OBJECTIVE To optimize the water extraction technology for Kaixin granules. METHODS UPLC-MS/MS method was established for the simultaneous determination of ginsenoside Rg1， ginsenoside Re， ginsenoside Rb1， tenuifolin， polygalaxanthone Ⅲ and 3， 6′-disinapoyl-sucrose. An orthogonal test was designed with extraction times， extraction duration， and the volume of added water as factors. Using the contents of the aforementioned six indicator components and the extract yield as evaluation indexes， analytic hierarchy process-entropy weight method was employed to determine the combined weights of each indicator. Subsequently， process optimization and validation were conducted by integrating grey relational analysis （GRA） and back propagation （BP） neural network. RESULTS The water extraction technology optimized by the orthogonal test and GRA was 10- fold water for the first decoction and 8-fold water for the subsequent two， extracting 3 times，extracting for 1 h each time； the average comprehensive score of the validation experiment was 91.10 （RSD＝0.31%， n＝3）. The water extraction technology optimized by BP neural network was extracting 3 times with 10-fold water added each time， extracting for 1.5 h each time； the average comprehensive score of the validation experiment was 95.89 （RSD＝0.73%， n＝3）. Considering practical production requirements， the optimal water extraction technology was extraction performed three times， with 10-fold water for the first decoction and 8-fold water for the subsequent two extractions， with an extraction time of 1 h each. CONCLUSIONS The optimized water extraction technology for Kaixin granules is stable and feasible.

Objective:To investigate the differences of spontaneous neural activity and functional connectivity between bilateral symmetrical voxels in the local brain regions at resting-state of methamphetamine (MA) dependent patients and healthy controls (HCs).Methods:Forty-six MA-dependent patients, admitted to and received drug rehabilitation treatment for the first time in our hospital from February 2014 to October 2019, and 46 HCs matched with age, gender and education level during the same period were enrolled in this study. The resting state functional magnetic resonance imaging (rs-fMRI) data of these subjects were collected; the static and dynamic regional homogeneity (ReHo, d-ReHo) and static and dynamic voxel-mirrored homotopic connectivity (VMHC, d-VMHC) were used to evaluate MA-related alterations of brain spontaneous activity and interhemispheric functional connectivity. The correlations of brief psychiatric rating scale (BPRS) scores with above values in the brain regions with significant inter-group differences were analyzed.Results:As compared with the HCs, the MA-dependent patients had significantly decreased ReHo in the left medial orbitofrontal cortex (mOFC), and significantly increased d-ReHo in the left mOFC, left middle frontal gyrus, bilateral inferior frontal gyrus, left precentral gyrus and left postcentral gyrus ( P<0.05). As compared with the HCs, the MA-dependent patients had significantly decreased VMHC in the bilateral mOFC, precentral gyrus and postcentral gyrus ( P<0.05). The ReHo, VMHC, d-ReHo, and d-VMHC were not significantly correlated with total scores and each factor scores of BPRS, and total dose of MA (after removing outliers) in MA-dependent patients ( P>0.05). Conclusion:During resting state, MA-dependent patients show obvious abnormalities in the coordination and stability of spontaneous neural activity and the coordination of interhemispheric activity in local brain regions, especially in the mOFC; abnormal ReHo, d-ReHo and VMHC in left mOFC may be important neuroimaging biomarkers for MA-dependence.

Objective:To investigate the correlation between serum PCT and CRP levels and clinical outcome in patients with acute brucellosis.Methods:From June 2014 to June 2020, 73 patients with acute brucellosis diagnosed in Anji County People's Hospital, Huzhou City were selected as acute brucellosis group and 68 patients with chronic brucellosis as chronic brucellosis group; another 60 healthy people were selected as control group. The levels of serum PCT and CRP of each group were measured by chemiluminescence assay and immunoturbidimetric assay. Patients with acute brucellosis were treated with rifampicin, doxycycline and rifapentine capsules for 9 weeks. The levels of serum PCT and CRP in three groups and patients with acute brucellosis with different therapeutic effects were compared. Univariate and multivariate Cox regression analysis were used to analyze the related factors affecting the efficacy of patients with acute brucellosis. The area under curve (AUC) and cut-off value of receiver operating characteristic (ROC) curve of PCT and CRP were used to evaluate the diagnosis of acute brucellosis.Results:The levels of serum PCT and CRP in acute brucellosis group [(3.25±0.49) ng/ml, (31.28±6.56) mg/L] were higher than those in chronic brucellosis group [(0.12±0.05) ng/ml, (5.21±0.89) mg/L] and control group [(0.03±0.01) ng/ml, (2.63±0.37) mg/L], and those in chronic brucellosis group were higher than those in control group ( P < 0.05). In acute brucellosis patients, 56 cases were effective and 17 cases were ineffective. The levels of serum PCT and CRP in ineffective patients were higher than those in effective patients ( P < 0.05). Univariate Cox regression analysis showed that there were significant differences in leukocyte count, neutrophil count, PCT and CRP levels among acute brucellosis patients with different therapeutic effects ( P < 0.05). Multivariate Cox regression analysis showed that leukocyte count, neutrophil count, PCT and CRP levels were the risk factors for therapeutic effect ( P < 0.05). The diagnostic evaluation showed that the sensitivity and specificity of PCT in the diagnosis of acute brucellosis were 95.24% and 80.00%, respectively; and the sensitivity and specificity of CRP in the diagnosis of acute brucellosis were 93.10% and 80.00%, respectively. Conclusion:The levels of serum PCT and CRP in patients with acute brucellosis are significantly increased, and they are risk factors for therapeutic effect, which should be used as reference indexes for diagnosis and treatment of acute brucellosis.

Objective:To investigate the topological alterations of brain functional networks in patients with chronic methamphetamine (MA) dependence.Methods:Resting-state functional magnetic resonance imaging was used to map the brain networks of 46 patients with MA-dependence (MA group) and 46 healthy controls (control group). Statistical methods were used to compare the differences of brain functional connection and topological parameters between the two groups, and the correlations between these topological parameters with significant inter-group differences and clinical measurements were analyzed.Results:(1) Brain functional connection: as compared with the control group, the MA group had significantly enhanced functional connectivity in the subnetworks consisting of several brain regions, including the inferior parietal lobule, posterior central gyrus, lateral occipital cortex, ventromedial occipital cortex, orbital gyrus, anterior central gyrus, fusiform gyrus, superior temporal gyrus and thalamus; as compared with the control group, the MA group had significantly attenuated functional connectivity in the subnetworks consisting of several brain regions, the orbit frontal cortex, precentral gyrus, paracenter lobule, inferior temporal gyrus, fusiform gyrus, parahippocampal gyrus, superior parietal lobule, postcentral gyrus, medioventral occipital cortex, lateral occipital cortex and amygdala. (2) Network topology attributes: the brain functional networks in all subjects from the MA group and control group held worldlet; but attribute of worldlet in the MA group was significantly reduced as compared with that in the control group ( P<0.05); moreover, the MA group had significantly decreased clustering coefficient, local efficiency, and modularity as compared with the control group ( P<0.05). In terms of regional topological attributes, such as betweenness centrality, the MA group presented evident reduction in the left superior frontal gyrus, right orbit frontal cortex, right middle temporal gyrus and right/left lateral occipital cortex as compared with the control group with significant differences ( P<0.05). (3)Correlation analysis: the betweenness centrality of right middle temporal gyrus exhibited a positive correlation with the age of patients using MA for the first time ( r=0.327, P=0.028); a positive correlation was found between the modularity and activating factor scores in Brief Psychiatric Rating Scale (BPRS) in MA group ( r=0.315, P=0.035). Conclusions:Part of the global/local topological attributes of the brain functional network of patients with MA addiction are damaged. The younger the patients are when they take MA for the first time, the lower the betweenness centrality of the right middle temporal gyrus; the more the local attributes are damaged; and furthermore, the deeper the network modularity, the severer the active symptoms in the psychotic symptoms.

The fourth affiliated hospital of Zhejiang university is responsible for training general practitioners in view of the basics of local general practitioners and the characteristics of chronic and frequently-occurring diseases in Yiwu city. This program is carried out relying on the high-quality faculty of medical alliances within Zhejiang university, and funded by the municipal government of Yiwu. The "4+6"training program is designed to elevate the competence of primary general practitioners. Such training fit the overall medical level of general practitioners, enhances people′s trust of general practitioners and the rate of diagnosis at primary level.

Objective To evaluate the effect of " elite small class" training mode in capacity building for general practitioners in Yiwu city. Methods The Fourth Affiliated Hospital of Zhejiang University School of Medicine worked with Yiwu Health Bureau, and held the first training class for general practitioners from December 6th in 2018 to April 5th in 2019.The mode of " elite small-class" was adopted. Theoretical assessment was carried out for trainees before and after the training and discussion was conducted after the training. Descriptive analysis of quantitative data and thematic analysis of qualitative data were carried out. Results The trainees′theoretical performance had been significantly improved after 4 months of theoretical learning and clinical rotation.The average score of the theoretical performance was increased from 66.94 to 72.59. Conclusions It was preliminarily found that the " elite small-class" training mode was suitable for the training of general practitioners in rural areas.Government support and trainee selection are key to training outcomes.

Objective To evaluate the clinical efficacy and safety of nanoparticle albumin-bound paclitaxel (Nab-P) in the treatment of advanced non-small cell lung cancer (NSCLC). Methods Fifty-six over 65 years old patients with advanced NSCLC treated with Nab-P monotherapy in department of chemotherapy of the People's Hospital of Zhongshan City from January 2014 to January 2017 were analyzed retrospectively. The chemotherapy regimen was Nab-P 260 mg/m2, on d1 or d1 + d8, every 21 day for a cycle, imaging examination was made for efficacy evaluation after every 2 cycles. Results All 56 patients had been evaluated for efficacy, and received a total of 186 cycles of chemotherapy. All patients had been completed 2 cycles or more than 2 cycles of chemotherapy, and the median number of chemotherapy cycles was 3. The treatment response rate (RR) was 25.0 ％ and the disease control rate (DCR) was 76.8 ％. The median progression free survival (PFS) time was 4.7 months. The main adverse reactions were neutropenia, nausea and vomiting, fatigue and peripheral nerve toxicity. However, the vast majorities of adverse reactions were grade 1-2, and can be improved after treatment. Conclusions Nab-P is effective in the treatment of advanced NSCLC in elderly patients. The adverse reactions are mild and tolerant, and it is worthy to be popularized.

Objective To investigate the expression of miRNA associated with hepatic fibrosis induced by Schistosoma ja-ponicum soluble egg antigen stimulation in mouse hepatocytes(AML12),so as to lay the foundation for clarifying the mecha-nism of schistosome infection leading to hepatic fibrosis. Methods The expressions of miR-122,miR-182,miR-23b,miR-27b and KSRP in AML12 cells treated with SEA were measured by q-PCR. KSRP protein in cell lyses was measured by Western blotting. AML12 cells were transfected with miR-27b precursor or anti-miR-27b for 24 h,then q-PCR was adopted to determine KSRP mRNA,and KSRP protein was detected by Western blotting. Results The expressions of miR-182,miR-23b and miR-27b were decreased and miR-122 was increased in AML12 cells following SEA treatment(all P<0.05). An increase of mRNA and protein of KSRP expression was also observed in AML12 cells after SEA stimulation(both P<0.05). In addition,KSRP mRNA expression was not changed significantly in AML12 cells transfected with anti-miR-27b or miR-27b precursor,and miR-27b precursor reduced KSRP protein expression as compared with the control. In contrast,the expression of KSRP protein was increased in the anti-miR-27b group and decreased in the miR-27b precursor group. Conclusions After the stimulation of SEA,the expressions of a variety of liver fibrosis-related miRNAs and KSRP change in murine hepatocytes,including miR-27b. And miR-27b can regulate the expression of KSRP. These findings might lay a foundation for further study on the molecular mechanism of fibrosis induced by schistosome infection.

Objective To identify a myeloid differentiation factor 88(MyD88)in Oncomelania hupensis,and characterize the role of MyD88 against Schistosoma japonicum infection. Methods The complete cDNA of MyD88 in O. hupensis was ob-tained by using rapid amplification of cDNA ends(RACE),and homologues sequences and conserved domains were aligned and the structure of MyD88 was predicted either. A phylogenetic tree of MyD88 was further constructed with other species. In ad-dition,the mRNA expression level of O. hupensis MyD88 before and after S. japonicum infection was investigated by real-time quantitative PCR(RT-qPCR). Results The cDNA of O. hupensis MyD88 consisted of 1406 bp open reading frame(ORF),en-coding 468 amino acid residues,which contained death domain and Toll/interlrukin-1 receptor(TIR)domain,the typical fea-tures of MyD88 family proteins. The predicted amino acid sequence of O. hupensis MyD88 shared 38%-52%identity with other mollusc. O. hupensis MyD88 was phylogenetically closeted to Biomphalaria glabrata MyD88. The O. hupensis MyD88 existed in all selected tissues and expressed highly in hemocyte,up-regulated after S. japonicum infection in all selected tissues except cephalopodium,especially higher in whole snail and hemocyte. Conclusion MyD88-dependent signaling pathway is present in O. hupensis and plays an important role in innate immune response against S. japonicum infection.

This paper introduced the development of medical specialists alliance in Zhejiang University. With Jinhua Central Hospital as an example,merits and setbacks of the 3-level trusteeship model in practice were discussed,with improvement recommendations raised for progress of the hierarchical medical system.