In general, bioassay-guided fractionation and isolation of bioactive constituents from botanical materials frequently ended up with the reward of a single compound. However, botanical materials typically exert their therapeutic actions through multi-pathway effects due to the intrinsic complex nature of chemical constituents. In addition, the content of bioactive compounds in botanical materials is largely dependent on humidity, temperature, soil, especially geographical origins, from which rapid and accurate identification of plant materials is pressingly needed. These long-standing obstacles collectively impede the deep exploitation and application of these versatile natural sources. To address the challenges, a new paradigm integrating biogravimetric analyses and machine learning-driven origin classification (BAMLOC) was developed. The biogravimetric analyses are based on absolute qHNMR quantification and in vivo zebrafish model-assisted activity index calculation, by which bioactive substance groups jointly responsible for the bioactivities in all fractions are pinpointed before any isolation effort. To differentiate origin-different botanical materials varying in the content of bioactive substance groups, principal component analysis, linear discriminant analysis, and hierarchical cluster analysis in conjunction with supervised support vector machine are employed to classify and predict production areas based on the detection of volatile organic compounds by E-nose and GC-MS. Expanding BAMLOC to Codonopsis Radix enables the identification of polyacetylenes and pyrrolidine alkaloids as the bioactive substance group for immune restoration effect and accurately determines the origins of plants. This study advances the toolbox for the discovery of bioactive compounds from complex mixtures and lays a more definitive foundation for the in-depth utilization of botanical materials.

Objective:To explore the relationship between the hypertensive snowbirds′ length of migratory stay and their blood pressure control and blood pressure levels.Methods:This study was a cross-sectional study. A population of snowbirds with hypertension was recruited between October and November 2022, and a structured questionnaire was used to collect their self-measured blood pressure and length of stay in Hainan Province. The blood pressure control status is determined based on self-measured blood pressure. According to the self-measured blood pressure to determine whether the blood pressure was well controlled. The associations between snowbirds′ length of stay and their blood pressure control as well as their self-measured blood pressure were analyzed using restricted cubic splines.Results:A total of 362 research subjects were included, 169(46.7%) of whom were male, and their age was (69.7±7.0) years old. The participants′ self-measured systolic blood pressure and diastolic blood pressure were (129.1±16.2) mmHg (1 mmHg=0.133 kPa) and (78.9±10.1) mmHg, respectively. Overall, 174 (48.1%) participants attained adequate blood pressure control. The median length of stay in Wuzhishan City was 7(6, 7) months. There was an inverted U-shaped association between snowbirds′ length of stay and blood pressure control (overall: P=0.023; nonlinearity: P=0.014), where participants with a length of stay of 7 months had the highest rate of blood pressure control. There is a U-shaped curve relationship between length of stay and systolic blood pressure (overall: P=0.001; nonlinearity: P=0.033), and a linear negative correlation with diastolic blood pressure ( β=-1.19, P=0.003). Conclusions:Compared with hypertensive snowbirds with too long or too short lengths of stay, snowbirds who stayed in Wuzhishan City for seven months have better blood pressure control, and systolic blood pressure is also lower.

Objective To investigate the association between single nucleotide polymorphisms(SNPs)of YTHDF1 rs6011668,HNRNPA2B1 rs2070601 and rs76558212 with the risk of gastric cancer.Methods A total of 457 cases with gastric cancer and 525 healthy controls were collected.The candidate SNPs were genotyped using Hi-SNP genotyping methods by multiplex rounds of PCR and high-throughput sequencing;the association between the three SNPs with the risk of gastric cancer was analyzed by test and Logistic regression.Multifactorial logistic regression and Risk Score(RS)model was used to analyze the influence of environmental and genetic factors on the risk of gastric cancer.Results YTHDF1rs6011668 TT genotype carriers had 3.075 times higher risk of gastric cancer than CC genotype carriers(95%CI:1.128～8.382,P = 0.028),and 2.961 times higher risk than CC/TC genotypes carriers(95%CI:1.091～8.033,P = 0.033).Subgroups-analysis revealed that TT genotype mainly increased the risk of gastric cancer in non-tea drinkers,pickled food eaters and fried food eaters(P<0.05).In addition,TT genotype carriers had the increased risk of gastric cancer infiltration,lymph node metastasis,distal metastasis and intermediate to advanced stages(P<0.05).The RS of the case and control groups were calculated by combining environmental and genetic factors.The higher the RS score,the higher the risk of gastric cancer was found in the RS quartile groups.Compared with the RS

Objective:To investigate prognostic factors for acral lentiginous melanoma (ALM) , and to construct a nomogram to verify the predictive value of these factors.Methods:Clinical data on 1 573 patients with ALM were collected from the Surveillance, Epidemiology, and End Results (SEER) database of National Cancer Institute in United States between 2004 and 2015. Data about patients′ age, gender, ulcer status, SEER staging, surgical protocols, T-, N- and M-staging, overall survival rates and disease-specific survival rates were extracted. Chi-square test was used to analyze the correlation of clinical characteristics with overall survival rates and melanoma-specific survival rates, and univariate and multivariate Cox proportional hazards regression models were used to investigate prognostic factors and establish predictive models.Results:Among the 1 537 patients with ALM, 714 were males, 823 were females, 818 were under 64 years of age, and 1 363 were Caucasian. Skin lesions occurred on the lower limbs and buttocks in 1 205 cases, and 974 cases had ulcers; according to the SEER staging, non-spread localized skin lesions were observed in 1 048 cases. There were significant differences in the mortality rate among patients of different ages at diagnosis, different gender, with different ulcer status, surgical status, and at different SEER stages, T-stages, N-stages and M-stages (all P < 0.001) . Univariate and multivariate Cox regression analysis showed that age ≥ 65 years, male, ulcers and distant lymph node metastasis in the SEER staging were associated with increased risk of death in the patients (all P < 0.05) , and the mortality rate was significantly higher in the patients with T2-, T3- or T4-stage ALM than in those with T1-stage ALM (all P < 0.05) , and higher in the patients with N1-, N2- and N3-stage ALM than in those with N0-stage ALM (all P < 0.05) . Conclusion:Age, gender, ulcer status, SEER stage, T-stage and N-stage are independent prognostic factors for overall survival rates and disease-specific survival rates of ALM.

The family of voltage-gated potassium Kv2 channels consists of the Kv2.1 and Kv2.2 subtypes. Kv2.1 is constitutively highly phosphorylated in neurons and its function relies on its phosphorylation state. Whether the function of Kv2.2 is also dependent on its phosphorylation state remains unknown. Here, we investigated whether Kv2.2 channels can be phosphorylated by protein kinase C (PKC) and examined the effects of PKC-induced phosphorylation on their activity and function. Activation of PKC inhibited Kv2.2 currents and altered their steady-state activation in HEK293 cells. Point mutations and specific antibodies against phosphorylated S481 or S488 demonstrated the importance of these residues for the PKC-dependent modulation of Kv2.2. In layer II pyramidal neurons in cortical slices, activation of PKC similarly regulated native Kv2.2 channels and simultaneously reduced the frequency of action potentials. In conclusion, this study provides the first evidence to our knowledge that PKC-induced phosphorylation of the Kv2.2 channel controls the excitability of cortical pyramidal neurons.
Action Potentials ; HEK293 Cells ; Humans ; Protein Kinase C/metabolism* ; Pyramidal Cells/enzymology* ; Shab Potassium Channels/genetics*

Hypertension is an important risk factor for the morbidity and mortality of cardiovascular and cerebrovascular diseases. Improving compliance is the key to the prevention and control of hypertension in community. This paper summarizes the improvement of compliance of patients with hypertension， analyzes the ideas and feasibility of assisting hypertension community prevention and control from three aspects： improving medication compliance， improving behavior compliance and digital intelligent management， and puts forward corresponding suggestions to improve the compliance of patients with hypertension.

Type 2 diabetes mellitus results from a combination of genetic and lifestyle factors, and the prevalence of T2DM is increasing worldwide. At present, there are many drawbacks in the clinical treatment of T2DM, so there is an urgent need for a new treatment method for improvement. In recent years, gene therapy has been proved to reverse T2DM related symptoms such as insulin resistance at the animal level, and no obvious side effects such as hypoglycemia have been found. Therefore, gene therapy may be the main development direction of T2DM therapy in the future. This article reviews the role of fibroblast growth factor related genes such as fibroblast growth factor 21, glucagon like peptide-1, peroxisome proliferator activated receptor and insulin in glucose and lipid metabolism and the development of T2DM, and summarized the application of various viral vectors in gene therapy of T2DM. The significance and existing problems of gene therapy in T2DM are discussed, and the possible development direction of gene therapy T2DM in the future is prospected.

Objective:To provide a theoretical basis for diagnosing and treating recurrent Kawasaki disease based on data analysis of clinical symptoms.Methods:Data analysis of children with recurrent Kawasaki disease admitted to Beijing Children′s Hospital of Capital Medical University from January 2016 to December 2019 was conducted, including comparisons of the initial onset and the recurrence on patients′ clinical features, auxiliary examination and treatment.Results:During the four-year scale, 3 041 children with Kawasaki disease were admitted to the department of Cardiology.The recurrence data involved 65 children[male∶female 3.1∶1, average aged(2.42 ± 2.04) years]. First, children′s fever duration was(5.66 ± 2.37) days in recurrence data, significantly shorter than that of their initial onset.The recurrence data also reported a lower incidence of rash and limb changes, together with respiratory and gastrointestinal symptoms.Then, 19 cases out of the 65 children got coronary artery lesion(CAL) at their initial onset.A relief of CAL was reported from 15 children when the disease recurred, along with 11 new-reported CAL cases.Intravenous immunoglobulin(IVIG) refractory Kawasaki disease cases accounted for nine at the initial onset and 12 at the recurrent onset, respectively.Five IVIG refractory recurrent cases reported significant relief after 2 g/kg IVIG treatment.Conclusion:The recurrent Kawasaki disease in children usually occurs among children under three years old, within the first year after the initial onset.Most of the recurrent cases report a shorter fever duration and less typical clinical symptoms than their first onset.In some cases, IVIG treatment showed effects initially but failed to work when the disease recurred.Therefore, glucocorticoid or infliximab should be considered for further treatment.

Objective: To explore the effect of hyperbaric oxygen preconditioning with different frequency on the survival rate of flap and ischemia-reperfusion injury in rats after transplantation, and to explore the best preconditioning conditions to improve the survival rate of rat flaps after transplantation. Methods: Thirty-six Sprague Dawley rats were randomly divided into four groups according to the random number table method, 9 groups in each group.Four groups of rats were pretreated with hyperbaric oxygen pretreatment for 0, 2, 4, and 6 days before the operation, control group, pretreatment 2 d group, pretreatment 4 d group, and pretreatment 6 d group. Taking the midline of the back of the rat as the axis, an ultra-long random flap with a pedicle at the tail end and about 1 cm from the superior iliac spine was designed and cut to a size of 10.0 cm×2.5 cm. The survival of the flaps in each group was observed and the final survival area and survival rate of the flaps were measured on the 7th day after surgery. On the 7th day after operation, the tissue was taken at a distance of 5 cm from the pedicle, and the histopathology was observed; The content of superoxide dismutase (SOD) and malondialdehyde (MDA) in flap tissue was detected by immunohistochemistry, and the expression rate of positive cells in each group was calculated. Immunofluorescence was used to detect the expression of interleukin-6 (IL-6) in the flap tissue. Results: On the 7th day after the operation, the survival area and survival rate of the transplanted flaps in the hyperbaric oxygen pretreatment group were significantly higher than those in the control group (P<0.05), and the pretreatment 4 d and 6 d groups were significantly higher than the pretreated 2 d group (P<0.05), but there was no significant difference between the pretreated 4 d group and the 6 d group (P=0.095). Pathological observation on the 7th day after operation showed that there was some necrosis in the control group, the vascular cells in the pretreated 2 d group had more vascular structures, and more neovascularization was observed in the pretreated 4 d group. The inflammatory cells were the least in the 6 d pretreatment group, and the neovascularization was the same as the pretreatment 4 d group. The absorbance A value of SOD in the control group was 0.009 7±0.000 3, and the positive expression rate was 20%, which was significantly lower than that in the hyperbaric oxygen pretreatment group. The difference was statistically significant (P<0.05). However, the absorbance A value of MDA in the control group was 0.055 1±0.003 0, and the positive expression rate was 55%, which was significantly higher than that in the hyperbaric oxygen pretreatment group. The difference was statistically significant (P<0.05). Among them, the SOD absorbance A value of the pretreated 2 d group was 0.023 8±0.003 0, and the positive expression rate was 30%, which was lower than the pretreatment 4 d group (absorbance A value 0.046 9±0.003 0, positive expression rate 35%) and 6 d group (absorbance A value 0.047 2±0.003 6, positive expression rate 40%), The MDA absorbance A value of the pretreated 2 d group was 0.037 2±0.003 2, and the positive expression rate was 30%, which was higher than the pretreatment 4 d group (absorbance A value 0.014 7±0.002 4, positive expression rate 5%) and 6 d group (absorbance A value 0.017 0±0.001 8, positive expression rate 10%), the difference was statistically significant (P<0.05). However, there was no significant difference in the expression of SOD and MDA between the pretreated 4 d group and the pretreated 6 d group (P>0.05). The expression of IL-6 in the hyperbaric oxygen pretreatment group was significantly lower than that in the control group (absorbance A value 44.937 0±0.594 0), the difference was statistically significant (P<0.05). The absorbance A value in the pretreated 2 d group was 41.698 0±0.724 0, which was significantly higher than the pretreatment 4 d group (absorbance A value 34.049 0±0.323 0) and 6 d group (absorbance A value 33.524 0±0.639 0). The difference was statistically significant (P<0.05). There was no significant difference in the expression of the pretreated 4 d group compared with the 6 d group (P=0.068). Conclusions Hyperbaric oxygen preconditioning can significantly promote the survival of rat flaps after transplantation. Preoperative hyperbaric oxygen preconditioning once daily for 4 consecutive days, can enhance the tolerance of flap tissue to ischemia and anoxia and reduce tissue ischemia-reperfusion injury.

Objective To explore the aberrance of brain activity in healthy young adults with apolipoprotein E (APOE) ε2, ε3 and ε4 allele by the method of functional connectivity density(FCD). Method Two hundred and thirteen young healthy adults underwent the 3 T resting-state functional MRI, the neuropsychological tests and genotype testing for ε2, ε3 and ε4 allele. Age-and gender-matched individuals,including 14 subjects with APOE ε2,31 subjects with APOE ε4 and 31 subjects with APOE ε3 were enrolled for final analysis.FCD mapping was used to compare the brain functional connective networks among the three groups.All results were corrected with a Gaussian random field(GRF)(voxel-level of P<0.01 and joint cluster-level of P<0.05). Correlation analysis was performed between abnormal short-and long-range FCD values and neuropsychological scores. Results Compared with APOE ε3 carriers, the short-and long-range FCD values of APOE ε2 carriers were increased in the frontal lobe,particularly in the medial prefrontal lobe(37 voxels,t=3.54),anterior cingulate cortex(36 voxels,t=3.19)and orbital frontal cortex(41 voxels, t=3.72), while APOE ε4 carriers showed decreased short-range FCD in the bilateral cuneus(38 voxels, t=-3.68). Moreover, the long-range FCD values of APOE ε4 group were decreased in right orbital frontal cortex(46 voxels,t=-4.56)and increased in the right inferior parietal lobe(31 voxels,t=3.49)compared with that of APOE ε2 group. No significant correlation was detected with Bonferroni correction. Conclusions The opposite FCD alteration in cuneus and inferior parietal lobe might be the early existence of inhibitory and compensatory mechanism modulated by the ε4 allele in the young age, while the increased FCD in frontal lobe might be the underlying protective mechanism of delaying the onset of Alzheimer's disease.