Objective: To analyze the association and dose response relationship between physical activity and inflammatory markers in college students, so as to provide a reference for promoting cardiometabolic health in college students. Methods: A cluster random sampling method was used to select 747 college students from two universities in Hefei, Anhui Province and Shangrao, Jiangxi Province from April to May 2019. Physical activity was assessed by using the International Physical Activity Questionnaire-Short Form (IPAQ-SF), and peripheral blood was collected to detect plasma inflammatory factor levels [including hypersensitive C reactive protein (hsCRP), interleukin-10 (IL-10), interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α)]. The differences between the groups were compared by using the χ 2 test and the Kruskal-Wallis rank sum test, and the association between physical activity and inflammatory markers was analyzed by using the Generalized Linear Model. The dose response relationship between physical activity and inflammatory markers was analyzed using the Restricted Cubic Spline Model. Results: The proportions of low physical activity, moderate physical activity, and high physical activity groups of college students were 15.9%, 53.7% and 30.4%, respectively. The levels of hsCRP, IL-10, IL-1β, IL-6 and TNF-α in the high physical activity group were 0.38(0.21, 1.10)mg/L, 70.74(47.90, 116.43)pg/mL, 1.75(1.21, 2.64)pg/mL, 4.33(2.93, 6.82) pg/mL , 5.27(3.89, 7.30)pg/mL,the levels in the low physical activity group were 0.80(0.31, 1.30)mg/L, 73.88 (47.90, 124.24)pg/mL, 1.88(1.42, 2.81) pg/mL, 4.82 (3.64, 6.67) pg/mL, 5.63 (4.34, 7.62)pg/mL, the levels in the moderate physical activity group were 0.63(0.25, 1.30)mg/L, 89.78(58.21, 127.65)pg/mL, 2.21(1.59, 3.27)pg/mL, 5.15( 3.72 , 7.72)pg/mL, 5.87( 4.63 , 8.00)g/mL, and the differences were statistically significant ( H=10.66, 11.38, 27.79, 14.13, 9.44, P <0.05). After adjusting for variables such as gender, body mass index, smoking, alcohol consumption and health status, the results of Generalized Linear Model showed that compared with the high physical activity group, the low physical activity group ( OR=2.20, 95%CI = 1.46- 3.31) and the moderate physical activity group ( OR=1.65, 95%CI =1.22-2.25) were more likely to have high levels of hsCRP, and the moderate physical activity group was more likely to have high levels of IL-1β ( OR=1.85, 95%CI =1.36-2.51), IL-6 ( OR=1.44, 95%CI =1.06-1.96), and TNF-α ( OR=1.43, 95%CI =1.05-1.94) ( P <0.05). The Restricted Cubic Spline Model showed that there was no linear dose response relationship between the time of moderate to vigorous physical activity weekly and IL-10, IL-6, II-1β, and TNF-α ( P <0.05). Conclusion There is an association between physical activity and inflammation in college students, and moderate to high intensity per week could reduce inflammation levels to promote cardiometabolic health in college students.

Cholangiocarcinoma (CCA) is a fatal malignancy with steadily increasing incidence and poor prognosis. Since most CCA cases are diagnosed at an advanced stage, systemic therapies, including chemotherapy, radiotherapy, targeted therapy, and immunotherapy, play a crucial role in the management of unresectable CCA. The recent advances in targeted therapies and immunotherapies brought more options in the clinical management of unresectable CCA. This review depicts the advances of targeted therapies and immunotherapies for unresectable CCA, summarizes crucial clinical trials, and describes the efficacy and safety of different drugs, which may help further develop precision and individualization in the clinical treatment of unresectable CCA.
Humans ; Cholangiocarcinoma/drug therapy* ; Immunotherapy/methods* ; Bile Duct Neoplasms/drug therapy* ; Molecular Targeted Therapy/methods*

Gelsemium elegans (G. elegans) is an extremely poisonous plant that is widely distributed in southern China and southeastern Asia. G. elegans poisoning events occur frequently in southern China, and are therefore an urgent public health problem requiring multidisciplinary action. However, the toxic components and toxicological mechanisms remain unclear. Here, we describe a systematic investigation on the toxic components of G. elegans, resulting in the isolation and identification of 120 alkaloids. Based on acute toxicity screening, the structure-toxicity relationship of Gelsemium alkaloids was proposed for the first time. Moreover, gelsedine- and humantenine-type alkaloids were detected in the clinical blood sample, and were confirmed to be causative in the poisoning. The most toxic compound, gelsenicine (1), had selective inhibitory effects toward ventral respiratory group (VRG) neurons in the medulla, which is the main brain region controlling respiration in the central nervous system. Gelsenicine (1) strongly inhibited the firing of action potentials in VRG neurons through its ability to stimulate GABA_A receptors, the main receptors involved in inhibitory neurotransmission. Application of GABA_A receptor antagonists successively reversed action potential firing in gelsenicine (1)-treated VRG neurons. Importantly, the GABA_A receptor antagonists securinine and flumazenil significantly increased the survival of poisoned animals. Our findings provide insight into the components and mechanisms of G. elegans toxicity, and should assist the development of effective emergency treatments for G. elegans poisoning.

BACKGROUND:As tissue engineering brings new hope to the worldwide problem of articular cartilage repair,the construction of light-curing 3D printed hydrogel scaffolds with biomimetic composition is of great significance for cartilage tissue engineering. OBJECTIVE:To construct a biomimetic methacryloylated hyaluronic acid/acellular Wharton's jelly composite hydrogel scaffold by digital light processing 3D printing technology,and to evaluate its biocompatibility. METHODS:Wharton's jelly was isolated and extracted from human umbilical cord,then decellulated,freeze-dried,ground into powder,and dissolved in PBS to prepare 50 g/L acellular Wharton's jelly solution.Methylallylated hyaluronic acid was prepared,lyophilized and dissolved in PBS to prepare 50 g/L methylallylated hyaluronic acid solution.Acellular Wharton's jelly solution was mixed with methacrylyacylated hyaluronic acid solution at a volume ratio of 1:1,and was used as bio-ink after adding photoinitiator.Methylacrylylated hyaluronic acid hydrogel scaffolds(labeled as HAMA hydrogel scaffolds)and methylacrylylated hyaluronic acid/acellular Wharton's jelly gel scaffolds(labeled as HAMA/WJ hydrogel scaffolds)were prepared by digital light processing 3D printing technology,and the microstructure,swelling performance,biocompatibility,and cartilage differentiation performance of the scaffolds were characterized. RESULTS AND CONCLUSION:(1)Under scanning electron microscope,the two groups of scaffolds showed a three-dimensional network structure,and the fiber connection of HAMA/WJ hydrogel scaffold was more uniform.Both groups achieved swelling equilibrium within 10 hours,and the equilibrium swelling ratio of HAMA/WJ hydrogel scaffold was lower than that of HAMA hydrogel scaffold(P＜0.05).(2)CCK-8 assay showed that HAMA/WJ hydrogel scaffold could promote the proliferation of bone marrow mesenchymal stem cells compared with HAMA hydrogel scaffold.Dead/live staining showed that bone marrow mesenchymal stem cells grew well on the two groups of scaffolds,and the cells on the HAMA/WJ hydrogel scaffolds were evenly distributed and more cells were found.Phalloidine staining showed better adhesion and spread of bone marrow mesenchymal stem cells in HAMA/WJ hydrogel scaffold than in HAMA.(3)Bone marrow mesenchymal stem cells were inoculated into the two groups for chondrogenic induction culture.The results of qRT-PCR showed that the mRNA expressions of agglutinoglycan,SOX9 and type Ⅱ collagen in the HAMA/WJ hydrogel scaffold group were higher than those in the HAMA hydrogel scaffold group(P＜0.05,P＜0.01).(4)These findings indicate that the digital light processing 3D bioprinting HAMA/WJ hydrogel scaffold can promote the proliferation,adhesion,and chondrogenic differentiation of bone marrow mesenchymal stem cells.

The five movements and six qi theory(hereinafter referred to as"movement qi theory")runs through Liu Wansu's med-ical theoretical system,which is mainly reflected in its influence on the theory of pathogenesis,the creation of fiery heat theory,and the influence of Liu Wansu's clinical diagnosis and treatment thoughts.The influence of movement qi theory on Liu Wansu's pathogen-esis theory includes three aspects:six qi alternation on pathogenesis,five movement hyperactivities on pathogenesis,and the root and branch of movement qi on pathogenesis.Liu's understanding of the pathogenesis of six qi and the philosophical thought of"water is good and fire is evil"mainly influenced the creation of Liu Wansu's"fire theory".The influence of movement qi theory on Liu Wansu's clinical diagnosis and treatment thoughts is mainly reflected in the classification of viscera,meridian and collateral diseases based on the theory of root and branch of middle qi,the diagnosis of pulses based on movement qi theory,the deduction of disease transmission and change using movement qi thinking,and the preparation of medicines based on qi.Liu Wansu initiated the innovation and debate of medical theory in the Jin and Yuan Dynasties,and had a profound impact on the rise of warm febrile diseases in the Ming and Qing Dynasties.

Humans ; Consensus ; Pancreatic Neoplasms/therapy* ; Neuroendocrine Tumors/therapy*

China has classified the Corona Virus Disease 2019(COVID-19) as a statutory category B infectious disease and managed it according to Category B since January 8, 2023.In view that Omicron variant is currently the main epidemic strain in China, in order to guide the treatment of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) infection in children with the times, refer to the Diagnosis and Treatment Protocol for Novel Coronavirus Infection (Trial 10 th Edition), Expert Consensus on Diagnosis, Treatment and Prevention of Novel Coronavirus Infection in Children (Fourth Edition) and the Diagnosis and Treatment Strategy for Pediatric Related Viral Infections.The Expert Consensus on the Diagnosis, Treatment and Prevention of Novel Coronavirus Infection in Children (Fifth Edition) has been formulated and updated accordingly on related etiology, epidemiology, pathogenic mechanism, clinical manifestations, auxiliary examination, diagnosis and treatment, and added key points for the treatment of COVID-19 related encephalopathy, fulminating myocarditis and other serious complications for clinical reference.

Objective:To investigate the clinical efficacy of thunder-fire moxibustion combined with external application of Chinese herbal ointment at the trigger point on lumbodorsal myofascial pain syndrome of cold-damp stagnation type.Methods:A total of 90 patients with lumbodorsal myofascial pain syndrome of cold-damp stagnation type admitted to Zhejiang Provincial Hospital of Integrated Traditional Chinese and Western Medicine from September 2021 to April 2022 were included in this study. They were randomly divided into three groups ( n = 30/group) using the random number table method. Patients in the Chinese herbal ointment group were treated by external application of Chinese herbal ointment at the trigger point. Patients in the thunder-fire moxibustion group were treated with thunder-fire moxibustion. Patients in the combined therapy group were treated with thunder-fire moxibustion combined with external application of Chinese herbal ointment at the trigger point. All patients were treated for 28 consecutive days. Clinical efficacy was compared among the three groups. Before and after treatment, the Visual Analogue Scale score, local tenderness score, Oswestry Disability Index score and Pittsburgh Sleep Quality Index score were compared among the three groups. Results:Total response rate (96.67%) in the combined therapy group was significantly higher than 73.33% in the thunder-fire moxibustion group and 66.67% in the Chinese herbal ointment group ( χ2 = 9.01, 4.70, both P < 0.05). Visual Analogue Scale score and local tenderness score in the combined therapy group were (1.96 ± 0.93) points and (1.00 ± 0.69) points, respectively, which were significantly lower than (2.43 ± 0.87) points and (1.37 ± 0.56) points in the thunder-fire moxibustion group and (2.77 ± 0.86) points and (1.50 ± 0.57) points in the Chinese herbal ointment group ( F = 6.22, 5.38, both P < 0.05). The Oswestry Disability Index score in the combined therapy group was (19.80 ± 3.80) points, which was significantly lower than (22.30 ± 2.82) points in the thunder-fire moxibustion group and (23.60 ± 3.71) points in the Chinese herbal ointment group ( F = 9.07, both P < 0.05). After treatment, the Pittsburgh Sleep Quality Index score in the combined therapy group was (5.30 ± 1.12) points, which was significantly lower than (6.50 ± 1.33) points in the thunder-fire moxibustion group and (6.73 ± 1.41) points in the Chinese herbal ointment group ( F = 10.59, both P < 0.05). Conclusion:Thunder-fire moxibustion combined with external application of Chinese herbal ointment at the trigger point is highly effective on lumbodorsal myofascial pain syndrome of cold-damp stagnation type than monotherapy. The combined therapy can markedly reduce pain and greatly improve lumbodorsal function and sleep quality.

Objective:This study comprehensively analyzed the genomic characterizations of human parainfluenza virus type 3 (HPIV3) strains circulating in six provinces and cities of China (Beijing, Henan, Jilin, Anhui, Gansu, and Shandong) during the period of 2019-2020. The aim was to elucidate the intricate genetic variations and molecular evolutionary trends within the HPIV3 genome.Methods:Based on genotypic differentiation, genetic divergence, and spatial and temporal distribution, 12 representative HPIV3 strains (including 7 of C3a subtype, 2 of C3b subtype and 3 of C3f subtype) were selected from the aforementioned provinces, and the complete genome sequence was successfully obtained by overlapping amplification of fragments using nested RT-PCR. Subsequently, a complete genome database of global representative HPIV3 strains was constructed and analyzed using bioinformatics tools.Results:The length of complete genome of the 12 HPIV3 strains in the present study varied between 15 227 bp and 15 370 bp, the G+ C content ranged from 35.1% to 35.3% and the nucleotide identity intermediated from 97.6% to 99.6%. Compared with the prototype strain (GenBank accession number: NC_001796.2), the nucleotide identity of 12 HPIV3 strains ranged from 94.2% to 94.5%. Analysis of the complete genome of HPIV3 available in China and globally showed that the genomic variation of HPIV3 was mainly shaped by substitution mutations, and no base deletions or gene recombination were observed.Only a six-base insertion (ATTAAA) was found in the F gene’s 3′UTR region of a representative strain originating from Jilin province (CHN/Jilin036/2019/C3b) in this study, and its potential pathogenic significance needs to be further investigated. Amino acid analysis of the encoded proteins revealed that the C3a lineage of HPIV3, widely prevalent both in China and worldwide, exhibits lineage-specific mutation sites in the N, P and L proteins. Furthermore, within the Chinese prevalent C3a strains, a distinctive mutation site (N216S) in L protein was also identified. Notably, specific variant sites have not been found in Chinese C3b and C3f branch strains. Based on the complete genome, the comprehensive evolutionary analysis showed that the time to the most recent common ancestor (tMRCA) of global HPIV3 strains was estimated to 1927 (95% HPD: 1901-1945), with an average molecular evolutionary rate of 5.29 × 10 -4 substitutions/site/year, while the average molecular evolutionary rate of HPIV3 strains in China is 5.24 × 10 -4 substitutions/site/year. In addition, each gene of HPIV3 was subjected to negative selection pressure, with the P, HN and F genes showing the most significant nucleotide variation and higher rates of molecular evolution than the other genes. Conclusions:This study reveals that the complete genome of HPIV3 strains circulating in six provinces and cities of China tend to evolve conservatively. Moreover, substitution emerge as the main driving force for molecular evolution of HPIV3.

Objective:To explore the effect of nursing interventions based on systematic concept in elderly patients with type 2 diabetes.Methods:From May 2018 to August 2019, 120 elderly patients with type 2 diabetes in Hangzhou Red Cross Hospital were selected by convenience sampling. The patients were randomly divided into observation group and control group with 60 cases each. Patients in each group were given nursing interventions based on systematic concept and routine nursing respectively. The anxiety, depression, benefit finding and coping modes of the two groups were compared before and after the intervention.Results:Before the intervention, there was no statistical difference between the two groups in the scores of anxiety, depression, benefit finding and behavior pattern ( P>0.05) . After intervention, the scores of anxiety and depression in the two groups decreased, and the scores in the observation group were lower than those in the control group, with statistically significant differences ( P<0.05) . After the intervention, the scores of benefit finding of the two groups increased, and that of the observation group was higher than that of the control group, and the differences were statistically significant ( P<0.05) . After intervention, the scores of confronting of the two groups increased, and that of observation group was higher than that of the control group, and the differences were statistically significant ( P<0.05) . After intervention, the scores of avoidance and resignation in the two groups decreased, and the scores in the observation group were lower than those in the control group, with statistically significant differences ( P<0.05) . Conclusions:Systematic concept nursing can reduce the anxiety and depression of elderly patients with type 2 diabetes, improve the benefit finding, increase the sense of benefit, and urge patients to adopt a positive coping style to deal with the disease.