A risk prediction model for acute kidney injury in patients with pulmonary tuberculosis during anti-tuberculosis treatment.

BACKGROUND: Acute kidney injury (AKI) is not a rare complication during anti-tuberculosis treatment in some patients with pulmonary tuberculosis (PTB). We aimed to develop a risk prediction model for early recognition of patients with PTB at high risk for AKI during anti-TB treatment. METHODS: This retrospective cohort study assessed the clinical baseline, and laboratory test data of 315 inpatients with active PTB who were screened for predictive factors from January 2019 to June 2020. The elements were analyzed by logistic regression analysis. A nomogram was established by the results of the logistic regression analysis. The prediction model discrimination and calibration were evaluated by the concordance index (C-index), ROC curve, and Hosmer-Lemeshow analysis. RESULTS: A total of 315 patients with PTB were enrolled (67 patients with AKI and 248 patients without AKI). Seven factors, including microalbuminuria, hematuria, cystatin-C (CYS-C), albumin (ALB), creatinine-based estimated glomerular filtration rates (eGFRs), body mass index (BMI), and CA-125 were acquired to develop the predictive model. According to the logistic regression, microalbuminuria (OR = 3.038, 95%CI 1.168-7.904), hematuria (OR = 3.656, 95%CI 1.325-10.083), CYS-C (OR = 4.416, 95%CI 2.296-8.491), and CA-125 (OR = 3.93, 95%CI 1.436-10.756) were risk parameter, while ALB (OR = 0.741, 95%CI 0.650-0.844) was protective parameter. The nomogram demonstrated good prediction in estimating AKI (C-index= 0.967, AUC = 0.967, 95%CI (0.941-0.984), sensitivity = 91.04%, specificity = 93.95%, Hosmer-Lemeshow analysis SD = 0.00054, and quantile of absolute error = 0.049). CONCLUSIONS: Microalbuminuria, hematuria, ALB reduction, elevated CYS-C, and CA-125 are predictive factors for the development of AKI in patients with PTB during anti-TB treatments. The predictive nomogram based on five predictive factors is achieved good risk prediction for AKI during anti-TB treatments.

Preliminary investigation of nitric oxide release from upconverted nanoparticles excited at 808 nm near-infrared for brain tumors.

Upconverted UCNPs@mSiO2-NH2 nanoparticles were synthesized via thermal decomposition while employing the energy resonance transfer principle and the excellent near-infrared (NIR) light conversion property of up-conversion. The 808 nm NIR-excited photocontrolled nitric oxide (NO) release platform was successfully developed by electrostatically loading photosensitive NO donor Roussin's black salt (RBS) onto UCNPs@mSiO2-NH2, enabling the temporal, spatial, and dosimetric regulation of NO release for biological applications of NO. The release of NO ranged from 0.015⁓0.099 mM under the conditions of 2.0 W NIR excitation power, 20 min of irradiation time, and UCNPs@mSiO2-NH2&RBS concentration of 0.25⁓1.25 mg/mL. Therefore, this NO release platform has an anti-tumor effect. In vitro experiments showed that under the NIR light, at concentrations of 0.3 mg/mL and 0.8 mg/mL of UCNPs@mSiO2-NH2&RBS, the activity of glioma (U87) and chordoma (U-CH1) cells, as measured by CCK8 assay, was reduced to 50 %. Cell flow cytometry and Western Blot experiments showed that NO released from UCNPs@mSiO2-NH2&RBS under NIR light induced apoptosis in brain tumor cells. In vivo experiments employing glioma and chordoma xenograft mouse models revealed significant inhibition of tumor growth in the NIR and UCNPs@mSiO2-NH2&RBS group, with no observed significant side effects in the mice. Therefore, NO released by UCNPs@mSiO2-NH2&RBS under NIR irradiation can be used as a highly effective and safe strategy for brain tumor therapy.

Multiple regression analysis of risk factors related to radiation pneumonitis.

BACKGROUND: Radiation pneumonitis (RP) is a severe complication of thoracic radiotherapy that may lead to dyspnea and lung fibrosis, and negatively affects patients' quality of life. AIM: To carry out multiple regression analysis on the influencing factors of radiation pneumonitis. METHODS: Records of 234 patients receiving chest radiotherapy in Huzhou Central Hospital (Huzhou, Zhejiang Province, China) from January 2018 to February 2021, and the patients were divided into either a study group or a control group based on the presence of radiation pneumonitis or not. Among them, 93 patients with radiation pneumonitis were included in the study group and 141 without radiation pneumonitis were included in the control group. General characteristics, and radiation and imaging examination data of the two groups were collected and compared. Due to the statistical significance observed, multiple regression analysis was performed on age, tumor type, chemotherapy history, forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), carbon monoxide diffusion volume (DLCO), FEV1/FVC ratio, planned target area (PTV), mean lung dose (MLD), total number of radiation fields, percentage of lung tissue in total lung volume (vdose), probability of normal tissue complications (NTCP), and other factors. RESULTS: The proportions of patients aged ≥ 60 years and those with the diagnosis of lung cancer and a history of chemotherapy in the study group were higher than those in the control group (P < 0.05); FEV1, DLCO, and FEV1/FVC ratio in the study group were lower than those in the control group (P < 0.05), while PTV, MLD, total field number, vdose, and NTCP were higher than in the control group (P < 0.05). Logistic regression analysis showed that age, lung cancer diagnosis, chemotherapy history, FEV1, FEV1/FVC ratio, PTV, MLD, total number of radiation fields, vdose, and NTCP were risk factors for radiation pneumonitis. CONCLUSION: We have identified patient age, type of lung cancer, history of chemotherapy, lung function, and radiotherapy parameters as risk factors for radiation pneumonitis. Comprehensive evaluation and examination should be carried out before radiotherapy to effectively prevent radiation pneumonitis.

Clinicopathological characteristics and its association with digestive system tumors of 1111 patients with Schistosomiasis japonica.

Schistosomiasis japonicum can cause different degrees of organ damage and complex human immune pathological reactions, which often invade the intestine and liver. The purpose of this study was to explore the pathological types and pathological changes of Schistosomiasis and their correlation with some digestive system tumors. Hematoxylin eosin staining was performed on the diseased tissues of 1111 Schistosomiasis cases. We counted the deposition sites of Schistosoma eggs, analyzed the pathological characteristics, and compared the clinicopathological characteristics of Schistosomiasis associated digestive system tumors and non-Schistosomiasis digestive system tumors. We found that Schistosoma japonicum can cause multi organ and multi system damage, with 469 cases of inflammation, 47 cases of adenoma, and 519 cases of adenocarcinoma. Other types include cysts, stromal tumors, malignant lymphomas, and neuroendocrine tumors. Schistosomiasis associated tumors, including gastric cancer, liver cancer, colon cancer and rectal cancer, were compared with non-Schistosomiasis tumors. There were significant differences in age, gender and tumor differentiation between the two groups. Our study shows Schistosomiasis is a systemic disease, causing multiple organ and system damage in the human body. Its clinicopathological types are diverse, and there may be a pathological change process of "Inflammation-adenoma-carcinoma". Schistosomiasis associated digestive system tumors differ from non-Schistosomiasis tumors in some clinicopathological features.

A specific reverse complement sequence for distinguishing Brucella canis from other Brucella species.

Canine brucellosis is primarily caused by Brucella canis, but other Brucella species can also cause the disease. Identifying sequences specific to B. canis and establishing PCR assays that can distinguish between B. canis and other Brucella species is essential to determine the etiology of canine brucellosis and the source of infection and to achieve effective control. We analyzed the gaps and SNPs of genomes I and II from B. canis strain RM6/66 and B. melitensis strain 16M using the Mauve genome alignment software, and the specificity of each of these differential regions was analyzed by BLAST. A 132 bp specific sequence was found between the DK60_915 (glycosyl hydrolase 108 family protein) and DK60_917 (aldose 1-epimerase) loci in B. canis chromosome 1. Further comparative analysis revealed that this is a reverse complement sequence between B. canis and other Brucella species. Then, three primers were designed based on the sequence that could detect B. canis with a 310 bp amplification product or other Brucella species with a 413 bp product. The PCR based on these primers had reasonable specificity and a sensitivity of 100 copies of Brucella DNA. The detection results for the blood samples of the aborted dogs showed a favorable accordance with the Bruce-ladder multiplex PCR assay. In conclusion, we found a specific reverse complement sequence between B. canis and other Brucella and developed a PCR method that allows a more comprehensive identification of the pathogen involved in canine brucellosis. These findings provide an effective means for preventing and controlling brucellosis.

Proteomic and Antibody Profiles Reveal Antigenic Composition and Signatures of Bacterial Ghost Vaccine of Brucella abortus A19.

Brucellosis is an important zoonotic disease that causes great economic losses. Vaccine immunisation is the main strategy for the prevention and control of brucellosis. Although live attenuated vaccines play important roles in the prevention of this disease, they also have several limitations, such as residual virulence and difficulty in the differentiation of immunisation and infection. We developed and evaluated a new bacterial ghost vaccine of Brucella abortus A19 by a new double inactivation method. The results showed that the bacterial ghost vaccine of Brucella represents a more safe and efficient vaccine for brucellosis. We further characterised the antigenic components and signatures of the vaccine candidate A19BG. Here, we utilised a mass spectrometry-based label-free relative quantitative proteomics approach to investigate the global proteomics changes in A19BGs compared to its parental A19. The proteomic analysis identified 2014 proteins, 1116 of which were differentially expressed compared with those in A19. The common immunological proteins of OMPs (Bcsp31, Omp25, Omp10, Omp19, Omp28, and Omp2a), HSPs (DnaK, GroS, and GroL), and SodC were enriched in the proteome of A19BG. By protein micro array-based antibody profiling, significant differences were observed between A19BG and A19 immune response, and a number of signature immunogenic proteins were identified. Two of these proteins, the BMEII0032 and BMEI0892 proteins were significantly different (P < 0.01) in distinguishing between A19 and A19BG immune sera and were identified as differential diagnostic antigens for the A19BG vaccine candidate. In conclusion, using comparative proteomics and antibody profiling, protein components and signature antigens were identified for the ghost vaccine candidate A19BG, which are valuable for further developing the vaccine and its monitoring assays.

[Precision of eDNA Metabarcoding Technology for Biodiversity Monitoring of Eukaryotic Phytoplankton in Lakes].

Environmental DNA (eDNA) metabarcoding provides a fast and efficient way to obtain biodiversity information that has been widely used in aquatic biodiversity monitoring and assessment. To facilitate the application of eDNA metabarcoding in China, the accuracy of metabarcoding data needs to be further assessed. Here, the eukaryotic phytoplankton in Dianchi Lake and the northern portion of Fuxian Lake were examined. The effect of sequencing depth on species diversity was also explored, and accuracy was evaluated by comparing the taxon overlap and coefficient of variation (CV) of the α diversity index among biological replicates. The results showed that:① Sequencing depth significantly affected the taxon number and accuracy of alpha diversity determinations. The suggested sequencing depth for metabarcoding of eukaryotic phytoplankton in Dianchi Lake and Fuxian Lake is at least 30000. ② The OTU overlap was 45.97%±1.67% among three biological replicates, the genera overlap was 64.21%±3.25%, and the CV of alpha diversity was less than 10%. ③ Seventy-five and 90 genera of eukaryotic algae were identified in Dianchi Lake and Fuxian Lake, respectively, covering 62.5% and 71.05% of the morphologically detected species, respectively. ④ There was no significant variation in the diversity of eukaryotic algae with depth in Dianchi Lake, while diversity showed significant vertical patterns in Fuxian Lake. Overall, eukaryotic algal diversity was significantly lower in Dianchi Lake compared to Fuxian Lake, and diversity in the southern portion of Dianchi Lake was significantly higher than that in the central and northern portions (P<0.05). Our study demonstrates the feasibility and accuracy of using eDNA-based techniques to monitor eukaryotic phytoplankton diversity, which supports the widespread application of eDNA metabarcoding in China.

Intractable hiccup due to giant hydronephrosis: A rare case report and literature review.

INTRODUCTION: Giant hydronephrosis (GH) is a rare disease that is found in adult patients. Although there are some common symptoms associated with hydronephrosis, such as surrounding organ compressed, its rarer symptoms can render diagnosis very difficult, and treatment should also vary according to the cause. PRESENTATION OF CASE: We here report an 82-year-old man who was admitted to the hospital for repeated intractable hiccups. After B-ultrasound and CT examination, the patient underwent laparoscopy surgery, which was converted to open nephrectomy, and the patient's intractable hiccup symptoms disappeared. DISCUSSION: GH is a rare disease, and its symptoms are diverse. The more unusual symptoms of cystic hypertonic compression of surrounding organs, such as intractable hiccups, should be taken into account. GH is mainly diagnosed via ultrasound examination and CT scan. The choice of treatment for GH needs to be based on the etiology and renal function of hydronephrosis, and consider malignant lesions. CONCLUSION: Giant hydronephrosis can present rare symptoms as "intractable hiccups". The selection of treatment should be made depending on the cause.

Clinical analysis of patients with acute pancreatitis complicated with hemorrhagic fever with renal syndrome and acute biliary pancreatitis.

Acute pancreatitis (AP) is a rare complication of hemorrhagic fever with renal syndrome (HFRS), and is difficult to diagnose. In this study, we retrospectively analyzed the clinical characteristics of 7 cases of HFRS complicated with AP and 105 cases of acute biliary pancreatitis (ABP).Medical records of 83 hospitalized patients with HFRS and 105 hospitalized patients with ABP in the affiliated Yijishan Hospital of Wannan Medical College were reviewed. The comparative analysis of patients between the 2 groups was conducted in terms of sex, age, duration of hospital stay, fever, hemorrhage, proteinuria, oliguria, laboratory results, radiologic examinations, and prognosis.A total of 83 patients were diagnosed with HFRS during study period. Only 8.43% (7/83) of the total HFRS patients were diagnosed with AP. The differences in the gender, age, and duration of hospital stay between the 2 investigated groups of patients were not statistically significant. The major symptoms for all 7 patients with HFRS complicated with AP and 105 patients with ABP were fever and upper abdominal pain. During the disease course of HFRS complicated with AP, 6 patients experienced hemorrhaging, and 7 patients underwent an oliguric stage, but none of the ABP patients experienced hemorrhaging and oliguria. Among the laboratory results of all patients, the differences in alanine aminotransferase and glycemia were not statistically significant. The other laboratory results (leucocyte count, platelet count, amylase, lipase, total bilirubin, direct bilirubin, creatinine, blood urea nitrogen, prothrombin time, activated partial thromboplastin time, and serum calcium level) were significantly different during hospitalization. All 7 patients with HFRS complicated with AP received conservative medical treatment and hemodialysis. In the patients with ABP, 21 patients were discharged from the hospital after conservative treatment, 53 patients were treated by endoscopic invasive treatment after stabilization, and 31 patients were treated by surgery after stabilization.AP is not a frequent complication in patients with HFRS. There are differences in clinical manifestations and laboratory findings between the HFRS complicated with AP group and the ABP group; these differences may help in the differential diagnosis and treatment of these 2 types of pancreatitis.

[CD4+ CD25+ regulatory T cells suppress CD4+ T cell responses in patients with persistent hepatitis C virus infection].

OBJECTIVE: To study the role of CD(4)(+) CD(25)(+) regulatory T cells (CD(4)(+) CD(25)(+) Treg cells) in CD(4)(+) T cell responses in patients with persistent infection of hepatitis C viruses. METHODS: Flow cytometry was used to determine the number of CD(4)(+) CD(25)(+) Treg cells and intracellular cytokine production by CD(4)(+) CD(25)(+) Treg cells in patients with chronic HCV infection. To assess their regulatory properties CD(4)(+) CD(25)(+) Treg cells were co-cultured with CD(4)(+) CD(25)(-) T cells from patients or controls; the expressions of Foxp3 were measured by RT-PCR. RESULTS: CD(4)(+) CD(25)(+) Treg cells comprised (13.5 +/- 1.8)% of peripheral CD(4)(+) T cells in the blood of persistent hepatitis C virus infected patients, which was significantly higher than that of healthy controls (5.3 +/- 0.8)% (P = 0.004). CD(4)(+) CD(25)(+) Treg cells highly expressed Foxp3 and mainly synthesized IL-10; CD(4)(+) CD(25)(+) Treg cells dramatically suppressed the proliferation of CD(4)(+) T cells and the production of IFN gamma; the suppressive activity of CD(4)(+) CD(25)(+) Treg cells in patients with persistent HCV-infection was higher than that in healthy controls (P = 0.034). These effects were dose-dependent but IL-10 and transforming growth factor beta independent. CONCLUSION: Patients with persistent hepatitis C virus infection show an increased number and suppressive activity of CD(4)(+) CD(25)(+) Treg cells, which could function in a highly regulatory capacity to suppress Th1 response.

Metformin can block precancerous progression to invasive tumors of bladder through inhibiting STAT3-mediated signaling pathways.

BACKGROUND: Metformin is the first line of oral antidiabetic drug in the biguanide class for treatment of type 2 diabetes. Increasing evidence has suggested that it is a potential anti-tumor drug. However, the mechanisms underlying inhibiting tumor development remain elusive, especially in bladder tumors. METHODS: T24 and J82 cell lines were used as an in vitro model, and 24 female SD rats were used to build an N-methyl-N-nitrosourea (MNU)-induced orthotopic rat bladder cancer model. Transfection of lentivirus-based shRNA was used to construct the STAT3-KNOCKDOWN T24 cell line. After metformin treatment, the viability of bladde cancer cells was determined by CCK8. Cell cycle distribution and apoptosis were assessed by flow cytometry. The migration and invasion abilities of cells were evaluated by wound healing and transwell asssays. The inactivation of stat3 pahtway was examined by qRTPCR, western blot and Immunofluorescence. RESULTS: Metformin can effectively inhibit precancerous progression to invasive cancer in an MNU-induced rat orthotopic bladder tumor model, although it could not completely suppress normal cells transforming into tumor cells. While the MNU could induce 50 % rats (4/8) to develop invasive bladder cancers, the rats co-administrated with metformin failed to develop invasive tumors but retained at precancerous or non-invasive stages, exhibiting as dysplasia, papillary tumor and/or carcinoma in situ (CIS). Accordingly, phosphorylation of signal transducer and activator of transcription 3 (STAT3), which is a well known oncogene, was significantly inhibited in the tumors of rats treated with metformin. In vitro experiments revealed that the metformin could efficiently inhibit STAT3 activation, which was associated with the cell cycle arrest, reduction of cell proliferation, migration and invasiveness, and increase in apoptotic cell death of bladder cancer cell lines. CONCLUSIONS: These findings provide for the first time the evidence that metformin can block precancerous lesions progressing to invasive tumors through inhibiting the activation of STAT3 pathway, and may be used for treatment of the non-invasive bladder cancers to prevent them from progression to invasive tumors.

[Diagnostic significance and clinical application of specific chimeric genes in soft tissue sarcomas by RT-PCR using paraffin-embedded tissues: a study of 103 specimens].

OBJECTIVE: To investigate the expression of the chimeric genes resulting from the specific chromosomal translocations in soft tissue sarcomas (STS) and its diagnostic significance for STS. METHODS: The variety of fusion transcripts were detected in 103 cases of STS, including 30 cases of synovial sarcoma (SS), 15 cases of rhabdomyosarcoma (RMS), 25 cases of Ewing's sarcoma/peripheral primitive neuroectodermal tumors (ES/pPNET), 12 cases of dermatofibrosarcoma protuberans (DFSP), 14 cases of aveolar soft part sarcoma (ASPS), 3 cases of leiomyosarcoma (LMS), 2 cases of malignant fibrous histocytoma (MFH), and 2 cases of fibrosarcoma (FS); and 20 cases of control tumors by reverse transcription-polymerase chain reaction (RT-PCR) using formalin fixed, paraffin embedded specimens. RESULTS: Of the 34 cases of SS 28 (93.3%) expressed SSX-SYT chimeric transcripts (14 were positive for SYT-SSX1, 9 for SYT-SSX2). Four of the six cases of alveolar RMS had a PAX3/PAX7-FKHR fusion transcript. None of the 9 cases of embryonic and polymorphic RMS expressed PAX3/PAX7-FKHR. Of the 25 cases of ES/pPNET, 19 were positive for EWS-FLI1 fusion transcript and 1 for EWS-ERG fusion transcript. COL1A1-PDGFB fusion transcript was expressed in 8 of the 12 cases (66.7%) of DFSP. Of the fourteen cases of ASPS, ten expressed ASPL-TFE3 fusion transcript. None of the 3 cases of LMS, 2 cases of MFH, 2 cases of FS, and 20 control cases contained any of the fusion transcript. CONCLUSION: Chimeric gene transcript resulting from specific chromosomal translocations is a reliable index for the molecular diagnosis of STS and RT-PCR assay for detection of specific fusion gene provides a useful tool for confirmation of the diagnosis of STS in diagnostically difficult cases and in retrospective studies.

[Detection of COL1A1/PDGFB fusion transcripts in dermatofibroscoma protuberans by revers transcriptase-polymerase chain reaction using paraffin-embedded tissues].

OBJECTIVE: To detect the COL1A1/PDGFB fusion transcripts and discuss its clinicopathological significance in dermatofibroscoma protuberans. METHODS: Formalin fixed, paraffin-embedded tumor specimens from 12 patients with DFSP were reviewed by light microscope and the expression of COL1A1/PDGFB mRNA resulting from the reciprocal translocation t(17;22) (q22;q13.1) was detected by one-step revers transcriptase-polymerase chain reaction. The following tumor specimens were included as controls: 2 fibrosarcoma, 2 malignant fibrous histocytoma, 3 leiomyosarcoma, 1 dermarofibroma and 1 nerve shealth tumor. RESULTS: The COL1A1/PDGFB fusion transcripts were detected in 8 (67%) of 12 samples from patients with DFSP. Nucleotide sequence analysis using the PCR products confirmed that different regions of the COL1A1 gene, respectively, were fused with of PDGFB gene. No COL1A1/PDGFB fusion transcripts were detected in the control tumors. CONCLUSION: Detection of specific COL1A1/PDGFB fusion transcripts in DFSP will help to diagnose the nature of DFSP and research the mechanism of its molecular histogenesis.

[Isolation, identification and functional characterization of human CD4+ CD25+ Treg cells from human peripheral blood].

AIM: To isolate CD4(+) CD25(+) Treg cells from human peripheral blood, and study their functional characteristics. METHODS: The expressions of Foxp3 in human CD4(+) CD25(+) Treg cells were test by RT-PCR. The regulatory properties of CD4(+) CD25(+) Treg cells were assessed by co-culturing with CD4(+) CD25(-) T cells and CD8(+) T cells, or adding exogenous IL-2. The detection of intracellular cytokine production of IL-4, IL-10 and IFN-gamma was done by flow cytometry. RESULTS: CD4(+) CD25(+) Treg cells highly expressed Foxp3 and mainly synthesized IL-10 that suppressed the proliferation of CD4(+) CD25(-) T and CD8(+) T cells. Its suppressive function was reversed by high concentration of IL-2 and (or) IL-4. CONCLUSION: CD4(+) CD25(+) Treg cells exhibited a subpopulation of immunoregulatory T cells with suppressive function, which could be reversed by high concentration of IL-2.