Clinical Characteristics and Epidemiological Analysis of Pneumocystis Jirovecii Pneumonia Infection in Kidney Transplant Patients with Trimethoprim-Sulfamethoxazole Dose Reduction Prophylaxis Strategy.

Background: The administration of trimethoprim-sulfamethoxazole (TMP-SMX) for the prophylaxis of Pneumocystis jirovecii pneumonia (PJP) has proven to be highly efficacious in individuals who have undergone kidney transplantation. Nevertheless, the potential for severe adverse reactions associated with this treatment cannot be overlooked, and the determination of an optimal dosage regimen continues to be a matter of investigation. The current study evaluated the effectiveness of low-dose TMP-SMX for PJP prophylaxis in kidney transplant patients and conducted an analysis of the clinical characteristics and epidemiological trends in patients with PJP infection. Methods: This retrospective analysis studied electronic medical records of 1763 kidney transplant recipients from 2017 to 2020. These patients were initially prescribed a daily half-strength TMP-SMX (40 mg/200 mg), and the efficacy of this regimen was assessed during a follow-up period of 3-51 months. Results: Under our PJP prevention and adjustment strategy, 24 patients were infected with PJP. The overall morbidity of PJP infection in our study was 1.36%, corroborates with findings from previously published studies. Among these 24 patients, up to 87.5% had their dosage adjusted due to increased creatinine or other adverse reactions, the most frequent dose was daily quarter-strength TMP-SMX (20 mg/100 mg). TMP-SMX prophylaxis successfully postponed and distributed the onset of PJP, with the mean duration from transplantation to the occurrence of PJP being 13.50±7.11 months. Conclusion: Daily administration of half-strength TMP-SMX can effectively prevent PJP, and prolonging prophylaxis with this medication may potentially reduce the incidence of infection.

A Network Pharmacology Study on the Cervix Prescription for Treatment of Cervical Cancer.

Purpose: Based on the method of network pharmacology to explore the mechanism of the cervical prescription (CP) in the treatment of cervical cancer (CC). Methods: We obtained the active ingredients and potential targets in the CP from the literature and the systematic pharmacological analysis platform of traditional Chinese medicine (BATMAN-TCM); the database was used to search for targets related to cervical cancer and to map CP and targets; the core targets were screened, and the protein-protein interaction network (PPI) was constructed using the TCM compound-target network and STRING database. Gene ontology (GO) and Kyoto Gene and Genome Encyclopedia (KEGG) pathway enrichment analysis of overlapping targets were performed using DAVID 6.8 online tool. Results: The CP contains 2 active ingredients, corresponding to 301 nonreactive targets; 10 GO biological process related items and 73 signal pathways were obtained. Cell experiments confirmed that the medicated serum of CP could effectively inhibit the proliferation and invasion ability of Hela cells. Conclusion: This study provides valuable information for TCM researchers and clinicians to better understand the main therapeutic targets and therapeutic roles of herbal decoctions in clinical settings. The results of our study preliminarily clarified that the cervical prescription has an inhibitory effect on cervical cancer cells.

Carcinogenicity risk associated with tacrolimus use in kidney transplant recipients: a systematic review and meta-analysis.

Background: Currently, tacrolimus is the preferred anti-rejection therapy for kidney transplant recipients due to its greater protection against acute rejections compared to cyclosporin A (CsA). Despite the advantages of kidney transplantation, it has been associated with an increased incidence of de novo malignancies. Furthermore, a systematic review in 2005 revealed no statistical difference in tumorigenicity between tacrolimus and CsA. This report provides an up to date systematic review and evaluation of all relevant studies in the literature to determine the risk of malignancy in kidney transplant recipients exposed to tacrolimus. Methods: A systematic literature search was performed using the Medline (PubMed and Ovid), Embase, Clinical Trials, and Cochrane databases (from creation to May 2021). We performed a meta-analysis of 11 studies with 36,985 kidney transplant recipients that compared the tacrolimus group with the control group. Outcomes of this study were incidence of malignancies and skin cancer risk. Risk of Bias was assessed in terms of whether there was random sequence generation, allocation concealment, blinding, completeness of results, selective reporting, etc. This meta-analysis was performed in accordance with PRISMA guidelines. Results: Of the 11 included studies, 8 were high quality studies, 1 was assessed as medium quality, and 2 were low quality studies. The results showed a significantly increased risk of overall malignancy associated with tacrolimus exposure compared to non-tacrolimus therapy [risk ratio (RR) =1.59; 95% confidence interval (CI): 1.19-2.11; P=0.002], and especially with sirolimus (SRL) (RR =2.58; 95% CI: 1.62-4.09; P<0.0001). The incidence of skin cancer was consistent with the overall study (RR =2.03; 95% CI: 1.25-3.28; P=0.004). However, there was no significant difference in the incidence of tumors between tacrolimus and cyclosporine A treatment (RR =1.12; 95% CI: 0.80-1.56; P=0.52), even in studies with long follow-up periods of more than 3 years. Discussion: The data demonstrated that patients treated with tacrolimus had a higher risk of carcinogenicity compared to patients treated with SRL. However, patients treated with tacrolimus had a similar incidence of carcinogenicity compared to patients treated with CsA. Further clinical studies are warranted to confirm these findings.

Efficacy and safety of roxadustat in the treatment of renal allograft anemia patients: a case series.

BACKGROUND: To observe the efficacy and safety of roxadustat, an inhibitor of proline hydroxylase, in renal allograft anemia patients. METHODS: This prospective study collected the clinical data of renal transplant patients treated with roxadustat for anemia at the Kidney Disease Center of the First Affiliated Hospital of Zhejiang University from April to August 2020. The patients were followed up every 2 weeks, and the changes in their hemoglobin index and any adverse reactions were recorded during 10 weeks of treatment. The efficacy of roxadustat for treatment of anemia after kidney transplantation was analyzed by comparing the change and increase in average hemoglobin levels before and after treatment. Rates of treatment response and achievement of the standard hemoglobin level were statistically analyzed. In addition, any potential adverse events and the glomerular filtration rate were recorded for 10 weeks to assess the safety of roxadustat in renal allograft anemia patients. RESULTS: After 10 weeks of roxadustat treatment, the mean hemoglobin level was 10.4±3.9 g/dL, which was significantly higher than at baseline. Over the entire period, treatment was observed to have a therapeutic effect at weeks 2-4, with mean hemoglobin levels increasing as treatment time increased. At the 10-week endpoint, the percentage of patients reaching the standard hemoglobin level and exhibiting a response to treatment was 52.4% and 71.4%, respectively. During the treatment, there was no rejection, and the glomerular filtration rate was stable. Only one person showed symptoms of fatigue, and there were no other obvious adverse reactions reported. CONCLUSIONS: Roxadustat significantly improves hemoglobin levels and can be safely used in renal transplant anemia patients.

Long non-coding RNA activated by transforming growth factor-ß promotes proliferation and invasion of cervical cancer cells by regulating the miR-144/ITGA6 axis.

NEW FINDINGS: What is the central question of this study? This study was designed to investigate the molecular mechanism and biological roles of long non-coding RNA activated by transforming growth factor-ß (lncRNA ATB) in the progression of cervical cancer. What is the main finding and its importance? Our study provided new insight into the cross-talk between lncRNA ATB, miR-144 and ITGA6, shedding light on the therapy for cervical cancer. ABSTRACT: The present study was designed to investigate the molecular mechanism and biological roles of long non-coding RNA activated by transforming growth factor-ß (lncRNA ATB) in the progression of cervical cancer. The expression levels of lncRNA ATB, miR-144 and integrin α6 (ITGA6) were detected in human cervical cancer cell lines using quantitative real-time PCR and western blotting. Cell viability was quantified by MTT assay at 12, 24, 36, 48 and 72 h after transfection, and cell invasion was determined by the Transwell migration assay. The association among lncRNA ATB, miR-144 and ITGA6 was disclosed by a dual-luciferase reporter assay. We found that lncRNA ATB was highly expressed in human cervical cancer cell lines. Further investigation indicated that lncRNA ATB functioned as a competitive endogenous RNA (ceRNA) for miR-144 to promote cervical cancer cell proliferation and invasion. We demonstrated that ITGA6 was a direct target of miR-144, and lncRNA ATB facilitated the proliferation and invasion of cervical cancer cells via the miR-144/ITGA5 axis. In conclusion, the lncRNA ATB/miR-144/ITGA6 axis might be a promising therapeutic target for cervical cancer.

A kind of fast shutter for Z pinch diagnosis device.

A kind of fast shutter for protecting the diagnosis devices in Z pinch experiments is introduced in this paper. The shutter is composed of a pulling rod, a magnetic core, and a solenoid. Different from the traditional coils which were used at the voltage of 220 V, the solenoid we used must endure the high voltage of 5-10 kV and the deformation which maybe caused by the 5-10 T intense magnetic field. A creative configuration for the solenoid is developed including the winding guide, insulating sleeve, and stainless-steel sleeve. The experimental results show that the configuration of the solenoid is effective. The velocity of the valve is nearly 19 m/s and the time jitter of the shutdown is within 75 µs.

Vaccination against type 1 angiotensin receptor prevents streptozotocin-induced diabetic nephropathy.

UNLABELLED: Recently, our group has developed a therapeutic hypertensive vaccine against angiotensin (Ang) II type 1 receptor (AT1R) named ATRQß-001. To explore its potential effectiveness on streptozotocin-induced diabetic nephropathy, male Sprague Dawley rats were randomly divided into two groups: a control and a diabetic model. After 1 week, the diabetic rats were divided into four subgroups (each with 15 rats) for 14-week treatments with saline, olmesartan, ATRQß-001, and Qß virus-like particle (VLP), respectively. In addition to lower blood pressure, ATRQß-001 vaccination ameliorated biochemical parameter changes of renal dysfunction, mesangial expansion, and fibrosis through inhibiting oxidative stress, macrophage infiltration, and proinflammatory factor expression. Furthermore, ATRQß-001 vaccination suppressed renal Ang II-AT1R activation and abrogated the downregulation of angiotensin-converting enzyme 2-Ang (1-7), similar to olmesartan treatment, while no obvious feedback activation of circulating or local renin-angiotensin system (RAS) was only observed in vaccine group. In rat mesangial cells, the anti-ATR-001 antibody inhibited high glucose-induced transforming growth factor-ß1 (TGF)-ß1/Smad3 signal pathway. Additionally, no significant immune-mediated damage was detected in vaccinated animals. In conclusion, the ATRQß-001 vaccine ameliorated streptozotocin-induced diabetic renal injury via modulating two RAS axes and inhibiting TGF-ß1/Smad3 signal pathway, providing a novel, safe, and promising method to treat diabetic nephropathy. KEY MESSAGES: Overactivation of RAS plays a crucial role in the development of the DN. Our aim was to verify the effectiveness of ATRQß-001 vaccine in STZ-induced DN. The ATRQß-001 modulated two RAS axes and inhibited TGF-ß1/Smad3 signal pathway. The vaccine therapy may provide a novel, safe, and promising method to treat DN.

A compact, coaxial shunt current diagnostic for X pinches.

A compact coaxial shunt was applied in X-pinches experiments on Qiangguang pulsed power generator. The coaxial shunt was designed to have a compact construction for smaller inductance and more, for conveniently assembling upon the X pinch load structure. The coaxial shunt is also a cheap current probe and was easily built by research groups. The shunt can monitor a 100 kA high current with a 100 ns rise time. The calibration results showed that the probe used in the experiments has a resistance of 3.2 mΩ with an uncertainty of 3%, and its response time to the step signal is less than 7 ns.

Increased prevalence of carbapenem resistant Enterobacteriaceae in hospital setting due to cross-species transmission of the bla NDM-1 element and clonal spread of progenitor resistant strains.

This study investigated the transmission characteristics of carbapenem-resistant Enterobacteriaceae (CRE) strains collected from a hospital setting in China, in which consistent emergence of CRE strains were observable during the period of May 2013 to February 2014. Among the 45 CRE isolates tested, 21 (47%) strains were found to harbor the bla NDM-1 element, and the rest of 24 CRE strains were all positive for bla KPC-2. The 21 bla NDM-1-borne strains were found to comprise multiple Enterobacteriaceae species including nine Enterobacter cloacae, three Escherichia coli, three Citrobacter freundii, two Klebsiella pneumoniae, two Klebsiella oxytoca, and two Morganella morganii strains, indicating that cross-species transmission of bla NDM-1 is a common event. Genetic analyses by PFGE and MLST showed that, with the exception of E. coli and E. cloacae, strains belonging to the same species were often genetically unrelated. In addition to bla NDM-1, several CRE strains were also found to harbor the bla KPC-2, bla VIM-1, and bla IMP-4 elements. Conjugations experiments confirmed that the majority of carbapenem resistance determinants were transferable. Taken together, our findings suggest that transmission of mobile resistance elements among members of Enterobacteriaceae and clonal spread of CRE strains may contribute synergistically to a rapid increase in the population of CRE in clinical settings, prompting a need to implement more rigorous infection control measures to arrest such vicious transmission cycle in CRE-prevalent areas.

[Contrast of Z-Pinch X-Ray Yield Measure Technique].

Resistive bolometer and scintillant detection system are two mainly Z-pinch X-ray yield measure techniques which are based on different diagnostic principles. Contrasting the results from two methods can help with increasing precision of X-ray yield measurement. Experiments with different load material and shape were carried out on the "QiangGuang-I" facility. For Al wire arrays, X-ray yields measured by the two techniques were largely consistent. However, for insulating coating W wire arrays, X-ray yields taken from bolometer changed with load parameters while data from scintillant detection system hardly changed. Simulation and analysis draw conclusions as follows: (1) Scintillant detection system is much more sensitive to X-ray photons with low energy and its spectral response is wider than the resistive bolometer. Thus, results from the former method are always larger than the latter. (2) The responses of the two systems are both flat to Al plasma radiation. Thus, their results are consistent for Al wire array loads. (3) Radiation form planar W wire arrays is mainly composed of sub-keV soft X-ray. X-ray yields measured by the bolometer is supposed to be accurate because of the nickel foil can absorb almost all the soft X-ray. (4) By contrast, using planar W wire arrays, data from scintillant detection system hardly change with load parameters. A possible explanation is that while the distance between wires increases, plasma temperature at stagnation reduces and spectra moves toward the soft X-ray region. Scintillator is much more sensitive to the soft X-ray below 200 eV. Thus, although the total X-ray yield reduces with large diameter load, signal from the scintillant detection system is almost the same. (5) Both Techniques affected by electron beams produced by the loads.

Acetyl-L-carnitine rescues scopolamine-induced memory deficits by restoring insulin-like growth factor II via decreasing p53 oxidation.

Alzheimer's disease (AD) is characterized by the cholinergic neurons loss and impairments of learning and memory. Scopolamine is common used to imitate AD pathological features and also causes an obvious oxidative stress. In this study, we found that intraperitoneal administration of supplementary acetyl-L-carnitine partially reverses the learning and memory defects induced by scopolamine. We also found that acetyl-L-carnitine reverses the impairment of long-term potentiation, dendritic abnormalities, and the impaired recruitment of synaptic protein. The beneficial effects of acetyl-L-carnitine may occur through amelioration of oxidative stress because it effectively decreases the levels of oxidative products and increases the activity of superoxide dismutase; this leads to a recovery in the suppressed activity of p53 caused oxidative stimuli, which in turn restores levels of insulin-like growth factor II, an important hormone for learning and memory. Our study provides the first evidence of the potential utility of acetyl-L-carnitine in treating the synaptic disorders prevalent in AD and other neurodegenerative diseases. This article is part of the Special Issue entitled 'The Synaptic Basis of Neurodegenerative Disorders'.

A compact capacitive probe for high-voltage diagnostic in Z-pinches.

A capacitive divider was arranged on Qiangguang pulsed power generator during a series of wire-array Z-pinch experiments. This divider was designed to measure the voltage acted on the gap of the cathode and anode boards. The probe has a compact construction and is conveniently assembled on the facility. It is also a cheap voltage probe and easy to build by research groups. The probe can monitor a 1 MV high voltage with a 100 ns rise time. The calibration results showed that the probe had an attenuation ratio of 3.3 × 10(5) and a response time less than 5 ns. The uncertainty was estimated to be 3%.