A Prospective Study of the Surgical Outcome of Simple Uvulopalatopharyngoplasty (UPPP), UPPP Combined With Genioglossus Advancement or Tongue Base Advancement for Obstructive Sleep Apnea Hypopnea Syndrome Patients With Multilevel Obstruction

ObjectivesTo investigate the surgical outcomes of different uvulopalatopharyngoplasty (UPPP).Methods All subjects underwent overnight polysomnography and were evaluated using the Epworth sleepiness scale (ESS), the Quebec sleep questionnaire and the snoring scale at the baseline and 3 and 12 months following operation. The primary endpoint was the overall effective rate representing the sum of the surgical success rate and effective rate.ResultsThe overall effective rate at 12 months post surgery was 55.6% for simple UPPP, 95.8% for UPPP+GA, and 92.3% for UPPP+TBA. The surgical success rate at 3 and 12 months postoperation for UPPP+GA or UPPP+TBA was significantly higher than simple UPPP (P<0.05). Marked improvement was observed in all patients in the snoring scale score and the ESS score 3 and 12 months following surgery compared to the baseline (P<0.05 in all).ConclusionUPPP, UPPP+GA, and UPPP+TBA are all effective in improving the surgical outcome of obstructive sleep apnea hypopnea syndrome (OSAHS) patients with multilevel obstruction. UPPP+TBA appears to be the most effective in treating OSAHS patients

Gender-specific association between the regular use of statins and the risk of irritable bowel syndrome: A population-based prospective cohort study

Introduction: In addition to lipid-lowering effects, statins might modulate the gut microbiome and alleviate systematic inflammation, which in turn, may have a protective effect against irritable bowel syndrome (IBS). The aim of our study was to evaluate the gender-specific association between statin exposure and the risk of IBS.Method: We undertook a prospective analysis based on the United Kingdom Biobank, a large ongoing cohort including 477,293 participants aged 37–73 years. We included participants based on information on their personal statin use and also those free of IBS and cancer at the baseline. We evaluated the gender-specific hazard ratio (HR) and 95% confidence interval (CI) with Cox proportional hazards regression, adjusting for demographic factors, lifestyle factors, comorbidities, and statin indications.Result: A total of 438,805 participants (206,499 males and 232,306 females) were included in the analysis. Among male participants, the regular use of statins was associated with a decreased risk of IBS (HR: 0.77; 95% CI: 0.61–0.97). This association persists across multiple sensitivity and subgroup analyses and did not show clear evidence of variance among the major types of statins. We did not find sufficient evidence of the association between the statin use and IBS risk in females (HR: 0.98; 95% CI: 0.82–1.16).Conclusion: Our study found that the regular use of statins was associated with a decreased risk of IBS in male participants. Further studies are required to confirm the beneficial effect of statins

Combination of 4-1BB and DAP10 promotes proliferation and persistence of NKG2D(bbz) CAR-T cells

Chimeric antigen receptor (CAR)-T cell therapy has been shown to have considerable therapeutic effects in hematological malignancies, and NKG2D(z) CAR-T cell therapy has been verified to be safe based on clinical trials. However, due to the poor persistence of NKG2D(z) CAR-T cells, their therapeutic effect is not obvious. Here, we constructed NKG2D(bbz) CAR-T cells that can simultaneously activate 4-1BB and DAP10 costimulatory signaling. They were found to be cytotoxic to the target cells in vitro and in vivo. They exhibited low differentiation, low exhaustion, and good proliferation. Importantly, the proportions of central memory T (Tcm) and stem cell-like memory T (Tscm) cell subsets were strikingly increased. After long-term incubation with the target cells, they displayed reduced exhaustion compared to NKG2D(z) CAR-T cells. Further, in the presence of the phosphoinositide 3-kinase (PI3K) inhibitor LY294002, they exhibited reduced exhaustion and apoptosis, upregulated Bcl2 expression, and an increased proportion of Tcm cell subsets. Finally, NKG2D(bbz) CAR-T cells had better antitumor effects in vivo. In summary, the results showed that NKG2D(bbz) CAR-T cells may be valuable for cellular immunotherapy of cancer

Association of FTH1-expressing circulating tumor cells with efficacy of neoadjuvant chemotherapy for patients with breast cancer: a prospective cohort study

Background The association between different phenotypes and genotypes of circulating tumor cells (CTCs) and efficacy of neoadjuvant chemotherapy (NAC) remains uncertain. This study was conducted to evaluate the relationship of FTH1 gene-associated CTCs (F-CTC) with/without epithelial-mesenchymal transition (EMT) markers, or their dynamic changes with the efficacy of NAC in patients with non-metastatic breast cancer. Patients and Methods This study enrolled 120 patients with non-metastatic breast cancer who planned to undergo NAC. The FTH1 gene and EMT markers in CTCs were detected before NAC (T0), after 2 cycles of chemotherapy (T1), and before surgery (T2). The associations of these different types of CTCs with rates of pathological complete response (pCR) and breast-conserving surgery (BCS) were evaluated using the binary logistic regression analysis. Results F-CTC in peripheral blood ≥1 at T0 was an independent factor for pCR rate in patients with HER2-positive (odds ratio [OR]=0.08, 95% confidence interval [CI], 0.01-0.98, P = .048). The reduction in the number of F-CTC at T2 was an independent factor for BCS rate (OR = 4.54, 95% CI, 1.14-18.08, P = .03). Conclusions The number of F-CTC prior to NAC was related to poor response to NAC. Monitoring of F-CTC may help clinicians formulate personalized NAC regimens and implement BCS for patients with non-metastatic breast cancer

Genomic Analyses Reveal Mutational Signatures and Frequently Altered Genes in Esophageal Squamous Cell Carcinoma

Esophageal squamous cell carcinoma (ESCC) is one of the most common cancers worldwide and the fourth most lethal cancer in China. However, although genomic studies have identified some mutations associated with ESCC, we know little of the mutational processes responsible. To identify genome-wide mutational signatures, we performed either whole-genome sequencing (WGS) or whole-exome sequencing (WES) on 104 ESCC individuals and combined our data with those of 88 previously reported samples. An APOBEC-mediated mutational signature in 47% of 192 tumors suggests that APOBEC-catalyzed deamination provides a source of DNA damage in ESCC. Moreover, PIK3CA hotspot mutations (c.1624G>A [p.Glu542Lys] and c.1633G>A [p.Glu545Lys]) were enriched in APOBEC-signature tumors, and no smoking-associated signature was observed in ESCC. In the samples analyzed by WGS, we identified focal (<100 kb) amplifications of CBX4 and CBX8. In our combined cohort, we identified frequent inactivating mutations in AJUBA, ZNF750, and PTCH1 and the chromatin-remodeling genes CREBBP and BAP1, in addition to known mutations. Functional analyses suggest roles for several genes (CBX4, CBX8, AJUBA, and ZNF750) in ESCC. Notably, high activity of hedgehog signaling and the PI3K pathway in approximately 60% of 104 ESCC tumors indicates that therapies targeting these pathways might be particularly promising strategies for ESCC. Collectively, our data provide comprehensive insights into the mutational signatures of ESCC and identify markers for early diagnosis and potential therapeutic targets

Industrial technology progress, digital finance development and corporate risk-taking: Evidence from China's listed firms.

Industrial technological progress, as an essential industrial-technological and institutional phenomenon, brings with it the possibility of high profits for firms but also implies new norms and rules of competition, which affect the willingness and propensity of firms to bear the costs of undertaking venture capital projects. This study empirically investigates the causal impact of industrial-technological progress on corporate risk-taking and the mechanism of digital financial growth on the relationship between the two, based on data from China's A-share listed businesses from 2011 to 2020. This paper finds that (1) industrial technological progress improves enterprise risk-taking levels. Moreover, digital financial development has an incentive effect on industrial technological progress and enterprise risk-taking levels. (2) Industrial technological progress under digital financial development generates financing constraint relaxation effects, input capital return enhancement effects, and innovation performance incentive effects, increasing enterprise risk-taking. (3) The positive moderating effect of digital financial development on the relationship between industrial technological progress and the risk-taking level of enterprises in the eastern regions and enterprises in the high-tech industry is more prominent. The study's findings provide a theoretical foundation and policy insights on the crucial elements of industrial-technological progress and enterprises' increased ability to take risks throughout the development of digital finance

Heterogeneity analysis.

Industrial technological progress, as an essential industrial-technological and institutional phenomenon, brings with it the possibility of high profits for firms but also implies new norms and rules of competition, which affect the willingness and propensity of firms to bear the costs of undertaking venture capital projects. This study empirically investigates the causal impact of industrial-technological progress on corporate risk-taking and the mechanism of digital financial growth on the relationship between the two, based on data from China’s A-share listed businesses from 2011 to 2020. This paper finds that (1) industrial technological progress improves enterprise risk-taking levels. Moreover, digital financial development has an incentive effect on industrial technological progress and enterprise risk-taking levels. (2) Industrial technological progress under digital financial development generates financing constraint relaxation effects, input capital return enhancement effects, and innovation performance incentive effects, increasing enterprise risk-taking. (3) The positive moderating effect of digital financial development on the relationship between industrial technological progress and the risk-taking level of enterprises in the eastern regions and enterprises in the high-tech industry is more prominent. The study’s findings provide a theoretical foundation and policy insights on the crucial elements of industrial-technological progress and enterprises’ increased ability to take risks throughout the development of digital finance.</div

Descriptive statistics.

Industrial technological progress, as an essential industrial-technological and institutional phenomenon, brings with it the possibility of high profits for firms but also implies new norms and rules of competition, which affect the willingness and propensity of firms to bear the costs of undertaking venture capital projects. This study empirically investigates the causal impact of industrial-technological progress on corporate risk-taking and the mechanism of digital financial growth on the relationship between the two, based on data from China’s A-share listed businesses from 2011 to 2020. This paper finds that (1) industrial technological progress improves enterprise risk-taking levels. Moreover, digital financial development has an incentive effect on industrial technological progress and enterprise risk-taking levels. (2) Industrial technological progress under digital financial development generates financing constraint relaxation effects, input capital return enhancement effects, and innovation performance incentive effects, increasing enterprise risk-taking. (3) The positive moderating effect of digital financial development on the relationship between industrial technological progress and the risk-taking level of enterprises in the eastern regions and enterprises in the high-tech industry is more prominent. The study’s findings provide a theoretical foundation and policy insights on the crucial elements of industrial-technological progress and enterprises’ increased ability to take risks throughout the development of digital finance.</div

Robustness tests.

Industrial technological progress, as an essential industrial-technological and institutional phenomenon, brings with it the possibility of high profits for firms but also implies new norms and rules of competition, which affect the willingness and propensity of firms to bear the costs of undertaking venture capital projects. This study empirically investigates the causal impact of industrial-technological progress on corporate risk-taking and the mechanism of digital financial growth on the relationship between the two, based on data from China’s A-share listed businesses from 2011 to 2020. This paper finds that (1) industrial technological progress improves enterprise risk-taking levels. Moreover, digital financial development has an incentive effect on industrial technological progress and enterprise risk-taking levels. (2) Industrial technological progress under digital financial development generates financing constraint relaxation effects, input capital return enhancement effects, and innovation performance incentive effects, increasing enterprise risk-taking. (3) The positive moderating effect of digital financial development on the relationship between industrial technological progress and the risk-taking level of enterprises in the eastern regions and enterprises in the high-tech industry is more prominent. The study’s findings provide a theoretical foundation and policy insights on the crucial elements of industrial-technological progress and enterprises’ increased ability to take risks throughout the development of digital finance.</div