OBJECTIVE To standardize the main processes and related technical links of the clinical comprehensive evaluation of drugs， and provide guidance and reference for improving the quality of comprehensive evaluation evidence and its transformation and application value. METHODS The construction of Guideline for the Workflow of Clinical Comprehensive Evaluation of Drugs was based on the standard guideline formulation method of the World Health Organization （WHO）， strictly followed the latest definition of guidelines by the Institute of Medicine of the National Academy of Sciences of the United States， and conformed to the six major areas of the Guideline Research and Evaluation Tool Ⅱ. Delphi method was adopted to construct the research questions； research evidence was established by applying the research methods of evidence-based medicine. The evidence quality classification system of the Chinese Evidence-Based Medicine Center was adopted for evidence classification and evaluation. The recommendation strength was determined by the recommendation strength classification standard formulated by the Oxford University Evidence-Based Medicine Center， and the recommendation opinions were formed through the expert consensus method. RESULTS & CONCLUSIONS The Guideline for the Workflow of Clinical Comprehensive Evaluation of Drugs covers 4 major categories of research questions， including topic selection， evaluation implementation， evidence evaluation， and application and transformation of results. The formulation of this guideline has standardized the technical links of the entire process of clinical comprehensive evaluation of drugs， which can effectively guide the high-quality and high-efficient development of this work， enhance the standardized output and transformation application value of evaluation evidence， and provide high-quality evidence support for the scientific decision-making of health and the rationalization of clinical medication.

AIM:The objective of this study was to investigate the ameliorative effect of Erjing pills(PL)on the functional impairment of the diabetic retinal neurovascular unit(NVU)in rats.METHODS:A diabetic retinopathy(DR)model was established using BN rats,which were then treated with freeze-dried Erjing pills powder.After 12 weeks,various assessments were conducted:retinal thickness was measured using OCT,fundus lesions were evaluated with FFA,and retinal cell structure,arrangement,and layer thickness were analyzed through HE staining.Additionally,transmission electron microscopy was employed to examine ultrastructural changes in retinal ganglion cells(RGCs),and retinal leakage was assessed using EB in vivo perfusion.The expression of ZO-1,a tight junction protein in the retina,was detected via immunohistochemistry,while Western blot analysis quantified the levels of ZO-1,occludin,and claudin-5 proteins in rat retinal tissue.Serum vascular endothelial growth factor(VEGF)levels were measured using an ELISA kit.RESULTS:Results showed that OCT,FFA,HE staining,and transmission electron microscopy indicated a significant reduction in retinal thickness in the MOD group compared to the CON group(P＜0.05).In contrast,the retinal thickness increased in the CDC,PLL,and PLH groups compared to the MOD group,with significant improvement observed in the PLH group(P＜0.05).Additionally,the number of RGCs increased,and sodium fluorescein leakage from fundus mi-crovessels decreased in the CON group relative to the administered groups.Transmission electron microscopy revealed ir-regular deformation of RGC nuclei,mitochondrial reduction and swelling,and organelle loss in the MOD group compared to the CON group.However,the CDC,PLL,and PLH groups demonstrated varying degrees of improvement in cellular layers.EB leakage assay results indicated a significant increase in retinal EB leakage in the MOD group compared to the CON group(P＜0.01).EB leakage was significantly reduced in the CDC group compared to the MOD group(P＜0.01),with some reduction also observed in the PLL and PLH groups(P＜0.05,P＜0.01).Immunohistochemistry and Western blot analyses revealed a significant decrease in the expression of retinal tight junction proteins ZO-1,occludin,and clau-din-5 in the MOD group compared to the CON group(P＜0.05).Protein expression was notably higher in the CDC group compared to the MOD group(P＜0.01),with increases also observed in the PLL and PLH groups(P＜0.05,P＜0.01).ELISA results showed that VEGF levels were significantly higher in the MOD group compared to the CON group(P＜0.01).The CDC,PLL,and PLH groups exhibited varying degrees of reduction in VEGF levels compared to the MOD group(P＜0.05,P＜0.01).CONCLUSION:These findings suggest that PL effectively ameliorates retinal NVU damage in DR rats.

AIM:The objective of this study was to investigate the ameliorative effect of Erjing pills(PL)on the functional impairment of the diabetic retinal neurovascular unit(NVU)in rats.METHODS:A diabetic retinopathy(DR)model was established using BN rats,which were then treated with freeze-dried Erjing pills powder.After 12 weeks,various assessments were conducted:retinal thickness was measured using OCT,fundus lesions were evaluated with FFA,and retinal cell structure,arrangement,and layer thickness were analyzed through HE staining.Additionally,transmission electron microscopy was employed to examine ultrastructural changes in retinal ganglion cells(RGCs),and retinal leakage was assessed using EB in vivo perfusion.The expression of ZO-1,a tight junction protein in the retina,was detected via immunohistochemistry,while Western blot analysis quantified the levels of ZO-1,occludin,and claudin-5 proteins in rat retinal tissue.Serum vascular endothelial growth factor(VEGF)levels were measured using an ELISA kit.RESULTS:Results showed that OCT,FFA,HE staining,and transmission electron microscopy indicated a significant reduction in retinal thickness in the MOD group compared to the CON group(P＜0.05).In contrast,the retinal thickness increased in the CDC,PLL,and PLH groups compared to the MOD group,with significant improvement observed in the PLH group(P＜0.05).Additionally,the number of RGCs increased,and sodium fluorescein leakage from fundus mi-crovessels decreased in the CON group relative to the administered groups.Transmission electron microscopy revealed ir-regular deformation of RGC nuclei,mitochondrial reduction and swelling,and organelle loss in the MOD group compared to the CON group.However,the CDC,PLL,and PLH groups demonstrated varying degrees of improvement in cellular layers.EB leakage assay results indicated a significant increase in retinal EB leakage in the MOD group compared to the CON group(P＜0.01).EB leakage was significantly reduced in the CDC group compared to the MOD group(P＜0.01),with some reduction also observed in the PLL and PLH groups(P＜0.05,P＜0.01).Immunohistochemistry and Western blot analyses revealed a significant decrease in the expression of retinal tight junction proteins ZO-1,occludin,and clau-din-5 in the MOD group compared to the CON group(P＜0.05).Protein expression was notably higher in the CDC group compared to the MOD group(P＜0.01),with increases also observed in the PLL and PLH groups(P＜0.05,P＜0.01).ELISA results showed that VEGF levels were significantly higher in the MOD group compared to the CON group(P＜0.01).The CDC,PLL,and PLH groups exhibited varying degrees of reduction in VEGF levels compared to the MOD group(P＜0.05,P＜0.01).CONCLUSION:These findings suggest that PL effectively ameliorates retinal NVU damage in DR rats.

Objective To investigate the antimicrobial resistance of Streptococcus pneumoniae strains isolated from multiple medical institutions across Hebei Province in 2015.Methods The bacterial data were collected from 53 member hospitals of Hebei Antimicrobial Resistance Investigation Net (HEBARIN) according to the unified surveillance program in Hebei province.WHONET 5.6 was used to review,analyze and summarize the surveillance data.The results were interpreted according to CLSI guideline 2014.Results A total of 2 408 strains of S.pneumoniae were included in this analysis.S.pneumoniae was the third most frequently isolated gram positive bacteria.More than 95％ of these S.pneumoniae strains were susceptible to vancomycin and moxifloxacin.However,96.4％,89.3％ and 67.4％ of these strains were resistant to erythromycin,clindamycin,and trimethoprim-sulfamethoxazole,respectively.The antimicrobial susceptibility profile was similar between the strains isolated from adults and those isolates from children.Conclusions The antimicrobial resistance profile ofS.pneumoniae isolates in Hebei Province is generally consistent with the nation-wide data,except higher resistance level to a few antimicrobial agents.We should be alert to and control the emergence of resistant S.pneumoniae.

Objective To study the effect of adeno associated virus hepatocyte growth factor K1(AAV‐HGFK1)on the prolifer‐ation of 4 different colorectal cell lines with or without KRAS or BRAF mutation .Methods The levels of epidermal growth factor receptor (EGFR) mRNA were determined in SW48 without KRAS or BRAF mutation ,Lovo with KRAS mutation ,SW620 with KRAS mutation ,HT29 with BRAF mutation by quantitative real time PCR ,respectively .After the infection of AAV‐HGFK1 ,the expressions of EGFR ,p‐EGFR and β‐actin were detected by Western blot and the proliferation of the cells were assayed using MTT .Results Lovo ,SW48 and HT29 expressed EGFR protein while SW620 did not .EGF promoted the proliferation of Lovo , SW48 and HT29 cells .AAV‐HGFK1 down‐regulated the phosphorylation of EGFR and significantly inhibited their proliferation . But EGF had no effect on proliferation of SW620 stimulated by EGF .Conclusion AAV‐HGFK1 exhibited its antitumor effects through EGF/EGFR signaling irrespective of the KRAS or BRAF mutation and may also act through other signaling pathways .

The control meaurees and endemic situation were analysed in Dali Prefecture,Yunnan Province. The infection rates of population and livestock decreased from 6.42% and 3. 81% in 2004 to 0.07% and 0.15% in 2008, respectively. No infected snail and acute schistosomiasis case were discovered in 2008. The proportion of villages with serious endemic situation decreased from 49.42% in 2004 to 7.51% in 2008, and 92.48% of villages reached the criteria of transmission control or transmission interruption. The endemic situation and snail status of Dali Prefecture have decreased significantly after the implementation of the comprehensive control project, but the consolidation and enlargement of the control result still remains a challenge.