Effects of weight loss on QTc in people with obesity: a systematic review and meta-analysis.

BACKGROUND AND AIMS: Overweight and obesity have been found to exhibit a statistically significant increase in corrected QT interval (QTc), a major contributing factor to sudden death. However, the influence of widely used weight loss strategies including diet, exercise, anti-obesity drugs, and bariatric surgery on QTc remains inconsistent. Therefore, the present systematic review and meta-analysis aim to quantitatively analyse and evaluate the effect of weight loss on QTc in obese patients after diet control with exercise intervention and anti-obesity drugs, as well as bariatric surgery. METHODS: Twenty randomised controlled trials (RCT) and observational studies were included in the meta-analysis on the effects of weight loss on QTc. The fixed-effects model was employed in the RCTs, and the random-effects model was employed due to the presence of statistical heterogeneity among observational studies. Subgroup analysis was conducted to understand the differences in distinct weight loss methods and follow-up time. RESULTS: Overall, the QTc of people with obesity after weight loss was shorter than that before (mean difference (MD) = 21.97 ms, 95% confidence interval (CI) = 12.42, 31.52, p < .0001). Subgroup analysis restricted to seven included studies whose intervention was diet control with exercise showed a decrease of QTc with statistical significance (MD = 9.35 ms, 95%CI = 2.56, 37.54, p = .007). In the remaining 11 studies, bariatric surgery was the weight loss method. The results also showed a shortening of QTc after surgery, and the difference was statistically significant (MD = 29.04 ms, 95%CI = -16.46, 41.62, p < .00001). A statistically significant difference in QTc shortening at 6 months compared to pre-operation values was further observed (MD = -31.01 ms, 95%CI = -2.89, -59.12, p = .03). The shortening of QTc at 12 months of follow-up was also significantly different from that before surgery (MD = 36.47 ms, 95%CI = 14.17, 58.78, p < .00001). Moreover, the differences became more pronounced as the follow-up time extended. CONCLUSIONS: We demonstrate that weight loss links to a shortened QTc, without considering the means of weight loss. Bariatric surgery has been found to result in a greater reduction in QTc.

Tumor-derived extracellular vesicles as a biomarker for breast cancer diagnosis and metastasis monitoring.

It is imperative to explore biomarkers that are both precise and readily accessible in the comprehensive management of breast cancer. A multicenter cohort, including 512 breast cancer patients and 198 nonneoplastic individuals, was recruited to detect the level of tumor-derived extracellular vesicles using our method based on dual DNA tetrahedral nanostructures. The level of tumor-derived extracellular vesicles was significantly higher in newly diagnosed breast cancer patients than in nonneoplastic individuals at a cutoff value of 3.58 U/µL. For postoperative metastasis monitoring, the level of tumor-derived extracellular vesicles was significantly higher in breast cancer patients with metastasis than in those without metastasis at a cutoff value of 3.91 U/µL. Its efficacy of diagnosis and metastasis monitoring was superior to traditional tumor markers. Elevated level of tumor-derived extracellular vesicles served as a predictive biomarker for diagnosis and metastasis monitoring in breast cancer patients.

Exploring the mechanism of dendrobine in treating metabolic associated fatty liver disease based on network pharmacology and experimental validation.

BACKGROUND: This study investigates the therapeutic mechanisms of dendrobine, a primary bioactive compound in Dendrobium nobile, for Metabolic Associated Fatty Liver Disease (MASLD) management. Utilizing network pharmacology combined with experimental validation, the clinical effectiveness of dendrobine in MASLD treatment was assessed and analyzed. RESULTS: The study demonstrates significant improvement in liver function among MASLD patients treated with Dendrobium nobile. Network pharmacology identified key targets such as Peroxisome Proliferator-Activated Receptor Gamma (PPARG), Interleukin 6 (IL6), Tumor Necrosis Factor (TNF), Interleukin 1 Beta (IL1B), and AKT Serine/Threonine Kinase 1 (AKT1), with molecular docking confirming their interactions. Additionally, dendrobine significantly reduced ALT and AST levels in palmitic acid-treated HepG2 cells, indicating hepatoprotective properties and amelioration of oxidative stress through decreased Malondialdehyde (MDA) levels and increased Superoxide Dismutase (SOD) levels. CONCLUSION: Dendrobine mitigates liver damage in MASLD through modulating inflammatory and immune responses and affecting lipid metabolism, potentially by downregulating inflammatory mediators like TNF, IL6, IL1B, and inhibiting AKT1 and Signal Transducer and Activator of Transcription 3 (STAT3). This study provides a theoretical basis for the application of dendrobine in MASLD treatment, highlighting its potential as a therapeutic agent.

Consequences of exposure to famine exposure on the later life eGFR decline among survivors of the Great Chinese Famine: a retrospective study.

BACKGROUND AND OBJECTIVES: Chronic kidney disease (CKD) significantly contributes to the socio-economic burden both in China and worldwide. Previous research has shown that experiencing childhood famine is linked to various chronic conditions like diabetes, hypertension, and proteinuria. However, the long-term effects of early life famine exposure on adult kidney function remain unclear. This study investigates whether exposure to the Chinese Great Famine (1959-1962) is associated with a decline in glomerular filtration rate (GFR) later in life. MATERIALS AND METHODS: CHARLS is a population-based observational study. We analyzed data from 8,828 participants in the 2011-2012 baseline survey, updated in 2014. Participants were categorized based on their birth year into fetal-exposed (1959-1962), childhood-exposed (1949-1958), adolescence/adult-exposed (1912-1948), and non-exposed (1963-1989) groups. The estimated GFR (eGFR) was calculated using the CKD-EPI-Cr-Cys equation (2021), with CKD defined as an eGFR below 60 mL/min/1.73 m2. RESULTS: Average eGFR values were 103.0, 96.8, 91.2, and 76.3 mL/min/1.73 m2 for the fetal-exposed, childhood-exposed, adolescence/adult-exposed, and non-exposed groups, respectively. The eGFR in the exposed groups was significantly lower compared to the non-exposed group. Specifically, famine exposure correlated with a lower eGFR (CE -9.14, 95%CI -9.46, -8.82), with the strongest association observed in the adolescence/adult-exposed group (CE -26.74, 95%CI -27.75, -25.74). Adjusting for variables such as demographics, physical and laboratory tests, complications, and personal habits like smoking and drinking did not qualitatively alter this association (CE -1.38, 95%CI -1.72, -1.04). Further stratification by sex, body mass index (BMI), alcohol consumption history, hypertension, diabetes, CESD score, and education level showed that the association remained consistent. CONCLUSIONS: Exposure to famine during different life stages can have enduring effects on GFR decline in humans.

Facet-Dependent Surface Restructuring on Nickel (Oxy)hydroxides: A Self-Activation Process for Enhanced Oxygen Evolution Reaction.

Unraveling the catalyst surface structure and behavior during reactions is essential for both mechanistic understanding and performance optimization. Here we report a phenomenon of facet-dependent surface restructuring intrinsic to ß-Ni(OH)2 catalysts during oxygen evolution reaction (OER), discovered by the correlative ex situ and operando characterization. The ex situ study after OER reveals ß-Ni(OH)2 restructuring at the edge facets to form nanoporous Ni1-xO, which is Ni deficient containing Ni3+ species. Operando liquid transmission electron microscopy (TEM) and Raman spectroscopy further identify the active role of the intermediate ß-NiOOH phase in both the OER catalysis and Ni1-xO formation, pinpointing the complete surface restructuring pathway. Such surface restructuring is shown to effectively increase the exposed active sites, accelerate Ni oxidation kinetics, and optimize *OH intermediate bonding energy toward fast OER kinetics, which leads to an extraordinary activity enhancement of ∼16-fold. Facilitated by such a self-activation process, the specially prepared ß-Ni(OH)2 with larger edge facets exhibits a 470-fold current enhancement than that of the benchmark IrO2, demonstrating a promising way to optimize metal-(oxy)hydroxide-based catalysts.

Serum alpha 1 antitrypsin potent act as an early diagnostic biomarker for cardiac amyloidosis.

Cardiac amyloidosis is a refractory cardiomyopathy with a poor prognosis and lacks effective treatments. N-terminal pro-brain natriuretic peptide (NT-proBNP) and troponin T are poor prognostic factors for myocardial amyloidosis. However, NT-proBNP and troponin also serve as markers of heart failure and myocardial infarction, lacking specificity. Whether abnormal elevation of alpha-1 antitrypsin in myocardial amyloidosis also predicts the poor prognosis of patients remains unknown. We conducted a retrospective single-center case-control study to analyze the serological and physical examination data of 83 cardiac amyloidosis patients and 68 healthy controls matched by gender and age. We aimed to explore the onset and prognostic factors of cardiac amyloidosis. The serum alpha-1 antitrypsin level (169.78 ± 39.59 mg/dl) in patients with cardiac amyloidosis was significantly higher than that in the normal control (125.92 ± 18.26 mg/dl). Logistic regression results showed that alpha-1 antitrypsin, free sialic acid, high-density lipoprotein cholesterol, apolipoprotein A/B ratio, and homocysteine were predictors of cardiac amyloidosis. Multivariable logistic regression showed that only alpha 1 antitrypsin was an independent risk factor for cardiac amyloidosis. Receiver operating characteristic curve analysis based on the Mayo stage and troponin level showed the cut-off value of 140.55 mg/dl for alpha-1 antitrypsin in predicting cardiac amyloidosis with 81.7% sensitivity and 83.9% specificity. Elevated alpha-1 antitrypsin levels may be an early diagnostic biomarker for cardiac amyloidosis.

High-grade serous papillary ovarian carcinoma combined with nonkeratinizing squamous cell carcinoma of the cervix: a case report.

Multiple primary malignant neoplasms are a rare gynecologic malignancy; particularly, cases originating from the heterologous organs, such as the ovary and cervix. Here, we report a case of two primary malignant neoplasms in a patient who had undergone laparoscopic radical hysterectomy + bilateral salpingo-oophorectomy + pelvic lymph node dissection + para-aortic lymphadenectomy + appendectomy + omentectomy + metastasectomy under general anesthesia. The patient experienced complete remission after six courses of postoperative chemotherapy with a standard Taxol and Carboplatin regimen. Genetic testing was performed to detect BRCA2 mutations, and poly (ADP-ribose) polymerase (PARP) inhibitors were used for maintenance therapy.

IRF3 activates RB to authorize cGAS-STING-induced senescence and mitigate liver fibrosis.

Cytosolic double-stranded DNA surveillance by cyclic GMP-AMP synthase (cGAS)-Stimulator of Interferon Genes (STING) signaling triggers cellular senescence, autophagy, biased mRNA translation, and interferon-mediated immune responses. However, detailed mechanisms and physiological relevance of STING-induced senescence are not fully understood. Here, we unexpectedly found that interferon regulatory factor 3 (IRF3), activated during innate DNA sensing, forms substantial endogenous complexes in the nucleus with retinoblastoma (RB), a key cell cycle regulator. The IRF3-RB interaction attenuates cyclin-dependent kinase 4/6 (CDK4/6)-mediated RB hyperphosphorylation that mobilizes RB to deactivate E2 family (E2F) transcription factors, thereby driving cells into senescence. STING-IRF3-RB signaling plays a notable role in hepatic stellate cells (HSCs) within various murine models, pushing activated HSCs toward senescence. Accordingly, IRF3 global knockout or conditional deletion in HSCs aggravated liver fibrosis, a process mitigated by the CDK4/6 inhibitor. These findings underscore a straightforward yet vital mechanism of cGAS-STING signaling in inducing cellular senescence and unveil its unexpected biology in limiting liver fibrosis.

Engineered bone marrow mesenchymal stem cell-derived exosomes loaded with miR302 through the cardiomyocyte specific peptide can reduce myocardial ischemia and reperfusion (I/R) injury.

BACKGROUND: MicroRNA (miRNA)-based therapies have shown great potential in myocardial repair following myocardial infarction (MI). MicroRNA-302 (miR302) has been reported to exert a protective effect on MI. However, miRNAs are easily degraded and ineffective in penetrating cells, which limit their clinical applications. Exosomes, which are small bioactive molecules, have been considered as an ideal vehicle for miRNAs delivery due to their cell penetration, low immunogenicity and excellent stability potential. Herein, we explored cardiomyocyte-targeting exosomes as vehicles for delivery of miR302 into cardiomyocyte to potentially treat MI. METHODS: To generate an efficient exosomal delivery system that can target cardiomyocytes, we engineered exosomes with cardiomyocyte specific peptide (CMP, WLSEAGPVVTVRALRGTGSW). Afterwards, the engineered exosomes were characterized and identified using transmission electron microscope (TEM) and Nanoparticle Tracking Analysis (NTA). Later on, the miR302 mimics were loaded into the engineered exosomes via electroporation technique. Subsequently, the effect of the engineered exosomes on myocardial ischemia and reperfusion (I/R) injury was evaluated in vitro and in vivo, including MTT, ELISA, real-time quantitative polymerase chain reaction (PCR), western blot, TUNNEL staining, echocardiogram and hematoxylin and eosin (HE) staining. RESULTS: Results of in vitro experimentation showed that DSPE-PEG-CMP-EXO could be more efficiently internalized by H9C2 cells than unmodified exosomes (blank-exosomes). Importantly, compared with the DSPE-PEG-CMP-EXO group, DSPE-PEG-CMP-miR302-EXO significantly upregulated the expression of miR302, while exosomes loaded with miR302 could enhance proliferation of H9C2 cells. Western blot results showed that the DSPE-PEG-CMP-miR302-EXO significantly increased the protein level of Ki67 and Yap, which suggests that DSPE-PEG-CMP-miR302-EXO enhanced the activity of Yap, the principal downstream effector of Hippo pathway. In vivo, DSPE-PEG-CMP-miR302-EXO improved cardiac function, attenuated myocardial apoptosis and inflammatory response, as well as reduced infarct size significantly. CONCLUSION: In conclusion, our findings suggest that CMP-engineered exosomes loaded with miR302 was internalized by H9C2 cells, an in vitro model for cardiomyocytes coupled with potential enhancement of the therapeutic effects on myocardial I/R injury.

HDAC inhibitors target IRS4 to enhance anti­AR therapy in AR­positive triple­negative breast cancer.

Triple­negative breast cancer (TNBC) is the most malignant subtype of breast cancer. Androgen receptor (AR) has been identified as a potential therapeutic target for AR­positive TNBC; however, clinical trials have not yet produced an effective treatment. The present study aimed to identify a novel treatment regimen to improve the prognosis of AR­positive TNBC. First, a combination of an AR inhibitor (enzalutamide, Enz) and a selective histone deacetylase inhibitor (chidamide, Chid) was used to treat AR­positive TNBC cell lines, and a synergistic effect of these drugs was observed. The combination treatment inhibited cell proliferation and migration by arresting the cell cycle at the G2/M phase. Subsequently, next­generation sequencing was performed to detect changes in gene regulation. The results showed that the PI3K/Akt signalling pathway was significantly inhibited by the combination treatment of Enz and Chid. Gene Set Enrichment Analysis revealed that the combination group was significantly enriched in KRAS signalling. Analysis of the associated genes revealed that insulin receptor substrate 4 (IRS4) may have a critical role in blocking the activation of KRAS signalling. In a mouse xenograft model, combination treatment also inhibited the PI3K/Akt signalling pathway by upregulating the expression of IRS4 and thereby suppressing tumour growth. In conclusion, the results of the present study revealed that combination treatment with Enz and Chid can upregulate IRS4, which results in the blocking of KRAS signalling and suppression of tumour growth. It may be hypothesised that the expression levels of IRS4 could be used as a biomarker for screening patients with AR­positive TNBC using Enz and Chid combination therapy.

Diverticular peroral endoscopic myotomy (D-POEM) for symptomatic oesophageal diverticulum: a multicentre cohort study with a minimum follow-up of 3 years.

OBJECTIVE: To evaluate the medium- and long-term outcomes of diverticular peroral endoscopic myotomy (D-POEM) for symptomatic oesophageal diverticulum. METHODS: Consecutive patients with symptomatic oesophageal diverticulum who underwent D-POEM from 1st May 2016 to 1st April 2020 in 6 centres were extracted and researched. Symptoms assessed by the modified Eckardt score were registered pre- and post-D-POEM at 1, 6, 12, 24 and 36 months. RESULTS: A total of 34 patients with Zenker's diverticulum (ZD, n = 12), mid-oesophageal diverticulum (MED, n = 12), and epiphrenic diverticulum (ED, n = 10) were included. Complete septotomy was achieved in a mean of 39.15 min, with 100% technical success. No severe intraoperative or postoperative complications were observed. Five patients exhibited subcutaneous emphysema, while 1 had mucosal injury. The mean Eckardt score was 8.59 preoperatively and 2.56 at 1 month, 2.09 at 6 months, 2.21 at 12 months, 2.15 at 24 months, and 2.21 at 36 months postoperatively. The total clinical success rates at 1, 6, 12, 24 and 36 months postoperatively were 97.1%, 97.1%, 94.1%, 91.2%, and 88.2%, respectively. With a median follow-up of 47.2 months, four patients suffered symptom relapse, with a total clinical success rate of 88.2%. A long disease duration, a high Eckardt score, and coexistence of achalasia were identified as risk factors for symptomatic recurrence by multivariable Cox analysis. CONCLUSIONS: D-POEM is an effective and durable treatment for patients with symptomatic oesophageal diverticulum.

Euphorbia factor L2 suppresses the generation of liver metastatic ascites in breast cancer via inhibiting NLRP3 inflammasome activation.

Metastasis is the leading cause of death in patients with breast cancer, in part due to the lack of effective treatments. Euphorbia factor L2 (EFL2) is a diterpenoid extracted from Euphorbia lathyris L. seeds, which has attracted increasing attention in recent years due to its anticancer effect. However, the role and molecular mechanism of EFL2 in breast cancer liver metastasis remain unclear. In the present study, a breast cancer liver metastasis model was constructed and the effect of EFL2 on ascites generation in mice was examined. H&E staining detected inflammatory cells and tumor cells in the liver, small intestine and tumor tissues. Western blotting and reverse transcription­quantitative PCR were used to detect the protein and mRNA expression of NLR family pyrin domain containing­3 (NLRP3) and related molecules in tumor tissues. Immunohistochemistry was used to detect the levels of CD4 and CD8 T cells in tumor tissue and immunofluorescence was used to further detect the expression level of NLRP3. Finally, the aforementioned experiments were further verified by overexpressing NLPR3. It was found that EFL2 inhibited generation of ascites in the model in a dose­dependent manner. Furthermore, EFL2 inhibited tumor cell metastasis and enhanced immune cell infiltration. Meanwhile, EFL2 dose­dependently downregulated the mRNA and protein expression of NLRP3 and related molecules in the model, and overexpression of NLRP3 abolished these beneficial effects of EFL2. Taken together, the present experimental data suggested that EFL2 has a significant inhibitory effect on ascites of breast cancer liver metastasis in vivo, which may inhibit tumor cell metastasis by downregulating NLRP3 expression, providing an experimental basis for treating breast cancer metastasis.

DNAJA1 promotes proliferation and metastasis of breast cancer by activating mutant P53/NF-κB pathway.

PURPOSE: Breast cancer is one of the most common tumors with high malignancy and metastatic rate. DNAJA1 is closely related to tumor progress in several tumors. However, the role and mechanisms of DNAJA1 in the metastasis and proliferation of breast cancer are unknown. METHODS: Immunohistochemistry and western blot were used to detect the protein expression genes. In vivo and vitro experiments were performed to evaluate the proliferation, invasive and metastatic abilities of breast cancer cells. RESULTS: DNAJA1 was high expressed in 234 cases of breast cancer tissues and associated with metastasis, p53 expression and poor survival for patients. Knock down of DNAJA1 decreased the number of plate clone formation and the OD value of CCK8 assays in breast cancer cells. Depletion of DNAJA1 also in decreased the invasive abilities of breast cancer cells. In vivo, knock down DNAJA1 decreased the growth of subcutaneous tumor and lung metastatic nodes. Mechanically, DNAJA1 could bind with P53-R175H and reduced its degradation. Up regulation of DNAJA1 in mutant P53-R175H breast cancer cell promoted the nuclear translocation of p65, activated NF-κB pathway and enhanced the transcription of its downstream genes such as MMP9, CXCL10 et al. Blockade of NF-κB pathway effectively rescued the effects of DNAJA1 on proliferation and metastasis in breast cancer. CONCLUSION: Our study reveals that DNAJA1 is up regulated in breast cancer and promotes breast cancer cells proliferation and metastasis via P53-R175H/NF-κB pathway. It might be a potential prognosis marker for the breast cancer patients.

[Advances in pharmacological effects of jujuboside B].

Ziziphi Spinosae Semen(ZSS) is an edible TCM derived from the dried ripe seeds of Ziziphus jujube Mill. var. spinosa(Bunge)Hu ex H. F. Chou(Rhamnaceae), which has the effects of nourishing the heart, tonifying the liver, calming the heart, tranquilizing the mind, arresting sweating, and promoting fluid production, and is widely used in the treatment and health care of diseases related to cardiovascular, nervous, and immune systems. Jujuboside B(JuB), one of the main active ingredients of ZSS, possesses various pharmacological effects with application values. This paper reviewed the chemical structure and pharmacological effects of JuB. JuB has sedative, hypnotic, antitumor, anti-platelet, anti-inflammatory, and other biological activities, which shows the potential thera-peutic effects on insomnia, tumors, coronary artery disease, airway inflammation, and liver injury. However, there are some limitations to the results of current studies. More comprehensive studies, including basic research and clinical trials, need to be carried out to provide more reliable evidence.

Euphorbia factor L1 suppresses breast cancer liver metastasis via DDR1-mediated immune infiltration.

Euphorbia factor L1 (EFL1), a lathyrane-type diterpenoid from the medicinal herb Euphorbia lathyris L., has been documented to possess various pharmacologic actives. However, the function of EFL1 on breast cancer is not clear. In this study, we explored the effect and mechanism of EFL1 on breast cancer liver metastasis. Female BALB/c mice were subjected to breast cancer-surgical hepatic implantation (SHI) to establish breast cancer liver metastasis model in vivo. At 10 days post-surgery, mice were administrated with EFL1 once daily for a total of 2 weeks. Serum AST and ALT activities, abdominal circumference, peritoneal fluid, tumor weight and volume were determined to assess liver and mesenteric re-metastasis of breast cancer. H&E staining was used to observe morphology changes in tumor, liver and small intestine tissues. ELISA was applied to observe inflammatory levels. Tumor DDR1 expression and immune infiltration were determined using western blotting, immunohistochemistry and flow cytometer methods. Our results showed that EFL1 administration improved liver function (AST and ALT activities), ascites, liver metastasis and mesenteric re-metastasis in SHI mice. Also, SHI-induced inflammatory cell infiltration and IL-1ß, IL-6, TNF-α generation in ascites were decreased by EFL1 treatment. Mechanism study revealed that EFL1 intervention enhanced the ratios of CD4+ and CD8+ and CD49b+(NK) T lymphocytes and decreased Treg cells through downregulating DDR1 in the tumor of SHI mice. Furthermore, overexpression of DDR1 abolished the anti-liver metastasis effect and pro-immune infiltration action of EFL1 in SHI mice. Together, our findings suggested that EFL1 protects against breast cancer liver metastasis in vivo by targeting DDR1-mediated immune infiltration.

Analysis of the influence factors of cervical lymph node metastasis in Papillary thyroid carcinoma: A retrospective observational study.

Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer, and surgery is crucial for curing PTC. PTC patients often experience lymph node metastasis (LNM) in the neck, and central lymph node metastasis (CLNM) significantly affects the recurrence rate of PTC. Therefore, the thoroughness of the surgery is particularly important for the treatment of PTC. However, there is still controversy regarding the choice of surgical approach. This study retrospectively analyzed the clinical data of 69 PTC patients treated at our hospital from December 2019 to April 2022 and clinically analyzed the high-risk factors for neck LNM. In this study, the patients aged ≤ 55 years were examined in which the number of patients with CLNM were 42 cases (80.77%), tumor diameter >2 cm were 15 cases (100%), the multifocal carcinoma were 38 cases (88.37%) and the involvement of membrane were 38 cases (80.85%), the number of patients whose had lateral cervical lymph node metastasis (LLNM), respectively 43 cases (82.69%), 14 cases (93.33%), 39 cases (90.7%) and 40 cases (85.11%),all of these factors were associated with cervical LNM (P < .05), but was not correlation with sex, double lobe carcinoma, extra glandular invasion and hashimoto (P > .05). The patient's age and number of cancers were independent risk factors for LNM in the central region of the neck (P < .05), while the patient's age, tumor size and number of cancers were significant risk factors for LNM in the lateral cervical region (P < .05). We concluded that cervical LNM was related with the high-risk factors of patient's age, tumor size, multifocal carcinoma in PTC. Especially, modified radical cervical dissection or selective cervical dissection was suggested in the PTC patients who were younger than 42.5 years old, with tumor diameter larger than 2 cm and multifocal carcinoma.

[Electroacupuncture improves obesity and promotes white adipose tissue browning by regulating central glucagon-like peptide-1].

OBJECTIVE: To observe the effect of electroacupuncture （EA） on white adipose tissue （WAT） browning by regulating central glucagon-like peptide-1 （GLP-1）, so as to explore the possible central mechanisms of EA in improving obesity. METHODS: Thirty male Wistar rats were randomly divided into normal group, model group, EA group, HM3D group, and EA+HM4D group, with 6 rats in each group. The obesity rat model was obtained by feeding with high-fat diet for 8 weeks. Adeno-associated virus combined with DREADDs was injected into bilateral nucleus of solitary tract （NTS）, with rAAV-GLP-1+rAAV-4D applied to the EA+HM4D group, rAAV-GLP-1+rAAV-3D applied to the HM3D group, and rAAV-GLP-1+rAAV-GFP applied to other 3 groups. After modeling, rats in the EA and EA+HM4D groups received EA treatment at bilateral "Zusanli"（ST36）, "Fenglong"（ST40）, "Guanyuan"（CV4） and "Zhongwan"（CV12）, with successive waves （2 Hz, 1 mA） for 10 minutes, 3 times a week, for a total of 8 weeks. Body mass of rats in each group were measured before and 2, 4, 6, and 8 weeks after intervention. Abdominal and perirenal WAT mass was weighed, serum triglyceride （TG） and total cholesterol （TC） contents were detected by using automatic analyzer, and nonestesterified fatty acid （NEFA） content was detected by using colorimetric assay kit. The morphology of abdominal WAT lipid droplets was observed by HE staining. The mRNA expressions of GLP-1 in NTS, AMPK in ventromedial nucleus of hypothalamus（VMH）, UCP1 and PGC-1α in subcutaneous fat were detected by real-time PCR. The protein expression levels of GLP-1, AMPK, phosphorylated-AMPK, UCP1 and PGC-1α were detected by Western blot. The activation level of GLP-1 neurons in NTS was observed by immunofluorescence. RESULTS: Compared with the normal group, abdominal WAT lipid droplets were enlarged, body weight, serum TG, TC, NEFA contents, abdominal and perirenal WAT mass, mRNA and protein expression levels of AMPK were significantly increased（P<0.01, P<0.05）, while GLP-1 neurons activation level, mRNA and protein expression levels of GLP-1, UCP1 and PGC-1α, and AMPK protein phosphorylation were decreased （P<0.01） in the model group. After EA intervention, body weight at 6 and 8 weeks after intervention and other indexes mentioned above were all significantly reversed （P<0.01, P<0.05） in the EA group in comparison with those of the model group. Compared with the EA group, the HM3D group had reduced abdominal WAT lipid droplets size, decreased serum TG, TC, and NEFA contents, and protein expression level of AMPK（P<0.01, P<0.05）, with increased mRNA and protein expression levels of GLP-1, UCP1 and PGC-1α, and phosphorylation level of AMPK protein（P<0.01, P<0.05）, while the EA+HM4D group had enlarged abdominal WAT lipid droplets, increased body weight 6 and 8 weeks after intervention, abdominal and renal WAT mass, and NEFA content （P<0.01, P<0.05）, with decreased serum TG content, activation level of GLP-1 neurons in the NTS, mRNA and protein expression levels of GLP-1, UCP1 and PGC-1α （P<0.01, P<0.05）, as well as down-regulated phosphorylation of AMPK protein and mRNA （P<0.01, P<0.05）. CONCLUSION: EA can effectively promote the browning of WAT, which may be related to the activation of GLP-1 neurons in the NTS, as well as the promotion of the phosphorylation of AMPK in the VMH and up-regulation of UCP1.

Native T1 mapping for non-invasive quantitative evaluation of renal function and renal fibrosis in patients with chronic kidney disease.

Background: To investigate the role of native T1 mapping in the non-invasive quantitative assessment of renal function and renal fibrosis (RF) in chronic kidney disease (CKD) patients. Methods: A prospective analysis of 71 consecutive patients [no RF (0%): 9 cases; mild RF (<25%): 36 cases; moderate RF (25-50%): 17 cases; severe RF (>50%): 9 cases] who were clinically diagnosed with CKD that was pathologically confirmed and who underwent magnetic resonance imaging (MRI) examination between October 2021 and September 2022 was performed. T1-C (mean cortical T1 value), T1-M (mean medullary T1 value), ΔT1 (mean corticomedullary difference) and T1% (mean corticomedullary ratio) values were compared. Correlations between T1 parameters and clinical and histopathological values were analyzed. Regression analysis was performed to determine independent predictors of RF. The areas under the receiver operating characteristic curve (AUC) were calculated to assess the diagnostic value of RF. Results: The T1-C, ΔT1 and T1% values (P<0.05) were significantly different in the CKD group, but T1-M was not (P>0.05). The ΔT1 and T1% values showed significant differences in pairwise comparisons among CKD subgroups (P<0.05) except for CKD 2 and 3. ΔT1 and T1% were moderately correlated with the estimated glomerular filtration rate (ΔT1: rs=-0.561; T1%: r=-0.602), serum creatinine (ΔT1: rs=0.591; T1%: rs=0.563), blood urea nitrogen (ΔT1: rs=0.433; T1%: rs=0.435) and histopathological score (ΔT1: rs=0.630; T1%: rs=0.658). ΔT1 and T1%, but not T1-C, were independent predictors of RF (P<0.05). ΔT1 and T1% were set as -410.07 ms and 0.8222 with great specificity [ΔT1: 91.7% (77.5-98.2%); T1%: 97.2% (85.5-99.9%)] to identify mild RF and moderate-severe RF. The optimal cutoff values for differentiating severe RF from mild-moderate RF were -343.81 ms (ΔT1) and 0.8359 (T1%) with high sensitivity [both 100% (66.4-100%)] and specificity [ΔT1: 90.6% (79.3-96.9%); T1%: 94.3% (84.3-98.8%)]. Conclusions: ΔT1 and T1% overwhelm T1-C for assessment of renal function and RF in CKD patients. ΔT1 and T1% identify patients with <25% and >50% fibrosis, which can guide clinical decision-making and help to avoid biopsy-related bleeding.

Impacts of gender and age on meibomian gland in aged people using artificial intelligence.

Purpose: To evaluate the effects of age and gender on meibomian gland (MG) parameters and the associations among MG parameters in aged people using a deep-learning based artificial intelligence (AI). Methods: A total of 119 subjects aged ≥60 were enrolled. Subjects completed an ocular surface disease index (OSDI) questionnaire, received ocular surface examinations including Meibography images captured by Keratograph 5M, diagnosis of meibomian gland dysfunction (MGD) and assessment of lid margin and meibum. Images were analyzed using an AI system to evaluate the MG area, density, number, height, width and tortuosity. Results: The mean age of the subjects was 71.61 ± 7.36 years. The prevalence of severe MGD and meibomian gland loss (MGL) increased with age, as well as the lid margin abnormities. Gender differences of MG morphological parameters were most significant in subjects less than 70 years old. The MG morphological parameters detected by AI system had strong relationship with the traditional manual evaluation of MGL and lid margin parameters. Lid margin abnormities were significantly correlated with MG height and MGL. OSDI was related to MGL, MG area, MG height, plugging and lipid extrusion test (LET). Male subjects, especially the ones who smoke or drink, had severe lid margin abnormities, and significantly decreased MG number, height, and area than the females. Conclusion: The AI system is a reliable and high-efficient method for evaluating MG morphology and function. MG morphological abnormities developed with age and were worse in the aging males, and smoking and drinking were risk factors.

Endoscopic total parathyroidectomy via anterior chest approach with forearm autotransplantation for secondary hyperparathyroidism: a comparison of surgical results with open total parathyroidectomy with autotransplantation.

Objective: This paper aimed to evaluate the clinical value of performing an endoscopic total parathyroidectomy through anterior chest approach with autotransplantation (EACtPTx+AT) in treating secondary hyperparathyroidism (SHPT) to summarize and share the clinical experience. Methods: 24 patients with SHPT were retrospectively analyzed:11 patients underwent open total parathyroidectomy with autotransplantation (OtPTx+AT Group) and 13 patients underwent endoscopic parathyroidectomy through anterior chest approach with autotransplantation (EACtPTx+AT Group). Comparing the two groups regarding the following factors: (1) operating conditions, such as the blood loss during the operation, the length of time spent on the operating table, the number of parathyroid glands removed, postoperative drainage volume and hospital stay. (2) clinical efficacy, parathyroid hormone (PTH) and serum calcium (Ca) levels. (3) postoperative complications. Results: First, there were no significant differences in the number of parathyroid gland resection, operation time, intraoperative blood loss and hospital stay between the two groups. While there were significant differences in postoperative drainage volume between the two groups. Second, the two groups preoperative PTH and preoperative serum calcium decreased significantly compared with those of the two groups after surgery and there was a statistically significant difference. Thirdly, there was no postoperative bleeding, hoarseness or choking in the two groups and no conversion to open surgery case in EACtPTx+AT group. Conclusion: Endoscopic treatment of SHPT using the anterior chest approach with forearm autotransplantation significantly improves clinical symptoms and lowers levels of PTH and serum calcium after the operation. The results confirm the operation's safety and effectiveness.