[Relationship between serum 1, 5-anhydroglucitol level and insulin resistance, microvascular complications in type 2 diabetes mellitus].

Objective: To explore the relationship between serum 1, 5-dehydratoglucitol (1, 5-AG) level and insulin resistance, microvascular complications in patients with type 2 diabetes mellitus (T2DM). Methods: The clinical data of 836 patients with T2DM admitted to the Changsha Central Hospital Affiliated to University of South China from May to December 2023 were retrospectively and cross-sectionally analyzed. Serum 1, 5-AG levels were detected by pyranose oxidase method. According to the microvascular complications (diabetic peripheral neuropathy, diabetic nephropathy, diabetic retinopathy), the patients were divided into simple group (no microvascular complications, n=490), complication group 1 (1 microvascular complications, n=217), and complication group 2 (2 or more microvascular complications, n=129). The relationship between serum 1, 5-AG level and the related indicators of insulin resistance in T2DM patients were explored by Spearman correlation analysis, and the influencing factors of microvascular complications in T2DM patients were explored by multiple ordered logistic regression analysis. Results: The levels of FBG(fasting blood glucose) [(7.37±0.56) mmol/L], FINS(fasting insulin) [(11.34±1.86) mU/L] and HOMA-IR(homeostatic model assessment of insulin resistance) (0.96±0.31) in simple group were lower than those in complication group 1 [(8.37±1.02) mmol/L, (16.26±2.32) mU/L, (1.32±0.41)], complication group 2 [(10.25±2.13) mmol/L, (18.53±2.67) mU/L, (1.54±0.44)], and FBG, FINS and HOMA-IR in complication group 1 were lower than those in complication group 2, and the differences were statistically significant (F=537.470, 791.690, 136.340, P<0.001). Serum 1, 5-AG level in simple group [77.16 (16.30, 128.07) µg/ml] was higher than that in complication group 1 [51.05 (14.67, 63.18) µg/ml] and complication group 2 [30.42 (12.53, 47.26) µg/ml], and the serum level of 1, 5-AG in complication group 1 was higher than that in complication group 2, and the difference was statistically significant (H=210.020, P<0.001). The results of Spearman correlation analysis showed that serum 1, 5-AG level was negatively correlated with FBG, FINS and HOMA-IR in T2DM patients (r=-0.431, -0.372, -0.546, P<0.001). The results of multiple ordered logistic regression analysis showed that Longer duration of diabetes (OR=2.261, 95%CI: 1.564-3.269), increased HbA1c (OR=2.040, 95%CI: 1.456-2.858), and increased HOMA-IR (OR=2.158, 95%CI: 1.484-3.137) and decreased 1, 5-AG (OR=2.512, 95%CI: 1.691-3.732) were independent risk factors for microvascular complications in T2DM patients (P<0.05). The results of ROC curve analysis showed that the area under the curve of serum 1, 5-AG in the identification of one microvascular complication was 0.763 (95%CI: 0.731-0.795), and the area under the curve of serum 1, 5-AG in the identification of two or more microvascular complications was 0.730 (95%CI: 0.692-0.767). Conclusion: Serum 1, 5-AG level is negatively correlated with insulin resistance in T2DM patients. Low serum 1, 5-AG level may be an independent risk factor for microvascular complications in T2DM patients.

[Clinical analysis of adverse reactions in patients with multidrug-resistant and rifampicin-resistant pulmonary tuberculosis treated with delamanid-containing regimen].

Objective: To explore the characteristics of adverse drug reactions during the 24-week therapy with delamanid-containing regimen for patients with multidrug-resistant and rifampicin-resistant pulmonary tuberculosis (MDR/RR-PTB). Methods: The prospective multicenter study was conducted from June 2020 to June 2023. A total of 608 eligible patients with MDR/RR-PTB were enrolled in 26 tuberculosis medical institutions in China including 364 males and 79 females, aged 39.6(19.0-68.0) years. Patients were treated with chemotherapy regimens containing delamanid. Patients were closely supervised during treatment of medication, and all adverse reactions occurring during treatment were monitored and recorded. The clinical characteristics of adverse reactions were evaluated by descriptive analysis. Chi-square test and multivariate logistic regression were used to analyze the related factors of QTcF interval prolongation (QT corrected with Fridericia's formula). Results: Of the 608 patients enrolled in this study, 325 patients (53.5%) reported 710 adverse events within 24 weeks of treatment. The top 6 most common complications were hematological abnormalities (143 patients, 23.5%), QT prolongation (114 patients, 18.8%), liver toxicity (85 patients, 14.0%), gastrointestinal reaction (41 patients, 6.7%), peripheral neuropathy (25 patients, 4.1%) and mental disorders (21 patients, 3.5%). The prolongation of QT interval mostly occurred in the 12th week after the first dose of medication. Serious adverse reactions occurred in 21 patients (3.5%). There were 7 patients (1.2%) with mental disorders, including 2 patients (0.3%) with severe mental disorders. Conclusions: The safety of dalamanid-based regimen in the staged treatment of MDR/RR-PTB patients was generally good, and the incidence of adverse reactions was similar to that reported in foreign studies. This study found that the incidence of QT interval prolongation in Chinese patients was higher than that reported overseas, suggesting that the monitoring of electrocardiogram should be strengthened when using drugs containing delamanid that may cause QT interval prolongation.

The differences between sinonasal respiratory epithelial adenomatoid hamartoma and nasal polyps: insights into immunopathology.

BACKGROUND: Respiratory epithelial adenomatoid hamartoma (REAH) is a benign lesion commonly occurring in the nasal cavity and sinuses. It is often accompanied by nasal polyps (NP). While the histological features of these two conditions have been studied, there is limited knowledge about their differences in the underlying immunopathology. METHODS: Nasal tissue specimens were collected from 8 patients with concurrent REAH and NP and 10 controls. The expression levels of inflammatory cytokines, tight junctions (TJ), and epithelial-mesenchymal transition (EMT)-related factors in the tissues were analyzed. The mRNA expression of the aforementioned factors was measured using qRT-PCR, while the expression of TJ and EMT-related proteins was analyzed through Western blotting and immunohistochemistry. RESULTS: Compared to the control group, levels of inflammatory cytokines (IFN-γ, IL-5, IL-17A, IL-31, IL-33, and TNF-α) and EMT-related factors (α-SMA, COL1A1, MMP9, TGF-ß1, and Vimentin) were significantly increased in both REAH and NP tissues. Conversely, E-Cadherin and TJ-related factors (Claudin-4 and Occludin) significantly decreased. When comparing REAH with NP, it was observed that the expression of IL-4, IL-5, and IL-33 was lower in REAH, while TNF-α was higher. Regarding TJ-related factors, the expression of Occludin was lower in REAH. Furthermore, in terms of EMT-related factors, except for E-Cadherin, the expressions of α-SMA, COL1A1, CTGF, MMP9, TGF-ß1, and Vimentin were higher in REAH. CONCLUSION: REAH and NP exhibit different immunopathological mechanisms. NP demonstrates a more severe inflammatory response, whereas REAH is characterized by a more pronounced TJ and EMT breakdown than NP.

Improved Tensor Current Limit from

A precision measurement of the ß^{+} decay of ^{8}B was performed using the Beta-decay Paul Trap to determine the ß-ν angular correlation coefficient a_{ßν}. The experimental results were combined with new ab initio symmetry-adapted no-core shell-model calculations to yield the second-most precise measurement from Gamow-Teller decays, a_{ßν}=-0.3345±0.0019_{stat}±0.0021_{syst}. This value agrees with the standard model value of -1/3 and improves uncertainties in ^{8}B by nearly a factor of 2. By combining results from ^{8}B and ^{8}Li, a tight limit on tensor current coupling to right-handed neutrinos was obtained. A recent global evaluation of all other precision ß decay studies suggested a nonzero value for right-handed neutrino coupling in contradiction with the standard model at just above 3σ. The present results are of comparable sensitivity and do not support this finding.

Identification and validation of a novel cuproptosis signature for stratifying different prognostic, immune, metabolic, and therapeutic landscapes in pancreatic adenocarcinoma.

OBJECTIVE: Pancreatic adenocarcinoma (PAAD) is a highly malignant cancer that urgently needs more effective therapeutic strategies. The discovery of cuproptosis brings great inspiration for the treatment and clinical assessment of cancers. MATERIALS AND METHODS: A novel cuproptosis-related (CR) risk signature was constructed using the Lasso regression analysis. Its prognostic value was assessed via a series of survival analyses and validated in four GEO cohorts. The effects of CR risk signature on tumor immune microenvironment (TIM) were explored through CIBERSORT, ESTIMATE, and ssGSEA algorithms. Using GESA, we investigated its associations with various patterns of programmed cell death (PCD) and the metabolism process. The somatic mutation features of each CR-risk group were also probed using 'maftools' R package and cBioPortal database. The potential linkages between CR risk score and the efficacy of multiple therapeutic approaches were elucidated using tumor mutation burden, the expressions of immune checkpoints, the TIDE score, and the GDSC database. Finally, we ascertained the biofunctions of LIPT1 (Lipoyltransferase 1) in pancreatic cancer (PC) cells through immunohistochemistry, qPCR (quantitative polymerase chain reaction), colony formation, and Transwell assays. RESULTS: LIPT1, LIAS (lipoyl synthase), PDP1 (Pyruvate dehydrogenase phosphatase1), and GCSH (Glycine cleavage system H protein) constituted the CR risk signature. The CR risk signature possessed a high prognostic value and could improve the traditional prognostic model. Moreover, the CR risk score was indicative of the changes in infiltration levels of CD8+T cells and macrophages, whereas it was not associated with the enrichment of various PCD patterns and multiple metabolic processes. As for therapeutic correlation, CR risk score was a potential biomarker for predicting the efficacy of ICBs but failed in targeted drugs and chemotherapeutic agents. Through qPCR and immunohistochemistry detection in clinical samples, we confirmed that LIPT1 was significantly downregulated in pancreatic adenocarcinoma (PAAD) samples. Experiments in vitro revealed that silencing LIPT1 promoted the proliferation, migration, and invasion of PANC-1 and SW1990 cells. CONCLUSIONS: The novel CR risk signature contributed to the risk stratification of PAAD patients. Cuproptosis regulatory genes, well represented by LIPT1, provided new insights into PAAD treatment and assessment.

[Analysis of surgical approaches and mandibular treatment strategies for different types of tumors involving parapharyngeal space].

In view of the surgical complexity of parapharyngeal space tumors involved, this paper summarized the disease data of patients with parapharyngeal space tumors involved in the Department of Oral and Maxillofacial Surgery, the First Hospital of Shanxi Medical University from January 2015 to January 2021. It also summarized the surgical approach and mandibular management, so as to explore surgical strategies for different characteristics of parapharyngeal space tumors involved. A total of 49 patients, including 28 males and 21 females, median age 52 years (range 24-72 years). They were treated with four surgical approaches for tumor resection, 25 cervical approach, 5 cheek and neck approach, 3 transoral approach, and 16 cervical-maxillary approach. Among the patients treated with cervical-maxillary approach, 3 patients were treated with mandible square resection, and 6 patients were treated with temporary mandible dissection. Seven cases were treated with tumor resection and partial mandibular resection. There are various surgical approaches and mandibular management methods involving tumors in the parapharyngeal space, and clinical decisions should be made based on tumor diameter, location, boundary, blood supply and pathological types.

New sights in ectopic varices in portal hypertension.

Ectopic varices and associated bleeding, although rare, pose a significant risk to patients with portal hypertension, carrying a relatively high mortality rate. These varices can occur in various anatomical regions, excluding the gastroesophageal region, which is typically associated with portal vein drainage. The limited data available in the literature, derived mostly from case reports and series, make the diagnosis and treatment of ectopic variceal bleeding particularly challenging. Furthermore, it is crucial to recognize that ectopic varices in different sites can exhibit variations in key decision-making factors such as aetiology and vascular anatomy, severity and bleeding risk and hepatic reserve. These factors significantly influence treatment strategies and underscore the importance of adopting individualized management approaches. Therefore, the objective of this review is to provide a comprehensive overview of the fundamental knowledge surrounding ectopic varices and to propose site-oriented, stepwise diagnosis and treatment algorithms for this complex clinical issue. A multidisciplinary treatment approach is strongly recommended in managing ectopic varices. In addition, to enhance clinical reference, we have included typical case reports of ectopic varices in various sites in our review, while being mindful of potential publication bias.

[Differentiation of temporal lobe epilepsy and temporal plus epilepsy using radiomics nomogram based on MPRAGE images].

A total of 82 patients with temporal lobe epilepsy (TLE) and temporal plus epilepsy (TPE)admitted in Xuanwu Hospital from January 1, 2019, to January 1, 2021 were restrospectively analyzed, including 41 males and 41 females, aged 2 to 52 (24±10) years. The patients were randomly divided into the training set (58 cases) and test set (24 cases) by Python. FreeSurfer software was used to segment the cortex of the affected hemisphere, defining 33 regions of interest (ROIs), and radiomics features were extracted by Python. After selecting features using the filter-based feature selection method, a radiomics model was constructed with a logistic regression classifier, and radiomics scores were calculated. Combining clinical characteristics with radiomics scores, a nomogram model was constructed using R software, the predictive accuracy of the model was assessed with the concordance index (C-index), and the model's goodness-of-fit was tested with the Hosmer-Lemeshow method. The results showed statistically significant differences between TLE and TPE patients in disease duration, intracranial electrode implantation, and hippocampal sclerosis (both P<0.05). The accuracy of the radiomics model in the training set and the test set was 91.4% and 87.5%, respectively. The nomogram model uses C-index to predict accuracy. Hosmer-Lemeshow method was used to test the goodness of fit, with AUCs of 0.95 (95%CI: 0.853-0.991) in the training set and 0.84 (95%CI: 0.676-0.999) in the test set. The study indicates that the radiomics nomogram model based on MPRAGE sequences can effectively differentiate TLE from TPE, providing reference for the development of personalized treatment plans in clinical practice.

Diagnostic value of serum squamous cell carcinoma antigen and cytokeratin fragment antigen 21-1 for sinonasal inverted papilloma: an exploratory study.

BACKGROUND: Serum tumor markers have not yet been developed for the clinical diagnosis and treatment of sinonasal inverted papilloma (SNIP), one of the most significant sinonasal tumors. Therefore, this study aimed to determine the diagnostic value of serum squamous cell carcinoma antigen (SCCA) and cytokeratin fragment antigen 21-1 (CYFRA 21-1) for SNIP. METHODS: Clinical data were obtained from 101, 56, and 116 patients with SNIP, sinonasal squamous cell carcinoma (SNSCC), and unilateral chronic rhinosinusitis (CRS), respectively. Preoperative serum SCCA and CYFRA 21-1 levels were compared, and logistic regression analyses were performed to screen serum tumor markers, which may be used to diagnose SNIP. Diagnostic cut-off values were determined using receiver operating characteristic (ROC) curves, and their diagnostic power was verified. RESULTS: Serum SCCA and CYFRA 21-1 differentiated SNIP from CRS with the cut-off values of 1.97 ng/mL and 2.64 ng/mL and the areas under the ROC curves (AUC) of 0.895 and 0.766, respectively, and the AUC of the combination of the two markers was 0.909. CYFRA 21-1 differentiated SNIP with malignant transformation from that without malignant transformation with a cut-off value of 3.51 ng/mL and an AUC of 0.938. CYFRA 21-1 distinguished SNIP with malignant transformation from SNSCC with a cut-off value of 3.55 ng/mL and an AUC of 0.767. CONCLUSIONS: This study provides novel potential diagnostic tools for SNIP by demonstrating the use of serum SCCA and CYFRA 21-1 in the diagnosis of SNIP.

[Serum glycocalyx markers in patients after cardiac arrest: association with outcomes].

Objective: To assess the levels of serum glycocalyx markers in the first 24 hours after cardiac arrest (CA) and investigate their relationship with 30-day outcomes. Methods: A retrospective cohort study was conducted on prospectively collected data from CA patients, who were admitted to the intensive care units of the Affiliated Hospital of Xuzhou Medical University and obtained return of spontaneous circulation for more than 24 hours between September 2021 and October 2022. Serum samples obtained at the 24-hour after CA were utilized to measure the levels of glycocalyx markers, including heparan sulfate (HS), hyaluronic acid (HA), and syndecan-1 (Sdc-1). Patients were allocated into good function (CPC1-2) and poor function (CPC3-5) groups on the basis of cerebral performance category (CPC) at 30 days post-CA. Logistic regression analysis was used to determine the association between serum glycocalyx markers and neurological outcomes. Patients were regrouped in light of 30-d mortality and Cox regression analysis was used to determine the association between serum glycocalyx markers and 30-d mortality. Results: A total of 71 patients were included in the study, including 31 (43.7%) females and 40 (56.3%) males, with an average age of (59.0±17.0) years. The poor function group (n=49) demonstrated significantly elevated levels of HS and HA when compared to the good function group (n=22) [HS: 2 461.0(1 623.0, 5 492.0) µg/L vs 1 492.0 (914.0, 2 550.0) µg/L, P=0.008; HA: 124.0(97.0, 365.0)µg/L vs 337.0(135.0, 1 421.0) µg/L, P=0.033]. Adjusted logistic regression analysis revealed that HS was independently associated with poor neurological outcome [odds ratio (OR)=0.389, 95% confidence interval (CI): 0.182-0.828, P=0.014]. In the 30-day mortality analysis, the death group (n=32) exhibited significantly higher levels of HS and HA when compared to the survival group (n=39) [HS: 1 880.0(1 011.0, 3 554.0) µg/L vs 2 500.0(1 726.0, 6 276.0) µg/L, P=0.027; HA: 162.0(99.0, 537.0) µg/L vs 813.0(148.0, 1 531.0) µg/L, P=0.025]. Adjusted Cox regression analysis indicated that elevated levels of HS and HA were independent risk factors (HS: HR=1.697, 95%CI: 1.126-2.557, P=0.011; HA: HR=1.336, 95%CI: 1.047-1.705, P=0.020) for 30-day mortality. Conclusions: High level of serum HS in 24 hours after CA may serve as a potential predictive marker for both neurological function and 30-day mortality. However, high level of serum HA appears to primarily predict 30-day mortality. Sdc-1 does not seem to contribute to outcome prediction.

CSK may be a potential prognostic biomarker reflecting the immune status of gastric cancer.

OBJECTIVE: C-terminal Src kinase (CSK), a sarcoma (Src) homologous family kinase, is one of the most important negative regulators. It acts as a tumor suppressor by inhibiting the activity of Src family tyrosine kinases. Paradoxically, CSK is highly expressed in a variety of common tumors. Therefore, we report the expression profile of CSK in pan-cancer patients, focusing on the prognostic value, immune infiltration pattern, and biological function of CSK in gastric cancer. MATERIALS AND METHODS: We used the TCGA database to analyze CSK expression, clinical relevance, prognostic significance, assessment of the tumor immune microenvironment, and GO and Kegg enrichment analysis based on co-expressed genes using a bioinformatics approach. RESULTS: CSK is a protective factor in gastric cancer, and its expression correlates with the level of immune cell infiltration and immune checkpoint molecules. CONCLUSIONS: Our findings suggest that CSK is an independent prognostic factor in gastric cancer and may predict molecular targeting and immunotherapy and provide ideas for its therapeutic strategy.

Abnormal cell wall structure caused by boron nutrient imbalance in orchards could affect psyllid feeding behaviour, resulting in epidemic variation of Asian citrus psyllid.

The control of Huanglongbing (HLB), one of the most destructive pests of citrus, relies heavily on the reduction of Asian citrus psyllid (ACP), Diaphorina citri Kuwayama. An in-depth understanding of ACP feeding behaviours among citrus plants is urgent for comprehensive management of orchards. An investigation was conducted in 37 citrus orchards in HLB epidemic areas, sampling shoots in the area with aggregation feeding of ACP (ACPf) and shoots in a neighbouring area without ACP feeding (CK), to study the interaction between leaf chemical composition and ACP psyllid feeding behaviours. Results of FTIR showed a strong absorption peak intensity, mainly representing functional groups originating from cell wall components in the leaf with ACP feeding. As compared with the control, cell wall components, such as alkali-soluble pectin, water-soluble pectin, total soluble pectin, cellulose, and hemicellulose, of the cell wall of ACPf increased by 134.0%, 14.0%, 18.0%, 12.5%, and 20.35%, respectively. These results suggest that cell wall mechanical properties significantly decreased in the term of decreases in pectin performance and cellulose mechanical properties. In addition, there was a remarkably lower boron (B) content in leaves and cell wall components with ACP feeding. Further analysis indicated that leaf B content significantly affected leaf cell wall components. Taken together, we provide evidence to demonstrate that the regional distribution of nutrient imbalance in orchards could affect psyllid feeding behaviour by weakening the cell wall structure, resulting in epidemic variation in ACP. This could help us to understand the management of psyllid infections in orchards with unbalanced nutrition.

SAPPHIRE: phase III study of sitravatinib plus nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer.

BACKGROUND: Checkpoint inhibitor (CPI) therapy revolutionized treatment for advanced non-small-cell lung cancer (NSCLC); however, most patients progress due to primary or acquired resistance. Sitravatinib is a receptor tyrosine kinase inhibitor that can shift the immunosuppressive tumor microenvironment toward an immunostimulatory state. Combining sitravatinib with nivolumab (sitra + nivo) may potentially overcome initial CPI resistance. PATIENTS AND METHODS: In the phase III SAPPHIRE study, patients with advanced non-oncogenic driven, nonsquamous NSCLC who initially benefited from (≥4 months on CPI without progression) and subsequently experienced disease progression on or after CPI combined with or following platinum-based chemotherapy were randomized 1 : 1 to sitra (100 mg once daily administered orally) + nivo (240 mg every 2 weeks or 480 mg every 4 weeks administered intravenously) or docetaxel (75 mg/m2 every 3 weeks administered intravenously). The primary endpoint was overall survival (OS). The secondary endpoints included progression-free survival (PFS), objective response rate (ORR), clinical benefit rate (CBR), duration of response (DOR; all assessed by blinded independent central review), and safety. RESULTS: A total of 577 patients included randomized: sitra + nivo, n = 284; docetaxel, n = 293 (median follow-up, 17.1 months). Sitra + nivo did not significantly improve OS versus docetaxel [median, 12.2 versus 10.6 months; hazard ratio (HR) 0.86, 95% confidence interval (CI) 0.70-1.05; P = 0.144]. The median PFS was 4.4 versus 5.4 months, respectively (HR 1.08, 95% CI 0.89-1.32; P = 0.452). The ORR was 15.6% for sitra + nivo and 17.2% for docetaxel (P = 0.597); CBR was 75.5% and 64.5%, respectively (P = 0.004); median DOR was 7.4 versus 7.1 months, respectively (P = 0.924). Grade ≥3 treatment-related adverse events were observed in 53.0% versus 66.7% of patients receiving sitra + nivo versus docetaxel, respectively. CONCLUSIONS: Although median OS was numerically longer with sitra + nivo, the primary endpoint was not met in patients with previously treated advanced nonsquamous NSCLC. The safety profiles demonstrated were consistent with previous reports.

Toripalimab plus axitinib versus sunitinib as first-line treatment for advanced renal cell carcinoma: RENOTORCH, a randomized, open-label, phase III study.

BACKGROUND: Immune checkpoint inhibitors in combination with tyrosine kinase inhibitors are standard treatments for advanced clear cell renal cell carcinoma (RCC). This phase III RENOTORCH study compared the efficacy and safety of toripalimab plus axitinib versus sunitinib for the first-line treatment of patients with intermediate-/poor-risk advanced RCC. PATIENTS AND METHODS: Patients with intermediate-/poor-risk unresectable or metastatic RCC were randomized in a ratio of 1 : 1 to receive toripalimab (240 mg intravenously once every 3 weeks) plus axitinib (5 mg orally twice daily) or sunitinib [50 mg orally once daily for 4 weeks (6-week cycle) or 2 weeks (3-week cycle)]. The primary endpoint was progression-free survival (PFS) assessed by an independent review committee (IRC). The secondary endpoints were investigator-assessed PFS, overall response rate (ORR), overall survival (OS), and safety. RESULTS: A total of 421 patients were randomized to receive toripalimab plus axitinib (n = 210) or sunitinib (n = 211). With a median follow-up of 14.6 months, toripalimab plus axitinib significantly reduced the risk of disease progression or death by 35% compared with sunitinib as assessed by an IRC [hazard ratio (HR) 0.65, 95% confidence interval (CI) 0.49-0.86; P = 0.0028]. The median PFS was 18.0 months in the toripalimab-axitinib group, whereas it was 9.8 months in the sunitinib group. The IRC-assessed ORR was significantly higher in the toripalimab-axitinib group compared with the sunitinib group (56.7% versus 30.8%; P < 0.0001). An OS trend favoring toripalimab plus axitinib was also observed (HR 0.61, 95% CI 0.40-0.92). Treatment-related grade ≥3 adverse events occurred in 61.5% of patients in the toripalimab-axitinib group and 58.6% of patients in the sunitinib group. CONCLUSION: In patients with previously untreated intermediate-/poor-risk advanced RCC, toripalimab plus axitinib provided significantly longer PFS and higher ORR than sunitinib and had a manageable safety profile TRIAL REGISTRATION: ClinicalTrials.gov NCT04394975.

Causal effects of diabetic retinopathy on depression, anxiety and bipolar disorder in the European population: a Mendelian randomization study.

PURPOSE: To verify the causal effects of diabetic retinopathy (DR) on depression, anxiety and bipolar disorder (BD). METHODS: Mendelian randomization (MR) analysis was performed to identify the causal relationships between DR and depression or anxiety or BD via using DR-related GWAS data (14,584 cases and 176,010 controls), depression-related GWAS data (59,851 cases and 113,154 controls), anxiety-related GWAS data (7016 cases and 14,745 controls) and BD-related GWAS data (41,917 cases and 371,549 controls). The inverse-variance weighted (IVW) model was adopted to estimate the causal relationship. The outcome was expressed as odds ratio (OR) with 95% confidence intervals (CI). RESULTS: The MR analysis results presented that DR was causally associated with a significantly increased risk of BD in the European population (IVW, OR = 1.06, 95%CI [1.03, 1.08], P = 2.44 × 10-6), while DR was unable to causally influence the risk of depression (IVW, OR = 1.01, 95%CI [0.99, 1.04], P = 0.32) and anxiety (IVW, OR = 0.97, 95%CI [0.89, 1.06], P = 0.48) in the European population. Subgroup analysis based on BD identified DR causally increased the risk of bipolar I disorder (BD I) but not bipolar II disorder (BD II). Sensitivity analysis results did not show any pleiotropy and heterogeneity in both groups of analyses, indicating that the results were stable and reliable. CONCLUSIONS: The results of the current MR analysis indicated a causal relationship between DR and BD in the European population, while there was no causal connection between DR and depression or anxiety. However, further research is needed to confirm these conclusions.

Linear Breit-Wheeler process driven by compact lasers.

We report a proposal to observe the two-photon Breit-Wheeler process in plasma driven by compact lasers. A high-charge electron bunch can be generated from laser plasma wakefield acceleration when a tightly focused laser pulse propagates in a subcritical density plasma. The electron bunch scatters with the laser pulse coming from the opposite direction and resulting in the emission of high brilliance x-ray pulses. In a three-dimensional particle-in-cell simulation with a laser pulse of ∼10 J, one could produce an x-ray pulse with a photon number higher than 3×10^{11} and brilliance above 1.6×10^{23} photons/s/mm^{2}/mrad^{2}/0.1%BW at 1 MeV. The x-ray pulses collide in the plasma and create more than 1.1×10^{5} electron-positron pairs per shot. It is also found that the positrons can be accelerated transversely by a transverse electric field generated in the plasma, which enables the safe detection in the direction away from the laser pulses. This proposal enables the observation of the linear Breit-Wheeler process in a compact device with a single shot.

[Clinical effect of free posterior interosseous artery perforator flap carrying superficial vein for reconstructing severe perioral scar hyperplasia and contracture].

Objective: To observe the clinical effect of free posterior interosseous artery perforator flap carrying superficial vein for reconstructing severe perioral scar hyperplasia and contracture. Methods: The retrospective observational study method was used. From August 2019 to March 2023, 11 patients with severe perioral scar hyperplasia and contracture after severe facial burns who met the inclusion criteria were admitted to General Hospital of TISCO (the Sixth Hospital of Shanxi Medical University). All patients were male and aged 23 to 56 years, with an average age of 31.3 years. After the perioral scar was removed and released, the wound area was 3.0 cm×2.0 cm to 10.5 cm×2.0 cm. The free posterior interosseous artery perforator flap carrying superficial vein was used to repair the wound, and the flap incision area was 3.5 cm×2.5 cm to 11.0 cm×2.5 cm. Among them, 6 patients required repair of wounds after resecting scar around ipsilateral upper and lower lips, and the lobular treatment of the flap was conducted. The wound in the flap donor area was directly sutured. After surgery, the survival of the flap and the occurrence of vascular crisis were observed. During follow-up after surgery, the appearance, texture, and color of the flap, the appearance of the flap donor area, and improvements of crooked mouth, drooling, limited mouth opening, and lip valgus in patients were observed. Results: All the flaps in patients completely survived after surgery, with no occurrence of vascular crisis. During follow-up of 6 to 36 months after surgery, the flap was not significantly bloated, was soft in texture, and had a similar color to that of the normal facial skin. Only linear scars were left in the flap donor area, and crooked mouth, drooling, limited mouth opening, and lip valgus in patients were significantly improved. Conclusions: The free posterior interosseous artery perforator flap carrying superficial vein can reconstruct severe perioral scar hyperplasia and contracture, with low incidence of postoperative flap vascular crisis, and the lobular treatment of flaps can repair wounds around unilateral upper and lower lips at the same time. After surgery, the appearance and function of the perioral area are significantly improved. The flap is a good choice for repairing small area of severe perioral scar hyperplasia and contracture.