Objective: To investigate the association between overweight, obesity, central obesity and hypertension, so as to provide the basis for formulating targeted hypertension prevention and control strategies. Methods: Permanent residents aged ≥18 years were selected in Wenzhou City, Zhejiang Province from June 2023 to August 2024 by a multistage cluster random sampling method. Data on demographic information, lifestyle, height, weight, waist circumference (WC), blood pressure, and blood biochemical indicators were collected through questionnaire surveys, physical examinations, and laboratory tests. The prevalence of hypertension was calculated and standardized using the data of the Sixth National Population Census in 2010. Body mass index (BMI) was calculated to determine overweight and obesity, while WC was used to identify central obesity. The association between overweight, obesity, central obesity and hypertension were analyzed using multivariable logistic regression models. Results: A total of 38 593 residents were surveyed, including 19 481 (50.48%) males and 19 112 (49.52%) females. The median age was 46.00 (interquartile range, 26.00) years. The rates of overweight, obesity, and central obesity were 32.74% (12 634 individuals), 10.27% (3 963 individuals), and 27.87% (10 755 individuals), respectively. There were 11 813 cases of hypertension, with a prevalence and standardized prevalence of 30.61% and 24.41%, respectively. Multivariable logistic regression analysis showed that after adjusting for demographic information, lifestyle, diabetes and dyslipidemia, the likelihood of hypertension in the overweight and obesity groups was 1.927 (95%CI: 1.815-2.045) times and 3.724 (95%CI: 3.404-4.073) times that of the normal BMI group, respectively. The likelihood of hypertension in the central obesity group was 2.346 (95%CI: 2.214-2.486) times that of the normal WC group. The likelihood of hypertension in the central obesity only, overweight only, overweight with central obesity, obesity only and obesity with central obesity groups was 1.586 (95%CI: 1.391-1.809), 1.704 (95%CI: 1.582-1.835), 2.433 (95%CI: 2.254-2.626), 1.768 (95%CI: 1.424-2.194), and 4.466 (95%CI: 4.053-4.921) times that of the normal BMI and WC group, respectively. Conclusions Overweight, obesity and central obesity were all associated with hypertension among adult residents. The highest likelihood of hypertension was observed among adult residents with both general obesity and central obesity.

Poly(ADP-ribosyl)ation (PARylation) is a specific form of post-translational modification (PTM) predominantly triggered by the activation of poly-ADP-ribose polymerase 1 (PARP1). However, the role and mechanism of PARylation in the advancement of acute kidney injury (AKI) remain undetermined. Here, we demonstrated the significant upregulation of PARP1 and its associated PARylation in murine models of AKI, consistent with renal biopsy findings in patients with AKI. This elevation in PARP1 expression might be attributed to trimethylation of histone H3 lysine 4 (H3K4me3). Furthermore, a reduction in PARylation levels mitigated renal dysfunction in the AKI mouse models. Mechanistically, liquid chromatography-mass spectrometry indicated that PARylation mainly occurred in receptor for activated C kinase 1 (RACK1), thereby facilitating its subsequent phosphorylation. Moreover, the phosphorylation of RACK1 enhanced its dimerization and accelerated the ubiquitination-mediated hypoxia inducible factor-1α (HIF-1α) degradation, thereby exacerbating kidney injury. Additionally, we identified a PARP1 proteolysis-targeting chimera (PROTAC), A19, as a PARP1 degrader that demonstrated superior protective effects against renal injury compared with PJ34, a previously identified PARP1 inhibitor. Collectively, both genetic and drug-based inhibition of PARylation mitigated kidney injury, indicating that the PARylated RACK1/HIF-1α axis could be a promising therapeutic target for AKI treatment.

Anxiety disorder is a major symptom of autism spectrum disorder (ASD) with a comorbidity rate of ~40%. However, the neural mechanisms of the emergence of anxiety in ASD remain unclear. In our study, we found that hyperactivity of basolateral amygdala (BLA) pyramidal neurons (PNs) in Shank3 InsG3680 knock-in (InsG3680^+/+) mice is involved in the development of anxiety. Electrophysiological results also showed increased excitatory input and decreased inhibitory input in BLA PNs. Chemogenetic inhibition of the excitability of PNs in the BLA rescued the anxiety phenotype of InsG3680^+/+ mice. Further study found that the diminished control of the BLA by medial prefrontal cortex (mPFC) and optogenetic activation of the mPFC-BLA pathway also had a rescue effect, which increased the feedforward inhibition of the BLA. Taken together, our results suggest that hyperactivity of the BLA and alteration of the mPFC-BLA circuitry are involved in anxiety in InsG3680^+/+ mice.
Animals ; Prefrontal Cortex/metabolism* ; Basolateral Nuclear Complex/metabolism* ; Mice ; Anxiety/metabolism* ; Nerve Tissue Proteins/genetics* ; Male ; Gene Knock-In Techniques ; Pyramidal Cells/physiology* ; Mice, Transgenic ; Neural Pathways/physiopathology* ; Mice, Inbred C57BL ; Microfilament Proteins

ObjectiveTo explore the protective mechanism of paeoniflorin on mice with ulcerative colitis （UC） through the adenosine monophosphate-activated protein kinase （AMPK）/mammalian target of rapamycin （mTOR） autophagy pathway. MethodUC mouse model was established by allowing mice freely drink 4% DSS， and 56 BALB/c male mice were randomly divided into model group， AMPK inhibitor group （20 mg·kg^-1）， paeoniflorin （50 mg·kg^-1） + inhibitor （20 mg·kg^-1） group， and high dose （50 mg·kg^-1）， medium dose （25 mg·kg^-1）， and low dose （12.5 mg·kg^-1） paeoniflorin groups. After seven days of drug intervention， the protective effect of paeoniflorin on mice with UC was determined by comparing the body weight， disease activity index （DAI） changes， and Hematoxylin-eosin （HE） staining results. Enzyme linked immunosorbent assay （ELISA） was used to detect the levels of tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6） in the serum of mice in each group， and immunofluorescence was utilized to detect microtubule-associated protein 1 light chain 3 （LC3） content in the colon， AMPK， mTOR proteins， and their phosphorylated proteins including p-AMPK and p-mTOR in the colon tissue were detected by Western blot， and the mRNA expression levels of AMPK， mTOR， Beclin1， LC3， and p62 were detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. ResultCompared with the blank group， the model group showed a decrease in body mass， an increase in DAI score， and severe pathological damage to the colon. The levels of inflammatory factors including TNF-α and IL-6 increased in serum （P<0.01）， while the protein levels of LC3 and p-AMPK/AMPK were down-regulated in colon tissue， and those of p-mTOR/mTOR were up-regulated （P<0.01）. The mRNA expression levels of AMPK and LC3 were down-regulated， while the mRNA expression levels of mTOR and p62 were up-regulated （P<0.01）. Compared with the model group and the paeoniflorin + inhibitor group， the mice treated with paeoniflorin showed an increase in body mass， a decrease in DAI score， a reduction in pathological damage to colon tissue， and a reduction in the levels of inflammatory factors of TNF-α and IL-6 in serum （P<0.05）. The protein levels of LC3 and p-AMPK/AMPK in colon tissue were up-regulated， while the protein levels of p-mTOR/mTOR were down-regulated （P<0.01）. The mRNA expression levels of AMPK， Beclin1， and LC3 were up-regulated， while the mRNA expression of mTOR and p62 were down-regulated （P<0.01）. The colon tissue of the inhibitor group was severely damaged， and the trend of various indicators was completely opposite to that of the high dose paeoniflorin group. ConclusionPaeoniflorin can enhance autophagy and reduce inflammatory damage in mice with UC by activating the AMPK/mTOR signaling pathway and thus play a protective role.

ObjectiveTo explore the mechanism of Huanglian Jiedutang in inhibiting the pyroptosis mediated by NOD-like receptor protein 3 （NLRP3） inflammasomes and alleviating the acute liver injury （ALI） induced by lipopolysaccharide （LPS） in the mouse model of sepsis. MethodFifty-four male C57BL/6 mice were randomized into blank， model， low- （3.08 g·kg^-1）， medium- （6.15 g·kg^-1）， and high-dose （12.30 g·kg^-1） Huanglian Jiedutang， and positive control （dexamethasone） groups （n=9）. The mice were administrated with Huanglian Jiedutang at different doses by gavage for 7 days， and then LPS （15 mg·kg^-1） was injected intraperitoneally for the modeling of sepsis. In the positive control group， dexamethasone （0.05 g·kg^-1） was injected intraperitoneally 1.5 h after modeling， and the mouse sepsis score （MSS） was recorded 12 h after modeling. The mice were sacrificed for the collection of blood and liver tissue samples. The levels of alanine transaminase （ALT） and aspartate transaminase （AST） were measured by a biochemical analyzer. The levels of tumor necrosis factor （TNF）-α， interleukin （IL）-6， IL-1β， and IL-18 in the serum were measured by enzyme-linked immunosorbent assay kits. Hematoxylin-eosin staining was used to observe the pathological changes in the liver tissue. The content of NLRP3 was observed by the immunofluorescence assay. The expression of apoptosis-associated speck-like protein containing CARD （ASC） was detected by immunohistochemistry. The protein levels of NLRP3， ASC， Caspase-1， and gasdermin D （GSDMD） in the liver tissue were determined by Western blot. Real-time quantitative polymerase chain reaction（Real-time PCR） was employed to determine the mRNA levels of GSDMD， Caspase-1， IL-1β， and IL-18. ResultCompared with the blank group， the model group showed elevated levels of ALT and AST （P<0.01） and risen levels of inflammatory cytokines in the serum （P<0.01）. In addition， the modeling resulted in edema and necrosis in the liver， and up-regulated the protein levels of GSDMD， NLRP3， ASC， and Caspase-1 （P<0.01） and the mRNA levels of GSDMD， Caspase-1， IL-1β， and IL-18 （P<0.01）. Compared with the model group， the drug intervention groups showed reduced content of inflammatory cytokines （P<0.01）， alleviated pathological damage in the liver tissue， and down-regulated protein levels of GSDMD， NLRP3， ASC， and Caspase-1 （P<0.05，P<0.01） and mRNA levels of GSDMD， Caspase-1， IL-1β， and IL-18 （P<0.05，P<0.01） in the liver tissue. ConclusionHuanglian Jiedutang can inhibit pyroptosis and reduce inflammation by inhibiting the activation of NLRP3 inflammasomes， thus demonstrating a therapeutic effect on acute liver injury in the mouse model of sepsis induced by LPS.

BACKGROUND:Previous brain studies have mostly focused on adults and fetuses,and the developmental characteristics of young children's brainstems have rarely been studied. OBJECTIVE:To observe the brainstem development characteristics of healthy young children and to explore the age-related differences and their correlation with sex. METHODS:From January 2019 to April 2022,a retrospective study of 3.0T MRI images of 174 children aged 2 to 6 years in the Affiliated Hospital of Inner Mongolia Medical University was conducted,and the median sagittal diameter,area and angle of the brainstem(including midbrain,pons and medulla oblongata)were measured. RESULTS AND CONCLUSION:There is an age-related increase in the anterior and posterior diameters of the midbrain,pons and medulla oblongata in the 2-5 years old group as well as in the longitudinal diameter and area of the midbrain,pons and medulla oblongata in the 2-6 years old group.Except for the longitudinal diameter of the medulla oblongata,all others show a positive correlation with age(r>0,P<0.05).In the 2-3 years old group and 4-5 years old group,the children are in the rapid growth and development stage,and these two age groups can be used as the key observation indicators for the development of young children.The anterior-posterior diameter,longitudinal diameter,area of the pons and total brainstem area are strongly correlated with age,which can be used as the key observation indicators for the brainstem development in young children.

BACKGROUND:Nowadays,there are increasing reports on the digitization and visualization system of acupuncture points for adults in traditional Chinese medicine,and the digitization and visualization system of acupuncture points for children in traditional Chinese medicine and the simulation system of acupuncture manipulation for Mongolian medicine training have been reported.However,there are no reports on relevant systems for children in Mongolian medicine. OBJECTIVE:To develop a simulation system of acupuncture points for children in Mongolian medicine,in the hope that it can be used for clinical teaching,manipulation practice and research on acupuncture safety. METHODS:Based on the tomographic anatomical dataset of preschool boys,a three-dimensional(3D)digital virtual anatomical model of children with multiple internal organs and tissues was constructed by using PhotoShop.2021 and Digihuman Reconstruction System software.The relevant annotation information database of 27 acupoints such as Dinghui acupoint of Mongolian medicine was compiled by the Unity database language.The Mongolian gold needle and silver needle were selected to record the acupuncture point teaching video on the 3D printed head and neck resin model of children.In Unity3D software,children's anatomical model,acupoint annotation information database and acupuncture operation video were integrated and coded,and a 3D digital children's Mongolian acupuncture acupoint visualization system integrating simulation acupuncture training,clinical teaching and acupuncture safety research was successfully created. RESULTS AND CONCLUSION:This study was based on real children's specimens.In order to reduce the error of two-dimensional segmentation,the manual layer-by-layer segmentation section image method was used to ensure the accuracy of the 3D model to the greatest extent.The Digihuman Reconstruction System was used to extract and save the individual segmentation data while maximizing the accuracy of the 3D model.PhotoShop.2021 software was used to complete the 3D reconstruction of the outer skin of the head and neck of children and the internal bony structure,cervical spinal cord,blood vessels and nerves,muscles and ligaments.After 3D reconstruction,the basic morphology of each independent structure and the integrity of the overall contour were verified in MeshLab software and the final fine adjustment and anatomical position confirmation were conducted using 3-matic research 13.0 software.The real anatomical morphology of the head and neck of preschool children was successfully simulated and restored.Unity3D software was used to integrate the 3D model of children,acupuncture operation video and acupoint annotation database,and the 3D digital Mongolian acupuncture acupoint visualization system for children was successfully constructed.Based on the real continuous fault ultra-thin dataset of preschool boys in China,China's first 3D digitization and visualization system of acupuncture points in the head and neck of children in Mongolian medicine was developed.Compared with the previous acupuncture soft works,this system is more suitable for the anatomical morphological development characteristics of Asian children,and has a high value of application in the fields of research on the safety of acupuncture in Mongolian medicine,clinical teaching and acupuncture simulation training.

【Objective】 To investigate the differences in efficacy and long-term prognosis between locally progressive low and intermediate rectal cancer patients receiving fluorouracil-based neoadjuvant chemotherapy alone (mFOLFOX6/CapeOX) and neoadjuvant radiotherapy, and to compare the therapeutic efficacy in the two groups. 【Methods】 We retrospectively analyzed the clinicopathological data of 118 patients with locally progressive low and intermediate rectal cancer who received neoadjuvant therapy from January 2019 to December 2021 at The First Affiliated Hospital of Xi’an Jiaotong University, including gender, age, body mass index (BMI), and other clinicopathological parameters. The t-test, Mann Whitney test, chi-square test or Fisher’s exact test were used to compare the differences between the two groups of patients who received neoadjuvant chemotherapy alone or neoadjuvant radiochemotherapy in terms of short-term efficacy, lymph node manifestations and long-term prognosis, respectively. Survival rates were calculated and survival curves were plotted using the Kaplan-Meier method. 【Results】 In terms of efficacy, patients in the neoadjuvant radiotherapy group achieved better tumor regression (Z=-2.05, P=0.04) and solid tumor efficacy (Z=-2.42, P=0.015), but the difference between the two groups in terms of downstaging effect of clinical stage was not statistically significant. The number of lymph nodes detected was significantly lower in the neoadjuvant radiotherapy group (neoadjuvant chemotherapy vs. neoadjuvant radiochemotherapy, 13.19±3.83 vs. 9.55±4.00, t=5.02, P<0.001), but the two groups did not differ significantly in the number of lymph node positives and lymph node positive ratio. In terms of long-term prognosis, there was no statistically significant difference in the overall survival rate or disease-free survival rate of the two groups. 【Conclusion】 Compared with neoadjuvant chemotherapy alone, neoadjuvant radiotherapy showed better short-term efficacy in patients with locally progressive low and intermediate rectal cancer, but there was no statistically significant difference between the two treatment regimens in terms of long-term prognosis.

Objective To compare the short-term clinical effects of Da Vinci robot-assisted thoracic surgery (RATS) and video-assisted thoracoscopic surgery (VATS) in the treatment of posterior mediastinal tumors, and to explore the advantages of RATS posterior mediastinal tumor resection. Methods The clinical data of patients who underwent posterior mediastinal tumors resection through the lateral chest approach admitted to the same medical group in the Department of Thoracic Surgery of the First Hospital of Lanzhou University between January 2019 to January 2023 were retrospectively analyzed. According to the different surgical methods, the patients were divided into a RATS group and a VATS group. The clinical data were compared between the two groups. Results A total of 85 patients were included in this study. There were 39 patients in the RATS group, including 25 females and 14 males, with an average age of 47.6±13.0 years, and 46 patients in the VATS group, including 14 males and 32 females, with an average age of 45.3±14.7 years. All patients completed the operation successfully. The hospitalization cost in the RATS group was significantly higher than that in the VATS group (P<0.001), and the white blood cell count and neutrophilic granulocyte percentage on the first day after operation in the RATS group were lower than those in the VATS group, and the differences were statistically significant (P<0.05). The operative time, intraoperative bleeding, postoperative hospital stay, white blood cell count and neutrophil percentage on the third postoperative day, visual analogue scale score on the first and third postoperative days, duration of analgesic pump use, postoperative 12 h oxygen saturation (no oxygen inhalation), postoperative down bed time, total thoracic drainage volume, duration of drainage tube retention, and postoperative complication rates were not statistically different between the two groups (P>0.05). There was no perioperative death, conversion to thoracotomy or serious perioperative complications in both groups. Conclusion RATS resection of posterior mediastinal tumor via lateral thoracic approach is safe and feasible, and its short-term effect is similar to that of VATS via lateral thoracic single-hole approach. It is worth further comparative study to explore its benefit and cost performance.

Objective:To evaluate the efficacy and safety of lenvatinib combined with camrelizumab as the second-line treatment for advanced intrahepatic cholangiocarcinoma (ICC).Methods:The clinical data of patients with advanced ICC undergoing the second-line treatment of lenvatinib combined with camrelizumab in the Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University from June 2021 to June 2022 were screened and analyzed. A total of 12 patients were enrolled, including seven males and five females, aged (67.5±8.6) years. Response evaluation criteria in solid tumor 1.1 was used to evaluate the efficacy of treatment. The safety assessment adopts the Adverse Event Evaluation Standard 5.0. Kaplan-Meier method was conducted to plot survival curves.Results:Among the 12 patients (after 1-7 cycles of immune and targeted therapy), three achieved partial response, four achieved stable disease, and five were defined as progression disease. Adverse events of different degrees occurred in seven cases, among which three patients had adverse events of grade ≥ 3: one with hypertension, which was managed after antihypertensive and symptomatic treatment; one with elevated serum total bilirubin, which was improved after reducing the dose of lenvatinib; one with liver dysfunction, which was considered as immune-related liver toxicity and alleviated after discontinuing camrelizumab. The 1-month, 3-month, and 6-month survival rates and progression-free survival rates of the patients were 100.0%, 91.7%, 66.7%, and 83.3%, 41.7%, and 25.0%, respectively. The median overall survival of patients was 14.7 months (95% CI: 9.2-21.2) and the median time to progression was 8.0 months (95% CI: 4.1-11.9). Conclusion:Combination of lenvatinib and camrelizumab could bring survival benefits with controllable adverse events as the second-line treatment of patients with advanced ICC.