14-3-3ζ Suppresses RANKL Signaling by Destabilizing TRAF6.

Macrophages are essential regulators of inflammation and bone loss. RANKL, a pro-inflammatory cytokine, is responsible for macrophage differentiation to osteoclasts and bone loss. We recently showed that 14-3-3ζ-knockout (YwhazKO) rats exhibit increased bone loss in the inflammatory arthritis model. 14-3-3ζ is a cytosolic adaptor protein that actively participates in many signaling transductions. However, the role of 14-3-3ζ in RANKL signaling or bone remodeling is unknown. We investigated how 14-3-3ζ affects osteoclast activity by evaluating its role in RANKL signaling. We utilized 14-3-3ζ-deficient primary bone marrow-derived macrophages (BMDMs) obtained from wildtype (Wt) and YwhazKO animals, and RAW cells generated using CRISPR-Cas9. Our results showed that 14-3-3ζ-deficient macrophages, upon RANKL stimulation, have bigger and stronger TRAP-positive multinucleated cells and increased bone resorption activity. The presence of 14-3-3ζ suppressed RANKL-induced MAPK and AKT phosphorylation, transcription factors (NFATC1 and p65) nuclear translocation, and subsequently, gene induction (Rank, Acp5, and Ctsk). Mechanistically, 14-3-3ζ interacts with TRAF6, an essential component of the RANKL receptor complex. Upon RANKL stimulation, 14-3-3ζ-TRAF6 interaction was increased, while RANK-TRAF6 interaction was decreased. Importantly, 14-3-3ζ supported TRAF6 ubiquitination and degradation by the proteasomal pathway, thus dampening the downstream RANKL signaling. Together, we show that 14-3-3ζ regulates TRAF6 levels to suppress inflammatory RANKL signaling and osteoclast activity. To the best of our knowledge, this is the first report on 14-3-3ζ regulation of RANKL signaling and osteoclast activation.

Interpretable CT radiomics model for invasiveness prediction in patients with ground-glass nodules.

AIM: To evaluate the performance of an interpretable computed tomography (CT) radiomic model in predicting the invasiveness of ground-glass nodules (GGNs). MATERIALS AND METHODS: The study was conducted retrospectively from 1 August 2017 to 1 August 2022, at three different centres. Two hundred and thirty patients with GGNs were enrolled at centre I as a training cohort. Centres II (n=157) and III (n=156) formed two external validation cohorts. Radiomics features extracted based on CT were reduced by a coarse-fine feature screening strategy. A radiomic model was developed through the use of the LASSO (least absolute shrinkage and selection operator) and XGBoost algorithms. Then, a radiological model was established through multivariate logistic regression analysis. Finally, the interpretability of the model was explored using SHapley Additive exPlanations (SHAP). RESULTS: The radiomic XGBoost model outperformed the radiomic logistic model and radiological model in assessing the invasiveness of GGNs. The area under the curve (AUC) values for the radiomic XGBoost model were 0.885 (95% confidence interval [CI] 0.836-0.923), 0.853 (95% CI 0.790-0.906), and 0.838 (95% CI 0.773-0.902) in the training and the two external validation cohorts, respectively. The SHAP method allowed for both a quantitative and visual representation of how decisions were made using a given model for each individual patient. This can provide a deeper understanding of the decision-making mechanisms within the model and the factors that contribute to its prediction effectiveness. CONCLUSIONS: The present interpretable CT radiomics model has the potential to preoperatively evaluate the invasiveness of GGNs. Furthermore, it can provide personalised, image-based clinical-decision support.

Sodium-glucose cotransporter 2 inhibitors and cancer: a systematic review and meta-analysis.

BACKGROUND: The effect of sodium-glucose cotransporter 2 (SGLT2) inhibitors on cancer has yet to be fully elucidated. OBJECTIVE: This systematic review and meta-analysis investigated the effects of SGLT2 inhibitors on cancer. METHODS: We searched the PubMed and ClinicalTrials.gov databases up to July 15, 2023, to identify eligible randomized, double-blind, placebo-controlled trials that lasted at least ≥24 weeks. The primary outcome was the overall cancer incidence, and the secondary outcomes were the incidences of various types of cancer. We used the Mantel-Haenszel method, fixed effects model, risk ratio (RR) and 95% confidence interval (CI) to analyze dichotomous variables. Subgroup analysis was performed based on the SGLT2 inhibitor type, baseline conditions, and follow-up duration. All meta-analyses were performed using RevMan5.4.1 and Stata MP 16.0. RESULTS: A total of 58 publications (59 trials) were included, comprising 113,909 participants with type 2 diabetes mellitus and/or chronic kidney disease and/or high cardiovascular risk and/or heart failure (SGLT2 inhibitor group, 63864; placebo group, 50045). Compared to the placebo SGLT2 inhibitors did not significantly increase the overall incidence of cancer (RR 1.01; 95% CI 0.94-1.08; p = 0.82). However, ertugliflozin did significantly increase the overall incidence of cancer (RR 1.29; 95% CI 1.01-1.64; p = 0.04). SGLT2 inhibitors did not increase the risks of bladder or breast cancer. However, dapagliflozin did significantly reduce the risk of bladder cancer by 47% (RR 0.53; 95% CI 0.35-0.81; p = 0.003). SGLT2 inhibitors had no significant effect on the risks of gastrointestinal, thyroid, skin, respiratory, prostate, uterine/endometrial, hepatic and pancreatic cancers. Dapagliflozin reduced the risk of respiratory cancer by 26% (RR 0.74; 95% CI 0.55-1.00; p = 0.05). SGLT2 inhibitors (particularly mediated by dapagliflozin and ertugliflozin but not statistically significant) were associated with a greater risk of renal cancer than the placebo (RR 1.39; 95% CI 1.04-1.87; p = 0.03). CONCLUSION: SGLT2 inhibitors did not significantly increase the overall risk of cancer or the risks of bladder and breast cancers. However, the higher risk of renal cancer associated with SGLT2 inhibitors warrants concern.

[Mid-term analysis of prospective cohort study of rivaroxaban in preventing CRT in breast cancer].

Objective: To explore the efficacy and safety of Rivaroxaban in preventing catheter related thrombosis (CRT) in patients with breast cancer who are undergoing central venous catheter chemotherapy, and provide basis for making standardized prevention and treatment strategies. Methods: In this research, a prospective cohort study was adopted, and breast cancer patients who received central venous catheter chemotherapy in Sanhuan Cancer Hospital during September 2020 to March 2022 were selected as a treatment group to take the rivaroxaban anticoagulation therapy with 10 mg.po.qd for one month. The control group got no preventive anticoagulation therapy. Vascular ultrasound examination was taken to confirm the occurrence of CRT, and a chi-square test was done for comparison the disparity between the groups. Logistic regression was applied to analyze the univariate and multivariate factors for the formation of CRT. Results: In the research, a total of 235 patients were selected, and there were a total of 19 035 days of catheterization with 81 days of catheterization on average. While in the control group, the incidence of CRT was 28.0% (33/118), the incidence of CRT in the treatment group was 20.5% (24/117), the difference was no significant (P=0.183). Subgroup analysis results showed that the peripherally inserted central catheter (PICC) was performed in 165 cases with the CRT incidence of 18.2% (30/165) and thrombosis was mostly seen around axillary vein, accounting for 63.3%. Subclavian vein catheterization was performed in 63 cases with the CRT incidence of 39.7% (25/63), and thrombosis was mostly seen around subclavian vein, accounting for 88.0% (22/25). Implantable venous access port was implanted in 7 cases around subclavian vein and internal jugular vein with the CRT incidence of 28.6% (2/7). The patients who developed CRT within 30 days after catheterization accounted for 54.4% (31/57), 22.8% (13/57) in a period during 30 days and 60 days) and 22.8% (13/57) in a period during 60 days and 180 days). The diagnosed CRT patients had been treated with rivaroxaban 15 mg.bid.po for 3 months. During the 3 months, 100.0% of the thrombosis waned, 71.9% (41/57) of the thrombosis waned within 30 days, 19.3% (11/57) in a period during 30 and 60days and 8.8% (5/57) in a period during 60 days and 90 days. Univariate and multivariate analysis indicated that the risk of CRT in subclavian vein catheterization was higher than that in PICC, respectively (OR=2.898, 95% CI:1.386-6.056 P=0.005), and the type of catheterization was an independent factor for the formation of thrombosis. Safety analysis result showed that in the prevention of CRT, rivaroxaban treatment did not induce drug-related bleeding, liver function damage, bone marrow suppression or any other side effects. While CRT diagnosed patients were treated with anticoagulation, they kept the central venous catheter, and the infusion was smooth. These patients all finished the anti-tumor treatment as planned, and no abnormalities like new thrombosis or pulmonary embolism were observed. Conclusions: In the mid-term analysis, the proportion of Rivaroxaban in preventing anticoagulant CRT decreases, but it don't reach statistical significance. The sample size should be further increased for observation. Rivaroxaban is proved effective and very safe in the treatment of CRT, and does not affect the concurrent chemotherapy. Medical personnel should carry out the policy of "early prevention, early detection and early treatment" for CRT so as to improve the patients' quality of life.

[The 504th case: Multiple lymph node enlargement, renal insufficiency, blindness, and white matter lesions of the brain].

A 65-year-old male patient was admitted for recurrent lymph node enlargement for 5 years and elevated creatinine for 6 months. This patient was diagnosed with angioimmunoblastic T-cell lymphoma 5 years ago and underwent multiple lines of anti-tumor therapy, including cytotoxic chemotherapy; epigenetic modifying drugs such as chidamide and azacitidine; the immunomodulator lenalidomide; and targeted therapy such as rituximab, a CD20-targeting antibody, and brentuximab vedotin, which targets CD30. Although the tumor was considered stable, multiple virus activation (including BK virus, JC virus, and cytomegalovirus) accompanied by the corresponding organ damage (polyomavirus nephropathy, cytomegalovirus retinitis, and progressive multifocal leukoencephalopathy) occurred during anti-tumor treatment. Anti-tumor therapy was suspended and ganciclovir was used. The serum viral load decreased and organ functions were stabilized. The purpose of this report was to raise clinicians' awareness of opportunistic virus reactivation during anti-tumor treatment.

[Efficacy and safety of first-line treatment with anti-CD38 monoclonal antibody-based regimen for primary plasma cell leukemia].

Objective: To analyze the efficacy and safety of first-line treatment with an anti-CD38 monoclonal antibody regimen for primary plasma cell leukemia (pPCL). Methods: Patients diagnosed with pPCL from December 1st, 2018 to July 26th, 2023, receiving first-line treatment of anti-CD38 monoclonal antibody-based regimens across multiple centers including Peking University People's Hospital, Fuxing Hospital of Capital Medical University, Qingdao Municipal Hospital, Shengjing Hospital of China Medical University, Handan Central Hospital, the First Affiliated Hospital of Harbin Medical University, the Fourth Hospital of Hebei Medical University and General Hospital of Ningxia Medical University were consecutively included. A total of 24 pPCL patients were included with thirteen being male and eleven being female. The median age [M(Q1, Q3)] was 60 (57, 70) years. Patients were grouped according to peripheral blood plasma cell (PBPC) percentage [5%-19% (n=14) vs ≥20% (n=10)]. Last follow-up date was September 26th, 2023. The median follow-up period was 9.1 (4.2, 15.5) months. Patients' data related with clinical baseline characteristics, efficacy, survival and safety were retrospectively collected. Cox proportional hazards regression model was used to analyze risk factors associated with survival. Results: Among 24 pPCL patients, 16 (66.7%) patients had anemia at diagnosis, 13(54.2%) patients had thrombocytopenia, 8 (33.3%) patients had a baseline estimated glomerular filtration rate (eGFR)<40 ml·min-1·(1.73m2)-1, 13 (54.2%) patients had elevated lactate dehydrogenase (LDH) levels. The median PBPC percentage was 16% (8%, 26%) . Fluorescence in situ hybridization testing indicated that patients harboring 17p deletion, t(4;14) or t(14;16) were 6 (25.0%), 4 (16.7%) and 4 (16.7%), respectively. The overall response rate was 83.3% (20/24). The median progression-free survival (PFS) was 20.5 (95%CI: 15.8-25.2) months, and the median overall survival (OS) was not reached. Estimated 1-year and 2-year PFS and OS rates were 75.0% and 89.1%, 37.5% and 53.4%, respectively. The median PFS and OS for patients with PBPC percentages 5%-19% and≥20% were not reached and 20.5 (95%CI:15.7-25.3) months, 17.8 months and not reached, respectively. There was no significant statistical difference of PFS and OS between two groups (all P>0.05). Multivariate Cox regression analysis showed that 1p32 deletion was the risk factor associated with PFS (HR=7.7, 95%CI: 1.1-54.9, P=0.043). Seventeen patients (70.8%) developed grade 3-4 hematologic toxicities. Twelve patients (50.0%) developed grade 3-4 thrombocytopenia. Sixteen patients (66.7%) developed infection. All hematologic toxicities and infections were improved after supportive treatment. Conclusion: First-line treatment with anti-CD38 monoclonal antibody-based therapy for pPCL is effective and safe.

[Successful treatment of high-risk pulmonary embolism with low-dose anticoagulation: a case report].

Reperfusion is considered as the cornerstone of the treatment of high-risk pulmonary embolism (PE). However, when thrombolysis is contraindicated and surgery or interventional therapy is not available, the treatment of high-risk PE becomes very difficult. To our knowledge, there are no reports of successful treatment of high-risk PE with low-dose anticoagulation. On November 30, 2021, a 56-year-old male patient with subarachnoid hemorrhage was admitted to the emergency department of the First Affiliated Hospital of Chongqing Medical University. On the second day of admission, the patient suddenly went into shock during aneurysm clipping. After implementing D-dimer, markers of myocardial injury, echocardiography and computed tomography pulmonary angiography, a high-risk PE was diagnosed. Due to the contraindication of thrombolysis and the refusal of endovascular treatment, he was eventually cured with low-dose anticoagulation combined with vasopressors.

Theoretical insights into the defect performance of the wide bandgap semiconductor BaS.

Wide bandgap semiconductors materials (WBGSMs) are of great interest for their applications in transparent electronics and power electronics. Recent studies have shown that BaS is a potential transparent conducting material but the knowledge of it is deficient. Herein, we systemically investigate its electronic structure and evaluate the effects of its intrinsic defects and extrinsic dopants by utilizing the hybrid density functional method. The obtained results show that BaS is an indirect bandgap semiconductor with a bandgap of 3.88 eV. Its electron-effective mass is very small (0.33 m0). We find that the intrinsic n-type conductivity of BaS is connected with the shallow donor defect sulfur vacancy (VS). Regarding extrinsic dopants (group IA atoms), we find that Li and Na are favorable n-type dopants, while K and Rb are p-type dopants. Among these impurities, the Li interstitial (Liint) configuration possesses the lowest formation energy of 0.114 eV. Based on thermodynamic simulations, we find that the electron density can reach 2.39 × 1020 cm-3 in Li-doped BaS at room temperature, which is comparable to those of typical WBGSMs In2O3, BaSnO3, and ß-Ga2O3. We expect BaS could replace typical WBGSMs in some applications. Moreover, its component elements Ba and S are non-toxic, cheap, and earth-abundant, making it a very competitive candidate for WBGSMs. Based on these results, we deem BaS a promising candidate for optoelectronic applications.

[Effect of early rehabilitation training on motor function and neural function of patients with brainstem hemorrhage after body-oriented individualized surgery].

Objective: To explore the effect of early rehabilitation training on motor function and neural function of patients with brainstem hemorrhage after stereotactic individualized operation. Methods: A total of 84 patients with brainstem hemorrhage after stereotactic individualized surgery admitted to Nanyang Central Hospital from January 2020 to January 2022 were selected as the study subjects.The patients were randomly divided into observation group (n=42) and control group (n=42) according to random number table method. The control group received conventional Western medicine treatment, and the observation group received early rehabilitation training on the basis of drug treatment in the control group. The motor function assessment [Fugl Meyer Assessment (FMA) scores], neural function [National Institutes of Health Stroke Scale (NIHSS) scores], ability of daily living [Barthel index (BI) scores], cerebral blood flow [mean blood flow (MBF), mean flow velocity (MFV), peripheral vascular resistance (PVR)] and nerve factor [serum neuron specific enolase (NSE), brain derived neurotrophic factor (BDNF), central nervous specific protein(S100ß)] levels were compared between the two groups before and after the treatment. In addition, the rehabilitation effect and complications of the two groups were observed. Results: The total effective rate (95.24%) in the observation group was higher than that in the control group (76.19%%) (P<0.05). After the treatment, the FMA scores, BI scores, MBF, MFV and BDNF levels of the two groups were higher than those before the treatment, and the observation group were higher than the control group (P<0.05). NIHSS scores, PVR, NSE and S100ß levels in the two groups after the treatment were lower than those before the treatment, and those in the observation group were lower than those in the control group (P<0.05). The incidence of complications in the observation group [7.14% (3/42)]was lower than that in the control group [23.81% (10/42), P<0.05]. Conclusion: For patients with brain stem hemorrhage after stereotactic individualized surgery, early rehabilitation training can improve the motor, neural function and daily living ability, rehabilitation effect, regulate cerebral hemodynamics and nerve factor levels, and reduce the incidence of complications.

[Research progress on influencing factors of early adiposity rebound in children and the effect on adolescent development in girls].

With the increasing rate of overweight and obesity in children worldwide, adiposity rebound(AR)closely related to obesity has become the spotlight, and early AR phase has a broad impact on pubertal development in girls, but the specific mechanism of action isn't very clear.This paper is review of the prevalence of early AR at home and abroad, and its influencing factors, the impact of AR on the adolescent development of girls and related mechanisms, to identify high-risk individuals with early AR, early AR to identify early adolescent development, and take early intervention measures to promote children's health.

[Distribution and reference intervals of daytime intraocular pressure in the eye health screening population of Handan].

Objective: To describe the distribution and establish reference intervals (RI) of daytime intraocular pressure (IOP) in the eye health screening population of Handan. Methods: This cross-sectional study included subjects who participated in eye health screening at the Physical Examination Center of Handan First Hospital from May 2021 to June 2022. A complete general and ocular examination was performed, including measurements of visual acuity and IOP (using Goldmann tonometry), slit lamp microscopy, fundus photography, and anterior and posterior segment optical coherence tomography. Subjects with factors that could cause significant changes in IOP or affect the accuracy of IOP measurement, or with an inability to measure IOP were excluded. Simple random sampling was used to select participants, who were grouped by gender and age (18 to <30, 30 to <40, 40 to <50, 50 to <60, 60 to <70, and ≥70 years). Central corneal thickness and IOP at 8 to 11 o'clock in one eye of each participant were recorded. The independent sample t test and ANOVA were used for statistical analysis, and the RI of IOP values was calculated by x¯±1.96s. Results: A total of 9 310 subjects had their IOP measured, and 3 491 participants (3 491 eyes) were randomly selected from 7 886 healthy subjects. The age of the participants was (47.74±14.47) years old, ranging from 18 to 90 years old. There were 1 694 males and 1 797 females. The central corneal thickness of all participants was (525.56±49.39) µm. The daytime IOP of all participants was (15.40±2.54) mmHg (1 mmHg=0.133 kPa), and the RI was 10.42 to 20.39 mmHg. The IOP was (15.49±2.58) mmHg for males and (15.29±2.49) mmHg for females, and the gender difference was statistically significant (P<0.05). The RI of daytime IOP values was 10.43 to 20.54 mmHg for males and 10.41 to 20.18 mmHg for females. There were significant differences in daytime IOP [(15.13±2.58), (15.33±2.53), (15.49±2.50), (15.53±2.55), (15.39±2.62), and (15.28±2.52) mmHg] among 6 age groups (P<0.05). Conclusions: The distribution of daytime IOP in different gender and age groups in the eye health screening population of Handan and the RIs derived from the distribution were roughly the same as the international normal IOP RI (10 to 21 mmHg). It is recommended to refer to the RI of daytime IOP values of different genders and ages for clinical decision.

Transferability of Liver Transplantation Experience to Complex Liver Resection for Locally Advanced Hepatobiliary Malignancy-Lessons Learnt From 3 Decades of Single Center Experience.

OBJECTIVE: To study the impact of LT experience on the outcome of CLR for locally advanced hepatobiliary malignancy. SUMMARY OF BACKGROUND DATA: Despite evolution in LT knowledge and surgical techniques in the past decades, there is yet data to evaluate the significance of LT experience in performing CLR. METHODS: Postoperative outcome after CLR between 1995 and 2019 were reviewed and correlated with LT experience in a single center with both LT and CLR service. CLR was defined as hepatectomy with vasculobiliary reconstruction, or multivisceral resection, central bisectionectomy (S4/5/8), or associating liver partition and portal vein ligation for staged hepatectomy. Spearman rank correlation and receiver operating characteristic analysis were used to define the association between CLR-related outcomes and LT experience. RESULTS: With cumulative single-center experience of 1452 LT, 222 CLR were performed during the study period [hepatectomy with biliary (27.0%), or vascular (21.2%) reconstruction, with multivisceral resections (9.9%), with associating liver partition and portal vein ligation for staged hepatectomy (18.5%)] mainly for hepatocellular carcinoma (53.2%), and hilar cholangiocarcinoma (14%). Median tumor size was 7.0 cm. Other features include macrovascular invasion (23.4%), and juxta-visceral invasion (14%). Major postoperative complication rate was 25.2% and mortality rate was 6.3%. CLR-complication rate was inversely associated with LT experience (R = -0.88, P < 0.005). Receiver operator characteristic analysis revealed the cutoff for LT experience to have the greatest influence on CLR was 95 with a sensitivity of 100% and Youden index of 1. Multivariable analysis showed that blood transfusion, prolonged operating time, LT experience < /=95 were associated with major postoperative complications. CONCLUSION: LT experience was complimentary to CLR for locally advanced hepatobiliary malignancy with improved postoperative outcome.

Development and validation of an individualized nomogram for predicting the high-volume (> 5) central lymph node metastasis in papillary thyroid microcarcinoma.

PURPOSE: Papillary thyroid microcarcinoma (PTMC) frequently presents a favorable clinical outcome, while aggressive invasiveness can also be found in some of this population. Identifying the risk clinical factors of high-volume (> 5) central lymph node metastasis (CLNM) in PTMC patients could help oncologists make a better-individualized clinical decision. METHODS: We retrospectively reviewed the clinical characteristics of adult patients with PTC in the Surveillance, Epidemiology, and End Results (SEER) database between Jan 2010 and Dec 2015 and in one medical center affiliated to Chongqing Medical University between Jan 2018 and Oct 2020. Univariate and multivariate logistic regression analyses were used to determine the risk factors for high volume of CLNM in PTMC patients. RESULTS: The male gender (OR = 2.02, 95% CI 1.46-2.81), larger tumor size (> 5 mm, OR = 1.64, 95% CI 1.13-2.38), multifocality (OR = 1.87, 95% CI 1.40-2.51), and extrathyroidal invasion (OR = 3.67; 95% CI 2.64-5.10) were independent risk factors in promoting high-volume of CLNM in PTMC patients. By contrast, elderly age (≥ 55 years) at diagnosis (OR = 0.57, 95% CI 0.40-0.81) and PTMC-follicular variate (OR = 0.60, 95% CI 0.42-0.87) were determined as the protective factors. Based on these indicators, a nomogram was further constructed with a good concordance index (C-index) of 0.702, supported by an external validating cohort with a promising C-index of 0.811. CONCLUSION: A nomogram was successfully established and validated with six clinical indicators. This model could help surgeons to make a better-individualized clinical decision on the management of PTMC patients, especially in terms of whether prophylactic central lymph node dissection and postoperative radiotherapy should be warranted.

A prospective study on vulvovaginal candidiasis: multicentre molecular epidemiology of pathogenic yeasts in China.

BACKGROUND: Vulvovaginal candidiasis (VVC) is frequent in women of reproductive age, but very limited data are available on the epidemiology in cases of VVC in China. OBJECTIVES: The current study has been conducted to reveal the prevalence, species distribution of yeast causing VVC and molecular genetics of Candida albicans in China. METHODS: Vaginal swabs were collected from 543 VVC outpatients recruited in 12 hospitals in China between September 2017 and March 2018. They were preliminarily incubated on Sabouraud dextrose agar and then positive subjects of which were then transmitted to our institute for further identification. CHROMagar™ was used to isolate Candida species, and all isolates were finally identified by DNA sequencing. Multilocus sequence typing (MLST) was used to analyse phylogenetic relationships of the various C. albicans isolates. RESULTS: Eleven different yeast species were identified in 543 isolates, among which C. albicans (84.7%) was the most frequent, followed by C. glabrata (8.7%). We obtained 117 unique diploid sequence types from 451 clinical C. albicans isolates and 92 isolates (20.4%) belonged to a New Clade. All the strains appearing in the New Clade were from northern China and they were isolated from non-recurrent VVC. CONCLUSIONS: Our findings suggest that C. albicans are still the main cause of VVC in China and the majority of C. albicans isolates belongs to Clade 1 with DST 79 and DST 45 being two most common. Moreover, the New Clade revealed in our study seems to be specific to northern China.

miR-30a-3p can inhibit the proliferation and promote the differentiation of chicken primary myoblasts.

1. Chicken muscle is an important factor in meat quality and its development is controlled by a complex regulatory network.2. The following study examined the expression of miR-30a-3p in Gushi chicken breast muscle tissue and found that it was differentially expressed at different embryonic stages, reaching a peak in the 14-day-old embryo (E14).3. The effect of miR-30a-3p on chicken primary myoblasts (CPMs) was explored. Results from both cell counting kit-8 (CCK-8) and 5-ethynyl-2'-deoxyuridine (EdU) showed that this can inhibit the proliferation of myoblasts, and through cell cycle experiments, the inhibition of myoblast proliferation was found, which may be due to G0/G1 arrest in the cell cycle.4. The effect of miR-30a-3p on the differentiation of myoblasts was studied. The results showed that miR-30a-3p can promote the expression of MYOD, myogenin (MYOG), and myosin heavy chain (MYHC) genes to promote the differentiation of myoblasts. Through MYHC protein immunofluorescence experiments, it was found that miR-30a-3p can effectively increase the area of myotubes.5. Finally, mRNA transcriptome data was analysed, which showed that miR-30a-3p has 51 potential target genes. Among them, forkhead box O3 (FOXO3), ankyrin repeat domain 1 (ANKRD1), and insulin-induced 1 (INSIG1) genes were differentially expressed at different developmental stages and were enriched in Gene Ontology (GO) terms, such as cell differentiation and cellular developmental process. The data showed that tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein gamma (YWHAG), BUB1 mitotic checkpoint serine/threonine kinase (BUB1), and growth arrest and DNA damage-inducible 45 (GADD45) genes were enriched in the cell cycle pathway.6. It can be speculated that miR-30a-3p plays roles through these genes in myoblast development. This research provides information for further improving knowledge of the chicken muscle development regulation network.

miR-181a-5p can inhibit the proliferation and promote the differentiation of chicken primary myoblasts.

1. Myoblast proliferation and differentiation is one of the most important biological processes in the development of skeletal muscle. MicroRNAs (miRNAs) play a crucial role in this process.2. In this study, the expression level of miR-181a-5p was detected, which found that miR-181a-5p was expressed differently in different tissues, different embryonic ages, and different differentiation stages of primary myoblasts in Gushi chickens.3. The effect of miR-181a-5p was further investigated on chicken primary myoblasts (CPMs). The results of cell counting kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU) and cell cycle showed that miR-181a-5p could inhibit the proliferation of CPM. The miR-181a-5p promoted the expression of MYOD, MYOG, and MYHC. MYHC protein immunofluorescence experiments showed that miR-181a-5p increased the area of myotubes.4. In total, 63 potential target genes of miR-181a-5p in mRNA transcriptome data analysis were identified. Functional enrichment analysis was performed on these target genes, and ASNS, SMYD1, and FOS were found to play regulatory roles in biological processes such as muscle development. It was speculated that miR-181a-5p played a role in myoblast development through these genes.5. In conclusion, miR-181a-5p can inhibit the proliferation of chicken myoblasts and promote the differentiation of chicken myoblasts. This study laid the foundation for further research on the regulatory mechanism of miR-181a-5p in the development of skeletal muscle and the formation of excellent meat quality traits in Gushi chicken.

[Risk factors of residual tumor in single small hepatocellular carcinoma after thermal ablation treatment].

Objective: To evaluate the risk factors of residual tumor after thermal ablation in patients with small hepatocellular carcinoma. Methods: This was a retrospective study recruiting 107 patients diagnosed as single hepatocellular carcinoma with maximum diameter ≤3 cm from December 2009 to August 2015 in National Cancer Center. The cohort enrolled 81 males and 26 females, including 83 patients younger than 70 years old. All patients were treated with radiofrequency ablation or microwave ablation, and evaluated by CT or MRI after 4-6 weeks compared with baseline data. Potentially related factors were analyzed such as patients' characteristics, tumor location and adjacent, ablation pattern, hepatitis B/C infection. A multivariate logistic regression analysis was conducted for the independence of risk factors. Results: Six patients (5.6%) with residual tumor was detected in the whole population of 101 cases. Univariate analysis suggested that tumor adjacent to vascular structure, poor differentiation, AFP≥200 µg/L were the risk factors of residue disease (all P<0.05). Multivariate logistic regression suggested that pathological type of poorly differentiated tumor was the only independent risk factor (HR=2.26,95%CI 0.25-20.50, P=0.030). Conclusions: Poorly differentiated pathology is an independent predictive factor for residual disease in small hepatocellular carcinoma after thermal ablation. Such patients should be routinely followed up after operation.

[Clinical characteristics and prognosis of patients with anti-glutamic acid decarboxylase antibody-related cerebellar ataxia].

The clinical data, diagnosis, treatment, and prognosis of 10 patients with anti-glutamic acid decarboxylase (GAD) antibody-related cerebellar ataxia in Department of Neurology, Peking Union Medical College Hospital, from May 2015 to November 2021 were retrospectively analyzed. There were 8 female patients with a median age of 55 years old. Patients mainly presented with gait ataxia (10/10), dizziness (8/10), diplopia (6/10), and dysarthria (5/10). Four of them were complicated with other autoimmune disease, including vitiligo (3/4), Hashimoto thyroiditis (1/4), thrombocytopenia (1/4), and small cell lung cancer (1/4). All patients received immunotherapy, 6 out of 10 exhibited a good response, and half of them had satisfied functional prognosis. Patients of anti-GAD antibody-related cerebellar ataxia may be complicated with other autoimmune diseases, but underlying tumor is rare. More than half of patients have a good response to immunotherapy and satisfied prognosis.

[Association of thrombocytopenia with mortality after surgery in patients with Standford type A aortic dissection].

Objective: To evaluate the association of thromboytopenia with mortality of Standford type A aortic dissection after cardiopulmonary bypass surgery. Methods: Total of 498 patients with Standford type A aortic dissection after surgery in Fuwai Hospital of the Chinese Academy of Medical Sciences from May 2017 to December 2018 were collected retrospectively. There were 350 males and 148 females, with a mean age of (51.7±12.0) years. The patients were divided into thrombocytopenia group (platelet count<75×1015/L, n=178) and normal platelet group (platelet count≥75×1015/L, n=320) according to the lowest platelet count within 72 hours after surgery. The perioperative in-hospital mortality and related complications were calculated by univariate and multivariate logistic regression analysis. The primary endpoint was in-hospital mortality, and the secondary endpoints included secondary thoracotomy, pneumonia, postoperative continuous renal replacement therapy, paraplegia, heart failure, length of hospital stay and intensive care unit (ICU) stay time. Results: The morbidity of thrombocytopenia after Standford type A aortic dissection surgery was 35.7% (178/498). Univariate logistic regression analysis showed that postoperative thrombocytopenia was significantly associated with in-hospital mortality and 7 secondary endpoints (P<0.05). Multivariate logistic regression analysis showed thrombocytopenia after aortic dissection surgery was significantly associated with increased postoperative mortality (OR=12.57, 95%CI: 2.26-69.93, P=0.004), secondary thoracotomy (OR=6.21, 95%CI: 1.31-29.46, P=0.022), continuous renal replacement therapy (OR=7.51, 95%CI: 2.53-22.34, P<0.001), paraplegia (OR=23.99, 95%CI: 1.47-392.21, P=0.026), heart failure (OR=4.71, 95%CI: 1.19-18.62, P=0.027) and longer ICU stay time (OR=1.86, 95%CI: 1.11-3.12, P=0.019). Conclusions: Thrombocytopenia after Standford type A aortic dissection after cardiopulmonary bypass surgery (the lowest platelet count within 72 hours) is strongly associated with postoperative in-hospital mortality. Trying to avoid the factors related to thrombocytopenia can prevent more complications at the same time.

[Preclinical evaluation of a veno-venous bypass device for liver transplantation based on the principle of magnetic levitation drive].

Objective: To explore the performance of a self-made venous-venous bypass (VVB) device for liver transplantation based on the principle of magnetic levitation drive. Methods: Experimental study was conducted from August 2020 to January 2022. Eight Bama minipigs underwent VVB of hepatic portal vein-femoral vein-internal jugular vein after occlusion of hepatic portal vein and inferior vena cava. The animals were divided into two groups according to the VVB devices used during VVB. A self-made VVB device was used in group A(n=5),and an imported VVB device was used in group B(n=3). The hemodynamic changes of the two groups of animals were compared at 6 time points including before vascular occlusion, during vascular occlusion, 30 minutes, 60 minutes, 90 minutes after the start of VVB, and 30 minutes after vascular opening. In addition,the changes of blood compatibility indexes,intestinal injury indexes,kidney injury indexes and internal environment indexes of the two groups of animals at each time point were compared. The independent samples t test was used for the quantitative data between the two groups with non-repeated measures,and the repeated measures analysis of variance was used for the quantitative data between the two groups with repeated measures. Results: During the VVB of the two devices,the venous drainage was sufficient,and the main manifestations were that the color of the intestine of the Bama miniature pig was ruddy, the peristalsis was normal, and the urine output was normal. There were no significant differences in hemodynamics,blood injure indexes,intestinal injury indexes,kidney injury indexes,neutropil gelatinase-associated lipocalin,and internal environment indexes(all P>0.05).The indexes at 30 minutes after vascular opening in the group A and the group B were as follows:mean arterial pressure were (71.0±7.7)mmHg(1 mmHg=0.133 kPa) and (74.0±8.7)mmHg,central venous pressure were (7.0±1.4)cmH2O(1 cmH2O=0.098 kPa) and (7.7±0.6)cmH2O,heart rate were (131±10) beats/minutes and (132±8)beats/minutes; red blood cell count were (6.43±0.89)×1012/L and (6.32±0.58)×1012/L,hemoglobin were (108.4±5.9)g/L and (110.0±3.5)g/L,free hemoglobin were (78.28±3.96)mg/L and (78.08±4.54)mg/L; intestinal fatty acid binding protein were (2.27±0.49)µg/L and (2.40±0.78)µg/L;creatinine were (68.30±9.77)µmol/L and (79.90±26.91)µmol/L,blood urea nitrogen were (3.94±1.39)mmol/L and (3.45±0.65)mmol/L;neutropil gelatinase-associated lipocalin were (4.02±0.53) µg/L and (3.86±0.23)µg/L;pH value were 7.27±0.04 and 7.23±0.03,lactic acid were (6.18±2.62)mmol/L and (4.30±0.50)mmol/L,concentrations of Na+ were (136.3±3.0)mmol/L and (137.6±1.6) mmol/L,concentrations of K+ were (3.89±0.42) mmol/L and (3.98±0.17)mmol/L,concentrations of Ca2+ were (1.40±0.03)mmol/L and(1.40±0.04)mmol/L;all indexes in the two group had no differences(all P>0.05). Conclusion: The self-made venous bypass device can be safely and effectively applied to VVB of Bama minipigs,and achieves the same performance as the imported venous bypass device.