Variation in quality of care by medical institute level in China: a systematic review protocol

INTRODUCTION: Quality variation has been widely witnessed and discussed in China. However, limited evidence reveals quality gaps by the medical institute level, especially between hospitals and primary care institutes. This systematic review will synthesise the available evidence on quality variation between medical institutes at different levels in China. By adopting a quality framework, we will also explore the detailed domains (structure, process and outcomes) and dimensions (safety, effectiveness, timeliness, patient-centredness, efficiency, integration and equity) of quality gaps. METHODS AND ANALYSIS: An extensive literature search will be conducted on eight key electronic databases: MEDLINE, Web of Science, Cochrane Library, Scopus, EMBASE, ProQuest, China National Knowledge Infrastructure and WANFANG database. The Grey Matter Checklist will be used to screen relevant grey literature. The publication time limit should be before 31 December 2022 when we plan to conduct a literature search. All kinds of studies that revealed the quality difference between medical institutes at different levels will be included, no matter if quality improvement intervention is involved. All quality measures and indicators will be recorded and sorted into appropriate domains and dimensions. For those studies that took the completion rate of standard operations to assess the quality, we will also record the name of the clinical pathways, guidelines or checklists used. Two reviewers will independently perform the study selection, data extraction and quality assessment process. A narrative or quantitative synthesis will be performed based on the available data. ETHICS AND DISSEMINATION: Ethics approval is not applicable. The results of this study will be submitted to a widely accepted peer-review journal. The findings will also be used to inform administration about quality gaps by different medical institute levels and, therefore, help them to design policies that will minimise the quality variation. PROSPERO REGISTRATION NUMBER: CRD42022345933

Analysis of the curative effect of cervical spondylotic radiculopathy with osseous foraminal stenosis using ultrasonic osteotome in anterior cervical surgery

PURPOSE: To explore the clinical efficacy and operation points of cervical radiculopathy with osseous foraminal stenosis treated with ultrasonic osteotome in anterior cervical surgery. METHODS: From January 2018 to June 2021，a retrospective analysis of 23 patients with cervical radiculopathy with bony foraminal stenosis during this period was retrospectively analyzed. Anterior Cervical Discectomy and Fusion (ACDF) was used for all cases in this group. Intraoperative use of ultrasonic osteotome to decompress the nerve in the intervertebral foramina. The operation time, intraoperative blood loss and complication rate were recorded in this group of patients. Interbody fusion was evaluated using Brantigan criteria. The IC-PACS imaging system was used to measure the intervertebral foramen area (IFA) before and after surgery to evaluate the range of decompression. The VAS (Visual Analogue Scale, VAS) score and NDI (Neck Disability Index, NDI) score before and after surgery were recorded to evaluate the clinical efficacy. RESULTS: All enrolled patients were followed up regularly for 1 year or more. The mean operative time was 61.5 ± 8.0 minutes. The average intraoperative blood loss was 88.3 ± 12.8 ml, and the average hospital stay was 8.1 ± 1.7d. Twenty one cases of successful fusion were followed up 1 year after operation, and the fusion rate was 91.3%. IFA expanded from 25.1 ± 4.0 mm2 before operation to 57.9 ± 3.4 mm2 at 1 year after operation, and the difference was statistically significant (P < 0.001). The VAS score and NDI score of patients 3 days after surgery, 3 months after surgery, and 1 year after surgery were significantly lower than those before surgery (P < 0.001). There was 1 case of dysphagia and 1 case of Cage subsidence after operation, and the complication rate was 8.6%. CONCLUSION: Anterior cervical surgery using ultrasonic osteotome in the treatment of cervical radiculopathy with bony foraminal stenosis has reliable clinical efficacy and high safety, and is worthy of clinical promotion

Secreted proteins MDK, WFDC2, and CXCL14 as candidate biomarkers for early diagnosis of lung adenocarcinoma

BACKGROUND: Early diagnosis of lung adenocarcinoma (LUAD), one of the most common types of lung cancer, is very important to improve the prognosis of patients. The current methods can’t meet the requirements of early diagnosis. There is a pressing need to identify novel diagnostic biomarkers. Secretory proteins are the richest source for biomarker research. This study aimed to identify candidate secretory protein biomarkers for early diagnosis of LUAD by integrated bioinformatics analysis and clinical validation. METHODS: Differentially expressed genes (DEGs) of GSE31210, gene expression data of early stage of LUAD, were analyzed by GEO2R. Upregulated DEGs predicted to encode secreted proteins were obtained by taking the intersection of the DEGs list with the list of genes encoding secreted proteins predicted by the majority decision-based method (MDSEC). The expressions of the identified secreted proteins in the lung tissues of early-stage LUAD patients were further compared with the healthy control group in mRNA and protein levels by using the UALCAN database (TCGA and CPTAC). The selected proteins expressed in plasma were further validated by using Luminex technology. The diagnostic value of the screened proteins was evaluated by receiver operating characteristic (ROC) analysis. Cell counting kit-8 assay was carried out to investigate the proliferative effects of these screened proteins. RESULTS: A total of 2183 DEGs, including 1240 downregulated genes and 943 upregulated genes, were identified in the GSE31210. Of the upregulated genes, 199 genes were predicted to encode secreted proteins. After analysis using the UALCAN database, 16 molecules were selected for further clinical validation. Plasma concentrations of three proteins, Midkine (MDK), WAP four-disulfide core domain 2 (WFDC2), and C-X-C motif chemokine ligand 14 (CXCL14), were significantly higher in LUAD patients than in healthy donors. The area under the curve values was 0.944, 0.881, and 0.809 for MDK, WFDC2, and CXCL14, 0.962 when combined them. Overexpression of the three proteins enhanced the proliferation activity of A549 cells. CONCLUSIONS: MDK, WFDC2, and CXCL14 were identified as candidate diagnostic biomarkers for early-stage LUAD and might also play vital roles in tumorigenesis. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-023-10523-z

Screening of Q-markers for the wine-steamed Schisandra chinensis decoction pieces in improving allergic asthma

BACKGROUND: Traditional Chinese medicine (TCM) posits that Chinese medicinal materials can only be clinically used after being processed and prepared into decoction pieces. Schisandra Chinensis Fructus (derived from the dried and mature fruits of Schisandra chinensis (Turcz.) Baill.) has been used as a traditional antiasthmatic, kidney strengthening, and hepatoprotective agent for 2000 years. The results of previous research show that decoction pieces of wine-steamed Schisandra chinensis (WSC) are more effective than raw decoction pieces of Schisandra chinensis (RSC) for treating cough and asthma. Steaming with wine was demonstrated to promote the dissolution of ingredients. However, the relationship between the changes in the components of the decoction pieces of WSC and the therapeutic effect remains unclear. METHODS: The efficacies of decoctions of RSC and WSC were compared using allergic asthma rats. The potential bioactive components in the serum of the WSC treatment group and the changes in the chemical composition of the RSC decoction pieces before and after wine steaming were determined by ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS/MS) and ultra-high-performance liquid chromatography tandem mass spectrometry (UPLC H-CLASS XEVO TQD) to speculate quality markers (Q-markers) related to the efficacy of WSC, which were subsequently verified based on a zebrafish inflammation model. RESULTS: Steaming RSC decoction pieces with wine was found to promote improvement of allergic asthma. Reverse tracing of 22 components detected in the serum of the high dose group of WSC (WSC-H) resulted in 12 ingredients being finally designated as potential effective components. Among these ingredients, 5 components, Schisandrin, Schisandrol B, Schisandrin A, Schisandrin B, and Gomisin D, had higher dissolution rates than RSC after steaming with wine. Validation by an inflammatory zebrafish model showed that these 5 ingredients had a dose-dependent effect and were therefore Q-markers for WSC in the treatment of allergic asthma. CONCLUSION: In this study, changes in the components of decoction pieces of RSC and WSC and Q-markers related to WSC efficacy were identified, providing valuable information for expanding the application of WSC and establishing a specific quality standard for WSC. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13020-023-00712-0

A blend of functional amino acids and grape polyphenols improves the pig capacity to cope with an inflammatory challenge caused by poor hygiene of housing conditions

BACKGROUND: Dietary supplementation with a blend of functional amino acids (AA) and grape extract polyphenols contributes to preserve intestinal health and growth performance of piglets during the post-weaning period. In the present experiment, we assessed if a supplementation with a mix of AA and grape extract polyphenols during the post-weaning period would persist to improve the pig capacity to cope with a subsequent challenge caused by poor hygiene of housing conditions. Eighty pigs weaned at 28 days of age were fed a standard diet supplemented (AAP) or not (CNT) with 0.2% of a blend of AA (glutamine, arginine, cystine, valine, isoleucine, and leucine) and grape extract polyphenols during the post-weaning period (from week 0 to 6). At week 6, pigs were transferred to a growing unit where 50% of pigs previously fed AAP and CNT diets were housed in good and the other 50% in poor hygiene conditions for 3 weeks (from week 7 to 9; challenge period). All pigs were fed a standard growing diet that was not supplemented with AAP. We measured pig growth performance, plasma indicators of inflammation, digestive integrity, and oxidative status, and scored fecal consistency. Differences were considered significant at P ≤ 0.05. RESULTS: One week post-weaning, pigs fed AAP had lower plasma concentrations of haptoglobin than CNT pigs (P = 0.03). Six weeks post-weaning, plasma concentrations of diamine oxidase (DAO) were lower (P = 0.03) whereas those of vitamin E and A were greater (P ≤ 0.05) in pigs fed AAP compared to CNT pigs. The prevalence of diarrhea was higher in CNT pigs compared to AAP pigs (P < 0.01). During the challenge period, only pigs previously fed CNT diet had lower growth rate in poor than good conditions (P ≤ 0.05). They had also greater plasma concentrations of haptoglobin and oxidative stress index (OSI) and lower plasma concentrations of vitamin E in poor than good hygiene conditions (P ≤ 0.05). CONCLUSIONS: Pigs fed AAP diet during post-weaning had less diarrhea and plasma concentrations of a digestive integrity marker, as well as greater plasma concentrations of antioxidant indicators during the post-weaning period. The beneficial effects of AAP supplementation persisted after the post-weaning period as evidenced by the absence of effects of the hygiene challenge on growth and health indicators in pigs previously fed APP. This clearly indicated a greater ability of pigs fed AAP to cope with the poor hygiene conditions. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12917-023-03580-w

2-Hydroxy-3-methylanthraquinone inhibits homologous recombination repair in osteosarcoma through the MYC-CHK1-RAD51 axis

BACKGROUND: Osteosarcoma is a malignant bone tumor that usually affects adolescents aged 15–19 y. The DNA damage response (DDR) is significantly enhanced in osteosarcoma, impairing the effect of systemic chemotherapy. Targeting the DDR process was considered a feasible strategy benefitting osteosarcoma patients. However, the clinical application of DDR inhibitors is not impressive because of their side effects. Chinese herbal medicines with high anti-tumor effects and low toxicity in the human body have gradually gained attention. 2-Hydroxy-3-methylanthraquinone (HMA), a Chinese medicine monomer found in the extract of Oldenlandia diffusa, exerts significant inhibitory effects on various tumors. However, its anti-osteosarcoma effects and defined molecular mechanisms have not been reported. METHODS: After HMA treatment, the proliferation and metastasis capacity of osteosarcoma cells was detected by CCK-8, colony formation, transwell assays and Annexin V-fluorescein isothiocyanate/propidium iodide staining. RNA-sequence, plasmid infection, RNA interference, Western blotting and immunofluorescence assay were used to investigate the molecular mechanism and effects of HMA inhibiting osteosarcoma. Rescue assay and CHIP assay was used to further verified the relationship between MYC, CHK1 and RAD51. RESULTS: HMA regulate MYC to inhibit osteosarcoma proliferation and DNA damage repair through PI3K/AKT signaling pathway. The results of RNA-seq, IHC, Western boltting etc. showed relationship between MYC, CHK1 and RAD51. Rescue assay and CHIP assay further verified HMA can impair homologous recombination repair through the MYC-CHK1-RAD51 pathway. CONCLUSION: HMA significantly inhibits osteosarcoma proliferation and homologous recombination repair through the MYC-CHK1-RAD51 pathway, which is mediated by the PI3K-AKT signaling pathway. This study investigated the exact mechanism of the anti-osteosarcoma effect of HMA and provided a potential feasible strategy for the clinical treatment of human osteosarcoma. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s10020-023-00611-y

Mutational analysis of the spike protein of SARS-COV-2 isolates revealed atomistic features responsible for higher binding and infectivity

Introduction: The perpetual appearance of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-COV-2), and its new variants devastated the public health and social fabric around the world. Understanding the genomic patterns and connecting them to phenotypic attributes is of great interest to devise a treatment strategy to control this pandemic. Materials and Methods: In this regard, computational methods to understand the evolution, dynamics and mutational spectrum of SARS-CoV-2 and its new variants are significantly important. Thus, herein, we used computational methods to screen the genomes of SARS-CoV-2 isolated from Pakistan and connect them to the phenotypic attributes of spike protein; we used stability-function correlation methods, protein-protein docking, and molecular dynamics simulation. Results: Using the Global initiative on sharing all influenza data (GISAID) a total of 21 unique mutations were identified, among which five were reported as stabilizing while 16 were destabilizing revealed through mCSM, DynaMut 2.0, and I-Mutant servers. Protein-protein docking with Angiotensin-converting enzyme 2 (ACE2) and monoclonal antibody (4A8) revealed that mutation G446V in the receptor-binding domain; R102S and G181V in the N-terminal domain (NTD) significantly affected the binding and thus increased the infectivity. The interaction pattern also revealed significant variations in the hydrogen bonding, salt bridges and non-bonded contact networks. The structural-dynamic features of these mutations revealed the global dynamic trend and the finding energy calculation further established that the G446V mutation increases the binding affinity towards ACE2 while R102S and G181V help in evading the host immune response. The other mutations reported supplement these processes indirectly. The binding free energy results revealed that wild type-RBD has a TBE of −60.55 kcal/mol while G446V-RBD reported a TBE of −73.49 kcal/mol. On the other hand, wild type-NTD reported −67.77 kcal/mol of TBE, R102S-NTD reported −51.25 kcal/mol of TBE while G181V-NTD reported a TBE of −63.68 kcal/mol. Conclusions: In conclusion, the current findings revealed basis for higher infectivity and immune evasion associated with the aforementioned mutations and structure-based drug discovery against such variants

Diagnostic performance of optical coherence tomography macular ganglion cell inner plexiform layer and retinal nerve fiber layer thickness in glaucoma suspect and early glaucoma patients at St. Paul’s hospital millennium medical college, Addis Ababa, Ethiopia

PURPOSE: To evaluate glaucoma diagnostic performance of ganglion cell inner plexiform layer and retinal nerve fiber layer parameters measured with cirrus HD optical coherence tomography (OCT). METHOD: Total of 188 eyes were included in our study. 49 eyes of healthy controls, 70 glaucoma suspect eyes and 69 early glaucomatous eyes. Complete ophthalmic examination was done including visual field test (with Humphrey field analyzer) and OCT scanning of ganglion cell inner plexiform layer (GCIPL) and retinal nerve fiber layer (RNFL) in different quadrants. Sensitivity, specificity and area under the receiver operating characteristic curve (AUROC) of each parameter was calculated to provide diagnostic ability between normal controls, glaucoma suspects or early glaucoma. RESULT: GCIPL and RNFL parameters had strong power in discriminating early glaucoma from healthy controls with all having AUROC of above 0.76. Of all the GCIPL and RNFL parameters, the only variable that could discriminate between glaucoma suspect and healthy controls was the combined parameter by OR-logic approach. Of all the parameters, the average and nasal RNFL parameters had the strongest power in discriminating between the two with AUROC of 0.81. All parameters had an overall good diagnostic performance with excellent sensitivity but the specificity was relatively poor. The combined parameter had the best specificity (62.2%) with excellent sensitivity (93.5%). CONCLUSION: Nasal RNFL parameters had the strongest power in discriminating between glaucoma suspect and healthy controls and the OR-logic combination of RNFL and GCIPL provides better diagnostic performance than single GCIPL, RNFL or ONH parameter