Objective To investigate the effect of interleukin-6 (IL-6) on the phagocytosis of MH-S alveolar macrophages and its related mechanisms. Methods A mouse acute lung injury (ALI) model was constructed by instilling lipopolysaccharide (LPS) into the airway. ELISA was used to detect the content of IL-6 in bronchoalveolar lavage fluid (BALF). In vitro cultured MH-S cells, in the presence or absence of signal transducer and activator 3 of transcription(STAT3) inhibitor Stattic (5 μmol/L), IL-6 (10 ng/mL~500 ng/mL) was added to stimulate for 6 hours, and then incubated with fluorescent microspheres for 2 hours. The phagocytosis of MH-S cells was detected by flow cytometry. Western blot analysis was used to detect the expression levels of phosphorylated Janus kinase 2 (p-JAK2), phosphorylated STAT3 (p-STAT3), actin-related protein 2 (Arp2) and filamentous actin (F-actin). Results The content of IL-6 in BALF was significantly increased after the mice were injected with LPS through the airway. With the increase of IL-6 stimulation concentration, the phagocytic function of MH-S cells was enhanced, and the expression levels of Arp2 and F-actin proteins in MH-S cells were increased. The expression levels of p-JAK2 and p-STAT3 proteins increased in MH-S cells stimulated with IL-6(100 ng/mL). After blocking STAT3 signaling, the effect of IL-6 in promoting phagocytosis of MH-S cells disappeared completely, and the increased expression of Arp2 and F-actin proteins in MH-S cells induced by IL-6 was also inhibited. Conclusion IL-6 promotes the expression of Arp2 and F-actin proteins by activating the JAK2/STAT3 signaling pathway, thereby enhancing the phagocytic function of MH-S cells.
Animals ; Mice ; Actins ; Disease Models, Animal ; Interleukin-6 ; Janus Kinase 2 ; Lipopolysaccharides ; Macrophages, Alveolar ; Signal Transduction

OBJECTIVE To explore the action mechanism of kushenol F （KSCF） in treating ulcerative colitis （UC） in mice. METHODS The potential targets of KSCF intervening in UC were predicted with network pharmacology and molecular docking. C57BL/6J mice were randomly divided by body weight into model group， positive control group （sulfasalazine， 703 mg/kg）， KSCF group （100 mg/kg）， and normal group， with 6 mice per group. The UC model of mice was induced by dextran sulfate sodium solution. During the modeling period， the mice were given relevant medicine intragastrically， once a day， for 7 consecutive days. After the last administration， the disease activity index （DAI） of the mice was scored； the length of the mice’s colon was measured； pathological changes in the colon tissue of mice were observed； the levels of lipopolysaccharide （LPS） in serum， myeloperoxidase （MPO）， nitric oxide （NO） and superoxide dismutase （SOD） in the colon were detected in mice； the expression levels of occludin and ZO-1 in colon tissue of mice were detected； the proportions of CD3+T， CD4+T， and CD8+T lymphocytes in the spleen and the ratio of CD4+/CD8+ were detected； changes in colonic microbiota were analyzed by 16S rDNA sequencing. RESULTS Results of network pharmacology indicated that KSCF may treat UC by regulating signaling pathways such as phosphatidylinositol-3 kinase/protein kinase B （PI3K/AKT） and nuclear factor kappa B （NF- κB）. Molecular docking results showed that KSCF bound most stably with NF-κB p65 protein. Animal experiment results demonstrated that， compared with the model group， the pathological characteristics of colon tissue in mice were improved in KSCF group. DAI scores， serum levels of LPS， the levels of MPO，NF-κB p65 phosphorylation and NLRP3 protein expression in the colon， and the proportion of CD8+T lymphocytes in the spleen were reduced significantly （P＜0.05）. Body weight， SOD levels， expression levels of occludin and ZO-1 in the colon， proportions of CD3+T and CD4+T lymphocytes， and the CD4+/CD8+ ratio in the spleen were significantly increased （P＜0.05）； the abundance of Firmicutes， Actinobacteria， Akkermansia， and Lactobacillus genera were increased， while Proteobacteria decreased； the microbial community structure tended towards that of the normal group. CONCLUSIONS KSCF alleviates UC by restoring intestinal microbial imbalance， enhancing immune response， and inhibiting colonic inflammatory responses， thereby improving intestinal barrier integrity.

The many-banded krait, Bungarus multicinctus, has been recorded as the animal resource of JinQianBaiHuaShe in the Chinese Pharmacopoeia. Characterization of its venoms classified chief phyla of modern animal neurotoxins. However, the evolutionary origin and diversification of its neurotoxins as well as biosynthesis of its active compounds remain largely unknown due to the lack of its high-quality genome. Here, we present the 1.58 Gbp genome of B. multicinctus assembled into 18 chromosomes with contig/scaffold N50 of 7.53 Mbp/149.8 Mbp. Major bungarotoxin-coding genes were clustered within genome by family and found to be associated with ancient local duplications. The truncation of glycosylphosphatidylinositol anchor in the 3'-terminal of a LY6E paralog released modern three-finger toxins (3FTxs) from membrane tethering before the Colubroidea divergence. Subsequent expansion and mutations diversified and recruited these 3FTxs. After the cobra/krait divergence, the modern unit-B of β-bungarotoxin emerged with an extra cysteine residue. A subsequent point substitution in unit-A enabled the β-bungarotoxin covalent linkage. The B. multicinctus gene expression, chromatin topological organization, and histone modification characteristics were featured by transcriptome, proteome, chromatin conformation capture sequencing, and ChIP-seq. The results highlighted that venom production was under a sophisticated regulation. Our findings provide new insights into snake neurotoxin research, meanwhile will facilitate antivenom development, toxin-driven drug discovery and the quality control of JinQianBaiHuaShe.

Objective:To investigate the association between dietary intake and physical activity category and their combined effects on all-cause and cause-specific mortality risk in patients with type 2 diabetes mellitus (T2DM).Methods:Between December 2013 and December 2021, a prospective cohort study was conducted on 19 863 T2DM patients in Changshu City, Qingjiangpu District (formerly Qinghe District), and Huai'an District, included in the national basic health service management. Information on deaths and underlying causes of death was obtained from the Jiangsu Provincial CDC and Prevention Death Surveillance System. Cox proportional hazards models were used to estimate the intensity of associations between dietary intake, physical activity, and their combined effects with all-cause and cause-specific mortality in patients with T2DM.Results:As of December 31, 2021, the research subjects had been followed up for 150 283 person-years, with a median follow-up time of 8.15 years. During the follow-up period, 3 293 people died, including 1 124 deaths from cardiovascular disease (CVD) and 875 deaths from cancer. Cox regression analysis showed that compared with the population of 0-1 recommended food group, those having more than five recommended food groups had a 19% lower risk of all-cause mortality [hazard ratio ( HR)=0.81, 95% CI: 0.70-0.94] and a 33% lower risk of all-cause mortality ( HR=0.67, 95% CI: 0.52-0.87). Compared with the T2DM population in the physical activity Q1 group, the risk of all-cause mortality, CVD mortality, and cancer mortality among the physical activity Q4 group reduced by 50% ( HR=0.50, 95% CI: 0.45-0.56), 50% ( HR=0.50, 95% CI: 0.41-0.61), and 27% ( HR=0.73, 95% CI: 0.60-0.88), respectively. The combined effect showed that compared with the population in the intake of food categories 0-2 and low physical activity groups, the risk of all-cause, CVD mortality, and cancer mortality in the intake of food categories 4-9 and high physical activity groups reduced by 55% ( HR=0.45, 95% CI: 0.38-0.53), 56% ( HR=0.44, 95% CI: 0.32-0.59), and 40% ( HR=0.60, 95% CI: 0.44-0.82), respectively. Conclusion:Type of dietary intake, physical activity, and their combined effects are associated with a reduced mortality risk in patients with T2DM.

Objective:To explore any effect of working memory training on executive functioning and ability in the activities of daily living after a stroke.Methods:Forty-six stroke survivors were randomly divided into an experimental group and a control group, each of 23. Both groups received conventional cognitive rehabilitation (including computer-assisted cognition training and virtual reality training using upper limb rehabilitation robots), while the experimental group also received working memory training. Before, as well as after 4 and 8 weeks of the treatment, both groups′ executive functioning was evaluated using the Trail Making test, the Frontal Assessment Battery and the Wisconsin Card Sorting Test-64. Ability in the activities of daily living was quantified using the functional independence measures (FIMs).Results:There were no significant differences between the two groups in any of the measurements before the training. After 4 weeks the average scores of the experimental group on all four instruments were significantly higher than the control group′s averages. After 8 weeks the average scores had improved significantly more. The treatment group performed significantly better than the control group throughout.Conclusions:Working memory training can improve executive functioning and the daily life of stroke survivors.

Protein tyrosine phosphatase H-type receptor (PTPRH) gene encodes a gastric cancer associated protein, which exerts its biological function through tyrosine phosphorylation in the post-translational COOH- terminal region. PTPRH is abnormally expressed in a variety of tumors, and its biological function is closely related to the occurrence, development and prognosis of tumors.
Humans ; Phosphorylation ; Protein Tyrosine Phosphatases ; Proteins ; Stomach Neoplasms ; Tyrosine

Objective To investigate the relationship between subgroups of central lymph node metastasis (sCLNM) and lateral lymph node metastasis (LNM) of unilatal papillary thyroid carcinoma (uPTC) with cervical lymph node negative(cN0).Methods The clinical and pathological data of 161 patients with cN0-uPTC who underwent total thyroidectomy+central lymph node dissection+lateral lymph node dissection from Jan.2016 to Dec.2016 were retrospectively analyzed.The relationship between the lymph node metastasis of each subarea in the central area of the affected side and the lymph node metastasis of the affected side was investigated.Results Binary logistic regression analysis of cN0-uPTC subregions in the affected central region showed:pre-laryngeal lymph node metastasis,pre-tracheal lymph node metastasis and paratracheal lymph node metastasis were independent risk factors for lymph node metastasis in the affected lateral region(P=0.008,0.016,0.035,respectively).Prelaryngeal lymph node metastasis was an independent risk factor for lymph node metastasis in the affected area Ⅱ (P=0.015).Pre-tracheal lymph node metastasis was an independent risk factor for lymph node metastasis in affected area Ⅲ (P=0.004).Pre-tracheal and para-tracheal lymph node metastasis were independent risk factors for lymph node metastasis in the affected Ⅳ area (P=0.035,0.011,respectively).Conclusions The lymph node metastasis pathway of thyroid cancer had certain regularity.The pre-laryngeal lymph node metastasis has the prediction value for the lymph node metastasis of the affected area Ⅱ.The pre-tracheal lymph node metastasis has the prediction value for the lymph node metastasis of the affected area Ⅲ.The pre-tracheal and paratracheal lymph node metastasis have the prediction value for lymph node metastasis of the affected area Ⅳ.Lymph node dissection in affected areas Ⅲ and Ⅳ needs to be considered in patients with pre-tracheal or paratracheal lymph node metastases.On this basis,lymph node dissection on the affected areas Ⅱ,Ⅲ,and Ⅳ might be considered if there is pre-laryngeal lymph node metastasis at the same time.

Objective:To analyze the factors related to metastasis of contralateral central lymph node (CLN) in cN0 papillary thyroid car-cinoma (PTC) and discuss the indications for CLN dissection. Methods:We enrolled 149 unilateral PTC patients who underwent total thyroidectomy and prophylactic bilateral (CLN) dissection. This work analyzed the relationship of gender, age, extrathyroidal extension, multifocality, thyroiditis, ipsilateral central lymph nodes, and prelaryngeal lymph node with CLNs. Results:The rates of metastasis to ip-silateral and contralateral central compartments were 73.2%and 23.5%, respectively. In univariate analysis, gender, age, tumor size, multifocality, and thyroiditis were not important in predicting contralateral central compartment lymph node metastasis (P=0.792, 0.097, 0.531, 0.269, and 1.000, respectively);by contrast, extrathyroidal extension (P=0.017), prelaryngeal lymph nodes (P=0.006), and ipsilateral CLNs (P<0.001) are related to CLN metastasis. However, multivariate analysis showed that ipsilateral central metastasis was an independent risk factor for lymph node metastasis in the contralateral central region when the number of ipsilateral central metas-tases is≥3 (P=0.010). Conclusion:Extracapsular invasion, prelaryngeal lymph nodes, and ipsilateral CLN influence the metastases of CLN. Bilateral CLN dissection should be performed when the number of ipsilateral central metastases is≥3 and there is merger of ex-tra-laryngeal lymph nodes or capsule invasion.

Objective:To retrospectively analyze the regularity and risk factors of skip metastasis (central lymph node negative and lat-eral lymph node positive) in papillary thyroid carcinoma (PTC). Methods:A total of 521 PTC patients underwent total thyroidectomy and central plus lateral lymph node dissection at The First Affiliated Hospital of Chongqing Medical University from January 2013 to De-cember 2016. Clinicopathological characteristics of the patients were collected and analyzed. Results:Skip metastasis rate of PTC was 8.3％(43/521). Tumors in the upper lobe (OR=3.401, 95％CI:1.770-6.536;P=0.001) and in the lateral part (OR=3.424, 95％CI:1.182-9.920;P=0.023) of the thyroid, as well as age above 45 (OR=2.856, 95％CI:1.488-5.482;P=0.002), were independent risk factors for skip metastases for this disease. Clinically node-negative (cN0) PTC patients with tumors in the upper lobe had higher possibility of skip metastases than those with clinically involved lateral neck nodes(cN1b) (P=0.022). Conclusion:Skip metastasis of PTC is not un-common. Thus, preoperative clinical assessment and imaging examination for lateral lymph node is necessary, especially for PTC pa-tients who are above 45 years old and with tumors in the upper lobe and/or unilateral area of thyroid. The lateral lymph node dissec-tion should be performed when necessary.