulation of CUMS, compared with control group 1 and control group 2, the serum levels of IL-1β and IL-18 in CUMS group and CUMS plus fluoxetine group were significantly increased ( P<0.05), while NLRP3-/- group had no significant change ( P>0.05). After fluoxetine administration, the serum levels of IL-1β and IL-18 in CUMS plus fluoxetine group were significantly lower than those in CUMS group ( P<0.05). (4) Western blotting results showed that after stimulation of CUMS, compared with control group 1 and control group 2, mice brain hippocampus NLRP3 expression, caspase-1 activation and induction of transcription factors-κB (nuclear factor-κB, NF-κB), IL-1β, IL-18 expression significantly increased ( P<0.05) in CUMS and CUMS plus fluoxetine group. After fluoxetine treatment, mice brain hippocampus NLRP3 expression, caspase-1 activation, NF-κB, IL-1β, and IL-18 expression in CUMS plus fluoxetine group had a significant reduction (restored to control 1 group by 99%, 91%, 97%, 95%, and 97% respectively). Conclusion:(1) CUMS may bring more NLRP3, caspase-1, NF-κB, IL-1β, and IL-18 expression in mice hippocampus, which cannot be seen, in the NLRP3 gene knockout mice; (2) The fluoxetine treatment may significantly decrease the NLRP3, caspase-1, NF-κB, IL-1β, IL-18 expression on depressive model mice, and improve depressive behavior.

Objective:To investigate the relationship between NOD-like receptors 3 (NLRP3) inflammasomes mediated inflammatory response and the pathogenesis of depression, and to investigate the effect of fluoxetine on this process.Methods:120 male C57BL/6J (wild-type) mice were randomly divided into control group 1, control group 2, chronic unpredictable mild stress (CUMS) group, and CUMS plus fluoxetine group. Another 30 male C57BL/6J (NLRP3-/-) mice were selected as NLRP3-/- group. Control group 1 and control group 2 had No treatment; CUMS group, CUMS plus fluoxetine group, and NLRP3-/- group were given chronic unpredictable mild stimulation for six weeks. After modeling, mice in control group 2 and CUMS plus fluoxetine group were intraperitoneally injected with fluoxetine (10 mg/(kg·d)). In contrast, mice in the other three groups were injected with the same amount of normal saline every day for four weeks. Behavioral tests were performed once a week before and after stress stimulation. Tail venous blood was drawn immediately before stress stimulation, three weeks later and six weeks after stress stimulation and was centrifuged at 3000 r/min for 10 min. The supernatant was kept and frozen for future use. Serum levels of interleukin-1β(IL-1β) and interleukin-18 (IL-18) were detected by enzyme-linked immunosorbent assay. After drug intervention (10 mg/(kg·d) fluoxetine or the same volume of normal saline), the mice in each group underwent behavioral tests once a week. The results included the sugar water preference test, forced swimming test (FST), and tail suspension test (TST). Tail venous blood was drawn from mice in each group at 1, 3, and 4 weeks after fluoxetine administration, and the supernatant was centrifuged and stored for later use. Serum levels of IL-1β and IL-18 were detected by enzyme-linked immunosorbent assay. At the above time points, 5 mice in each group were sacrificed each time, and fresh hippocampal tissues were collected and stored at a low temperature. NLRP3, urinary winter peptidase (caspase-1), the induction of transcription factors-KB (nuclear factor-κB, NF-κB), IL-1β and the IL-18 in the hippocampus brain regions were detected by using Western Blot.Results:(1) Model establishment: After six weeks of CUMS, compared with control group 1 and control group 2, the sugar water consumption of mice in CUMS group and CUMS+fluoxetine group was significantly reduced, and the immobility time of FST and TST was significantly prolonged, which proved that the model establishment was successful. After CUMS, NLRP3-/- group mice did not show depression-like changes in FST, sugar water preference test, and TST, which indicated that the model failed to be established. (2) After intraperitoneal fluoxetine injection, there were no significant differences in sugar water consumption, FST and TST immobility time between control group 2 and control group 1 ( P>0.05), and the sugar water consumption of mice in CUMS plus fluoxetine group was significantly increased, compared with CUMS group ( P<0.05). The immobility time of FST and TST was significantly shortened ( P<0.05). (3) The results of the enzyme-linked immunosorbent assay showed that after stimulation of CUMS, compared with control group 1 and control group 2, the serum levels of IL-1β and IL-18 in CUMS group and CUMS plus fluoxetine group were significantly increased ( P<0.05), while NLRP3-/- group had no significant change ( P>0.05). After fluoxetine administration, the serum levels of IL-1β and IL-18 in CUMS plus fluoxetine group were significantly lower than those in CUMS group ( P<0.05). (4) Western blotting results showed that after stimulation of CUMS, compared with control group 1 and control group 2, mice brain hippocampus NLRP3 expression, caspase-1 activation and induction of transcription factors-κB (nuclear factor-κB, NF-κB), IL-1β, IL-18 expression significantly increased ( P<0.05) in CUMS and CUMS plus fluoxetine group. After fluoxetine treatment, mice brain hippocampus NLRP3 expression, caspase-1 activation, NF-κB, IL-1β, and IL-18 expression in CUMS plus fluoxetine group had a significant reduction (restored to control 1 group by 99%, 91%, 97%, 95%, and 97% respectively). Conclusion:(1) CUMS may bring more NLRP3, caspase-1, NF-κB, IL-1β, and IL-18 expression in mice hippocampus, which cannot be seen, in the NLRP3 gene knockout mice; (2) The fluoxetine treatment may significantly decrease the NLRP3, caspase-1, NF-κB, IL-1β, IL-18 expression on depressive model mice, and improve depressive behavior.

OBJECTIVE：To establish a method for the determination of pyrrotinib concentration in plasma ，and apply it in clinic. METHODS ：After precipitated with methanol ，the plasma sample was determined by LC-MS/MS using imatinib as internal standard. The determination was performed on Ultimate AQ-C 18 column with mobile phase consisted of methanol （containing 0.1％ formic acid ）and water （containing 0.1％ formic acid ）（gradient elution ）at the flow rate of 0.4 mL/min. The column temperature was 40 ℃，and the sample size was 5 µL. The ion source was electrospray ionization source ，and the positive ion scanning was carried out in multiple reaction mode. The ion pairs for quantitative analysis were m/z 583.4→138.3（pyrrotinib）and m/z 494.5→ 393.4（internal standard ），respectively. Thirty breast cancer patients taking pyrrotinib were collected from the Affiliated Hospital of Qingdao University during Jun.-Nov. 2020 to determine their steady-state trough concentrations of pyrrotinib after a week of treatment. RESULTS ：The linear range of pyrrotinib were 5-300 ng/mL（r＝0.999 3）. The lower limit of quantification was 5 ng/mL. RSDs of intra-day and inter-day were not higher than 9.30％，and relative errors （REs）ranged －6.70％-5.04％. REs of stability tests were in the range of －1.92％-5.42％. The extraction method ，matrix effect and residual effect did not affect the quantitative analysis of the substance to be tested. The steady-state trough concentrations of pyrrotinib were 32.6-82.8 ng/mL，with an average plasma concentration of 53.8 ng/mL；there was about 2.54 fold individual difference. CONCLUSIONS ：Established LC-MS/MS method is simple ，sensitive and accurate ，and can be used for the plasma concentration monitoring of pyrrotinib in breast cancer patient.

Objective:To explore the possibility of hepatitis B core antibody (anti-HBc) in predicting hepatitis B virus surface antigen (HBsAg) clearance.Methods:Sixty cases with chronic hepatitis B who were previously treated with peginterferon α-2a combined with nucleos(t)ide analogues (NAs) antiviral therapy were divided according to the HBsAg clearance or non-clearance; 41 cases in the clearance group and 19 cases in the non-clearance group. Double antigen sandwich method was used to detect patients anti-HBc quantitative levels during the course of treatment and at baseline, 24, 48, 72 and 96 weeks. Logistic regression analysis and receiver operating characteristic curve (ROC) were used to evaluate the predictive ability of related influencing factors for HBsAg clearance.Results:With antiviral treatment prolongation, anti-HBC quantitative levels in the overall population showed a progressive downward trend in the clearance group and the non-clearance group, but the anti-HBC level in the clearance group was significantly higher than non-clearance group at the baseline and successive detection time points during the antiviral treatment ( P < 0.05). Multivariate logistic regression showed that baseline quantitative anti-HBC level, HBsAg decline at week 24 (log10 IU / ml), and alanine aminotransferase (ALT) > 1.5 times the upper limit of normal value (ULN) were all influencing factors for HBsAg clearance during the treatment ( OR = 0.156, P = 0.026; OR = 0.134, P = 0.023; OR = 0.239, P = 0.028). Among them, the baseline quantitative anti-HBc level was the best independent predictor for HBsAg clearance ( OR = 0.235; P = 0.004), and the sensitivity and specificity for predicting HBsAg clearance at > 3.40 log10 IU/ mL were 56.1% and 89.5%, respectively. Logistic regression model was used as a reference to construct combined predictors in order to improve the prediction accuracy. Among them, the combined factor 3 had the highest predictive value (the area under the ROC curve had reached up to 0.870; 95%CI was 0.781 ~ 0.960; P < 0.001). The cut-off value of combined factor 3 was > 0.386, and the sensitivity and specificity were 80.5% and 78.9%, respectively. In addition, the combined index had further improved the predictive value, which is the combination of any two or more indexes based on the baseline quantitative anti-HBC level, and HBsAg clearance predictive rate had reached 94.12% ~ 100%. Conclusion:The baseline quantitative anti-HBC level has the highest predictive value for HBsAg clearance. The combination of ALT > 1.5×ULN and HBsAg decline at 24 weeks during the treatment can more precisely predict HBsAg clearance. Therefore, it is a reliable non-invasive biomarker.

The current outpatient payment method based on fee-for-service induced serious demand, which increased the waste of medical insurance fund. The authors briefly introduced ambulatory patient groups(APG)with the same concept of diagnosis-related groups. According to the current situation of outpatient medical insurance payment and the degree of informatization in China, suggestions are put forward: launch a pilot project first and starting with chronic disease to promote reform; improve the quality of outpatient electronic medical records, and develop APG suitable for China; under the background of aging, cooperate with the total budget to ensure the security of medical insurance.

Preventive treatment of diseases is a traditional Chinese medicine (TCM) concept that conforms to the demand of modern healthcare emphasizing prevention. This concept, however, calls for close and orderly collaboration between general hospitals and primary community healthcare institutions, in order to encourage coordinated regional development. The authors described the new healthcare mode of " One Center, One Platform, and One Network" jointly built and run by Dongguan Municipal Health Bureau and Dongguan TCM Hospital. This practice has pioneered a full-range, closed-loop and one-stop service chain featuring preventive treatment. Such an innovative TCM health management system has realized information interconnection of preventive treatment, and upgraded the capacity and effectiveness of community medical services, hence expanding the number of beneficiaries.

OBJECTIVE： To study the effects of Wuzhi soft capsule and imatinib mesylate tablet on the pharmacokinetics of imatinib in rats. METHODS： The rats were divided into single administration group and consecutive administration group. The single administration group was divided into imatinib group one （ig administration of blank soybean oil+imatinib suspension 10   mg/kg）， low-dose， medium-dose and high-dose of Wuzhi soft capsule+imatinib group （ig administration of Wuzhi soft capsule solution 134， 268， 536 mg/kg+imatinib suspension 10 mg/kg）， with 6 rats in each group. Each group was given imatinib suspension intragastrically 30 min after intragastric administration of blank soybean oil/Wuzhi soft capsule solution. The consecutive administration group was divided into imatinib group two （ig administration of blank soybean oil+imatinib suspension 10 mg/kg）， Wuzhi soft capsule low-dose+imatinib group （ig administration of Wuzhi soft capsule solution 134 mg/kg+imatinib suspension 10 mg/kg）， with 6 rats in each group. Each group was given blank soybean oil/Wuzhi soft capsule solution intragastrically for consecutive 14 d， once a day； 30 min after last administration， ig imatinib suspension. About 100 μL blood was collected before imatinib， 0.5， 1， 2， 2.5， 3， 4， 5， 6， 8， 12， 24 and 36 h after medication. The plasma concentration of imatinib was determined by HPLC-MS/MS. The pharmacokinetic parameters were fitted by using DAS 2.0 software. RESULTS： After single administration， compared with imatinib group one， cmax， t1/2， AUC0-36 h and AUMC0-36 h in low-dose， medium-dose and high-dose of Wuzhi soft capsule+imatinib group were increased significantly （P＜0.05 or P＜0.01）. After consecutive administration， compared with imatinib group two， cmax， t1/2 and AUMC0-36 h of imatinib+low-dose of Wuzhi soft capsule group were increased significantly （P＜0.05 or P＜0.01）. CONCLUSIONS： Single administration and consecutive administration of Wuzhi soft capsule influence the pharmacokinetics of imatinib， increase plasma concentration of imatinib and prolong half-time.

Objective: To observe the changes of liver function, virology and serology and the safety of drug withdrawal in pregnant women who are chronic hepatitis B virus (HBV) carriers. Methods: A prospective clinical cohort was established to enroll pregnant women who are chronic HBV carriers and they were divided into the nucleoside/nucleotide analogs (NAs) intervention group and the non-NAs intervention group according to patients' wishes. Liver function, HBV DNA and HBV serological markers were detected at gestation, postpartum 6 weeks, 12 weeks, 24 weeks, 36 weeks and 48 weeks. Results: 351 patients were enrolled, 320 in the NAs intervention group and 31 in the non-NAs intervention group. The proportion of postpartum hepatitis flares in both groups was higher than that in pregnancy (39.4% vs 12.5%, P < 0.001; 38.7% vs 3.2%, P = 0.001). Six weeks postpartum was the peak period of hepatitis flares, and 96.0% (121/126) of the hepatitis flares occurred within 24 weeks postpartum. At 6 weeks postpartum, there were 6 cases of alanine aminotransferase (ALT) ≥ 10 times upper limit of normal (ULN) in the NAs intervention group. The rate of the hepatitis flare after drug withdrawal was 16.7% (34/203). Conclusion Regardless of the presence or absence of NAs intervention, pregnant women who are chronic HBV carriers have a certain proportion of hepatitis flares during pregnancy and postpartum, and the hepatitis flare even have a tendency to be severe. Therefore, drug withdrawal after delivery is not always safe, which requires close observation and classification. At 6 weeks postpartum, the incidence of hepatitis flares was high, and those who meet the treatment indications can get better therapeutic effects if given appropriate treatment. The vast majority (96%) of postpartum hepatitis flares occur within 24 weeks, so it is recommended to follow up to at least 24 weeks postpartum after discontinuation.