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.

Diagnostic performance of transvaginal sonography vs. magnetic resonance imaging for rectovaginal septum deep infiltrating endometriosis: a head-to-head comparative meta-analysis.

AIM: We aimed to compare the diagnostic performance of transvaginal sonography (TVS) versus magnetic resonance imaging (MRI) in identifying deep infiltrating endometriosis (DIE) in the rectovaginal septum (RVS) of affected patients. MATERIALS AND METHODS: An extensive search was conducted in the PubMed, Embase databases to identify available publications up to November 2023. Studies evaluating the diagnostic perfor-mance of TVS and MRI for DIE in patients with rectovaginal septum involvement were all included. Sensitivity and specificity analyses employed the DerSi-monian and Laird method, complemented by the Freeman-Tukey double arc-sine trans-formation. Additionally, the study quality was rigorously evaluated using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) method. RESULTS: The meta-analysis encompassed 8 articles with a total of 721 patients. It revealed that the overall sensitivity of TVS was 0.51 (95% CI: 0.31-0.72), contrasted with 0.74 (95% CI: 0.66-0.82) for MRI. This finding suggests a higher sensitivity of MRI compared to TVS (P=0.04). Conversely, the overall specificity was 0.97 (95%CI: 0.94-1.00) for TVS and 0.93 (95% CI: 0.84-0.99) for MRI, indicating a comparable level of specificity between the two modalities (P=0.22). CONCLUSION: Our meta-analysis reveals that MRI exhibits higher sensitivity and comparable specificity to TVS in patients with DIE of the RVS. However, the limited number of articles included may affect the evidence of these results. Therefore, further d number of articles included may affect the evidence of these results. Therefore, further research with larger sample sizes and prospective designs is essential to validate these findings.

Sleeve gastrectomy links the attenuation of diabetic kidney disease to the inhibition of renal tubular ferroptosis through down-regulating TGF-ß1/Smad3 signaling pathway.

PURPOSE: To investigate how sleeve gastrectomy (SG), a typical operation of bariatric surgery, attenuated symptom, and progression of diabetic kidney disease (DKD). METHODS: DKD model was induced by high-fat diet (HFD) combined with streptozocin in Wistar rats. SG was performed, and the group subjected to sham surgery served as control. The animals were euthanized 12 weeks after surgery, followed by sample collection for the subsequent experiment. The HK-2, a renal proximal tubular epithelial cell line derived from human, was utilized to investigate the potential mechanisms. RESULTS: SG improved metabolic parameters and glucose homeostasis, and could alleviate DKD in terms of renal function indices as well as histological and morphological structures in DM rats, accompanied with a significant reduction in renal tubular injury. Compared with sham group, SG reduced the renal tubular ferroptosis. To further clarify the mechanism involved, in vitro experiments were performed. In the presence of high glucose, renal tubular TGF-ß1 secretion was significantly increased in HK-2 cell line, which led to activation of ferroptosis through TGF-ß1/Smad3 signaling pathway. Inhibition of TGF-ß1 receptor and phosphorylation of Smad3 significantly ameliorated TGF-ß1-mediated ferroptosis. In vivo experiments also found that SG improved the hyperglycemic environment, reduced renal TGF-ß1 concentrations, and down-regulated the TGF-ß1/Smad3 signaling pathway. CONCLUSIONS: With the capacity to lower the glucose, SG could attenuate the ferroptosis by inhibiting TGF-ß1/Smad3 signaling pathway in DKD rats, and eventually attenuated DKD.

[Electrophysiological properties of neurons in the visual sensory layers of the superior colliculus in early postnatal mice].

Objective: To investigate the action potential firing patterns of neurons in the visual sensory layers of the superior colliculus in early postnatal mice and the electrophysiological characteristics of neurons with different firing patterns. Methods: This experimental study utilized whole-cell patch-clamp recordings performed on neurons in the visual sensory layers of the superior colliculus using brain slices from 57 healthy male C57BL/6J mice aged 14 to 20 days (weighing 5.0 to 8.9 g) using brain slices. In current-clamp mode, action potential characteristics were analyzed based on the first action potential generated by depolarizing current, and the firing patterns of neurons were recorded using step depolarizing currents. Neuronal firing patterns were analyzed using hierarchical clustering, and the active electrical properties of neurons with different firing patterns were compared. Results: A total of 135 neurons from the visual sensory layers of the superior colliculus were successfully recorded. Cluster analysis of the neuronal firing patterns identified three types of firing patterns: tonic firing (97, 72%), phasic firing (26, 19%), and single firing (12, 9%). The number of action potentials for each firing pattern was 13.30±7.38, 3.73±3.61, and 0.83±0.39, respectively, with significant differences (P<0.001). There was no significant difference in the membrane potential response to step currents among the three firing pattern types (P>0.05). The action potential amplitudes were (60.45±12.22), (53.67±13.20), and (44.04± 12.92) mV, and the afterhyperpolarization amplitudes were (13.45±13.79), (12.02±13.11), and (20.75±2.85) mV, respectively. The maximum rising slopes were (171.29±77.46), (130.14±61.83), and (78.89±37.08) V/s, and the maximum falling slopes were (-76.33±33.61), (-68.17±31.65), and (-47.97±13.92) V/s, respectively, with all differences being statistically significant (all P<0.05). There were no significant differences in the resting membrane potential, action potential threshold, half-width, and afterhyperpolarization duration among the three firing pattern types (all P>0.05). Conclusions: In the early postnatal mice, neurons in the visual sensory layers of the superior colliculus exhibit three distinct firing patterns: tonic, phasic, and single firing. These firing pattern types show significant differences in action potential amplitude, afterhyperpolarization amplitude, maximum rising slopes, and maximum falling slopes.

[Diagnostic and intervention value of implantable cardiac monitor in patients over 60 years of age with unexplained syncope].

Objective: To investigate the value of implantable cardiac monitor (ICM) in the diagnosis and treatment of patients over 60 years old with unexplained syncope. Methods: This was a multi-center, prospective cohort study. Between June 2018 and April 2021, patients over the age of 60 with unexplained syncope at Beijing Hospital, Fuwai Hospital, Beijing Anzhen Hospital and Puren Hospital were enrolled. Patients were divided into 2 groups based on their decision to receive ICM implantation (implantation group and conventional follow-up group). The endpoint was the recurrence of syncope and cardiogenic syncope as determined by positive cardiac arrhythmia events recorded at the ICM or diagnosed during routine follow-up. Kaplan-Meier survival analysis was used to compare the differences of cumulative diagnostic rate between the 2 groups. A multivariate Cox regression analysis was performed to determine independent predictors of diagnosis of cardiogenic syncope in patients with unexplained syncope. Results: A total of 198 patients with unexplained syncope, aged (72.9±8.25) years, were followed for 558.0 (296.0,877.0) d, including 98 males (49.5%). There were 100 (50.5%) patients in the implantation group and 98 (49.5%) in the conventional follow-up group. Compared with conventional follow-up group, patients in the implantation group were older, more likely to have comorbidities, had a higher proportion of first degree atrioventricular block indicated by baseline electrocardiogram, and had a lower body mass index (all P<0.05). During the follow-up period, positive cardiac arrhythmia events were recorded in 58 (58.0%) patients in the ICM group. The diagnosis rate (42.0% (42/100) vs. 4.1% (4/98), P<0.001) and the intervention rate (37.0% (37/100) vs. 2.0% (2/98), P<0.001) of cardiogenic syncope in the implantation group were higher than those in the conventional follow-up group (all P<0.001). Kaplan-Meier survival analysis showed that the cumulative diagnostic rate of cardiogenic syncope was significantly higher in the implantation group than in the traditional follow-up group (HR=11.66, 95%CI 6.49-20.98, log-rank P<0.001). Multivariate analysis indicated that ICM implantation, previous atrial fibrillation, diabetes mellitus or first degree atrioventricular block in baseline electrocardiogram were independent predictors for cardiogenic syncope (all P<0.05). Conclusions: ICM implantation improves the diagnosis and intervention rates in patients with unexplained syncope, and increases diagnostic efficiency in patients with unexplained syncope.

Effect of surface gallium termination on the formation and emission energy of an InGaAs wetting layer during the growth of InGaAs quantum dots by droplet epitaxy.

Self-assembled quantum dots (QDs) based on III-V semiconductors have excellent properties for applications in quantum optics. However, the presence of a 2D wetting layer (WL) which forms during the Stranski-Krastanov growth of QDs can limit their performance. Here, we investigate WL formation during QD growth by the droplet epitaxy technique. We use a combination of photoluminescence excitation spectroscopy, lifetime measurements, and transmission electron microscopy to identify the presence of an InGaAs WL in these droplet epitaxy QDs, even in the absence of distinguishable WL luminescence. We observe that increasing the amount of Ga deposited on a GaAs (100) surface prior to the growth of InGaAs QDs leads to a significant reduction in the emission wavelength of the WL to the point where it can no longer be distinguished from the GaAs acceptor peak emission in photoluminescence measurements. However increasing the amount of Ga deposited does not suppress the formation of a WL under the growth conditions used here.

Chronotype and insomnia may affect the testosterone levels with a sexual difference: a Mendelian randomization.

OBJECTIVE: To evaluate the causal effects of sleep traits (i.e., chronotype, insomnia, and sleep duration) on bioavailable testosterone (BT), sex hormone-binding globulin (SHBG), and total testosterone (TT) levels in women and men. METHODS: We performed Mendelian randomization (MR) using random-effect inverse-variance weighted (IVW) and 7 other MR analyses. Exposure data for sleep traits were obtained from the largest-to-date genome-wide association study (GWAS) from 339,926 to 1,331,010 individuals. Summary data for testosterone levels were obtained from GWAS based on the UK Biobank. RESULTS: For women, our study supported that chronotype was associated with decreased BT (IVW: ß = - 0.042, 95% CI - 0.060, - 0.023, p = 1.17E-05) and TT (IVW: - 0.053, 95% CI - 0.075, - 0.031, p = 2.30E-06). Besides, insomnia can significantly increase BT (IVW: ß = 0.025, 95% CI 0.009, 0.041, p = 0.002). These findings were significant in most sensitivity analyses. For men, statistical significance was found between chronotype and BT (ß = - 0.027, 95% CI - 0.048, - 0.005, p = 0.016), and insomnia and TT (ß = - 0.028, 95% CI - 0.049, 0.007, p = 0.009) in IVW. However, the effect estimates were not broadly consistent with other sensitivity analyses. Our study did not find support for causal effects of sleep duration on testosterone levels in both women and men. CONCLUSION: Our study reveals the sex differences in the effects of sleep traits on testosterone levels. A healthy sleep habit is vital for the maintenance of testosterone homeostasis in women. Further studies are warranted to investigate the associations between sleep traits and testosterone levels in men.

[Clinical and molecular characteristics and prognosis of classical hairy cell leukemia and hairy cell leukemia variant].

Objective: To evaluate the clinical characteristics, treatment response, and outcomes in patients with classical hairy cell leukemia (cHCL) and HCL variant (HCL-V). Methods: This is a retrospective case series study. Between January 2011 and December 2021, clinical data of 30 patients newly with diagnosed HCL at Peking Union Medical College Hospital were analyzed. The main outcome measures include clinical characteristics, treatment efficacy and survival. The Kaplan-Meier method was used for survival analysis. Results: Twenty-one cases of cHCL and 9 cases of HCL-v were included. The median age at diagnosis was 55.5 (range, 30-86) years, with the ratio of male to female 2.75∶1. The main clinical manifestations included fatigue in 11 cases (36.7%), abdominal distension in 7 cases (23.3%), and infection in 4 cases, while 8 cases were asymptomatic. Splenomegaly was reported in 24 cases (80.0%), including 7 (23.3%) with megalosplenia. The white blood cell count, lymphocyte count, and the proportion of peripheral hairy cells in HCL-v group were significantly higher than those in cHCL group, whereas the development of anemia, thrombocytopenia, and monocytopenia in cHCL group was more remarkable than that in HCL-v group (all P<0.05). The BRAF-V600E gene mutation was detected only in cHCL patients (11/14 vs. 0/9, P<0.001). In terms of immunophenotype, the expression of CD25, CD103, CD123 and CD200 in cHCL group (20/20, 20/20, 4/7, 7/17) were all stronger than those in HCL-v group (3/9, 7/9, 0/4, 2/8). Twenty-two patients were treated, of which 13 cases (12 cases of cHCL and 1 case of HCL-v) with cladribine, and 9 cases (4 cHCL and 5 HCL-v) with interferon. Complete remission rate and overall response rate were comparable between cladribine and interferon treatment groups (both P<0.05). The median follow-up time was 31 (range, 1-125) months, and the median overall survival (OS) of the entire group was 125 months. The 5-year OS rate in HCL-v patients represented a trend of inferior (50.0% vs. 95.0%, P=0.207). Conclusions: The clinical features of HCL are unspecific, which includes fatigue, splenomegaly and recurrent infection. The clinical features, immunophenotype, treatment response and prognosis of HCL-v are different from those of cHCL. BRAF-V600E gene mutation is suggested as a key marker for differential diagnosis. Cladribine is recommended as front-line regimen of cHCL patients with satisfactory efficacy and prognosis. Conversely, response and clinical outcome in HCL-v patients still need to be improved.

[The 502nd case: thrombocytopenia, splenomegaly, disseminated intravascular coagulation, and spontaneous rupture of the spleen].

A young man with a history of thrombocytopenia for seven years presented with splenomegaly and fever and rapidly evolved to disseminated intravascular coagulation (DIC) and hemorrhagic shock. Spontaneous rupture of the spleen was diagnosed. The critical patient underwent an emergency splenectomy. Pathological examination revealed splenic peliosis, an extremely rare disease with unknown etiology and pathogenesis. Despite the high mortality rate due to spontaneous splenic rupture with DIC, the patient was successfully treated and the details of the case are presented in this report.

[Study on reproductive toxicity of nano-cadmium sulfide with different particle sizes on male mice].

Objective: To investigate the reproductive toxicity of cadmium sulfide nanoparticles (Nano-CdS) with different particle sizes on male mice. Methods: In January 2019, 30 SPF grade male mice were randomly divided into a control group, an experimental group[CdS Ⅰ group (particle size approximately 5 nm), and a CdS Ⅱ group (particle size approximately 50 nm) ], with 10 mice in each group. The experimental group was orally gavaged with 100 mg/kg, once a day, while the control group was gavaged with an equal volume of physiological saline for 45 consecutive days. After 45 days, levels of cadmium accumulation in testis were determined directly by AAS, deformity and testicular histopathological changes were also observed. Serum testosterone levels were measured by enzyme-linked immunosorbentassay (ELISA), expression levels of P450scc, 17ß-HSD and P450c17 mRNA were determined by real-time PCR. P450c17 protein was determinated by Western Blot. Results: The histopathological results showed that the testes of the experimental group mice showed varying degrees of damage; Ultrastructural observation showed that the ultrastructure of mouse testicular cells in each experimental group showed varying degrees of mitochondrial expansion and disappearance of cristae, as well as irregular nuclear membranes. The degree of damage in CdS Ⅰ group was milder than that in CdS Ⅱ group. Compared with the control group, the cadmium content in the testes of the CdS Ⅰ and CdS Ⅱ groups significantly increased (P=0.001, 0.001), and the CdS Ⅱ group was higher than the CdS Ⅰ group (P=0.001). Compared with the control group, the levels of testosterone in the CdS Ⅰ and CdS Ⅱ groups decreased with statistical significance (P=0.001, 0.001). Real time fluorescence quantitative PCR results showed that compared with the control group, the experimental group's P450scc, 17ß-HSD. The expression levels of 17ß-HSD and P450c17 mRNA were significantly reduced, with statistically significant differences (P=0.001, 0.001, 0.001), and CdS Ⅱ group 17ß-HSD. The expression levels of 17ß-HSD and P450c17 mRNA were significantly lower than those of CdS Ⅰ group (P=0.001, 0.036). The Western Blot assay results showed that the expression levels of P450c17 protein in the testes of CdS Ⅰ and CdS Ⅱ groups of mice were significantly reduced, with statistical significance (P=0.001, 0.001) ; And the CdS Ⅱ group was significantly lower than the CdS Ⅰ group (P=0.001). According to Spearman correlation analysis, testosterone levels are correlated with P450scc, P450c17, 17ß-HSD mRNA. There is a highly positive correlation between 17ß-HSD mRNA levels, with statistically significant differences (r(s)=0.88, 0.80, 0.70, P=0.001, 0.001, 0.004) . Conclusion: Nano cadmium sulfide may induce reproductive toxicity by reducing the expression levels of key enzyme genes and enzyme protein activity in testosterone and its synthesis in mice, and the CdS Ⅱ group has a stronger toxic effect.

Effectiveness of vitamin D supplementation on knee osteoarthritis - A target trial emulation study using data from the Osteoarthritis Initiative cohort.

OBJECTIVE: To assess the real-world effectiveness of vitamin D supplementation in patients with knee osteoarthritis (KOA) by replicating a randomized controlled trial (RCT) design in an observational study. METHOD: This study emulated a target trial using data from the Osteoarthritis Initiative (OAI). Eligible participants were ≥45 years, had symptomatic KOA and did not take vitamin D supplements in the past 30 days. A participant can enter the trial more than once. Participants were included in vitamin D group if they took ≥1,000 IU/day for ≥4 days/week in the past 30 days at the first follow-up visit after baseline. The control group did not use vitamin D in the past 30 days. Optimal propensity score matching at 1:1 ratio was performed. The primary outcome was change in knee pain 2 years after baseline measured by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Secondary outcomes included WOMAC physical function and quantitative joint space width (JSW). Standardized mean difference (SMD) was used to compare the findings with previous RCTs. RESULTS: A total of 236 person-trials in the vitamin D group were pair-matched with a control. Compared to the control group, vitamin D supplementation did not reach significant changes in WOMAC pain (SMD = -0.04, 95%CI [-0.21, 0.13]), physical function and radiographic JSW over 2 years. The SMDs were consistent with the effect sizes reported in previous RCTs. CONCLUSION: Target trial emulation in the OAI cohort demonstrated findings close to published RCTs. This supports the future use of target trial emulation in evaluating other systemic therapies for KOA.

Three novel structural variations at the major histocompatibility complex and IL12B predispose to psoriasis.

BACKGROUND: Structural variations (SVs; defined as DNA variants ≥ 50 base pairs) have been associated with various complex human diseases. However, research to screen the whole genome for SVs predisposing to psoriasis is lacking. OBJECTIVES: To investigate the association of SVs and psoriasis. METHODS: Using imputation, we performed a genome-wide screen of SVs on five independent cohorts with 45 386 participants from the Han Chinese population. Fine-mapping analysis, genetic interaction analysis and RNA expression analysis were conducted to explore the mechanism of SVs. RESULTS: In total, we obtained 4535 SVs and identified two novel deletions [esv3608550, odds ratio (OR) 2·73 (P < 2·00 × 10-308 ); esv3608542, OR 0·47 (P = 7·40 × 10-28 )] at 6q21·33 (major histocompatibility complex), one novel Alu element insertion [esv3607339; OR 1·22 (P = 1·18 × 10-35 )] at 5q33·3 (IL12B) and confirmed one previously reported deletion [esv3587563; OR 1·30 (P = 9·52 × 10-60 )] at 1q21·2 (late cornified envelope) for psoriasis. Fine-mapping analysis including single-nucleotide polymorphisms (SNPs) and small insertions/deletions revealed that esv3608550 and esv3608542 were independently associated with psoriasis, and a novel independent SNP [rs9378188; OR, 1·65 (P = 3·46 × 10-38 )] was identified at 6q21·33. By genetic interaction analysis and RNA expression analysis, we speculate that the association of two deletions at 6q21·33 with psoriasis might relate to their influence on the expression of HLA-C. CONCLUSIONS: We have constructed the most comprehensive SV map for psoriasis thus far and enriched the genetic architecture and pathogenesis of psoriasis, and highlight the non-negligible impact of SVs on complex diseases.

Enterococcus faecium HDRsEf1 inhibits Lipopolysaccharide-induced downregulation of zona occludens -1 expression via toll-like receptor 2/4-mediated c-Jun N-terminal kinase/activator protein-1 signalling pathways.

AIMS: Zona occludens-1 (ZO-1) is a key regulatory tight junction protein that plays an important role in maintaining gastrointestinal health. In this study, we investigated the protective effect and regulation mechanism of the probiotic Enterococcus faecium HDRsEf1 on tight junction protein ZO-1 at the cellular and molecular levels. METHODS AND RESULTS: We established lipopolysaccharide (LPS)-induced intestinal epithelial cell injury model and detected the protective effect of HDRsEf1 on ZO-1 in IPEC-J2 cells by real-time polymerase chain reaction and Western blot. The results showed that HDRsEf1 inhibited the downregulation of ZO-1 expression induced by LPS. HDRsEf1 stabilized the destruction of the ZO-1 structure caused by LPS in an immunofluorescence assay. Through gene overexpression and siRNA interference tests, we found that transcription factor activator protein 1 (AP-1) inhibited the level of ZO-1 expression. Silencing experiment further supported that the protective effect of HDRSEF1 might be mediated by suppression of LPS-provoked activation of apoptosis signal-regulating kinase 1 (ASK1)/mitogen-activated protein kinase kinase 7 (MKK7)/c-Jun N-terminal kinase (JNK) signalling pathways. In addition, HDRsEf1 could stabilize ZO-1 expression by increasing toll-like receptor 2 (TLR2) expression and competing with LPS for the TLR4 binding site. More interestingly, we also found that HDRsEf1 could stabilize ZO-1 expression through inhibiting the production of tumour necrosis factor-α (TNF-α) induced by LPS. CONCLUSIONS: HDRsEf1 could protect the IPEC-J2 cell against LPS induced downregulation of ZO-1 expression by inhibiting the activation of TLR2/4-mediated JNK-AP-1 and signalling cascade and the production of TNF-α. SIGNIFICANCE AND IMPACT OF THE STUDY: This study can provide a theoretical basis for probiotics to regulate the expression of intestinal tight junction proteins, and supply technical support for probiotics to prevent and treat animal intestinal infectious diseases.

The relationship between serum 25-hydroxyvitamin-D level and sweat function in patients with type 2 diabetes mellitus.

AIMS: The objective of this study is to explore the relationship between serum 25-hydroxyvitamin-D(25-(OH)2D3) level and sweat function in patients with type 2 diabetes mellitus (T2DM). METHODS: A cross-sectional study of 1021 patients with T2DM who underwent 25-(OH)2D3 level detections and sweat function tests was carried out. These individuals were divided into deficient groups (n = 154 cases), insufficient groups (n = 593 cases) and sufficient groups (n = 274 cases). Spearman correlation analysis and multivariate stepwise linear regression analysis were implemented to determine the association of 25-(OH)2D3 level and sweat function. RESULTS: The total presence of sweating dysfunction was 38.59%. Patients with a lower level of serum 25-(OH)2D3 had more severe sweat secretion impairment (P < 0.05). As the decrease of serum 25-(OH)2D3 level, the presence of sweating dysfunction increased (P < 0.05). 25-(OH)2D3 level was positively correlated with sweat function parameters, age and duration of T2DM were negatively correlated with sweat function parameter (P < 0.05). Multivariate stepwise linear regression analysis explored a significant association between serum 25-(OH)2D3 level with sweat function (P < 0.05). CONCLUSIONS: Serum 25-(OH)2D3 level was positively correlated with sweat function in patients with T2DM.

[The crucial toxic components of ambient fine particles promoted the maturation and differentiation of megakaryocytes].

Objective: To reveal the crucial toxic components of ambient fine particles (PM2.5) that affect the maturation and differentiation of megakaryocytes. Methods: Human megakaryocytes were exposed to the organic fractions, metallic fractions and water-soluble fractions of PM2.5 at two exposure doses (i.e. actual air proportion concentration or the same concentration), respectively. The cell viability was performed to screen the non-cytotoxic levels of toxic components of PM2.5 using the CCK-8 assay. CellTiter-Blue assay, morphological observation, flow cytometry analysis and WGA staining assay were used to evaluate the cell morphological changes, occurrence of DNA ploidy, alteration in the expressions of biomarkers and platelet formation, which were key indicators of the maturation and differentiation of megakaryocytes. Results: Compared to the control group, both metallic and organic components of PM2.5 resulted in a lag in megakaryocytes with an increase in cell volume and the onset of DNA ploidy. Flow cytometry analysis showed that CD33 (the marker of myeloid-specific) decreased and CD41a (a megakaryocyte maturation-associated antigen) increased in metallic and organic components of PM2.5 treatment groups. Moreover, compared to the control group, budding protrusions increased in metallic and organic components of PM2.5 treatment groups. The water-soluble components had no effect on the maturation and differentiation of macrophages. Conclusion: Metallic and organic components of PM2.5 are the crucial toxic components that promote the maturation and differentiation of megakaryocytes.

Efficient Qubit Measurement with a Nonreciprocal Microwave Amplifier.

The act of observing a quantum object fundamentally perturbs its state, resulting in a random walk toward an eigenstate of the measurement operator. Ideally, the measurement is responsible for all dephasing of the quantum state. In practice, imperfections in the measurement apparatus limit or corrupt the flow of information required for quantum feedback protocols, an effect quantified by the measurement efficiency. Here, we demonstrate the efficient measurement of a superconducting qubit using a nonreciprocal parametric amplifier to directly monitor the microwave field of a readout cavity. By mitigating the losses between the cavity and the amplifier, we achieve a measurement efficiency of (72±4)%. The directionality of the amplifier protects the readout cavity and qubit from excess backaction caused by amplified vacuum fluctuations. In addition to providing tools for further improving the fidelity of strong projective measurement, this work creates a test bed for the experimental study of ideal weak measurements, and it opens the way toward quantum feedback protocols based on weak measurement such as state stabilization or error correction.

Incidence and associated predictors of adverse pregnancy outcomes of maternal syphilis in China, 2016-19: a Cox regression analysis.

OBJECTIVE: This study aimed to investigate the incidence and associated predictors of adverse pregnancy outcomes (APOs) among pregnant women infected with syphilis. DESIGN: Cox regression analysis. SETTING: China. POPULATION OR SAMPLE: Pregnant women who were tested for and diagnosed with syphilis during the index pregnancy and delivered at a gestational age ≥28 weeks between 2016 and 2019. METHODS: Data were extracted from China's Information System of Prevention of Mother-to-Child Transmission of Syphilis Management. Descriptive analysis provided profiles and pregnancy outcomes of maternal syphilis, as well as the incidence of APOs. Log-rank tests and Cox proportional hazard models were used to investigate factors influencing APOs in infected mothers with singleton births. MAIN OUTCOME MEASURES: The incidence of APOs and the hazard ratios of associated predictors using Cox proportional hazard model. RESULTS: Syphilis treatment data were available from 83.86% of diagnosed women. Including deliveries from the total study population, 13.33% experienced APOs. Cox regression indicated that APOs were more likely in women tested and diagnosed in the late trimester, at delivery or postpartum. Women who accepted non-standardised treatment and who received standardised treatment had less risk of APOs. CONCLUSIONS: China has made huge progress over the last decades in the prevention of mother-to-child transmission of syphilis, but the incidence of APOs among pregnant women infected with syphilis remains high. It is essential to further strengthen access to early detection and standardised treatment of infected women to reduce the risk of APOs. TWEETABLE ABSTRACT: Access to early detection and standardised treatment reduces the risk of APOs due to maternal syphilis.

Endovascular treatment of visceral aneurysms and pseudoaneurysms.

Visceral artery aneurysm (VAA) is a rare and potentially life-threatening condition, defined as true artery aneurysms and pseudoaneurysms of splanchnic circulation and renal artery. This study reports our experience in the diagnosis and endovascular treatment of visceral artery aneurysms (VAAs) over a 10-year period. Between 2008 and 2018, a total of 24 VAAs in 21 patients were diagnosed by clinical symptoms and a combination of imaging techniques, such as Doppler ultrasound, computed tomography angiogram, and catheter angiogram. All patients underwent endovascular treatment to exclude aneurysms. Oral antiplatelet medicine was administered, and imaging examination was performed during follow-up. Technical success was achieved in all 21 patients, and no periprocedural complications occurred. Endovascular coiling alone was employed in 10 aneurysms. Coiling was combined with gelfoam in 2 aneurysms. Coiling was assisted by stent in 4 aneurysms. Covered stents were deployed in 8 aneurysms individually. Clinical symptoms disappeared or highly improved in all patients after treatment. None of the patients showed recurrent symptoms after discharge. However, two cases with new aneurysms after 6 and 8 months, respectively, and one case with in-stent thrombosis after 12 months were reported during follow-up. This study may justify the efficacy of percutaneous endovascular coil embolization and stent deployment. It also provides beneficial experience about how to choose appropriate various endovascular strategies based on both clinical symptoms and aneurysm anatomy condition.

Inverse association between bone mineral density and fibrinogen in menopausal women.

OBJECTIVE: Inflammatory diseases are risk factors for osteoporosis. We aimed to explore whether fibrinogen, which is linked to chronic inflammation, is associated with bone mineral density (BMD) in menopausal women. METHODS: In this cross-sectional study, we analyzed 339 menopausal women from Zhejiang Province between January 2016 and October 2019. Linear regression analysis was performed to assess the relationship between fibrinogen and BMD. RESULTS: Significant inverse association was observed between the serum fibrinogen level and BMD in menopausal women. The mean BMD in each quartile of fibrinogen level was 0.901, 0.897, 0.892, and 0.855 g/cm2, respectively (p = 0.027). After adjusting for age, body mass index, metabolic profiles, blood inflammatory factors, and serum levels of estradiol, calcium, phosphorus, and alkaline phosphatase, fibrinogen levels remained significantly associated with BMD (regression coefficients for quartiles 1-3 vs. quartile 4 were 0.046, 0.027, and 0.036, respectively; p for trend <0.05). CONCLUSIONS: Higher fibrinogen levels were associated with lower BMD in menopausal women, which was independent of age, body mass index, estradiol, and other factors. Therefore, serum fibrinogen can be used as a new predictor of reduced BMD in menopausal women.

A novel variant in PAX6 as the cause of aniridia in a Chinese family.

BACKGROUND: Aniridia is a kind of congenital human pan-ocular anomaly, which is related to PAX6 commonly. METHODS: The ophthalmic examinations including visual acuity, slit lamp and fundoscopy examination were performed in a Chinese aniridia pedigree. The targeted next-generation sequencing of aniridia genes was used to identify the causative mutation. RESULTS: A novel heterozygous PAX6 nonsense mutation c.619A > T (p.K207*) was identified in the Chinese autosomal dominant family with aniridia. Phenotype related to the novel mutation included nystagmus, keratopathy, absence of iris, cataract and foveal hypoplasia. CONCLUSIONS: The novel nonsense variation in PAX6 was the cause of aniridia in this family, which expanded the spectrum of the PAX6 mutation.