Pharmacological prevention of bone loss and fractures following solid organ transplantations: Protocol for a systematic review and network meta-analysis.

INTRODUCTION: Solid organ transplant (SOT) recipients can experience bone loss caused by underlying conditions and the use of immunosuppressants. As a result, SOT recipients are at risk for decreased bone mineral density (BMD) and increased fracture incidences. We propose a network meta-analysis (NMA) that incorporates all available randomized control trial (RCT) data to provide the most comprehensive ranking of anti-osteoporotic interventions according to their ability to decrease fracture incidences and increase BMD in SOT recipients. METHODS: We will search MEDLINE, EMBASE, Web of Science, CINAHL, CENTRAL and CNKI for relevant RCTs that enrolled adult SOT recipients, assessed anti-osteoporotic therapies, and reported relevant outcomes. Title and full-text screening as well as data extraction will be performed in-duplicate. We will report changes in BMD as weighted or standardized mean differences, and fracture incidences as risk ratios. SUCRA scores will be used to provide rankings of interventions, and quality of evidence will be examined using RoB2 and CINeMA. DISCUSSIONS: To our knowledge, this systematic review and NMA will be the most comprehensive quantitative analysis regarding the management of bone loss and fractures in SOT recipients. Our analysis should be able to provide physicians and patients with an up-to-date recommendation for pharmacotherapies in reducing incidences of bone loss and fractures associated with SOT. The findings of the NMA will be disseminated in a peer-reviewed journal.

Analysis of medical malpractice liability disputes related to novel antineoplastic drugs and research on risk prevention and control strategies.

OBJECTIVE: To investigate the general characteristics of litigation cases of medical malpractice liability disputes (MMLDs) related to novel antineoplastic drugs (NADs), the drugs involved, as well as the common types of medical errors related to NADs and their damages in the process of diagnosis and treatment, with the aims of improving the level of rational medication use in the clinical application of NADs and actively prevent medical disputes. METHODS: The China Judgments Online was searched for the cause of action using the key word "MMLDs" along with the name of 77 kinds of NADs. A total of 39 NAD litigation cases meeting the inclusion criteria from 1 January 2009 to 31 December 2021 were analyzed, and each potential adverse drug reaction (ADR) was reviewed to determine a causality assessment using the Naranjo algorithm for non-drug-induced liver injury (DILI) cases and the updated Roussel Uclaf Causality Assessment Method (RUCAM) for the DILI cases. Risk prevention and control strategies were recommended. RESULTS: Cases that met the inclusion criteria increased substantially each year during the last six years, from three cases in 2009-2015 to 36 cases in 2016-2021. There were more cases in Eastern China than in other geographic regions. Most cases involved tertiary hospitals, patients between 25 and 60 years of age, and patients who were predominately male. There were 18 kinds of NADs involved in medical errors. The most common consequences of NADs were closely related to the death, disability, and increased treatment costs caused by ADRs, inadequate indications, delayed diagnosis and treatment, and misdiagnosis and mistreatment. The most frequent medical errors were medical technology errors, medical ethics errors and medical record writing/safekeeping errors. In two cases involving DILI, one case was unable to undergo further RUCAM scoring because the liver function indicators of the patient before and after treatment were not published. CONCLUSION: The establishment of mechanisms to reduce the risks associated with the clinical application of NADs is warranted. Healthcare services must maintain strict adherence to the specific requirements of GPCANADs and drug instructions and strictly grasp the indications, contraindications, usage, and dosage of drugs, and strengthen the notification and management of off-label drug use. Monitoring patients for ADRs and preparing rescue and treatment measures for high-risk drugs may serve to reduce damages related to NADs. For DILI cases, medical and appraisal institutions should use RUCAM score to assess causal relationships.

Lidocaine Ameliorates Diabetic Peripheral Neuropathy in Streptozotocin-Induced Diabetic Rats through Modulating the c-Jun Signaling Pathway.

As one of the common complications of diabetes mellitus (DM), Diabetic Peripheral Neuropathy (DPN) threatens human lives seriously. Emerging evidences have confirmed the protective effects of lidocaine on DPN. However, the possible role and underlying mechanisms of lidocaine in DPN have not been clarified. In this study, the potential role of lidocaine in DPN is explored, and the possible mechanisms are investigated. The rat DPN model is constructed through administration of streptozotocin (STZ, 60 mg/kg). All rats are randomly divided into four groups, including the control group, DPN group, lidocaine (3.78 mg/time) group, and lidocaine combined with the SP600125 (15 mg/kg) group. Mechanical threshold, thermal latency, and blood glucose of rats before and after treatment are detected, and Nerve Conduction Velocity (NCV) is assessed. Moreover, qRT-PCR and western blot assays are carried out to determine the expressions of the c-Jun signaling pathway. The experimental results demonstrate that lidocaine remarkably downregulates the mRNA and protein expressions of the c-Jun signaling pathway in serum and DRGs induced with DPN. Besides, lidocaine combined with SP600125 can obtain better effects than lidocaine alone. It is clearly evident that lidocaine has a certain therapeutic effect on DPN.

Brassinosteroids promote thermotolerance through releasing BIN2-mediated phosphorylation and suppression of HsfA1 transcription factors in Arabidopsis.

High temperature adversely affects plant growth and development. The steroid phytohormones brassinosteroids (BRs) are recognized to play important roles in plant heat stress responses and thermotolerance, but the underlying mechanisms remain obscure. Here, we demonstrate that the glycogen synthase kinase 3 (GSK3)-like kinase BRASSINOSTEROID INSENSITIVE2 (BIN2), a negative component in the BR signaling pathway, interacts with the master heat-responsive transcription factors CLASS A1 HEAT SHOCK TRANSCRIPTION FACTORS (HsfA1s). Furthermore, BIN2 phosphorylates HsfA1d on T263 and S56 to suppress its nuclear localization and inhibit its DNA-binding ability, respectively. BR signaling promotes plant thermotolerance by releasing the BIN2 suppression of HsfA1d to facilitate its nuclear localization and DNA binding. Our study provides insights into the molecular mechanisms by which BRs promote plant thermotolerance by strongly regulating HsfA1d through BIN2 and suggests potential ways to improve crop yield under extreme high temperatures.

Inflorescence Transcriptome Sequencing and Development of New EST-SSR Markers in Common Buckwheat (Fagopyrum esculentum).

Common buckwheat (Fagopyrum esculentum M.) is known for its adaptability, good nutrition, and medicinal and health care value. However, genetic studies of buckwheat have been hindered by limited genomic resources and genetic markers. In this study, Illumina HiSeq 4000 high-throughput sequencing technology was used to sequence the transcriptome of green-flower common buckwheat (Gr) with coarse pedicels and white-flower Ukrainian daliqiao (UD) with fine pedicels. A total of 118,448 unigenes were obtained, with an average length of 1248 bp and an N50 of 1850 bp. A total of 39,432 differentially expressed genes (DEGs) were identified, and the DEGs of the porphyrins and chlorophyll metabolic pathway had significantly upregulated expression in Gr. Then, a total of 17,579 sequences containing SSR loci were detected, and 20,756 EST-SSR loci were found. The distribution frequency of EST-SSR in the transcriptome was 17.52%, and the average distribution density was 8.21 kb. A total of 224 pairs of primers were randomly selected for synthesis; 35 varieties of common buckwheat and 13 varieties of Tartary buckwheat were verified through these primers. The clustering results well verified the previous conclusion that common buckwheat and Tartary buckwheat had a distant genetic relationship. The EST-SSR markers identified and developed in this study will be helpful to enrich the transcriptome information and marker-assisted selection breeding of buckwheat.

The therapeutic effect to eldecalcitol + bisphosphonate is superior to bisphosphonate alone in the treatment of osteoporosis: a meta-analysis.

BACKGROUND: Osteoporosis is a metabolic bone disease. Bisphosphonate (BP) and eldecalcitol (ELD) are two clinical first-line drugs for osteoporosis patients. However, the effect of ELD + BP vs. BP alone on osteoporosis treatment is still unclear. The present meta-analysis was conducted to evaluate the different therapeutic effect of BP + ELD vs. BP alone in osteoporosis treatment. METHODS: Eligible documents that selected from online databases including PubMed, Embase, and Cochrane Library were included in this study (updated to March 3, 2020). The quality assessment of the included studies was based on the guidelines of Cochrane. Meta-analysis was performed according to criteria such as intervention plan and outcome. The indicators including bone mineral density (BMD) in all enrolled studies were included in the current analysis. Pooled odds ratios (ORs) and weighted mean differences (WMDs) with 95% confidence intervals (CI) were calculated using fixed- or random-effects models. Then, heterogeneity analysis was performed based on Cochran's Q test and I2 statistics. RESULTS: A total of 4 studies (456 cases) with high quality were enrolled in this study. The effect of ELD + BP was superior to BP alone based on indicators including femoral neck BMD (FN-BMD) and total hip BMD (TH-BMD) in patients with followed up ≤ 6 months. Moreover, the effect of ELD + BP was superior to BP alone based on lumbar spine BMD (LS-BMD) in patients with 12 months followed up. CONCLUSION: Therapeutic effect of ELD + BP was superior to BP alone in osteoporotic patients based on the influence of BMD.

Correction to: The therapeutic effect to eldecalcitol + bisphosphonate is superior to bisphosphonate alone in the treatment of osteoporosis: a meta-analysis.

An amendment to this paper has been published and can be accessed via the original article.

General characteristics, economic burden, causative drugs and medical errors associated with medical damage litigation involving severe cutaneous adverse drug reactions in China.

WHAT IS KNOWN AND OBJECTIVE: To investigate the general characteristics, economic burden, causative drugs and medical errors associated with litigation involving severe cutaneous adverse drug reactions (SCADRs) in China, with the aims of improving rational medication use and reducing the extent of damage from SCADRs. METHODS: This study analysed 150 lawsuit judgements involving SCADRs from 2005 to 2019, collected from China Judgments Online. RESULTS AND DISCUSSION: In total, 50% of lawsuits stemmed from SCADRs occurring in general hospitals. The average time elapsed from the date of occurrence of the SCADRs to the end of litigation procedures was 1055 days. Of the patients involved, 51% were female and more than two thirds (69%) were under 60 years old. The most common outcome of SCADRs was death (39%), followed by disabilities (30%). The average responsibility of the medical provider was 48 ± 29%. The average amount of compensation was $43 424. Of the cases studied, 51% of SCADRs were Stevens-Johnson syndrome or toxic epidermal necrolysis, which together accounted for 75% of cases with known clinical subtype. The overall average economic burden of SCADRs was $99 178, of which indirect costs made up the largest proportion (more than 60%). The most common causative drug groups were antimicrobial drugs (49%), Chinese patent medicine and Chinese herbal medicine (17%), and antipyretic analgesics (16%). Finally, 61% of medical errors were found to stem from violation of duty of care, 20% from violation of informed consent and 18% from violations related to the medical record writing and management system. WHAT IS NEW AND CONCLUSION: Severe cutaneous adverse drug reactions not only severely affect patient survival and quality of life, but also impose a heavy economic burden in terms of health care and societal costs. Medical providers should be better educated on strategies to reduce risk to patients and establish mechanisms of risk sharing and management.

Propagation properties of radially and azimuthally polarized chirped Airy-Gaussian vortex beams through slabs of right-handed materials and left-handed materials.

By using Huygens-Fresnel diffraction integral formula and the transfer matrix method, the analytical expression of radially and azimuthally polarized chirped Airy-Gaussian vortex beams through left-handed materials and right-handed materials can be obtained. We study the effects of the chirp factor and the distribution factor on the radially and azimuthally polarized chirped Airy-Gaussian vortex beams in the propagation process, including the light intensity, the phase distribution, the propagation path, the peak intensity, and the radiation force. The focal position of the beams can be adjusted by the chirp parameter.

Transcriptome Analyses of Two Citrus Cultivars (Shiranuhi and Huangguogan) in Seedling Etiolation.

Citrus species are among the most important fruit crops. However, gene regulation and signaling pathways related to etiolation in this crop remain unknown. Using Illumina sequencing technology, modification of global gene expression in two hybrid citrus cultivars-Huangguogan and Shiranuhi, respectively-were investigated. More than 834.16 million clean reads and 125.12 Gb of RNA-seq data were obtained, more than 91.37% reads had a quality score of Q30. 124,952 unigenes were finally generated with a mean length of 1,189 bp. 79.15%, 84.35%, 33.62%, 63.12%, 57.67%, 57.99% and 37.06% of these unigenes had been annotated in NR, NT, KO, SwissProt, PFAM, GO and KOG databases, respectively. Further, we identified 604 differentially expressed genes in multicoloured and etiolated seedlings of Shiranuhi, including 180 up-regulated genes and 424 down-regulated genes. While in Huangguogan, we found 1,035 DEGs, 271 of which were increasing and the others were decreasing. 7 DEGs were commonly up-regulated, and 59 DEGs down-regulated in multicoloured and etiolated seedlings of these two cultivars, suggesting that some genes play fundamental roles in two hybrid citrus seedlings during etiolation. Our study is the first to provide the transcriptome sequence resource for seedlings etiolation of Shiranuhi and Huangguogan.

[Diagnosis and treatment of coincident vesical transitional cell carcinoma and prostate cancer: a report of 5 cases].

OBJECTIVE: To improve the diagnosis and treatment of coincident vesical transitional cell carcinoma (VTCC) and prostate cancer. METHODS: We analyzed the clinical data of 5 cases of coincident VTCC and prostate cancer. RESULTS: The 5 patients, at the mean age of 66.2 years, were diagnosed as having grade II - III VTCC by cystoscopy and biopsy, 1 with a history of prostate cancer, and the other 4 with prostate cancer confirmed by postoperative pathological examination. Two of the patients were treated by radical cystoprostatectomy, 1 by radical cystoprostatectomy and ileum conduit surgery, 1 by transurethral resection of bladder tumor, and the other 1 by palliative ureterocutaneostomy due to cardiopulmonary problems. The follow-up lasted 8 -26 months. One of them died of diffused metastasis 20 months after surgery, 1 survived with the tumor untreated, and the other 3 remained tumor free. CONCLUSION: Coincident VTCC and prostate cancer is easy to be missed in diagnosis. PSA detection, rectal palpation, transrectal ultrasonography, biopsy, and cystoscopy are the main diagnostic options for this disease. Its treatment should be based on the classification and clinical staging of the two cancers. Coincident VTCC and prostate cancer does not suggest poor prognosis.

[Photolysis kinetics of propisochlor in water].

Propisochlor in water was irradiated at room temperature by a 400 W high pressure mercury lamp and sunlight, respectively. Influence of light and initiative concentration of propisochlor on the photolysis were studied. The results showed that under the irradiation of sunlight the photolysis fitted first order kinetics with only 5.5% degradation after one hour's irradiation in the quartz tube, that was a slow rate; while under the irradiation of high pressure mercury lamp the photolysis can be described by a double-chamber model, in which the degradation rate can reach 80.9% after 1 h. The higher the initiative concentration of propisochlor was, the slower the photolysis rate became, and the photolysis of propisochlor was influenced by the increasing photo-products. The six main photodegradation products were identified using GC-MS method. The aromatic ring was proved to be intact during the process. And the photolysis mechanism was then assumed on the basis of the photo-products detected.