Objective To observe the changes to,and possible mechanism of,intestinal permeability in pigs without direct injury after an abdominal-and intestinal-penetrating injury from firearms in cold environment at high altitudes.Methods Fifty-five experimental pigs were divided into two groups:high-altitude cold group(HC)and low-altitude normal temperature group(LN).According to the observation time,each group was divided into five experimental subgroups:0h,2h,4 h,8h,and 24 h.There were six pigs in each HC subgroup and five pigs in each LN subgroup.After euthanasia,intestinal tissues were taken,and the levels of the inflammatory factors TNF-α,and IL-6 in intestinal homogenate and the concentrations of intestinal permeability-related proteins DAO and D-lactate acid in blood were detected by ELISA method.The intestinal tissues of experimental pigs were taken at 0 h and 8 h for LN and 8 h for HC,and intestinal pathological changes were observed and scored after HE staining.The concentrations of Occludin,ZO-1,Claudin-3,TLR4,NF-κB,and MLCK(proteins related to intestinal permeability)were detected by Western blot to explore the effect of a cold environment at high altitude on secondary intestinal permeability changes after injury and the possible mechanisms.Results Both the HC group and LN group experienced typical abdominal intestinal penetrating injuries,and there were no significant differences in their abdominal infection scores or intestinal adhesion(P＞0.05).The levels of DAO and D-LA in the serum of experimental pigs in the HC and LN groups gradually increased over time.The levels of DAO and D-LA in the HC group were significantly higher than those in the LN group at all time points(P＜0.01 or P＜0.001).The fastest increase in DAO and D-LA in the HC group was 4 h to 8 h,while in the LN group,it was 8 h to 24 h.The pathological score of intestinal tissue in the HC group was significantly higher than that in the LN group of experimental pigs(P＜0.01).The inflammatory factors TNF-α and IL-6 both increased over time in the intestinal tissue of LN and HC groups.The most significant time point for a increase of inflammatory factors in the HC group was 4 h to 8 h,while in the LN group,it was 8 h to 24 h.The intestinal tissue IL-6 and TNF-α levels of experimental pigs in the HC group were higher than those in the LN group the entire time(P＜0.05,P＜0.01,or P＜0.001).The levels of occludin and ZO-1 in the HC group at 8 h decreased significantly compared to those of the LN group at the 8 h time point(P＜0.05),while claudin-3 showed a significant decrease in LN(P＜0.001).In the HC group,TLR4,NF-κB,and MLCK were both higher than those in the LN group at 8 h,and the difference was statistically significant(P＜0.05).Conclusions A high-altitude cold environment can lead to a secondary increase in intestinal permeability after abdominal-penetrating firearm injury,and its mechanism may be related to the TLR4/NF-κB/MLCK pathway.

Objective:To explore the clinical efficacy of ceftazidime/avibactam(CZA)plus aztreonam(ATM)for New Delhi metallo-β-lactamase(NDM)carbapenem-resistant Klebsiella pneumoniae(CRKP)infection after kidney transplantation.Methods:Clinical data are retrospectively reviewed for 11 RT recipients infected with NDM metallo-β-lactamase CRKP admitted into First Affiliated Hospital of Xi 'an Jiaotong University and Affiliated Renji Hospital of Shanghai Jiao Tong University from November 2018 to December 2019.Based upon treatment protocol, they are divided into two groups of ceftazidime/avibactam plus aztreonam(CZA-ATM, 5 cases)and other effective antibiotics(OAA, 6 cases).Age, gender, infection type, drug resistance gene, changes in body temperature and leucocyte count, treatment course and prognosis are summarized.Results:A total of 11 patients with NDM-producing CRKP infection after RT are recruited.There are seven males and four females with an age range of(19~66)(38.9±14.4)years.There are mixed pulmonary and urinary tract infections(3 cases), urinary tract infection(2 cases), pulmonary infection(1 case)and perirenal infection(5 cases).All isolates harbore NDM carbapenemase gene, 5 isolates carry Klebsiella pneumoniae carbapenemase(KPC)gene and 1 isolate contained both imipenemase metallo-β-lactamase(IMP)and verona integron-encoded metallo-β-lactamase(VIM)gene concurrently.Ceftazidime-avibactam plus aztreonam(CZA-ATM)is prescribed in five patients while the remainders receive OAA.No adverse reactions occurred in individuals on CZA-ATM and 2 cases on OAA have adverse reactions with a poor appetite and diarrhea.After 30-day infection, the curative cases of CZA-ATM and OAAs groups reach 4 and 5 respectively.No death occurred in neither groups at Day 30.And 90-day mortality is 0 and 1 respectively.Conclusions:For RT patients infected with NDM-producing CRKP, CZA-ATM combination therapy may be another effective treatment.

Kidney Transplantation/adverse effects* ; Magnetics ; Anastomosis, Surgical ; Magnetic Phenomena

Perfluoroalkyl and polyfluoroalkyl substances (PFASs), as a group of persistent organic pollutants among environmental endocrine disruptors, are widely used in industrial production and daily life. PFASs are widely and persistently present in the environment and organisms due to their bioaccumulation, long half-life, and low degradability properties. Published studies have proved that PFASs have immunotoxicity, endocrine toxicity, neurotoxicity, reproductive toxicity, and hepatotoxicity. At present, several epidemiological studies have been conducted on the effects of PFASs on allergic diseases, the research endpoints include asthma, allergic rhinitis, atopic dermatitis, and the expression of allergic biomarkers such as serum immunoglobulin E (IgE), but no consistent results have been observed yet. PFASs have the potential to activate several signaling pathways, including the peroxisome proliferator-activated receptor (PPAR), nuclear factor-κB (NF-κB), and JAK/STAT pathways. These mechanisms, along with increasing mast cell calcium influx and sex hormone synergistic effects, may contribute to immunomodulation in allergic diseases. At present, the exact human effect of PFASs exposure on allergic diseases and the related mechanisms are still uncertain. This review focused on the impacts of PFASs on asthma, allergic rhinitis, and atopic dermatitis and their possible mechanisms, so as to provide research ideas for the prevention, diagnosis, and treatment of allergic diseases.

Objective To analyze the microflora structure and abundance of ileum and colon of SPF male SD rats by high-throughput sequencing technique. MethodsThe ileal and colonic lumen contents of 30 SPF male SD rats were collected, the total bacterial DNA in the contents was extracted and amplified by PCR. The V3-V4 region of bacterial 16S rRNA in the samples was sequenced using Illumina NovaSeq sequencing platform. Then the species structure and abundance of the intestinal flora were analyzed at the phylum and genus level based on validated data. The diversity and differences between ileal and colonic flora were analyzed using the QIIME software (amplicon) analysis tool. The Tax4Fun program was applied to predict the dominant gene enrichment pathways of ileal and colonic flora. ResultsAt the phylum level, the dominant microflora in the ileum of male SD rats were Firmicutes and Actinobacteria, accounting for more than 98%. The dominant colonic microbial community were mainly Firmicutes and Bacteroidetes, accounting for more than 95%. At the genus level, Lactobacillus and Alistipes were the predominant bacteria in the ileum. The colon was dominated by Lactobacillus and Romboutsia. In terms of flora diversity, the alpha diversity of colonic flora including richness index (Chao1 index) and diversity index (Shannon index) were significantly higher than those of ileum (P < 0.01), and the structural variability of the composition of its flora species was smaller than that of ileum; the ileal flora with significant structural variability were mainly of the phylum Firmicutes, Romboutsia, Peptostreptococcaceae, while the colonic flora had significant structural differences in Bacteroidales. In terms of flora function, the ileal flora dominant genes were significantly enriched in lipid-like metabolism, polyketide metabolism, membrane transport, biodegradation and other pathways, while the colonic flora dominant genes were significantly enriched in glycan biosynthesis metabolism, energy metabolism, biosynthesis of cofactor and vitamins and other products, and other pathways. ConclusionThere are significant differences in structure and abundance between the ileal and colonic flora of SPF male SD rats, and the abundance and diversity of colonic flora are higher than those of ileal flora.

Humans ; Living Donors ; Tissue and Organ Harvesting ; Nephrectomy ; Printing, Three-Dimensional ; Technology ; Laparoscopy

Objective:Discuss the etiological characteristics of pulmonary infection after renal transplantation and the diagnostic value of metagenomics nextgeneration sequencing (mNGS) technique.Methods:A total of 40 patients with pulmonary infection who were admitted to the Department of Renal Transplantation of the First Affiliated Hospital of Medical College, Xi'an Jiaotong University from January, 2018 to January, 2021 were selected, and identification of pathogens through routine pathogen detection methods and mNGS. The routine pathogen detection methods included: blood culture, bronchoalveolar lavage fluid (BALF) and sputum culture and smear staining, lung histopathology, antigen detection and PCR, etc. BALF were used to search for pathogens by mNGS. Combined with the results of the two groups to give accurate anti-infection treatment, the clinical data were retrospectively analyzed.Results:Eventually 36 patients were cured and discharged, and 4 patients deaths. In 40 cases of pulmonary infection, the BALF mNGS pathogens detection of BALF was positive in 37 cases and negative in 3 patients, with a detection sensitivity of 92.5%. In addition, there were 15 cases of single pulmonary infection and 22 cases of mixed pulmonary infection, including 8 cases of bacterial infection, 9 cases of viral infection and 20 cases of fungal infection, among which pneumocystis (20/40, 50%) and cytomegalovirus (10/40, 25%) were the most common. In contrast, the positive rate of pathogens by routine detection were only 30% (12/40), and the difference between the two detection methods was statistically significant ( χ2=32.92, P<0.05). The diagnostic rates of mixed pulmonary infection were 55% and 10% respectively, the difference was statistically significant ( χ2=18.46, P<0.05), the single type pulmonary infection was 30% and 20% respectively, the difference was not statistically significant( χ2=2.99, P>0.05). Conclusions:mNGS has more advantages than routine pathogen detection methods in terms of pathogen species and distribution, detection time, sensitivity, mixed infection diagnosis rate and benefit. Using mNGS can be more efficient to find pathogens of pulmonary infection after renal transplantation, take accurate treatment, reduce costs, and improve cure rate, such as worth wide application..

Objective:To study the protective effects of different concentrations of curcumin on lung injury of rats in dry heat environment.Methods:Fifty Sprague-Dawley rats were randomly (random number) divided into five groups ( n = 10 each group): normal control group (NC), dry heat control group (DHC), and three different concentrations of curcumin pretreated dry-heat groups (50 mg/kg, 100 mg/kg, and 200 mg/kg). Rats in the NC and DHC groups were given a gavage of normal saline, and rats in the curcumin pretreatment groups were given a gavage of curcumin with different concentrations, once a day for 7 consecutive days. At 8th day, all groups except for the NC group were transferred to the climate cabin (The Simulated Climate Cabin for Special Environment of Northwest of China), with a temperature of (41 ± 0.5) and relative humidity of (10 ± 1)%. Rats in each group were anesthetized and sampled after reaching the state of heat stroke at 150 min, and same done to the NC group. Lung tissues were harvested and pathological changes were observed by HE staining. Lung wet/dry (W/D) weight ratio was detected and lung injury indicators such as total protein, white blood cell count and neutrophil count in bronchoalveolar lavage fluid (BALF) were also determined. Results:The lung injury pathology score, W/D weight ratio, total protein, white blood cell count and neutrophil count in BALF were the lowest in the NC group, and the highest in the DHC group, with significant difference ( P <0.01). With the increase of the concentration in the curcumin pretreatment groups, lung injury pathology score, W/D weight ratio, total protein, white blood cell count and neutrophil count in BALF were all declined. There were significant differences among the different concentration groups of curcumin and the NC and DHC groups ( P <0.01). Correlation analysis indicated that lung injury scores were correlated with W/D weight ratio of lung tissue, alveolar total protein content in BALF, white blood cell count, and neutrophil count (correlation coefficient r = 0.879, r = 0.935, r = 0.916, and r = 0.880, respectively, P <0.01). Conclusions:Pretreatment with different concentrations of curcumin can exert protective effects on lung injury of heat stroke rats in dry heat environment. Curcumin may have important clinical value in prevention and treatment of lung injury caused by heat stroke in dry heat environment.

Objective:To compare the in vitro antibacterial activities of Cefpodoxime proxetil and Cefixime against common pathogens of community acquired pneumonia in children, and to provide basis for guiding the rational use of antibiotics in clinical practice. Methods:The pathogens of 100 cases of community acquired pneumonia in Children′s Hospital of Jiangxi Province from June 2018 to October 2019 were analyzed retrospectively.The sensitivity and resis-tance of these pathogens to Cefpodoxime proxetil and Cefixime were measured separately by the broth dilution method (tube) recommended by the Clinical & Laboratory Standards Institute (CLSI), and the results were compared.Results:(1)The 50% minimum inhibitory concentration(MIC 50) and MIC 90 values of Cefpodoxime proxetil to Streptococcus, Haemophilus influenzae and Moraxella catarrhalis were all within the sensitive range, showing that Cefpodoxime proxetil had a strong antibacterial effect.The MIC 50 values of Cefixime to Streptococcus pneumoniae and Haemophilus influenza were within the sensitive range, while the MIC 90 values showed that these two types of bacteria were resistant to Cefixime.The remaining bacteria were resistant to Cefpodoxime proxetil and Cefixime to varying degrees.(2)The minimum bactericidal concentration (MBC) ranges of Cefpodoxime proxetil to Streptococcus pneumoniae and Haemophilus influenzae were significantly lower than those of Cefixime to these two types of bacteria, indicating that Cefpodoxime proxetil had stronger bactericidal activities than Cefixime.The MBC 50 and MBC 90 values of the two drugs to Moraxella catarrhalis, β-Streptococcus pyogenes and Streptococcus lactis were still within the sensitive range of MIC, suggesting that both drugs had a strong bactericidal effect.The remaining bacteria showed resistance to the two drugs to varying degrees.(3)The sensitivity rates of 100 selected pathogens to Cefpodoxime proxetil and Cefixime were 70.00% (70/100 strains) and 57.00% (57/100 strains), respectively.The resistance rates of the 100 pathogens to the two drugs were 22.00% (22/100 strains) and 39.00% (39/100 strains), respectively, and the difference between the two groups was statistically significant ( χ2=7.40, P=0.03). Conclusions:Cefpodoxime proxetil has high sensitivity to common pathogens of children with community-acquired pneumonia, so it can be used as the initial empirical treatment of respiratory tract bacterial infection in children.It is also an appropriate sequential antibiotic therapy for common respiratory tract bacterial infection in children.

Objective:To explore the pathogenesis, diagnosis and treatment of pneumocystis jirovecii pneumoniae (PJP) after renal transplantation.Methods:A total of 20 PJP patients were selected from January 2018 to January 2020. The major symptoms included fever, chest tightness, dyspnea and cough with minimal sputum. Chest computed tomography (CT), laboratory tests and metagenomic next-generation sequencing (mNGS) of bronchoscopic pulmonary alveolar perfusion fluid (BALF) were performed. They received cotrimoxazole (SMZ: 18.75-25 mg/kg + TMP: 3.75-5 mg/kg q6 h) and basic regimen of caspofungin (50-70 mg/d) for 14-21 days. At the same time, bacterial, fungal or viral infections were treated, immunosuppressants were tapered or discontinued, supportive therapy and methylprednisolone, immunoglobulin and continuous renal replacement therapy (CRRT) were provided. Chest CT examination was performed for 5-7 days to evaluate the therapeutic effect and clinical data were retrospectively analyzed.Results:Among them, fever was predominant in 13 cases with an average body temperature of (38.8±0.68) ℃ while chest tightness and dyspnea occurred in 7 cases. Fourteen patients presented hypoxemia, 13 received non-invasive ventilator assisted breathing, 1 received mechanical ventilation via endotracheal intubation and the remainders received mask oxygen therapy. Seventeen patients were cured and discharged from hospital for 12~90 days. Three patients died of respiratory and circulatory failures due to deteriorating pulmonary infection. And 19 patients had elevated renal function initially and basically normalized around 2 weeks.Conclusions:PJP is one of the most serious complications after renal transplantation. Timely diagnosis and targeted treatment are essential. And mNGS examination plays a crucial role in the diagnosis of PJP. The basic anti-infective scheme of compound sulfamethoxazole plus carbophennet is efficacious. At the same time, appropriate tapering or discontinuation of immunosuppressants, supportive therapy and assisted respiration are also important.