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.

Measurement accuracy in silicon photonic ring resonator thermometers: identifying and mitigating intrinsic impairments.

Silicon photonic ring resonator thermometers have been shown to provide temperature measurements with a 10 mK accuracy. In this work we identify and quantify the intrinsic on-chip impairments that may limit further improvement in temperature measurement accuracy. The impairments arise from optically induced changes in the waveguide effective index, and from back-reflections and scattering at defects and interfaces inside the ring cavity and along the path between light source and detector. These impairments are characterized for 220 × 500 nm Si waveguide rings by experimental measurement in a calibrated temperature bath and by phenomenological models of ring response. At different optical power levels both positive and negative light induced resonance shifts are observed. For a ring with L = 100 µm cavity length, the self-heating induced resonance red shift can alter the temperature reading by 200 mK at 1 mW incident power, while a small blue shift is observed below 100 µW. The effect of self-heating is shown to be effectively suppressed by choosing longer ring cavities. Scattering and back-reflections often produce split and distorted resonance line shapes. Although these distortions can vary with resonance order, they are almost completely invariant with temperature for a given resonance and do not lead to measurement errors in themselves. The effect of line shape distortions can largely be mitigated by tracking only selected resonance orders with negligible shape distortion, and by measuring the resonance minimum wavelength directly, rather than attempting to fit the entire resonance line shape. The results demonstrate the temperature error due to these impairments can be limited to below the 3 mK level through appropriate design choices and measurement procedures.

Experimental Demonstration of a Large Transverse Emittance Ratio 11∶1 in the Relativistic Heavy Ion Collider for the Electron-Ion Collider.

The Electron-Ion Collider (EIC), to be constructed at Brookhaven National Laboratory, will collide polarized high-energy electron beams with hadron beams, achieving luminosities of up to 1.0×10^{34} cm^{-2} s^{-1} in the center-of-mass energy range of 20-140 GeV. To achieve such high luminosity, the EIC will employ small and flat beams at the interaction point. In the hadron storage ring of the EIC, the ratio of horizontal to vertical emittances is approximately 11∶1. In contrast, in previous or existing hadron colliders, the horizontal and vertical emittances are typically similar or closely matched. At the Relativistic Heavy Ion Collider (RHIC), we experimentally demonstrated a large transverse emittance ratio of 11∶1 with gold ion beams at a particle energy of 100 GeV per nucleon, thanks to stochastic cooling and fine decoupling. Furthermore, we demonstrated collisions with flat beams, featuring a transverse beam size ratio of 3∶1 for the first time at the RHIC.

Maternal androgen excess inhibits fetal cardiomyocytes proliferation through RB-mediated cell cycle arrest and induces cardiac hypertrophy in adulthood.

PURPOSE: Maternal hyperandrogenism during pregnancy is associated with adverse gestational outcomes and chronic non-communicable diseases in offspring. However, few studies are reported to demonstrate the association between maternal androgen excess and cardiac health in offspring. This study aimed to explore the relation between androgen exposure in utero and cardiac health of offspring in fetal and adult period. Its underlying mechanism is also illustrated in this research. METHODS: Pregnant mice were injected with dihydrotestosterone (DHT) from gestational day (GD) 16.5 to GD18.5. On GD18.5, fetal heart tissue was collected for metabolite and morphological analysis. The hearts from adult offspring were also collected for morphological and qPCR analysis. H9c2 cells were treated with 75 µM androsterone. Immunofluorescence, flow cytometry, qPCR, and western blot were performed to observe cell proliferation and explore the underlying mechanism. RESULTS: Intrauterine exposure to excessive androgen led to thinner ventricular wall, decreased number of cardiomyocytes in fetal offspring and caused cardiac hypertrophy, compromised cardiac function in adult offspring. The analysis of steroid hormone metabolites in fetal heart tissue by ultra performance liquid chromatography and tandem mass spectrometry showed that the content of androgen metabolite androsterone was significantly increased. Mechanistically, H9c2 cells treated with androsterone led to a significant decrease in phosphorylated retinoblastoma protein (pRB) and cell cycle-related protein including cyclin-dependent kinase 2 (CDK2), cyclin-dependent kinase 4 (CDK4), and cyclin D1 (CCND1) in cardiomyocytes. This resulted in cell cycle arrest at G1-S phase, which in turn inhibited cardiomyocyte proliferation. CONCLUSION: Taken together, our results indicate that in utero exposure to DHT, its metabolite androsterone could directly decrease cardiomyocytes proliferation through cell cycle arrest, which has a life-long-lasting effect on cardiac health. Our study highlights the importance of monitoring sex hormones in women during pregnancy and the follow-up of cardiac function in offspring with high risk of intrauterine androgen exposure.

Diabetes and long duration leading to speech-, low/mid-, and high- frequency hearing loss: current evidence from the China National Health Survey 2023.

PURPOSE: To examine the effect of diabetes, duration of diabetes, and blood glucose on speech-, low/mid-, and high-frequency hearing loss. METHODS: In this cross-sectional study, 2821 participants aged 20-87 years in the China National Health Survey were included. Diabetes was defined as valid fasting blood glucose (FBG) of ≥ 7.0 mmol/L, a self-reported history of diabetes or the use of anti-diabetic medications. Speech-(500, 1000, 2000, and 4000 Hz), low/mid- (500, 1000 and 2000 Hz), and high-frequency (4000, 6000, and 8000 Hz) hearing loss was defined as pure tone average of responding frequencies > 20 dB HL in the better ear, respectively. RESULTS: In fully adjusted models, for speech-, low/mid-, and high-frequency hearing loss, compared with no diabetes, those with diabetes (OR[95%CI]: 1.44 [1.12, 1.86], 1.23 [0.94, 1.61], and 1.75 [1.28, 2.41], respectively) and with diabetes for > 5 years duration (OR[95%CI]: 1.63 [1.09, 2.42], and 1.63 [1.12, 2.36], 2.15 [1.25, 3.70], respectively) were at higher risk. High FBG level was associated with a higher risk of speech-, low/ mid-, and high-frequency hearing loss. And there were stronger associations between HL and diabetes, longer duration and higher in "healthier population" (no hypertension, no dyslipidemia and younger age). CONCLUSION: Diabetes, longer duration, and higher FBG level were independently associated with hearing loss for speech-, low/mid- and high-frequency hearing loss, particularly in higher frequency and "healthier population". Paying more attention to hearing loss in those populations could lower the burden of hearing loss.

[Comparison of robotic-assisted single-incision-plus-one-port laparoscopic pyeloplasty and single-incision laparoscopic pyeloplasty in the treatment of pediatric ureteropelvic junction obstruction].

Objective: To compare the efficacy of robotic-assisted single-incision-plus- one-port laparoscopic pyeloplasty (R-SILP+1) with single-incision laparoscopic pyeloplasty (SILP) in pediatric ureteropelvic junction obstruction (UPJO). Methods: The clinical data of 47 children with UPJO who underwent surgery from October 2020 to September 2022 in the Department of Pediatric Surgery of Fujian Provincial Hospital were retrospectively analyzed. According to the surgical method chosen by parents, the children were divided into R-SILP+1 group and SILP group. Baseline data, operative time, intraoperative anastomosis time, volume of blood loss, postoperative hospitalization time, complications, total costs, preoperative and postoperative renal parenchymal thickness (PT), anterior posterior diameter of renal pelvis (APD), and differential renal function (DRF) before and after operation were compared between the two groups, and the clinical efficacy of the two kinds of operation was evaluated. Results: Among the 47 children, 27 were in R-SILP+1 group, including 16 males and 11 females, aged (6.6±3.5) years; 20 were in SILP group, including 12 males and 8 females, aged (6.5±3.5) years. The operations were successful in both groups without conversion to open operation. There were no significant differences between the two groups in baseline data, volume of blood loss, complications, APD and PT at postoperative 6 months, APD, PT and DRF at postoperative 12 months (all P>0.05). Compared with the SILP group, the operative time [(153.0±14.4) vs (189.9±32.6) minutes, P<0.001], intraoperative anastomosis time [(68.8±16.8) vs (97.5±12.0) minutes, P<0.001], postoperative hospitalization time [(6.0±1.3) vs (9.0±1.3) d, P<0.001] were shorter, but the total cost was higher[(57 390±7 664) vs (30 183±4 219) yuan RMB, P<0.001]. Conclusions: Compared with the SILP group, R-SILP+1 can achieve considerable efficacy in treating pediatric UPJO, and has certain advantages in shortening operative time, intraoperative anastomosis time, and postoperative hospitalization time. However, the cost is high.

[Analysis of pollen sensitization characteristics of artemisia allergic rhinitis in three urban and rural areas of Inner Mongolia].

Objective: To investigate the distribution rules of artemisia pollen and the clinical sensitization characteristics of allergic rhinitis (AR) induced by artemisia pollen in three urban and rural areas of Inner Mongolia. Methods: From March to October 2019, in 3 central cities (Chifeng, Hohhot, Ordos) and rural areas of Inner Mongolia, an epidemiological investigation method combining multi-stage stratified random sampling and face-to-face questionnaire survey was adopted to screen suspected AR patients, and skin prick test (SPT) was applied for diagnosis. At the same time, pollen monitoring was carried out in 3 areas to analyze the distribution and clinical sensitization characteristics of artemisia pollen.SPSS26.0 statistical software was used to process all the data. Chi-square test was used to compare rates among different age, sex, region and nationality, Spearman test was used to describe correlation analysis, and pairwise comparison of positive rates among multiple samples was used Bonferroni method. Results: Among the 6 393 subjects, 1 093 cases were diagnosed with AR, and the prevalence of AR was 17.10% (1 093/6 393). Among them, pollen-induced allergic rhinitis, the prevalence of PiAR was 10.97% (701/6 393), accounting for 64.14%(701/1 093).The highest incidence was in the youth group (20-39 years old), accounting for 46.94% (329/701).The diagnosed prevalence was higher in females than in males (11.35% vs. 10.64%, χ2 value 12.304, P<0.001).The prevalence rate of ethnic minority was higher than that of Han nationality (13.01% vs. 10.65%, χ2 value 6.296, P=0.008).The prevalence in urban areas was also significantly higher than that in rural areas (18.40% vs. 5.50%, χ2 value 10.497, P<0.001).There was significant difference in prevalence rate among the three regions in Inner Mongolia (6.06% in Chifeng, 13.46% in Hohhot, 16.39% in Ordos, χ2 value 70.054, P<0.001).The main clinical symptoms of artemisia PiAR were sneezing (95.58%), nasal congestion (91.73%) and nasal itching (89.30%).Allergic conjunctivitis accounted for 79.60% (558/701), chronic sinusitis for 55.63% (390/701), asthma for 23.25% (163/701).The pattern of artemisia pollen sensitization was mainly multiple sensitization, and the frequency of clinical symptoms and clinical diseases induced by hypersensitization with other allergens accounted for more than that caused by single artemisia pollen. The spread period of Artemisia pollen in the three regions was from June to October, and the peak state was in August in summer. The peak time of clinical symptoms in artemisia PiAR patients was about 2 weeks earlier than the peak time of pollen concentration, and the two were significantly positively correlated (R=0.7671, P<0.001). Conclusion: Artemisia pollens are the dominant pollens in late summer and early autumn in Inner Mongolia, and the prevalence of artemisia PiAR is high. Controlling the spread of Artemisia pollens is of great significance for the prevention and treatment of AR.

[Association of urinary cadmium levels with peripheral leukocyte classification counts among middle-aged and older adults aged 40-89 in selected areas of China].

Objective: To investigate the association of urinary cadmium levels with peripheral leukocyte classification counts among middle-aged and older adults aged 40 to 89 years in selected areas of China. Methods: The research was based on the survey of the impact of soil quality of agricultural land on human health in typical areas conducted in 2019-2020. A total of 5 600 middle-aged and older adults aged 40 to 89 years were included by using a multi-stage stratified random sampling method. Baseline characteristics of the subjects were collected and physical examinations were performed. Random midstream urine was collected to measure urinary cadmium and urinary creatinine and fasting venous blood was collected to measure the leukocyte count, neutrophil count, lymphocyte count, monocyte count and eosinophil count. The linear mixed effect model was used to analyse the association of urinary cadmium levels with leukocyte classification counts, and the dose-response relationship between them was analyzed by using the restricted cubic spline (RCS) function. Results: The age of the subjects was (63.17±12.02) years; 2 851 (50.91%) were males; and the M (Q1, Q3) of urinary creatinine-corrected urinary cadmium levels was 2.69 (1.52, 4.69) µg/g·creatinine. After adjusting for confounding factors, the results of linear mixed effects model analysis showed that for each 1-unit increase in urinary creatinine-corrected urinary cadmium level, the percentage change [% (95%CI)] of leukocyte count and lymphocyte count was -1.70% (-2.61%, -0.79%) and -1.57% (-2.86%, -0.26%), respectively. RCS function showed a negative linear relationship between urinary creatinine-corrected urinary cadmium levels and leukocyte counts and lymphocyte counts, respectively (all Pnon-linear>0.05). Conclusion: Urinary cadmium levels are negatively associated with leukocyte count and lymphocyte count among middle-aged and older adults aged 40 to 89 years in selected areas of China.

[HVPG minimally invasive era: exploration based on forearm venous approach].

Objective: The transjugular or transfemoral approach is used as a common method for hepatic venous pressure gradient (HVPG) measurement in current practice. This study aims to confirm the safety and effectiveness of measuring HVPG via the forearm venous approach. Methods: Prospective recruitment was conducted for patients with cirrhosis who underwent HVPG measurement via the forearm venous approach at six hospitals in China and Japan from September 2020 to December 2020. Patients' clinical baseline information and HVPG measurement data were collected. The right median cubital vein or basilic vein approach for all enrolled patients was selected. The HVPG standard process was used to measure pressure. Research data were analyzed using SPSS 22.0 statistical software. Quantitative data were used to represent medians (interquartile ranges), while qualitative data were used to represent frequency and rates. The correlation between two sets of data was analyzed using Pearson correlation analysis. Results: A total of 43 cases were enrolled in this study. Of these, 41 (95.3%) successfully underwent HVPG measurement via the forearm venous approach. None of the patients had any serious complications. The median operation time for HVPG detection via forearm vein was 18.0 minutes (12.3~38.8 minutes). This study confirmed that HVPG was positively closely related to Child-Pugh score (r = 0.47, P = 0.002), albumin-bilirubin score (r = 0.37, P = 0.001), Lok index (r = 0.36, P = 0.02), liver stiffness (r = 0.58, P = 0.01), and spleen stiffness (r = 0.77, P = 0.01), while negatively correlated with albumin (r = -0.42, P = 0.006). Conclusion: The results of this multi-centre retrospective study suggest that HVPG measurement via the forearm venous approach is safe and feasible.

[Short-term outcomes of the TRIANGLE operation after neoadjuvant chemotherapy in locally advanced pancreatic cancer].

Objective: To investigate the safety and efficacy of the TRIANGLE operation after neoadjuvant chemotherapy in locally advanced pancreatic cancer(LAPC). Methods: This study is a retrospective case series analysis. Between January 2020 and December 2022, a total of 103 patients were diagnosed as LAPC who underwent neoadjuvant chemotherapy at the Pancreas Center, the First Affiliated Hospital of Nanjing Medical University. Among them, 26 patients (25.2%) underwent the TRIANGLE operation. There were 15 males and 11 females,with a age of (59±7) years (range: 49 to 74 years). The pre-treatment serum CA19-9(M(IQR)) was 248.8(391.6)U/ml (range: 0 to 1 428 U/ml),and the serum carcinoembryonic antigen was 4.1(3.8)µg/L(range: 1.4 to 13.4 µg/L). The neoadjuvant chemotherapy regimens included: mFOLFIRINOX regimen in 6 cases(23.1%), GnP regimen in 14 cases(53.8%), and mFOLFIRINOX+GnP regimen in 6 cases(23.1%). The follow-up duration extended until June 2023 or until the occurrence of the patient's death or loss to follow-up. The Kaplan-Meier method was employed to estimate the 1-year and 3-year overall survival rates. Results: After neoadjuvant chemotherapy,CA19-9 levels decreased by 92.3(40.1)%(range:2.1% to 97.7%). Evaluation of the response to treatment revealed 13 cases(50.0%) of stable disease,11 cases(42.3%) of partial response,and 2 cases(7.7%) of complete response. The surgical operation consisted of 12 cases(46.2%) of pancreaticoduodenectomy,12 cases(46.2%) of distal pancreatectomy,and 2 cases(7.7%) of total pancreatectomy. Margin determination was based on the "standardised pathology protocol" and the "1 mm" principle. No R2 and R1(direct) resections were observed,while the R0 resection rate was 61.5%(16/26), and the R1(1 mm) resection rate was 38.5%(10/26).The R1(1 mm) resection rates for the anterior margin,posterior margin,transected margin,portal vein groove margin,and uncinate margin were 23.1%(6/26),19.2%(5/26),12.5%(3/24),2/14, and 1/12, respectively. The overall postoperative complication rate was 57.8%(15/26),with major complications including grade B/C pancreatic fistula 25.0%(6/24,excluding 2 cases of total pancreatectomy),delayed gastric emptying in 23.1%(6/26),wound complications 11.5%(3/26),postoperative hemorrhage 7.7%(2/26), chylous fistula 7.7%(2/26) and bile fistula 3.8%(1/26). No reoperation was performed during the perioperative period(<90 days). One patient died on the 32nd day postoperatively due to a ruptured pseudoaneurysm. A total of 25 patients were followed up,with a follow-up time of 21(24)months(range: 8 to 42 months). During the follow-up period,8 cases(32.0%) died due to tumor recurrence and metastasis,while 17 patients(68.0%) remained alive,including 11 cases of disease-free survival,5 cases of distant metastasis,and 1 case of local recurrence. The overall survival rates at 1- and 3-year after the initiation of neoadjuvant chemotherapy were 95.8% and 58.9%, respectively. The overall survival rates at 1- and 3-year after surgery were 77.7% and 57.8%, respectively. Conclusion: Performing pancreatoduodenectomy according to the Heidelberg triangle protocol in LAPC patients after neoadjuvant chemotherapy might increase the R0 resection rate without increasing perioperative mortality or the incidence of major postoperative complications.

Optical wavefront phase-tilt measurement using Si-photonic waveguide grating couplers.

Silicon photonic wavefront phase-tilt sensors for wavefront monitoring using surface coupling grating arrays are demonstrated. The first design employs the intrinsic angle dependence of the grating coupling efficiency to determine local wavefront tilt, with a measured sensitivity of 7 dB/°. The second design connects four gratings in an interferometric waveguide circuit to determine incident wavefront phase variation across the sensor area. In this device, one fringe spacing corresponds to 2° wavefront tilt change. These sensor elements sample a wavefront incident on the chip surface without the use of bulk optic elements, fiber arrays, or imaging arrays. Both sensor elements are less than 60 µm across and are potential unit cell sensor elements for large arrays that monitor wavefront shape across an image or pupil plane in adaptive optics systems for free-space optical communications, astronomy, and beam pointing applications.

Preoperative prediction of mediastinal lymph node metastasis in non-small cell lung cancer based on 18F-FDG PET/CT radiomics.

AIM: To establish and verify a 2-[18F]-fluoro-2-deoxy-d-glucose (FDG) positron-emission tomography (PET)/computed tomography (CT)-based radiomics nomogram to predict mediastinal lymph node metastasis (LNM) in non-small cell lung cancer (NSCLC) patients preoperatively. MATERIALS AND METHODS: This retrospective study enrolled 155 NSCLC patients (primary cohort, n=93; validation cohort, n=62). For each patient, 2,704 radiomic features were extracted from the primary lung cancer regions. Four procedures including the Mann-Whitney U-test, Spearman's correlation analysis, minimum redundancy-maximum relevance (mRMR), and least absolute shrinkage and selection operator (LASSO) binary logistic regression were utilised for determining essential features and establishing a radiomics signature. After that, a nomogram was established. The nomogram's potential was assessed based on its discrimination, calibration, and clinical usefulness. The radiomics signature and nomogram predictive performances were evaluated with respect to the area under the receiver operating characteristic curve (AUC), specificity, accuracy, and sensitivity. RESULTS: The radiomics signature composed of eight selected features had good discriminatory performance of LNM versus non-LNM groups an AUC of 0.851 and 0.826 in primary and validation cohorts, respectively. The nomogram also indicated good discrimination with an AUC of 0.869 and 0.847 in the primary and validation cohorts, respectively. Furthermore, good calibration was demonstrated utilising the nomogram. CONCLUSIONS: An 18F-FDG PET/CT-based radiomics nomogram that integrates the radiomics signature and age was promoted to predict mediastinal LNM within NSCLC patients, which could potentially facilitate individualised therapy for mediastinal LNM before treatment. The nomogram was beneficial in clinical practice, as illustrated by decision curve analysis.

Effects of gonadotropin-inhibitory hormone on testicular development and reproduction-related gene expression in roosters.

Gonadotropin-inhibitory hormone (GnIH) plays a crucial role in regulating reproduction in the hypothalamus of poultry and has been intensely investigated since its discovery. This study aimed to assess the effects of GnIH on testicular development, as well as on reproduction-related hormone release and gene expression levels in roosters. The administration of exogenous GnIH resulted in a significant reduction in testis weight, testis volume and semen quality (p < 0.05). Additionally, exogenous GnIH significantly up-regulates the expression of GnIH, and down-regulates the expression of PRL (p < 0.05). GnIH application also decreased the GnRH, vasoactive intestinal peptide (VIP) and luteinizing hormone ß subunit(LHß)gene expression levels. Meanwhile, by neutralizing the effects of endogenous GnIH through immunization, testicular development on day 150 in roosters was significantly promoted. Compared to the control condition, GnIH immunization significantly down-regulated the expression of the VIP and PRL genes (p < 0.05). In conclusion, we found that exogenous GnIH treatment inhibited testicular development, reduces PRL gene expression, and suppressed reproductive performance in roosters. Conversely, GnIH immunization down-regulated VIP and PRL genes, activates the reproductive system, and promotes the reproductive activity and testicular development of roosters.

Comparative transcriptomic analysis reveals candidate genes for seasonal breeding in the male Lion-Head goose.

1. Due to seasonal breeding, geese breeds from Southern China have low egg yield. The genetic makeup underlying performance of local breeds is largely unknown, and few studies have investigated this problem. This study integrated 21 newly generated and 50 publicly existing RNA-seq libraries, representing the hypothalamus, pituitary and testis, to identify candidate genes and importantly related pathways associated with seasonal breeding in male Lion-Head geese.2. In total, 19, 119 and 302 differentially expressed genes (DEGs) were detected in the hypothalamus, pituitary and testis, respectively, of male Lion-Head geese between non-breeding and breeding periods. These genes were significantly involved in the neuropeptide signalling pathway, gland development, neuroactive ligand-receptor interaction, JAK-STAT signalling pathway, cAMP signalling pathway, PI3K-Akt signalling pathway and Foxo signalling pathway.3. By integrating another 50 RNA-seq samples 4, 18 and 40 promising DEGs were confirmed in hypothalamus, pituitary and testis, respectively.4. HOX genes were identified as having important roles in the development of testis between non-breeding and breeding periods of male Lion-Head geese.

[Recommendations for the diagnosis and treatment of gout in China].

Gout is a metabolic disease resulting from the accumulation of monosodium urate (MSU) in joints, leading to crystal-induced arthritis. In China, gout is common, but there is insufficient knowledge regarding standardized criteria for the diagnosis and treatment of this condition. Based on evidence and guidelines from China and other countries, the Chinese Rheumatology Association developed standardized criteria for the diagnosis and treatment of gout in China. The purpose was to standardize gout diagnosis methods as well as treatment opportunities and strategies in order to reduce misdiagnosis, missed diagnosis, and irreversible damage.

[Self-reported quality of life in patients with coronary heart disease and analysis of the associated factors].

Objective: To investigate the quality of life and associated factors in patients with coronary heart disease (CHD) in China. Methods: A cross-sectional study of 25 provinces and cities in China was performed from June to September 2020. A questionnaire was used to collect the socio-demographic and clinical information of patients with CHD, while the European Five-dimensional Quality of Life Scale (EQ-5D) was used to assess the quality of life. Multiple linear regression model was performed to analyze the associated factors. Results: The median age of the 1 075 responders was 60 (52, 67) years, and 797 (74.1%) were men. The EQ-5D and EQ-VAS indices were 0.7 (0.5, 0.8) and 60.0 (40.0, 80.0). Among the five dimensions in the quality of life scale, the frequency of anxiety/depression was the highest (59.8%), while problems in self-care was the lowest (35.8%). In the multiple linear regression model, female, increasing age, obesity, comorbidity(ies), anxiety/depression, social media channels, and receiving the CABG therapy were associated with the lower EQ-5D index (all P<0.05). In addition, increasing age, obesity, comorbidity (ies), depression, anxiety and depression, social media channels, and receiving the CABG therapy were associated with lower EQ-VAS index (all P<0.05). Conclusion: Over half of the patients with CHD in China have a low quality of life, which is related to gender, age, obesity, treatment pathway, the presence or absence of comorbidity (ies), and psychological state. In addition to managing the adverse effects of traditional socio-demographic factors on the quality of life, clinical practices should pay attention to the psychological state of patients. Moreover, establishing a WeChat group for doctor-patient communication could improve the quality of life of CHD patients.

[Clinical characteristics of patients with rheumatic diseases and abnormal liver function].

Objective: To investigate the clinical characteristics of patients with rheumatic diseases and abnormal liver function, as well as determine the proportion and severity of liver function abnormalities. Methods: Cross-sectional study. Data were collected from patients registered in the Chinese Rheumatism Date Center from 2011 to 2021. The rheumatic diseases analyzed in this study were rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Sjogren syndrome (SS), ankylosing spondylitis (AS), and gout. Patient data, including demographic characteristics [ such as age, sex, body mass index,(BMI), and smoking history], liver function test results [including alanine aminotransferase (ALT), aspartate aminotransferase, alkaline phosphatase(ALP), and total bilirubin], and use of anti-rheumatic immune drugs and liver-protective drugs, were collected and compared between groups with normal and abnormal liver functions. In addition, the proportions of abnormal liver function were compared between sex and age groups. Results: A total of 116 308 patients were included in this study, including 49 659 with RA, 17 597 with SLE, 9 039 with SS, 11 321 with AS, and 28 692 with gout. The lowest proportion of liver function abnormalities was observed in patients with RA[11.02% (5 470/49 659)], followed by those with SS[17.97% (1 624/9 039)] and AS [18.22% (2 063/11 321) ], whereas patients with SLE [21.14% (3 720/17 597) ] and gout [28.73% (8 242/28 692)] exhibited the highest proportion of these abnormalities. Elevated ALT, mostly classified as grade 1, was the most commonly noted liver function abnormality, whereas elevated ALP was the least common. Some patients who took liver-protective drugs had normal liver function, with the lowest percentage observed in patients with gout [7.45% (36/483) ] and ranging from 21.7% to 30.34% in patients with RA, SLE, SS, and AS. The proportion of liver function abnormalities was higher in males than in females for all disease types [RA: 13.8%(1 368/9 906) vs. 10.3%(4 102/39 753); SLE: 33.6% (479/1 424) vs. 20.0% (3 241/16 173); SS: 25.4%(111/437) vs. 17.6%(1 513/8 602); AS: 20.1%(1 629/8 119) vs. 13.6% (434/3 202); and gout: 29.3% (8 033/27 394) vs. 16.1% (209/1 298)]. In RA, SLE, and AS, the proportions of liver function abnormalities were similar across all age groups. In SS, the proportion of liver function abnormalities increased with age [<40 years: 14.9%(294/1 979); 40-59 years: 18.1%(858/4 741); ≥60 years: 20.4%(472/2 319)], whereas a reversal of this trend was observed in gout [<40 years: 34.9%(4 294/12 320); 40-59 years: 25.5%(2 905/11 398);≥60 years: 21.0%(1 042/4 971)]. Conclusions: The proportions of combined liver function abnormalities in patients with rheumatologic diseases were high, and the utilization rates of liver-protective drugs were low. It is necessary to pay more attention to monitoring patients' liver function, timely administer liver-protective drugs, and optimize liver-protective regimens during the treatment of rheumatic diseases.

[Current status and influencing factors for physicians in different departments prescribing novel hypoglycemic agent with cardiovascular benefits].

Objective: To investigate the knowledge, use and barriers when prescribing GLP-1RA and SGLT2i among cardiologists, endocrinologists and general practitioners, and explore the influencing factors that hinder the use of these medications. Methods: A questionnaire was conducted among physicians in the above departments in Peking University Third Hospital and health service institutions at all levels in its medical consortium. A total of 342 physicians were involved. Among them, 40.6% (139) were cardiologists, 28.9% (99) were endocrinologists and 30.4% (104) were general practitioners; 66.7% (270) came from Beijing while 33.3% (72) from other provinces. The survey included clinicians' knowledge and current use of GLP-1RA and SGLT2i, and the possible reasons that influenced the prescription of these medications. Medical therapies of physicians were investigated by simulating different clinical scenarios. The difference of measures among physicians in different departments was compared. Results: A total of 342 physicians were involved, with the average age of 40 (35, 46) years old and the average working time of 13 (7, 20) years. Among them, 40.6% (139) were male. 77.5% (265) physicians had comprehensive knowledge of SGLT2i and prescribed it, which was higher than that for GLP-1RA (70.5%, 241) (P<0.001). 21.1% (72) physicians prescribed SGLT2i more than 20 times per month, which was higher than that for GLP-1RA (8.2%, 28) (P<0.001). Endocrinologists had more knowledge and prescribed more GLP-1RA and SGLT2i compared with other physicians (both P values<0.001). 38.1% (53) cardiologists, 22.2% (22) endocrinologists, and 30.8% (32) general practitioners believed patients needed an endocrinologist to evaluate and adjust GLP-1RA, which was the primary barrier for the use of medications (P=0.042). 27.4% (38) cardiologists, 14.1% (14) endocrinologists, and 30.8% (32) general practitioners believed patients needed an endocrinologist to evaluate and adjust SGLT2i, which was the primary barrier for the use of medications (P=0.018). 21.6% (30) cardiologists, 45.5% (45) endocrinologists, and 31.7% (33) general practitioners believed side effects of SGLT2i was the primary barrier for the use of medications (P<0.001). For patients with unqualified glycemic control and cardiovascular complications, 65.4% (75) cardiologists, 69.7% (69) endocrinologists, and 43.3% (45) general practitioners chose the above medications (P<0.001). For patients with qualified glycemic control, combined with cardiovascular complications and diabetic organ damage, 35.3% (49) cardiologists, 52.5% (52) endocrinologists, and 25.0% (26) general practitioners chose the above medications (P<0.001). Conclusions: Physicians had more knowledge and prescription of SGLT2i than that of GLP-1RA. Endocrinologists had more knowledge and prescription of the above medications than other physicians. The side effect of medications was potential primary barrier for the use of the novel hypoglycemic agent with cardiovascular benefits. In clinical practice, most of physicians considered that high-risk patients with cardiovascular comorbidities need to be referred to cardiologist or endocrinologist to adjust clinical therapies.

The Anti-Inflammatory Effect of miR-140-3p in BMSCs-Exosomes on Osteoarthritis.

PURPOSE OF THE STUDY Articular cartilage injury is a common disease in daily life, with a high incidence. The aim of this study was to investigate the effect and mechanism of miRNA-140-3p in bone mesenchymal stem cells (BMSCs)-derived exosomes under hypoxia on inflammatory articular chondrocytes. MATERIAL AND METHODS To simulate the pathological status of arthritis, rat chondrocytes were used to establish the osteoarthritis (OA) model by IL-1ß (10 µg/ml) as a modulating in vitro, and exosomes were isolated by differential ultra-high speed centrifugation. The cell counting kit-8, wound healing and flow cytometry assays were utilized to assess proliferation, migration and apoptosis of chondrocytes, respectively. Lipogenic and chondrogenic differentiation of chondrocytes were detected by oil red O staining and toluidine blue staining individually. The expressions of miR-140-3p and chondrocyte-specific gene mRNA were investigated using qRT-PCR. Western blot was applied to assess chondrocyte associated proteins and BMSC-Exo surface protein markers, and immunohistochemistry was adopted to detect the staining of collagen I and II. RESULTS Under scanning electronic microscope, the shape of exosomes was almost round. Exosome treatment prominently impaired the inhibition of chondrocytes' proliferative and migrative ability by IL-1ß. It was found hypoxia had a more marked impact on proliferation, expression of collagen II and apoptosis in OA chondrocytes than normoxia, as well as a stronger effect on weakening adipose differentiation and enhancing chondrogenic differentiation in inflammatory chondrocytes. Furthermore, incubation with BMSC-Exo overexpressing miR-140-3p can remarkably increase the survival rate and migration in inflammatory chondrocytes. In addition, overexpression of miR-140-3p was found to enhance the chondrogenic differentiation of inflammatory chondrocytes. Furthermore, we found that the healing effect of exosomes on inflammatory chondrocytes under hypoxic conditions was produced by a rise in miR-140-3p expression within them and that hypoxia-mediated upregulation of miR-140-3p expression occurred through HIF-1α. CONCLUSIONS Under hypoxia, BMSC-Exo enhanced the chondrogenic phenotype, increased the viability of inflammatory chondrocytes. The overexpression of miR-140-3p in BMSC-Exo is beneficial to protect joints and delaying the pathogenesis in OA. Key words: HIF-1α, apoptosis, lipogenic differentiation, chondrogenic differentiation.

[Study on formulation and revision of standard limit for formaldehyde in the "Standards for indoor air quality（GB/T 18883-2022）" in China].

Formaldehyde, as an important pollutant in indoor air, has always been of great concern. In the newly issued "Standards for indoor air quality (GB/T 18883-2022)", the standard limit of formaldehyde has been restricted to 0.08 mg/m3. In order to better promote the implementation and application of this new standard, this study reviewed and interpreted the relevant technical content for determining the standard limit, including the indoor concentration and human exposure levels of formaldehyde, the health effects of formaldehyde, and the derivation of safety reference values. It also proposed prospect for the future development and revision of quality standards for formaldehyde in indoor air.