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.

Objective:To discuss the promotive effect of Shengji Yuhong Ointment extract(SYOE)on skin wound healing of zebrafish,and to clarify its mechanism.Methods:A total of 320 wild-type AB strain zebrafish were used to establish a wound model by making an incision on the lateral abdomen.The zebrafish were randomly divided into control group,low dose of SYOE group(raised in water containing 0.625 mg·L-1 SYOE),high dose of SYOE group(raised in water containing 1.250 mg·L-1 SYOE),and allantoin group(raised in water containing 1.000 mng·L-1 allantoin),and there were 80 zebrafish in each group.The wound areas were recorded by photographs on days 7,14,and 21 after injury,and the wound healing rates were calculated.The skin tissue samples from the wound sites of the zebrafish in various groups were collected at different time points to prepare histological sections.HE staining was used to observe the widths of skin wound edges of the zebrafish on days 0,7,14,and 21 in various groups;Sirius red staining was used to detect the collagen levels in the wound tissues of the zebrafish on days 2,4,6,and 8 after injury in various groups;enzyme-linked immunosorbent assay(ELISA)was used to detect the levels of type Ⅰ collagen(Col Ⅰ)and α-smooth muscle actin(α-SMA)in the wound tissues on day 4 after injury;real-time quantitative PCR(RT-qPCR)was used to analyze the mRNA expression levels of Col Ⅰ-encoding genes(col1a1a,col1a1b,and col1a2)and α-SMA as wall as key factors of the transforming growth factor β(TGF-β)/Smad signaling pathway(tgfb1a,smad2,and smad3a)in the wound tissues of the zebrafish in various groups on day 4 after injury.Results:The wound healing assessment results showed that compared with control group,the wound healing rates of the zebrafish in low dose of SYOE group,high dose of SYOE group,and allantoin group were significantly increased on days 7,14,and 21 after injury(P＜0.05 or P＜0.01);the wound healing rate in high dose of SYOE group achieved 84％on day 21.The HE staining results showed that compared with control group,the widths of skin wound edges of the zebrafish in low dose of SYOE group,high dose of SYOE group,and allantoin group were significantly decreased on days 14 and 21 after injury(P＜0.05 or P＜0.01).The Sirius red staining results showed that compared with control group,the collagen levels in the skin wound tissue of the zebrafish in low dose of SYOE group,high dose of SYOE group,and allantoin group were significantly increased on days 6 and 8 after injury(P＜0.01).The ELISA results showed that on day 4 after injury,compared with control group,the levels of Col Ⅰ and α-SMA in the skin wound tissue of the zebrafish in low dose of SYOE group,high dose of SYOE group,and allantoin group were significantly increased(P＜0.05 or P＜0.01).The RT-qPCR results showed that on day 4 after injury,compared with control group,the expression levels of col1a1b,col1a2,α-SMA,tgfb1a,and smad2 mRNA in the skin wound tissue of the zebrafish in low dose of SYOE group were significantly increased(P＜0.05 or P＜0.01),while the expression levels of col1a1a,col1a1b,col1a2,α-SMA,tgfb1a,smad2,and smad3a mRNA in the skin wound tissue of the zebrafish in high dose of SYOE group and allantoin group were significantly increased(P＜0.01).Conclusion:SYOE can increase the collagen deposition in skin wound of zebrafish,promote wound healing,and upregulate the expression of genes related to the TGF-β/Smad signaling pathway.

Objective:To investigate the effect of Chinese Herbal Anti-Alopecia and Hair Growth Solution(CHAaHGS)on the hair growth through in vitro experiments on the human dermal papilla cells(HDPCs),in vivo experiments in the C57BL/6 mice,and human efficacy tests,and to clarify its potential mechanism.Methods:The HDPCs were divided into control group,CHAaHGS group,and minoxidil group.MTT method was used to detect the proliferation activities of HDPCs in various groups;enzyme-linked immunosorbent assay(ELISA)method was used to detect the levels of vascular endothelial growth factor(VEGF),hepatocyte growth factor(HGF),insulin-like growth factor-1(IGF-1),and transforming growth factor β1(TGF-β1)in the supernatant of HDPCs in various groups;real-time fluorescence quantitative PCR(RT-qPCR)method was used to detect the expression levels of VEGF,HGF,IGF-1,TGF-β1,and alkaline phosphatase(ALP)mRNA in the HDPCs in various groups;Western blotting method was used to detect the expression levels of β-catenin,dishevelled segment polarity protein 1(DVL1),glycogen synthase kinase 3β(GSK-3β),phosphorylated GSK-3β(p-GSK-3β),and wingless-type MMTV integration site family member 3a(Wnt3a)proteins in the HDPCs in various groups.A total of 18 mice were randomly divided into control group,CHAaHGS group,and minoxidil group,with 6 mice in each group.The mouse hair loss model was established using hair removal cream,and corresponding drug treatments were administered immediately after hair removal.The lengths and weights of newly grown hair on day 21 of the mice in various groups were detected;HE staining was used to observe the morphology of hair follicles in the dorsal depilated skin areas of the mice in various groups on day 7;ELISA method was used to detect the levels of VEGF,HGF,IGF-1,and TGF-β1 in the skin tissue of dorsal depilated areas of the mice in various groups.Sixty subjects were randomly divided into control group and CHAaHGS group,with 30 subjects in each group.The numbers of hair loss and hair densities of the subjects in various groups were detected at weeks 0,4,8,and 12.Results:The MTT assay results showed that compared with control group,the proliferation activity of the cells in 50 mg·L-1CHAaHGS group was significantly increased(P＜0.01).The ELISA assay results showed that compared with control group,the levels of VEGF,HGF,and IGF-1 in the cell supernatant of HDPCs in CHAaHGS group were significantly increased(P＜0.05 or P＜0.01),and the TGF-β1 level was significantly decreased(P＜0.01).The RT-qPCR results showed that compared with control group,the expression levels of VEGF,HGF,IGF-1,and ALP mRNA in the cells in CHAaHGS group were significantly increased(P＜0.05 or P＜0.01),and the TGF-β1 mRNA expression level was significantly decreased(P＜0.01).The Western blotting results showed that compared with control group,the expression levels of β-catenin,DVL1,p-GSK-3βand Wnt3a proteins in the cells in CHAaHGS group were significantly increased(P＜0.05 or P＜0.01),and the GSK-3β protein expression level was significantly decreased(P＜0.05).In animal experiments,on day 21,compared with control group,the length of newly grown hair of the mice in CHAaHGS group was significantly increased(P＜0.05),and the hair weight was significantly increased(P＜0.01).On day 7,the HE staining results showed that compared with control group,the hair follicle spacing of the mice in CHAaHGS group was significantly decreased(P＜0.05),and the number of hair follicles was significantly increased(P＜0.01);the ELISA assay results showed that compared with control group,the levels of VEGF,HGF,and IGF-1 in skin tissue of dorsal depilated area of the mice in CHAaHGS group were significantly increased(P＜0.05 or P＜0.01),and the TGF-β1 level was significantly decreased(P＜0.05).In human efficacy test,compared with control group,the number of hair loss of the subjects in CHAaHGS group was significantly decreased at week 12(P＜0.01),and the local hair density was increased(P＜0.05).Conclusion:CHAaHGS promotes hair growth,and the mechanism may be related to its ability to increase the proliferation activity of HDPCs,induce the secretion of VEGF,HGF,and IGF-1,and activate the Wnt/β-catenin signaling pathway.

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.