This article reports two cases of proteinuria caused by anti-vascular endothelial growth factor (VEGF) drugs in the treatment of liver cancer and ovarian cancer, respectively. Hypertension, massive albuminuria and renal insufficiency occurred in the patient with liver cancer during the use of toripalimab/camrelizumab combined with lenvatinib and regorafenib, and urinary protein was 4.02 g/24 h. The patient with ovarian cancer developed hypertension, proteinuria and 1.13 g/24 h urinary protein during the use of bevacizumab. Renal biopsy showed thrombotic microangiopathy in the glomeruli of both patients. Anti-VEGF drugs-associated glomerular microangiopathy was considered. The patient with liver cancer had no improvement after halving the dose of lenvatinib, and the effect was not good after treatment with low-dose corticosteroids combined with renin-angiotensin-aldosterone system inhibitors. After stopping anti-VEGF drugs, the proteinuria in both patients turned negative.

【Objective】 To understand the structural characteristics of lapsed apheresis donors in our blood center and provide guidance for further improving recruitment and retention strategies by retrospectively analyzing the characteristics of lapsed apheresis donors in our center in recent years. 【Methods】 The apheresis donation and lapsed apheresis donors in Zhejiang Blood Center from 2016 to 2020 were statistically analyzed, and the general information of lapsed donors, including gender, blood type, age, education level and occupation composition, were compared and analyzed. The lapse of novel and long-term donors with different frequency were retrospectively analyzed. The SPSS 19.0 statistical software package was used for data analysis. 【Results】 In 2020, the total lapse of apheresis donors decreased by 16.6% as compared with 2016(P<0.05). The lapse rate of donors with blood groups A, B, O and AB was 1∶1∶1∶1, higher in female donors(59.0%) than males(50.0%), and dominated by age group of 18-35(66.3%). With the increase of age, the lapse rate decreased. Donors lapsed were mainly with college or above educational background(60.8%), with high proportion in students and the staff. In 2020, the lapse of novel apheresis donors decreased by 34.1% as compared with 2016, but the average lapse rate of novel apheresis donors was still as high as 70.5%. The average lapse rate of blood donors with different frequency was 52.5%, and the lapse rate decreased significantly with the increase of apheresis donation frequency. The average lapse rate of novel blood donors with whole blood donation experience was lower than those without (56.1% vs 82.9%). 【Conclusion】 Multiple measures for recruitment and retention have effectively reduced the lapse of apheresis donors. However, apheresis donors who are 18-35 years old, with college degree or above, students and staff were the main groups from lapsing. In addition, low-frequency and novel apheresis donors without whole blood donation experience were more likely to be lapsing. Targeted and personalized blood donation services should be further provided, and the management of " full cycle of blood donation" should be strengthened to reduce the lapsing, so as to retain more blood donors.

This study analyzed the current status of the cultivation process of professional postgraduates of clinical medicine, combining with the case of the auxiliary teaching model of Academic Salons on the WeChat platform in Xiangya Hospital of Central South University. We collected students' satisfaction evaluation of this auxiliary teaching model by questionnaire survey. Through analyzing the results and feedback, we found that the overall satisfaction of this auxiliary teaching model is 71.43%, and the model has a remarkable effect in broadening knowledge, inspiring thinking of clinical diagnosis and treatment, improving ability of scientific research, increasing learning interest, enhancing the ability to link theory with practice, and using the knowledge flexibly. However, there are still some shortcomings in early publicity, understanding students' interests and needs, and improving students' autonomous learning ability. Therefore, using the WeChat platform to carry out academic salons is a good auxiliary teaching model for cultivating the scientific research ability of professional postgraduates of clinical medicine.

Objective:To investigate the effect of fluorofenidone on renal interstitial fibrosis in rats with unilateral ureteral obstruction (UUO) and to observe the effect of fluorofenidone on the expressions of collagen type Ⅰ (Col Ⅰ),collagen type Ⅲ (Col Ⅲ),α-smooth muscle actin (α-SMA),connective tissue growth factor (CTGF),platelet derived growth factor (PDGF) in the renal tissues of UUO rats.Methods:Male Sprague-Dawley (SD) rats were randomly divided into a sham-operated group,a UUO group,and a flurofenidone group (n=5).UUO model was induced by ligating the left ureter in rats.The rats were treated with 125 mg/(kg.d) fluorofenidone by gastric gavage in the fluorofenidone group at 24 h before the operation,and the rats were treated with the identical dose of 0.5％ sodium carboxyl methyl cellulose (CMC-Na) in the other 2 groups.The rats were sacrificed at 14 days after UUO.Pathological changes of the renal tissue were observed by HE and Masson staining,the mRNA expressions of Col Ⅰ,Col Ⅲ,α-SMA,PDGF and CTGF were detected by real-time PCR,and the protein expressions of Col Ⅰ,Col Ⅲ,PDGF and CTGF were detected by immunohistochemical staining.Results:The renal interstitial damage index,relative collagen area and mRNA and protein expressions of Col Ⅰ and Col Ⅲ in the renal tissues of the rats in the UUO group significantly increased (P＜0.05),and fluorofenidone could reduce these indexes (P＜0.05).Compared with the sham-operated group,the protein expressions ofα-SMA,PDGF,CTGF and the mRNA expressions of PDGF and CTGF in the renal tissues of the rats in the UUO group were increased,but fluorofenidone could decrease the protein expressions of α-SMA,PDGF,CTGF and the mRNA expressions of PDGF and CTGF (P＜0.05).Conclusion:Fluorofenidone (125 mg/kg·d) could attenuate renal interstitial fibrosis through inhibition offibroblast proliferation,myofibroblastic activation,PDGF and CTGF expression.

Objective To investigate the effects of fluorofenidone(AKF-PD)on diabetic kidney disease in db/db mice and its possible mechanisms.Methods(1)Fifty-six mice aged 8 weeks(half male and half female),including 42 db/db mice and 14 wild-type mice were studied.Fortytwo db/db mice randomly were divided into model group(mock-treated diabetic db/db mice),AKF-PD(250 mg· kg-1· d-1)treatment group and losartan(20 mg· kg-1· d-1)treatment group.Wild-type mice and model mice were treated with vehicle(0.5％sodium carboxymethylcellulose),while the treatment groups received either AKF-PD or losartan.After 18 weeks,the blood glucose and urinary albumin were measured,the pathological changes of kidney were observed by PAS staining.The protein expressions of type Ⅳ collagen and fibronectin(FN)in kidney tissue were detected by immunohistochemistry.(2)Mouse glomerular mesangial cells(MES-13 cells)were divided into six groups:normal glucose group(5.5 mmol/L glucose),hypertonic group(5.5 mmol/L glucose+19.5 mmol/L mannitol),high glucose group(25.0 mmol/L glucose),AKF-PD group(25.0 mmol/L glucose+400 mg/L AKF-PD)and losartan group(25.0 mmol/L glucose+2 μmol/L losartan).After 72 h treatment,the expressions of type Ⅰ collagen,type Ⅳ collagen and transforming growth factor-β1(TGF-β1)mRNA were detected by realtime PCR,and the content of TGF-β1 protein in the culture supernatant was detected by ELISA.Results(1)Compared with the wild type mice,model mice had increased weight,blood glucose and glomerulosclerosis index(all P ＜ 0.01),accompanied with heavy albuminuria,glomerular hypertrophy,mesangial area expansion and deposition of collagen type Ⅳ and FN(all P ＜ 0.01).Compared with model mice,in AKF-PD and losartan groups 24 h urinary albumin and glomerulosclerosis index decreased(all P ＜ 0.01),glomerular hypertrophy and mesangial area expansion alleviated,and the protein expressions of collagen type Ⅳ and FN were inhibited(all P ＜ 0.01).(2)Compared with the normal glucose group,the mRNA expressions of type Ⅰ collagen and type Ⅳ collagen increased in high glucose group,meanwhile the mRNA and protein expressions of TGF-β1 increased(all P ＜ 0.01).In AKF-PD and losartan groups the expressions of type Ⅰ collagen,type Ⅳ collagen and TGF-β1 were inhibited as compared with high glucose group(all P ＜ 0.05).Conclusion Fluorofenidone may play an anti-fibrotic effect in db/db mice by reducing the expression of TGF-β1 and inhibiting collagen synthesis in glomerular mesangial cells.

Objective To investigate effects of pirfenidone (PFD) on diabetic nephropathy model in db/db mice and to explore its possible mechanisms.Methods (1) Wild-type mice were as the normal control group,and db/db mice were divided into model group and PFD group,with 6 mice in each group.In the PFD group mice were administered continuously by 250 mg· kg-1· d-1 PFD for 18 weeks,and mice in the other two groups were administered by 0.5％ sodium carboxymethyl cellulose.Blood glucose and 24 h urinary albumin were measured.The pathological changes of renal tissue were evaluated by PAS staining,PASM staining,Masson staining and Sirius red staining.The expression of collagen type Ⅳ in kidney tissues was detected by immunohistochemistry.(2) Mouse mesangial cells (SV40 MES-13 cells) were cultured as research objects.They were divided into control group,hyperosmolar group,high glucose (HG) group,and 50,100,200,400,800,1600 mg/L PFD+HG group.BrdU cell proliferation test was used to evaluate cell proliferation rate.Cells were divided into control group,hyperosmolar group,HG group and PFD+HG group.The mRNA expressions of α-smooth muscle actin (α-SMA),collagen type Ⅰ,collagen type Ⅳ,transforming growth factor-β1 (TGF-β1),interleukin (IL)-1β,IL-6 and monocyte chemotactic protein-1 (MCP-1) were detected by real-time PCR.Results (1) Compared with normal control group,the model mice had higher weight,blood glucose and 24 h urinary albumin,accompanied with glomerular hypertrophy,mesangial area expansion,tubulointerstitial fibrosis and deposition of collagen type Ⅳ (all P ＜ 0.05).Compared with those in model group,in PFD group 24 h urinary albumin decreased,glomerular hypertrophy,mesangial area expansion and tubulointerstitial fibrosis alleviated,and the protein expression of collagen type Ⅳ inhibited (all P＜0.05).(2) Compared with those in HG group,MES-13 cell proliferation rates of 100,200,400,800,1600 mg/L PFD+HG groups decreased (all P ＜ 0.05),and the mRNA expressions of α-SMA,collagen type Ⅰ,collagen type Ⅳ,TGF-β1,IL-1β,IL-6 and MCP-1 reduced in 400 mg/L PFD+HG group (all P ＜ 0.05).Conclusions PFD can inhibit high glucose-induced proliferation and activation of glomerular mesangial cells,decrease the expression of TGF-β1 and proinflammatory factors,as well as reduce the synthesis of collagen,which improve renal fibrosis of db/db mice.

Objective To evaluate immune protective effects of Treponema pallidum(Tp)pcD/Tp92 DNA vaccine delivered through different inoculation routes against Tp-induced skin infection in New Zealand rabbits. Methods A total of 108 New Zealand rabbits were randomly and equally divided into 6 groups:A1 and A2 groups treated with intramuscular injection of empty plasmids pcD and pcD/Tp92 DNA vaccine respectively for 2 sessions, B1, B2, C1 and C2 groups firstly treated with intramuscular injection of the pcD/Tp92 DNA vaccine for 1 session for primary immunization, then receiving nasogastric feeding with pcD/Tp92 DNA vaccine, pcD/Tp92 DNA vaccine+cytosine-phosphate-guanine(CpG)oligodeoxynucleotide (ODN), and recombinant Tp92 protein, and recombinant Tp92 protein+CpG ODN respectively for booster immunization. Enzyme-linked immunosorbent assay(ELISA)was conducted to detect the serum level of anti-Tp92 IgG antibody at week 0, 2, 4, 6, 8 after immunization, the SIgA level in the nasopharyngeal region and vaginal mucosa at week 8 after immunization, as well as levels of interleukin-2(IL-2)and interferon-γ (IFN-γ)in the culture supernatant of rabbit spleen cells at week 8 after immunization, and methyl thiazolyl tetrazolium(MTT)assay was performed to estimate proliferative activity of rabbit splenic lymphocytes in three rabbits from each group. At week 10 after immunization, other 15 rabbits from each group were subcutaneously inoculated with Tp standard strain, and changes of skin lesions at the inoculation site during early-stage infection were observed and recorded. Results At week 8 after immunization, the C2 group showed significantly higher serum level of anti-Tp92 IgG antibody(1.825 ± 0.175), supernatant levels of IL-2 (154.7 ± 14.6)and IFN-γ(277.4 ± 24.4), and proliferative activity of T cells(3.57 ± 0.24)compared with the A2(1.372 ± 0.322, 112.3 ± 13.4, 232.8 ± 25.3, 3.08 ± 0.22, respectively, all P<0.05), B1(0.893 ± 0.297, 76.6 ± 21.5, 165.7 ± 22.6, 2.12 ± 0.14, respectively, all P<0.05)and B2(1.294 ± 0.124, 97.3 ± 18.7, 211.3 ± 24.6, 2.88 ± 0.18, respectively, all P<0.05)groups. In addition, effective immunoprotection was achieved in the C2 group with more production of mucosa-specific SIgA antibody, as well as the lowest Tp-positive rate (6.67%) and ulcer formation rate (6.67%) in skin lesions at the inoculation sites. Conclusion The effective vaccination strategy, namely intramuscular injection of the pcD/Tp92 DNA vaccine for primary immunization followed by nasogastric feeding with mucosal adjuvant CpG ODN combined with recombinant Tp92 protein for booster immunization, can induce the strongest mucosal immune responses and immune protective effects.

OBJECTIVE: To establish the evaluation index system for equalization of basic public health services and to test its value in practice. METHODS: We developed the index system through expert scored evaluation and then chose a city in Hunan for the research object. The sources of data and the methods of collection for each indicator were identified. The reliability and validity of index system was tested. The methods of AHP (analytic hierarchy process) and TOPSIS (technique for order preference by similarity to an ideal solution) were applied to comprehensively evaluate the public health services among nine counties in the city. RESULTS: The Cronbach's alpha coefficient, which described reliability test result on evaluation index system for equalization of basic public health services, was 0.750. The cumulative contribution rate reached 89.32% after validity test with extraction of 5 common factors through factor-analysis. The sorting results from AHP or TOPSIS method are very close except two districts. CONCLUSION Evaluation index system for equalization of basic public health services established in this study is in good validity and reliability, which can be objectively applied to analyze the current status of basic public health services.
China ; Health Services ; standards ; Health Services Research ; Public Health ; Reproducibility of Results ; Surveys and Questionnaires

Fibrosis can occur in different organs with high incidence rate and great danger. It still lacks effective drugs for prevention of fibrosis. Fluorofenidone is a newly developed drug with anti-fibrotic activity, which provides a new hope for treating the progressive fibrotic diseases. Recent studies have shown that fluorofenidone is a multifunctional small molecule with anti-inflammatory, antioxidative and anti-apoptotic eff ects. It can inhibit the activation and proliferation of myofibroblasts, promote the degradation of extracellular matrix and regulate the cellular signal transmission. Fluorofenidone can be applied to attenuate the progression of renal, hepatic and pulmonary fibrosis.
Apoptosis ; Extracellular Matrix ; Fibrosis ; Humans ; Kidney ; pathology ; Liver Cirrhosis ; Pulmonary Fibrosis ; Pyridones ; pharmacology ; Signal Transduction

OBJECTIVE: To develop a scientific and effective evaluation index system for equalization of basic public health services. METHODS: Through 2 rounds of expert evaluation, based on the relative importance of expert scoring on each index, index was screened according to the scores of mean and coefficient of variation and the weight were determined. RESULTS: The two rounds of consulting experts response rates were more than 90%, and the average authority coefficients were 0.779 and 0.781. The coordination coefficients were 0.229 and 0.349. The evaluation index system of basic public health services was composed of 3 first level, 17 second level and 47 third level indicators after 2 rounds of consultation. CONCLUSION The evaluation index system of basic public health services is reasonable, and it can be used to evaluate the equalization of basic public health services.
Health Services ; standards ; Health Services Research ; Public Health ; standards