Artificial Intelligence-Assisted Prescription Determination for Orthokeratology Lens Fitting: From Algorithm to Clinical Practice.

OBJECTIVES: To explore the potential of artificial intelligence (AI) to assist prescription determination for orthokeratology (OK) lenses. METHODS: Artificial intelligence algorithm development followed by a real-world trial. A total of 11,502 OK lenses fitting records collected from seven clinical environments covering major brands. Records were randomly divided in a three-way data split. Cross-validation was used to identify the most accurate algorithm, followed by an evaluation using an independent test data set. An online AI-assisted system was implemented and assessed in a real-world trial involving four junior and three senior clinicians. RESULTS: The primary outcome measure was the algorithm's accuracy (ACC). The ACC of the best performance of algorithms to predict the targeted reduction amplitude, lens diameter, and alignment curve of the prescription was 0.80, 0.82, and 0.83, respectively. With the assistance of the AI system, the number of trials required to determine the final prescription significantly decreased for six of the seven participating clinicians (all P <0.01). This reduction was more significant among junior clinicians compared with consultants (0.76±0.60 vs. 0.32±0.60, P <0.001). Junior clinicians achieved clinical outcomes comparable to their seniors, as 93.96% (140/149) and 94.44% (119/126), respectively, of the eyes fitted achieved unaided visual acuity no worse than 0.8 ( P =0.864). CONCLUSIONS: AI can improve prescription efficiency and reduce discrepancies in clinical outcomes among clinicians with differing levels of experience. Embedment of AI in practice should ultimately help lessen the medical burden and improve service quality for myopia boom emerging worldwide.

Analysis of Key Genes and miRNA-mRNA Networks Associated with Glucocorticoids Treatment in Chronic Obstructive Pulmonary Disease.

Background: Some patients with chronic obstructive pulmonary disease (COPD) benefit from glucocorticoid (GC) treatment, but its mechanism is unclear. Objective: With the help of the Gene Expression Omnibus (GEO) database, the key genes and miRNA-mRNA related to the treatment of COPD by GCs were discussed, and the potential mechanism was explained. Methods: The miRNA microarray dataset (GSE76774) and mRNA microarray dataset (GSE36221) were downloaded, and differential expression analysis were performed. Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed on the differentially expressed genes (DEGs). The protein interaction network of the DEGs in the regulatory network was constructed with the STRING database, and the key genes were screened through Cytoscape. Potential downstream target genes regulated by differentially expressed miRNAs (DEMs) were predicted by the miRWalk3.0 database, and miRNA-mRNA regulatory networks were constructed. Finally, some research results were validated. Results: ① Four DEMs and 83 DEGs were screened; ② GO and KEGG enrichment analysis mainly focused on the PI3K/Akt signalling pathway, ECM receptor interaction, etc.; ③ CD2, SLAMF7, etc. may be the key targets of GC in the treatment of COPD; ④ 18 intersection genes were predicted by the mirwalk 3.0 database, and 9 pairs of miRNA-mRNA regulatory networks were identified; ⑤ The expression of miR-320d-2 and TFCP2L1 were upregulated by dexamethasone in the COPD cell model, while the expression of miR-181a-2-3p and SLAMF7 were downregulated. Conclusion: In COPD, GC may mediate the expression of the PI3K/Akt signalling pathway through miR-181a-2-3p, miR-320d-2, miR-650, and miR-155-5p, targeting its downstream signal factors. The research results provide new ideas for RNA therapy strategies of COPD, and also lay a foundation for further research.

Effect of electroacupuncture of "Jiaji" (EX-B2) on NOD-like receptor protein 3 mediated pyroptosis in spinal cord tissue of rats with acute spinal cord injury. / å¤¹è„Šç”µé’ˆå¯¹æ€¥æ€§è„Šé«“æŸä¼¤å¤§é¼ è„Šé«“ç»„ç»‡NODæ ·å—ä½“çƒ­è›‹ç™½ç»“æž„åŸŸç›¸å ³è›‹ç™½3介导的细胞焦亡的影响.

OBJECTIVES: To observe the effect of electroacupuncture (EA) stimulation of "Jiaji"(EX-B2) on motor function, histomorphology, and expression of NOD-like receptor protein 3 (NLRP3) and N-terminal domain of gasdermin D (GSDMD-N) in the spinal cord tissue of rats with spinal cord injury (SCI), so as to explore its mechanism underlying improvement of SCI. METHODS: Forty eight female SD rats were randomly divided into sham surgery (sham), SCI model (model), EA, and NLRP3 agonist (monosodium urate, MSU) combined with Jiaji EA (MSU+EA) groups, with 12 rats in each group which were further divided into 3 d and 7 d subgroups, with 6 rats at each time point. Two EA groups received EA stimulation of EX-B2 with a frequency of 100 Hz, electrical current of 1-2 mA for 30 min, once a day for 3 or 7 days. After 5 min, 6 h, and 24 h of modeling, rats of the MSU+EA group received intraperitoneal injection of MSU (200 µg/kg, 200 µg/mL) . The motor function was evaluated using Basso-Beattie-Bresnahan (BBB) scale, the morphological structure of rat spinal cord tissue was observed by H.E. staining. The expression of pyroptosis related factors NLRP3, cleaved Caspase-1 and GSDMD-N of the spinal cord was observed by using immunohistochemistry and Western blot separately, the expression and localization of Iba-1 and GSDMD-N in the spinal cord tissue were observed using immunofluorescence double staining method. RESULTS: Compared with the sham group, the BBB scores after modeling and on day 3 and 7 were decreased (P<0.05), while the average OD values (immunoactivity) and expression levels of NLRP3, cleaved Caspase-1 and GSDMD-N proteins, and the immunofluorescence intensity of Iba-1/GSDMD-N (co-expression) of the spinal cord tissues on day 3 and 7 were significantly increased in the model group (P<0.05). In comparison with the model group, the BBB scores on day 3 and 7 were obviously increased (P<0.05), while the immunoactivity and expression levels of NLRP3, cleaved Caspase-1 and GSDMD proteins, and the immunofluorescence intensity of Iba-1/GSDMD-N on day 3 and 7 significantly down-regulated in the EA group (P<0.05) but not in the MSU+EA group (P>0.05), suggesting an elimination of the effects of EA after administration of NLRP3 agonist (MSU). H.E. staining showed obvious bleeding area in the spinal cord tissue, loose tissue and inflammatory cell infiltration on day 3 after modeling, and basic absorption of the bleeding, loose tissue, obvious vacuolar changes of the white matter area, loss and contraction of neurons with infiltration of a large number of inflammatory cells, which was milder in the EA group but not in the MSU+EA group. CONCLUSIONS: EA of EX-B2 can improve the motor function of SCI rats, which may be related to its functions in inhibiting pyroptosis of microglia mediated by NLRP3/Caspase-1 signaling pathway.

[Research progress of acupuncture-moxibustion in treatment of spinal cord injury through mediating inflammatory reaction].

Inflammatory reaction after spinal cord injury (SCI) is the main obstacle to the recovery of neural function. In the occurrence and development of SCI, the complex regulatory mechanisms are involved in inflammatory reaction, including the activation of inflammatory cells (e.g.macrophages and microglia), and the release of cytokines (e.g. tumor necrosis factor, interleukin and chemokines). Acupuncture-moxibustion is significantly effective in clinical treatment of SCI, and its mechanism is related to adjusting the function of inflammatory cells after SCI, modulating the expression of cytokines and the activation of NLRP3 inflammatory bodies, as well as the expression of high mobility group protein B1 and calcitonin gene related peptide. This article summarizes the research progress of mechanism of inflammatory reaction after SCI and the effects of acupuncture-moxibustion intervention in recent years so that the new ideas can be provided to clarify the pathogenesis of SCI and the effect of acupuncture-moxibustion intervention.

Site-directed mutagenesis identified the key active site residues of 2,3-oxidosqualene cyclase HcOSC6 responsible for cucurbitacins biosynthesis in Hemsleya chinensis.

Hemsleya chinensis is a Chinese traditional medicinal plant, containing cucurbitacin IIa (CuIIa) and cucurbitacin IIb (CuIIb), both of which have a wide range of pharmacological effects, including antiallergic, anti-inflammatory, and anticancer properties. However, few studies have been explored on the key enzymes that are involved in cucurbitacins biosynthesis in H. chinensis. Oxidosqualene cyclase (OSC) is a vital enzyme for cyclizing 2,3-oxidosqualene and its analogues. Here, a gene encoding the oxidosqualene cyclase of H. chinensis (HcOSC6), catalyzing to produce cucurbitadienol, was used as a template of mutagenesis. With the assistance of AlphaFold2 and molecular docking, we have proposed for the first time to our knowledge the 3D structure of HcOSC6 and its binding features to 2,3-oxidosqualene. Mutagenesis experiments on HcOSC6 generated seventeen different single-point mutants, showing that single-residue changes could affect its activity. Three key amino acid residues of HcOSC6, E246, M261 and D490, were identified as a prominent role in controlling cyclization ability. Our findings not only comprehensively characterize three key residues that are potentially useful for producing cucurbitacins, but also provide insights into the significant role they could play in metabolic engineering.

A cohort study using IL-6/Stat3 activity and PD-1/PD-L1 expression to predict five-year survival for patients after gastric cancer resection.

OBJECTIVES: The expression/activation of IL-6, p-Stat3, PD-1 and PD-L1 in gastric cancer (GC) tissues were examined to evaluate their abilities in predicting the survival prognosis in postoperative patients with GC. METHODS: The clinicopathological data and paraffin-embedded tissues of 205 patients who underwent gastric cancer resection were collected at the First Affiliated Hospital of Shihezi University School of Medicine, and the patients were followed-up annually after surgery. Immunohistochemistry (IHC) was used to detect the expression of IL-6, p-Stat3, PD-1 and PD-L1 proteins using tissue microarrays derived from these patients. Statistical analyses were performed using non-parametric tests, Spearman's correlation, ROC curves, Kaplan-Meier survival analysis, Cox single-factor and multifactor regression models. In comparison, the analyses were also performed for GC patients from public databases (407 patients from TCGA and 433 patients from GEO, respectively). RESULTS: (1) The expression levels of IL-6, p-Stat3, PD-1 and PD-L1 in GC tissues were significantly higher than adjacent normal tissues (ANT) (81.01% vs. 52.78%, P<0.001; 100% vs. 93.41%, P<0.001; 58.58% vs. 40.12%, P<0.001; 38.20% vs. 26.90%, P = 0.025, respectively). The mean optical density (MOD) values of IL-6, p-Stat3, PD-1 and PD-L1 were significantly higher in GC tissues. (2) The higher the levels of IL-6 (P<0.001), p-Stat3 (P<0.001), and PD-L1 (P = 0.003) were, the worse the survival prognoses were observed, respectively, among GC patients. The expression of PD-1 was not correlated with the prognosis of GC patients (P>0.05). The lower the degree of cell differentiation (P<0.001) was, the worse the survival prognoses were observed among GC patients. (3) Independent risk factors for postoperative prognosis in GC patients included age (≥60 years old), poor cell differentiation, invasion depth (T3/T4), lymph node metastasis (N1-3), distant metastasis (M1), and high levels of IL-6 (2+/3+). (4) A multi-factor combination (cell differentiation+IL-6+p-Stat3+PD-1+PD-L1) appeared to be the best survival predictor for GC patients as indicated by AUC (AUC 0.782, 95% CI = 0.709, 0.856, P<0.001). This combination may be the optimal predictor for postoperative survival of GC patients. (5) The levels of IL-6, p-Stat3, PD-1 and PD-L1 correlated with the infiltration levels of various tumor-infiltrating immune cells. (6) The analyses of ROC curves, calibration, DCA and Kaplan-Meier (KM) survival curves in TCGA dataset confirmed that the nomogram model could accurately predict the prognosis in GC patients. CONCLUSIONS: (1) The expressed levels of IL-6, p-Stat3, PD-1 and PD-L1 are higher in GC tissues than in adjacent normal tissues. (2) The high levels of IL-6, p-Stat3 and PD-L1 are correlated with poor survival in GC patients. (3) The high levels of IL-6, p-Stat3, PD-1 and PD-L1 have influences in GC tumor microenvironment. (4) The multi-predictor combination of "IL-6+p-Stat3+PD-1+cell differentiation" serves as an optimal survival predictor for postoperative GC patients and better than the TNM staging system. As these molecules can be examined in preoperative biopsies, these observations may provide a useful guide for clinicians to strategize individualized surgical plans for GC patients before surgery.

The discovery of potentially active diterpenoids to inhibit the pyroptosis from Callicarpa arborea.

Pyroptosis is a programmed-inflammatory cell death, which leads to release of inflammatory cellular contents and formation of inflammation. Uncontrollable pyroptosis can result in serious immune diseases, such as cytokine release syndrome (CRS), sepsis, disseminated intravascular coagulation (DIC), and acute organ damage, including acute respiratory distress syndrome (ARDS) and acute kidney injury (AKI). Members of the Callicarpa genus are significant raw materials for traditional Chinese medicine, widely used for analgesia, hemostasis, and anti-inflammation. Previously, we have reported some ent-clerodane diterpenoids from Callicarpa arborea, shown potent inhibitory effects against pyroptosis. In this study, we went on investigating this kind of diterpenoids, and yielded 66 ent-clerodane diterpenoids, including 52 new compounds, from Callicarpa arborea. Their structures featured with a 5/6- (1-25) or a 6/6- (26-66)-fused double-ring scaffolds, were elucidated using spectroscopic data, electrostatic circular dichroism (ECD) and X-ray diffraction analyses. Screening for the inhibitory activity against pyroptosis by detecting of IL-1ß secretion in J771A.1 cells, revealed 28 compounds with an IC50 below 10.5 µM. Compound 1 was the most potent with an IC50 of 0.68 µM and inhibited the J774A.1 macrophage pyroptosis by blocking the NLR pyrin domain containing 3 (NLRP3) inflammasome activation. An in vivo study further revealed that compound 1 decreased infiltration of CD11b + F4/80 + macrophages into lung and attenuated the lipopolysaccharide (LPS)-induced lung injury. Taken together, this study indicated the potential of compound 1 as a candidate for pyroptosis-related inflammation treatment, as well as provided the chemical and pharmacological basis for the further development of Callicarpa genus as a herbal medicine.

Physiological integration between Bermudagrass ramets improves overall salt resistance under heterogeneous salt stress.

Connected ramets of colonal plants often suffer from different environmental conditions such as light, nutrient, and stress. Colonal Bermudagrass (Cynodon dactylon [L.] Pers.) can form interconnected ramets and this connection facilitates the tolerance to abiotic stress, which is a kind of physiological integration. However, how bermudagrass responds to heterogeneously distributed salt stress needs to be further elucidated. Here, we demonstrated that severance of stolons aggravated the damage of salt-stressed ramets, displaying higher relative electrolytic leakage (EL), lower content of chlorophyll, higher accumulation of Na+ , and serious oxidative damages. This finding implied the positive effects of the physiological integration of bermudagrass on salt tolerance. The unstressed ramets connected with the stressed one were mildly injured, implying the supporting and sacrifice function of the unstressed ramets. Physiological integration did not mediate the translocation of Na+ among ramets, but induced a higher expression of salt overly sensitive (SOS) genes in the stressed ramets, consequently reducing the accumulation of Na+ in leaves and roots. In addition, physiological integration upregulated the genes expression and enzymes activity of catalase (CAT) and peroxidase (POD) in both stressed and unstressed ramets. This granted a stronger antioxidant ability of the whole clonal plants under salt stress. Enhanced Na+ transfer and increased reactive oxygen species (ROS) scavenging are mechanisms that likely contribute to the physiological integration leading to the salt tolerance of bermudagrass.

Spiroarborin, an ent-Clerodane Homodimer from Callicarpa arborea as an Inhibitor of the Eleven-Nineteen Leukemia (ENL) Protein by Targeting the YEATS Domain.

A spiro ent-clerodane homodimer with a rare 6/6/6/6/6-fused pentacyclic scaffold, spiroarborin (1), together with four new monomeric analogues (2-5), were isolated from Callicarpa arborea. Their structures were elucidated by comprehensive spectroscopic data analysis, quantum-chemical calculations, and X-ray diffraction. A plausible biosynthetic pathway of 1 was proposed, and a biomimetic synthesis of its derivative was accomplished. Compound 1 showed a potent inhibitory effect by directly binding to the YEATS domain of the 11-19 leukemia (ENL) protein with an IC50 value of 7.3 µM. This gave a KD value of 5.0 µM, as recorded by a surface plasmon resonance binding assay.

Curcumin increases crizotinib sensitivity through the inactivation of autophagy via epigenetic modulation of the miR-142-5p/Ulk1 axis in non-small cell lung cancer.

Drug resistance is a critical factor responsible for the recurrence of non-small cell lung cancer (NSCLC). Previous studies suggest that curcumin acts as a chemosensitizer and radiosensitizer in human malignancies, but the underlying mechanism remains elusive. In the present study, we explored how curcumin regulates the expression of miR-142-5p and sensitizes NSCLC cells to crizotinib. We found that miR-142-5p is significantly downregulated in NSCLC tissue samples and cell lines. Curcumin could increase crizotinib cytotoxicity by epigenetically restoring the expression of miR-142-5p. Furthermore, curcumin treatment suppressed the expression of DNA methylation-related enzymes, including DNMT1, DNMT3A, and DNMT3B, in NSCLC cells. In addition, the upregulation of miR-142-5p expression increased crizotinib cytotoxicity and induced apoptosis in tumor cells in a similar manner to that of curcumin. Strikingly, miR-142-5p overexpression suppressed crizotinib-induced autophagy in A549 and H460 cells. Mechanistically, miR-142-5p inhibited autophagy in lung cancer cells by targeting Ulk1. Overexpression of Ulk1 abrogated the miR-142-5p-induced elevation of crizotinib cytotoxicity in A549 and H460 cells. Collectively, our findings demonstrate that curcumin sensitizes NSCLC cells to crizotinib by inactivating autophagy through the regulation of miR-142-5p and its target Ulk1.

Detection of rabies virus via exciton energy transfer between CdTe quantum dots and Au nanoparticles.

Rabies is a fatal encephalitis caused by the rabies virus. The diagnosis of the disease depends in large part on the exposure history of the victim and clinical manifestations of the disease. Rapid rabies diagnosis is an important step in its prevention and control. Therefore, for accurate and timely diagnosis and prevention of rabies, we developed nanomaterials for a novel photoelectrochemical biosensing approach (PBA) for the rapid and reliable diagnosis of rabies virus. This approach uses high-efficiency exciton energy transfer between cadmium telluride quantum dots and Au nanoparticles and is low cost, and easy to miniaturize. By constructing PBA, rabies virus can be detected quickly and with a high degree of sensitivity and specificity; the minimum detection concentration limit for rabies virus is approximately 2.16 ffu/mL of rabies virus particles, or 2.53 × 101 fg/mL of rabies virus RNA. PBA could also detect rabies virus in the brain and lung tissue from rabid dogs and mice with better sensitivity than RT-PCR.

CCT4 suppression inhibits tumor growth in hepatocellular carcinoma by interacting with Cdc20.

BACKGROUND: The chaperonin containing t-complex (CCT) proteins play an important role in cell cycle-related protein degradation in yeast and mammals. The role of the chaperonin containing t-complex 4 (CCT4), one subtype of CCT proteins, in the progress of hepatocellular carcinoma (HCC) was not fully elucidated. Here, we aimed to explore the mechanisms of CCT4 in HCC. METHODS: In this study, we used the UALCAN platform to analyze the relationship between CCT4 and HCC, and the association of CCT4 with the overall survival (OS) of HCC patients was also analyzed. CCT4 expression in HCC tumor tissues and normal tissues was also determined by western blot (WB) assay. Lentivirus vector was used to knock down the CCT4 expression, and quantitative polymerase chain reaction and WB were used to determine the level of CCT4 in HCC cell lines. Cell counting kit-8 (CCK-8) and 5-ethynyl-2'-deoxyuridine (EdU) assays were used to detect the cell proliferation, and flow cytometry (FCM) was performed to evaluate the effect of CCT4 on the apoptosis of HCC cells. Co-immunoprecipitation (co-IP) assay and WB were used to explore the mechanisms of CCT4 regulating the growth of HCC. Data were calculated from at least three replicate experiments and expressed as mean ± standard deviation. Student's t test, paired t test, and Kaplan-Meier analysis were used to compare across different groups. RESULTS: We found CCT4 was upregulated in HCC tissues compared with normal tissues, and its high expression was associated with poor prognosis (P < 0.001). CCT4 was significantly increased in HCC tumor tissues compared with normal tissues (0.98 ±â€Š0.12 vs. 0.23 ±â€Š0.05, t = 7.73, P < 0.001). After being transfected with CCT4 short-hairpin RNA (shRNA), CCT4 was decreased in mRNA level and protein level in both Huh7 (mRNA level: 0.41 ±â€Š0.07 vs. 1.01 ±â€Š0.11, t = 8.09, P = 0.001; protein level: 0.61 ±â€Š0.03 vs. 0.93 ±â€Š0.07, t = 7.19, P = 0.002) and Hep3b cells (mRNA level: 0.55 ±â€Š0.11 vs. 1.04 ±â€Š0.15, t = 4.51, P = 0.011; protein level: 0.64 ±â€Š0.10 vs. 0.95 ±â€Š0.08, t = 4.32, P = 0.012). CCK8 assay indicated that CCT4 knockdown inhibited cell proliferation in both Huh7 (OD value of 3 days: 0.60 ±â€Š0.14 vs. 0.97 ±â€Š0.16, t = 3.13, P = 0.036; OD value of 4 days: 1.03 ±â€Š0.07 vs. 1.50 ±â€Š0.12, t = 5.97, P = 0.004) and Hep3b (OD value of 3 days: 0.69 ±â€Š0.14 vs. 1.10 ±â€Š0.11, t = 3.91, P = 0.017; OD value of 4 days: 1.12 ±â€Š0.12 vs. 1.48 ±â€Š0.13, t = 3.55, P = 0.024) cells. EdU assay showed that CCT4 knockdown inhibited the cell proliferation in both Huh7 (EdU positive rate: [31.25 ±â€Š3.41]% vs. [58.72 ±â€Š3.78]%, t = 9.34, P = 0.001) and Hep3b cells (EdU positive rate: [44.13 ±â€Š7.02]% vs. [61.79 ±â€Š3.96]%, t = 3.79, P = 0.019). FCM assay suggested that CCT4 knockdown induced apoptosis in HCC cells (apoptosis rate of Huh7: [9.10 ±â€Š0.80]% vs. [3.66 ±â€Š0.64]%, t = -9.18, P = 0.001; apoptosis rate of Hep3b: [6.69 ±â€Š0.72]% vs. [4.20 ±â€Š0.86]%, t = -3.84, P = 0.018). We also found that CCT4 could regulate anaphase-promoting complex (APC)Cdc20 activity via interacting with Cdc20. Furthermore, CCT4 knockdown induced securin (0.65 ±â€Š0.06 vs. 0.44 ±â€Š0.05, t = -4.69, P = 0.009) and B-cell lymphoma-2 (Bcl-2) interacting mediator of cell death (Bim; 0.96 ±â€Š0.06 vs. 0.61 ±â€Š0.09, t = -5.65, P = 0.005) accumulation. The upregulation of securin inhibited cell growth by downregulating cyclin D1 (0.65 ±â€Š0.05 vs. 1.04 ±â€Š0.07, t = 8.12, P = 0.001), and the accumulation of Bim inhibited Bcl-2 (0.77 ±â€Š0.04 vs. 0.87 ±â€Š0.04, t = 3.00, P = 0.040) and activated caspase 9 (caspase 9: 0.77 ±â€Š0.04 vs. 0.84 ±â€Š0.05, t = 1.81, P = 0.145; cleaved caspase 9: 0.64 ±â€Š0.06 vs. 0.16 ±â€Š0.07, t = 1.81, P = 0.001), which led to elevated apoptosis. CONCLUSIONS: Overall, these results showed that CCT4 played an important role in HCC pathogenesis through, at least partly, interacting with Cdc20.

Effectiveness of inactivated SARS-CoV-2 vaccines against the Delta variant infection in Guangzhou: a test-negative case-control real-world study.

The effectiveness of inactivated SARS-CoV-2 vaccines against the Delta variant, which has been associated with greater transmissibility and virulence, remains unclear. We conducted a test-negative case-control study to explore the vaccine effectiveness (VE) in real-world settings. We recruited participants aged 18-59 years who consisted of SARS-CoV-2 test-positive cases (n = 74) and test-negative controls (n = 292) during the outbreak of the Delta variant in May 2021 in Guangzhou city, China. Vaccination status was compared to estimate The VE of SARS-CoV-2 inactivated vaccines. A single dose of inactivated SARS-CoV-2 vaccine yielded the VE of only 13.8%. After adjusting for age and sex, the overall VE for two-dose vaccination was 59.0% (95% confidence interval: 16.0% to 81.6%) against coronavirus disease 2019 (COVID-19) and 70.2% (95% confidence interval: 29.6-89.3%) against moderate COVID-19 and 100% against severe COVID-19 which might be overestimated due to the small sample size. The VE of two-dose vaccination against COVID-19 reached 72.5% among participants aged 40-59 years, and was higher in females than in males against COVID-19 and moderate diseases. While single dose vaccination was not sufficiently protective, the two-dose dosing scheme of the inactivated vaccines was effective against the Delta variant infection in real-world settings, with the estimated efficacy exceeding the World Health Organization minimal threshold of 50%.

Impact of type 2 diabetes on adenoma detection in screening colonoscopies performed in disparate populations.

BACKGROUND: The Black/African Ancestry (AA) population has a higher prevalence of type 2 diabetes mellitus (T2DM) and a higher incidence and mortality rate for colorectal cancer (CRC) than all other races in the United States. T2DM has been shown to increase adenoma risk in predominantly white/European ancestry (EA) populations, but the effect of T2DM on adenoma risk in Black/AA individuals is less clear. We hypothesize that T2DM has a significant effect on adenoma risk in a predominantly Black/AA population. AIM: To investigate the effect of T2DM and race on the adenoma detection rate (ADR) in screening colonoscopies in two disparate populations. METHODS: A retrospective cohort study was conducted on ADR during index screening colonoscopies (age 45-75) performed at an urban public hospital serving a predominantly Black/AA population (92%) (2017-2018, n = 1606). Clinical metadata collected included basic demographics, insurance, body mass index (BMI), family history of CRC, smoking, diabetes diagnosis, and aspirin use. This dataset was combined with a recently reported parallel retrospective cohort data set collected at a suburban university hospital serving a predominantly White/EA population (87%) (2012-2015, n = 2882). RESULTS: The ADR was higher in T2DM patients than in patients without T2DM or prediabetes (35.2% vs 27.9%, P = 0.0166, n = 981) at the urban public hospital. Multivariable analysis of the combined datasets showed that T2DM [odds ratio (OR) = 1.29, 95% confidence interval (CI): 1.08-1.55, P = 0.0049], smoking (current vs never OR = 1.47, 95%CI: 1.18-1.82, current vs past OR = 1.32, 95%CI: 1.02-1.70, P = 0.0026), older age (OR = 1.05 per year, 95%CI: 1.04-1.06, P < 0.0001), higher BMI (OR = 1.02 per unit, 95%CI: 1.01-1.03, P = 0.0003), and male sex (OR = 1.87, 95%CI: 1.62-2.15, P < 0.0001) were associated with increased ADR in the combined datasets, but race, aspirin use and insurance were not. CONCLUSION: T2DM, but not race, is significantly associated with increased ADR on index screening colonoscopy while controlling for other factors.

[Research on regularity of traditional Chinese medicine in treatment of Alzheimer's disease based on data mining].

To explore prescription medication regularity in the treatment of Alzheimer's disease with traditional Chinese medicine(TCM). With Alzheimer's disease or senile dementia as the subject, collecting and sorting out the journal papers in CNKI were collected as the data source to establish the literature research database of Alzheimer's disease prescriptions, and then the association rule analysis, factor analysis and systematic cluster analysis on the included TCM were conducted. Among the 113 prescriptions included in the standard, the single herb Acori Tatarinowii Rhizoma was the most common. The herbs were mainly warm and flat among four pro-perties, mainly sweet, bitter and spicy among five flavors. The drugs were mainly distributed in five internal organs, and the most commonly used drugs were deficiency tonifying drugs as well as blood activating and stasis removing drugs. In the association rule analysis, it was found that there were 6 drug pairs with the highest association strength. Eight common factors were extracted from the factor analysis, and they were classified into 6 categories in the systematic cluster analysis. The results have shown that the overall principles in treating Alzheimer's disease with modern Chinese medicine are tonifying deficiency, invigorating circulation, activating blood and dispelling phlegm.

Chromobacterium violaceum infection on lower limb skin: A case report.

RATIONAL: Chromobacterium violaceum is a motile gram-negative bacterium. This bacterium commonly grows in tropical or subtropical areas in sewage and can cause opportunistic infections. PATIENT CONCERNS: A 50-year-old Chinese man had a skin ulcer in the middle of his left leg in front of the tibia. The diameter of the wound was 3.0 cm, the exudation was obvious, and necrotic tissue was attached to the wound. One week previously, he was working in a field where he accidentally punctured his left leg. DIAGNOSIS: C violaceum infection was diagnosed as per the results of pathogen culture from the infection site. INTERVENTIONS: He was treated with piperacillin/tazobactam (3.375 g/12 h iv) and levofloxacin (0.5 g/24 h iv) for 5 days. OUTCOMES: The patient showed good response to therapy and was discharged on day 18 after wound healing. LESSONS: C violaceum rarely infects humans. When an infection is suspected, samples should be immediately sent for microbial culture. Timely treatment on the basis of drug sensitivity test results can prevent further complications.

SWL-1 Reverses Fluconazole Resistance in Candida albicans by Regulating the Glycolytic Pathway.

Candida albicans is a ubiquitous clinical fungal pathogen. Prolonged use of the first-line antifungal agent fluconazole (FLC) has intensified fungal resistance and limited its effectiveness for the treatment of fungal infections. The combined administration of drugs has been extensively studied and applied. SWL-1 is a lignin compound derived from the Traditional Chinese Medicine Schisandra chinensis. In this study, we show that SWL-1 reverses resistance to fluconazole in C. albicans when delivered in combination, with a sharp decrease in the IC50 of fluconazole from >200 to 3.74 ± 0.25 µg/ml, and also reverses the fluconazole resistance of C. albicans in vitro, with IC50 from >200 to 5.3 ± 0.3 µg/ml. Moreover, killing kinetics curves confirmed the synergistic effects of fluconazole and SWL-1. Intriguingly, when SWL-1 was administered in combination with fluconazole in a mouse model of systemic infection, the mortality of mice was markedly decreased and fungal colonization of the kidney and lung was reduced. Further mechanistic studies showed that SWL-1 significantly decreased intracellular adenosine 5'-triphosphate (ATP) levels and inhibited the function of the efflux pump responsible for fluconazole resistance of C. albicans. Proteomic analysis of the effects of SWL-1 on C. albicans showed that several enzymes were downregulated in the glycolytic pathway. We speculate that SWL-1 significantly decreased intracellular ATP levels by hindering the glycolysis, and the function of the efflux pump responsible for fluconazole resistance of C. albicans was inhibited, resulting in restoration of fluconazole sensitivity in FLC-resistant C. albicans. This study clarified the effects and mechanism of SWL-1 on C. albicans in vitro and in vivo, providing a novel approach to overcoming fungal resistance.

The Predictive Value of microRNA-134 and microRNA-1233 for the Early Diagnosis of Acute Exacerbation of Chronic Obstructive Pulmonary Disease with Acute Pulmonary Embolism.

Background: The differential diagnosis of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) with acute pulmonary embolism (APE) complications are difficult because of the variability of clinical presentations and the shortage of an unfailing screening biomarkers or instruments. Objective: Aimed to detect and compare the expression of serum microRNAs (miR-1233, miR-134) in AECOPD patients complicated with APE. Patients/Methods: Blood samples were collected from 52 AECOPD patients (13 patients with APE complications, 39 patients without APE) and 10 patients with stable COPD. Serum miRNAs expression was detected with real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). The levels of plasma D-dimers were determined by detection with an enzyme-linked immunosorbent assay (ELISA). The receiver-operator characteristic (ROC) curve was used for evaluating the diagnostic accuracy of the studied miRNAs. Results: According to the Wells score, 42 of the 52 AECOPD patients were unlikely to have APE (≤4 points), whereas the remaining 10 (>4 points) were likely to have APE. There were 4 cases (4/13 30.8%) in the AECOPD combined with APE group with a Wells score of >4 points. The expression levels of miR-1233 and miR-134 in the serum were considerably upregulated in the AECOPD+APE group compared with the AECOPD group and the stable COPD group (P<0.05). The areas under the curve (AUCs) for miR-134 and miR-1233 were, respectively, 0.931 (95% CI 0.863-0.999) (P<0.05) and 0.884 (95% CI 0.79-0.978) (P<0.05) and were higher compared with the AUC for D-dimer of 0.628 (95% CI 0.447-0.809), the AUC for age-adjusted D-dimer of 0.705 (95% CI 0.525-0.885) and the AUC for Wells score of 0.577 (95% CI 0.389-0.765). Conclusion: Our study indicated that serum miR-1233 and miR-134 have high clinical value in the early diagnosis of AECOPD patients combined with APE, or could be used as potential biomarkers for clinical identification of AECOPD with or without APE complication.

Synergistic Intra- and Intermolecular Noncovalent Interactions for Ultralong Organic Phosphorescence.

Metal-free ultralong organic phosphorescence (UOP) materials have attracted significant attention owing to their anomalous photophysical properties and potential applications in various fields. Here, three pyrimidine-based organic luminogens, 9-(pyrimidin-2-yl)-9H-carbazole, 9-(4,6-dimethylpyrimidin-2-yl)-9H-carbazole, and 9-(5-bromopyrimidin-2-yl)-9H-carbazole are designed and synthesized, which show efficient yellow UOP with the longest lifetimes up to 1.37 s and the highest absolute phosphorescence quantum yields up to 23.6% under ambient conditions. Theoretical calculations, crystal structures, and photophysical properties of these compounds reveal that intramolecular hydrogen bonding, intermolecular π-π interactions, and intermolecular electronic coupling are responsible for forming dimers and generating highly efficient UOP. Their efficacy as solid materials for data encryption is demonstrated.

An innovative medical consultation model in mainland China.

PURPOSE: The purposes of this paper are two-fold: first, to introduce a new concept of primary care consultation system at a mainland Chinese hospital in response to healthcare reform; and second, to explore the factors associated with change resistance and acceptance from both patients' and medical staff's perspectives. DESIGN/METHODOLOGY/APPROACH: A survey design study, with two questionnaires developed and distributed to patients and medical staff. Convenience and stratified random sampling methods were applied to patient and medical staff samples. FINDINGS: A 5-dimension, 21-item patient questionnaire and a 4-dimension, 16-item staff questionnaire were identified and confirmed, with 1020 patients (91.07 percent) and 202 staff (90.18 percent) as effective survey participants. The results revealed that patient resistance mainly stems from a lack of personal experiences with visiting general practice (GP) and being educated or having lived overseas; while staff resistance came from occupation, education, GP training certificate, and knowledge and experience with specialists. Living in overseas and knowledge of GP concepts, gender and education are associated with resistance of accepting the new practice model for both patients and staff. ORIGINALITY/VALUE: There are few Chinese studies on process reengineering in the medical sector; this is the first study to adopt this medical consultation model and change in patients' consultation culture in Mainland China. Applying organizational change and process reengineering theories to medical and healthcare services not only extends and expands hospital management theory but also allows investigation of modern hospital management practice. The experience from this study can serve as a reference to promote this new consultation model in Chinese healthcare reform.