Therapeutic Effectiveness of Leukocyte- and Platelet-rich Fibrin for Diabetic Foot Ulcers: A Retrospective Study.

OBJECTIVE: Diabetic foot ulcer (DFU) is one of the most serious complications of diabetes. Leukocyte- and platelet-rich fibrin (L-PRF) is a second-generation autologous platelet-rich plasma. This study aims to investigate the clinical effects of L-PRF in patients with diabetes in real clinical practice. METHODS: Patients with DFU who received L-PRF treatment and standard of care (SOC) from 2018 to 2019 in Tongji Hospital were enrolled. The clinical information including patient characteristics, wound evaluation (area, severity, infection, blood supply), SOC of DFU, and images of ulcers was retrospectively extracted and analyzed. L-PRF treatment was performed every 7±2 days until the ulcer exhibited complete epithelialization or an overall percent volume reduction (PVR) greater than 80%. Therapeutic effectiveness, including overall PVR and the overall and weekly healing rates, was evaluated. RESULTS: Totally, 26 patients with DFU were enrolled, and they had an ulcer duration of 47.0 (35.0, 72.3) days. The severity and infection of ulcers varied, as indicated by the Site, Ischemia, Neuropathy, Bacterial Infection, and Depth (SINBAD) scores of 2-6, Wagner grades of 1-4, and the Perfusion, Extent, Depth, Infection and Sensation (PEDIS) scores of 2-4. The initial ulcer volume before L-PRF treatment was 4.94 (1.50, 13.83) cm3, and the final ulcer volume was 0.35 (0.03, 1.76) cm3. The median number of L-PRF doses was 3 (2, 5). A total of 11 patients achieved complete epithelialization after the fifth week of treatment, and 19 patients achieved at least an 80% volume reduction after the seventh week. The overall wound-healing rate was 1.47 (0.63, 3.29) cm3/week, and the healing rate was faster in the first 2 weeks than in the remaining weeks. Concurrent treatment did not change the percentage of complete epithelialization or healing rate. CONCLUSION: Adding L-PRF to SOC significantly improved wound healing in patients with DFU independent of the ankle brachial index, SINBAD score, or Wagner grade, indicating that this method is appropriate for DFU treatment under different clinical conditions.

[siRNAs targeting La, hVAP-33, eIF2Bgamma, and HCV IRES inhibit the replication and expression of HCV in Huh7 cells].

OBJECTIVE: To investigate the in vivo functional roles of the La autoantigen (La), the human homologue of the 33-kDa vesicle-associated membrane protein-associated protein (hVAP-33), and the subunit gamma of the human eukaryotic initiation factors 2B (eIF2Bgamma) as co-infection factors supporting chronic infection with hepatitis C virus (HCV). METHODS: Small interfering (si)RNAs were designed against the HCV internal ribosome entry site (IRES) and transfected into Huh7 cells chronically infected with the HCV pseudovirus (designated as Huh7-HCV cells). The IRES siRNA producing the most effective silencing was selected for further analysis by fluorescence quantitative polymerase chain reaction (qPCR). siRNAs designed against La, hVAP-33, and eIF2Bgamma and the IRES-specific siRNA were then transfected, respectively or in various combinations, into the Huh7-HCV cell line for 48 h. The delta CT values were calculated and used to compare the HCV inhibitive efficacies of the siRNAs in isolation or in combination. Western blotting analysis was used to compare the quantity of core protein expression in each group. RESULTS: The four gene-specific siRNAs, in isolation or in combination, caused inhibition of HCV replication and gene and protein expressions to varying degrees. The combination of La + IRES siRNAs produced the strongest inhibition of HCV core antigen expression. The combinations of hVAP-33 + IRES siRNAs and eIF2Bgamma + IRES siRNAs produced stronger inhibitions of HCV replication and gene and protein expressions than either hVAP-33 siRNA or eIF2Bgamma siRNA alone. CONCLUSION: La, hVAP-33, and eIF2Bgamma act as co-infection factors of HCV chronic infection in vivo. HCV replication and gene and protein expression can be inhibited significantly by RNA interference of these co-infection factors and/or HCV IRES.

Nickel oral bioavailability in contaminated soils using a mouse urinary excretion bioassay: Variation with bioaccessibility.

To assess the health risk of nickel (Ni) in contaminated soils, studies rarely evaluated Ni bioavailability in the gastrointestinal (GI) tract, limiting the accurate regulation of contaminated sites. Here, for 15 soil samples contaminated by Ni-electroplating, Ni oral relative bioavailability (RBA, relative to NiSO4) was measured using a mouse urinary excretion bioassay. Nickel-RBA varied from 7.89% to 33.8% at an average of 19.1 ± 18.6%. The variation was not explained well by variation in soil properties including Ni speciation and co-contamination of other metals, which showed weak correlation with Ni-BRA (R2 < 0.36). In comparison, the Ni-RBA variation was explained well by the variation of soil-Ni solubility in simulated human gastric or gastrointestinal fluids, i.e., Ni bioaccessibility. Determined using the gastric (GP) and intestinal phases (IP) of solubility bioaccessibility research consortium (SBRC), physiologically based extraction test methods (PBET), and unified BARGE method (UBM), Ni bioaccessibility explained 54-71% variation of the Ni-RBA, suggesting that Ni oral bioavailability was predominantly controlled by Ni solubility in the GI tract. The results highlight the suitability of using simple, fast, and cost-effective bioaccessbility assays to predict site-specific Ni oral bioavailability.

Financial barrier against access to diagnostic procedures among enteric fever suspects in highly-endemic areas of China.

There is currently no public financial system that fully covers enteric fever suspects in China. This study aimed at documenting the level of access to definitive diagnostic procedures, especially haemoculture, for these patients and examining the effect of health insurance on access to such care. A hospital-based cross-sectional study was conducted in six counties of Yunnan province, using a structured questionnaire and data extraction from medical records. In total, 714 subjects were recruited. Chi-square test and logistic regression were employed for analysis of data. The majority of the subjects were young adults (52%) and farmers (55%) from low-income families (49%). Only 407 (57%) could afford haemoculture routinely advised by their doctors. Of these, 123 (30%) had haemoculture positive for Salmonella Typhi. After adjustment for income, not getting haemoculture was marginally associated with percentage of reimbursement from the insurance (p value for trend=0.047). Illiteracy was also an independent risk factor for this outcome. The poor coverage of haemoculture for patients suspected of having enteric fever in this endemic area was due to financial barrier. The current health-insurance system inadequately relieved the problem. Further financial reform to help patients suspected with enteric fever is required.

Whole-genome sequencing reveals origin and evolution of influenza A(H1N1)pdm09 viruses in Lincang, China, from 2014 to 2018.

The continuous variation of the seasonal influenza viruses, particularly A(H1N1)pdm09, persistently threatens human life and health around the world. In local areas of southwest china, the large time-scale genomic research on A(H1N1)pdm09 is still insufficient. Here, we sequenced 45 whole-genome sequences of influenza A(H1N1)pdm09 viruses in Lincang, China, from 2014 to 2018, by next-generation sequencing technology to characterize molecular mechanisms of their origin and evolution. Our phylogenetic analyses suggest that the A(H1N1)pdm09 strains circulating in Lincang belong to clade 6B and the subclade 6B.1A predominates in 2018. Further, the strains in 2018 possess elevated evolutionary rate as compared to strains in other years. Several newly emerged mutations for HA (hemagglutinin) in 2018 are revealed (i.e., S183P and R221K). Intriguingly, the substitution R221K falls into the RBS (receptor binding site) of HA protein, which could affect antigenic properties of influenza A(H1N1)pdm09 viruses, and another substitution S183P near to RBS with a high covering frequency (11/14 strains) in 2018 is exactly located at the epitope B. Notably, the NA (neuraminidase) protein harbors a new mutation I23T, potentially involved in N-glycosylation. Based on the background with a higher evolutionary rate in 2018 strains, we deeply evaluate the potential vaccine efficacy against Lincang strains and discover a substantive decline of the vaccine efficacy in 2018. Our analyses reaffirm that the real-time molecular surveillance and timely updated vaccine strains for prevention and control of influenza A(H1N1)pdm09 are crucial in the future.

[Expression of TGF-beta1/Smad protein in rat liver fibrosis model and the role of IFN-gamma].

OBJECTIVE: To study the impact of IFN-gamma on liver fibrosis and its possible mechanism. Thirty healthy male SD rats were randomly divided into two groups: fibrosis model group, IFN-gamma treatment group. Experimental liver fibrosis was induced by subcutaneous injection of CCl4. After 12-week-treatment, serum hyalurnic acid and TGF-beta1 was examined, histopathological changes and degrees of fibrosis were observed by optical microscopy. Meanwhile, the expression of TGF-beta1, TbetaR- I and Smad2/3 proteins was detected by immunohistochemistry and quantified by using computerized image analysis. RESULTS: (1) Pathological observation of hepatic specimens: histological examination showed that there were significant difference between normal group and fibrosis model group by comparing with the degrees of inflammation and fibrosis (P < 0.05). And the difference between fibrosis model group and IFN-gamma treatment group was significant (P < 0.05). (2) Changes of the hepatic fibrosis index (serum HA and TGF-beta1): the levels of serum HA, TGF-beta1 in fibrosis model group were higher than IFN-gamma treatment groups (P < 0.05). (3) Changes of gene protein levels about TGF-beta1/Smad: the expressions of TGF-beta1, TbetaR- I and Smad2/3 in rat hepatic tissue were detected with immunohistochemistry techniques. The expressions of the three items in model group were higher than normal group (P < 0.01). The difference between model group and IFN-gamma treatment group was significant (P < 0.05); CONCLUSION: IFN-gamma treatment group had significant results on treating experimental hepatic fibrosis. By the way of inhibiting expressions of TGF-beta1, TbetaR- I, Smad2/3, IFN-gamma treatment group exerted its anti-fibrosis effect.

Spatiotemporal transmission and determinants of typhoid and paratyphoid fever in Hongta District, Yunnan Province, China.

BACKGROUND: Typhoid and paratyphoid fever are endemic in Hongta District and their prevalence, at 113 per 100,000 individuals, remains the highest in China. However, the exact sources of the disease and its main epidemiological characteristics have not yet been clearly identified. METHODS AND FINDINGS: Numbers of typhoid and paratyphoid cases per day during the period 2006 to 2010 were obtained from the Chinese Center of Disease Control (CDC). A number of suspected disease determinants (or their proxies), were considered for use in spatiotemporal analysis: these included locations of discharge canals and food markets, as well as socio-economic and environmental factors. Results showed that disease prevalence was spatially clustered with clusters decreasing with increasing distance from markets and discharge canals. More than half of the spatial variance could be explained by a combination of economic conditions and availability of health facilities. Temporal prevalence fluctuations were positively associated with the monthly precipitation series. Polluted hospital and residential wastewater was being discharged into rainwater canals. Salmonella bacteria were found in canal water, on farmland and on vegetables sold in markets. CONCLUSION: DISEASE TRANSMISSION IN HONGTA DISTRICT IS DRIVEN PRINCIPALLY BY TWO SPATIOTEMPORALLY COUPLED CYCLES: one involving seasonal variations and the other the distribution of polluted farmland (where vegetables are grown and sold in markets). Disease transmission was exacerbated by the fact that rainwater canals were being used for disposal of polluted waste from hospitals and residential areas. Social factors and their interactions also played a significant role in disease transmission.

Rule of Chinese medicine syndrome differentiation in the patients with thoracic diseases at perioperation stage.

OBJECTIVE: To study the rule of syndrome differentiation in the patients with thoracic diseases at perioperation stage. METHODS: A standard was created referring to the related literature, and it was applied to differentiate the Chinese medicine syndrome in 150 patients before and three days after thoracic operation. RESULTS: Before operation, Chinese medicine syndromes were as differentiated as phlegm type in 45.3%, blood stasis type in 17.3%, and qi-stagnancy type in 16.0%. The patients with asthenia syndrome markedly increased after operation, accounting for 34.0% (51 patients, including qi-, yin-, and blood-deficiency syndromes). The most frequently seen intermixed syndromes were qi-deficiency with phlegm-stasis syndrome and Pi ()-deficiency with phlegm-dampness syndrome. The intermixed syndromes revealed in 37.5% and 42.0% of the patients before and after operation, respectively. CONCLUSIONS: The syndrome in the patients with thoracic disease before operation was mostly the excessive syndrome, mainly the phlegm syndrome type; at postoperation stage, Chinese medicine syndrome in patients become asthenia in essence with excessive superficiality, which is mostly revealed as Pi-deficiency with phlegm-dampness.

[Burden of disease regarding paratyphoid fever A - based on the Syndromic Surveillance System on Fever].

OBJECTIVE: To evaluate the burden of paratyphoid fever A in Hongta district, Yuxi city, Yunnan province from May 1, 2008 to April 30, 2009 so as to provide information for the development of comprehensive intervention measures. METHODS: Based on the Fever Syndromic Surveillance System, information as attendance rate of patients with fever, rate of patients being sampled, laboratory testing rate, sensitivity on the detection of blood culture and the rate of case reporting etc. were calculated. According to the pyramid model of food-borne disease on disease burden, the local actual incidence of paratyphoid fever A was estimated and analyzed. RESULTS: Under the Fever Syndromic Surveillance System, there were 6642 fever cases being detected, among whom 6570 cases were sampled and undergone testing, with the sampling rate as 98.92% and all the samples received laboratory testing. There were 354 positive cases of paratyphoid fever A reported, all from the Hongta district. Data showed that the attendance rate of the feverish patients was 73.53%, with the highest rate seen in whose under 10 years old (100%). Assumed that the sensitivity of paratyphoid fever blood culture was 70%, and the case reporting rate was 90%, we estimated that the annual incidence of paratyphoid fever A in Hongta was 220.33 (95%CI: 170.1 - 521.4) per 100 thousand, with 965 (95%CI: 745 - 2284) as new cases. Among all the age groups, the incidence in the age group from 15 to 44 years old was estimated to be at the highest (318.27 per 100 thousand). CONCLUSION: Hongta seemed to be an endemic region for paratyphoid fever A, with the highest incidence occurred in the age group of between 15 and 44 years old. These findings highlighted the urgent need to carry out further investigation on the risk factors and to implement targeted effective prevention and control measures.

[Typhoid and paratyphoid fever in Yunnan province: distributional patterns and the related meteorological factors].

OBJECTIVE: To characterize the spatial distribution of typhoid and paratyphoid fever (TPF) in Yunnan province, China and to determine the effectiveness of meteorological factors on the epidemics of TPF. METHODS: Data of reported TPF cases in Yunnan province (2001 - 2007) from the China Information System for Diseases Control and Prevention was applied to GIS-based spatial analyses to detect their spatial distribution and clustering of TPF incidence at the county level. Panel data analysis was used to identify the relationships between the TPF incidence and meteorological factors including monthly average temperature, monthly cumulative precipitation and monthly average relative humidity. RESULTS: During the study period, the average incidence of TPF in Yunnan province was 23.11/100 000, with majority of the TPF cases emerged in summer and autumn. Although widely distributed, two TPF clusters were detected in Yunnan province based on the spatial analysis: one area around Yuxi city with the average annual incidence as 207.45/100 000 and another at the junctions of Yunnan province with Burma and Laos. Based on results from panel data analysis, the incidence of TFP was shown to be associated with meteorological factors such as temperature, precipitation, relative humidity and one month lag of temperature increase [10°C increase in the monthly average temperature: IRR = 1.30 (95%CI: 1.24 - 1.36); 10% increase in monthly average relative humidity: IRR = 1.07 (95%CI: 1.05 - 1.09); 100 mm rise in monthly cumulative precipitation: IRR = 1.02 (95%CI: 1.00 - 1.03); and 10°C average temperature increase, the last month: IRR = 1.73 (95%CI: 1.64 - 1.82)]. CONCLUSION: Areas with high TPF incidence were detected in this study, which indicated the key areas for TPF control in Yunnan province. Meteorological factors such as temperature, precipitation and humidity played a role in the incidence of TPF.

Effect of Yiqi Bufei recipe [see text] on patients with pulmonary incompetence after pneumonectomy.

OBJECTIVE: To study the effect of Yiqi Bufei Recipe ([see text], YBR) on surgical tolerability, pulmonary compensatory function and post-operation rehabilitation in patients with pulmonary incompetence (PI) after pneumonectomy. METHODS: YBR intervention was applied to 60 patients with PI after pneumonectomy (as test group), the pulmonary and cardiac functions changes before and after operation, occurrence of postoperative complications, mortality, and the number of hospitalization days and intensive care unit (ICU) confinement period were observed. Meantime, for the negative and positive controls, the same parameters were observed comparatively in 60 patients with normal lung function, and in 60 patients with PI undergoing a similar operation but untreated with Chinese herbs. RESULTS: Lung function in the test group showed insignificant change before and after operation (P >0.05), while significant decrease was seen in the two control groups (P<0.05). Furthermore, the incidences of post-operation complications and mortality as well as the number of hospitalization days and the ICU confinement period in the test group were significantly lower than those in the positive control group respectively (P <0.05). CONCLUSION: YBR could relieve lung injury after pneumonectomy, improve surgical tolerability, reduce the length of postoperative hospitalization days and ICU confinement period, and lower the incidence of postoperative complications and mortality in patients with PI after pneumonectomy.