ObjectiveTo explore the possible mechanisms of electroacupuncture at Fengchi （GB 20）， Waiguan （TE 5）， and Yanglingquan （GB 34） in treating chronic migraine from the perspective of nociceptive sensitization. MethodsForty SPF-grade SD rats were randomly divided into blank group， model group， electroacupuncture group， electroacupuncture + agonist group， and inhibitor group， with 8 rats in each group. Except for the blank group， rats were injected intraperitoneally with nitroglycerin to establish a chronic migraine rat model. After successful modeling， the electroacupuncture group received electroacupuncture at bilateral "Fengchi" （GB 20）， "Waiguan" （TE 5）， and "Yanglingquan" （GB 34） for 30 minutes each session. The electroacupuncture + agonist group received the same electroacupuncture treatment and additional injection of protein kinase C （PKC） agonist Phorbol 12-myristate 13-acetate （1.0 ng/μl， 25 μl） via the infraorbital foramen. The inhibitor group received PKC inhibitor Chelerythrine Chloride （1.0 ng/μl， 10 μl） via the infraorbital foramen. The blank group， model group， and inhibitor group underwent restraint for 30 minutes without other interventions. All groups were continuously intervened for 5 days. After the intervention， the nociceptive thresholds （mechanical and thermal pain） of the periorbital area and hind paw were measured. The expression levels of transient receptor potential vanillic acid subtype 1 （TRPV1）， phosphorylated TRPV1 （p-TRPV1）， PKC proteins， Trpv1， Pkc mRNA， and the average fluorescence intensity of transient receptor potential vanillic acid subtype 1 （TRPV1） and PKC in the trigeminal ganglion were detected using Western Blot， real-time fluorescence quantitative PCR， and immunofluorescence methods. ResultsCompared with the blank group， the mechanical and thermal pain thresholds of the periorbital area and hind paw were reduced in the model group， and the protein levels of TRPV1， PKC， p-TRPV1， as well as the mRNA expression of Trpv1 and Pkc， and the average fluorescence intensity of TRPV1 and PKC in the trigeminal ganglion significantly increased （P＜0.05 or P＜0.01）. Compared with the model group， the electroacupuncture group exhibited increased mechanical and thermal pain thresholds in the periorbital and hind paw areas， and decreased protein levels of TRPV1， PKC， p-TRPV1， mRNA expression of Trpv1 and Pkc， and average fluorescence intensity of TRPV1. In the electroacupuncture + agonist group， the average fluorescence intensity of TRPV1 in the trigeminal ganglion decreased. The inhibitor group exhibited increased mechanical pain thresholds in the periorbital area and thermal pain thresholds in the hind paw， along with decreased protein levels of TRPV1， PKC， p-TRPV1， and the average fluorescence intensity of TRPV1 and PKC （P＜0.05 or P＜0.01）. Compared with the electroacupuncture group， the electroacupuncture + agonist group showed an increase in the protein levels of TRPV1， PKC， p-TRPV1， and the mRNA expression of Trpv1 （P＜0.05 or P＜0.01）. ConclusionElectroacupuncture at the "Fengchi" （GB 20）， "Waiguan" （TE 5）， and "Yanglingquan" （GB 34） acupoints can increase the mechanical and thermal pain thresholds in chronic migraine rats and alleviate nociceptive sensitization. The mechanism may be related to the inhibition of PKC/TRPV1 pathway.

Objective:To analyze the clinical characteristics,diagnosis and treatment of pediatric myocardial infarction (MI) patients with coronary artery lesions (CAL) after Kawasaki disease (KD).Methods:Clinical data including baseline characteristics, KD and CAL information, clinical symptoms at MI onset, electrocardiogram (ECG) and imaging findings, MI treatment, and clinical outcomes of 41 MI patients with CAL after KD admitted to the Children′s Hospital of Fudan University from January 2017 to August 2024 were analyzed retrospectively.Results:(1) Demographic characteristics: a total of 41 patients were included (36 males and 5 females). The age at MI was 4.6 (2.3, 5.7) years, and time from KD onset to MI was 397 (50, 1 095) d. (2) Treatment of acute KD: only 15 patients (37%) received standard initial treatment within 10 days of KD onset with intravenous immunoglobulin 2 g/kg. The other 26 cases (63%) received non-standard treatment or no treatment. (3) Treatment of CAL before MI: the time from KD onset to CAL was 14 (10, 116) d, with CAL not identified before MI onset in 15 patients. Among the 26 cases diagnosed with CAL prior to MI, 9 cases received only single or dual antiplatelet drug, of which 7 cases received oral dipyridamole. The remaining 16 cases received antiplatelet drug combined with warfarin, but only 1 case achieved the target international standardized ratio of 1.5-2.5. Out of all 41 cases, only 1 case (2%) received standard antithrombotic treatment before MI onset. (4) Clinical symptoms of MI: at MI onset, 32 patients presented with different clinical symptoms, with typical MI symptoms such as chest tightness, chest pain, precordial discomfort in 18 cases, and cardiopulmonary arrest accompanied by syncope or convulsions in 10 cases. Other non-specific symptoms included abdominal pain, nausea, vomiting and pallor. Nine patients were asymptomatic and were found to have silent MI on follow-up. (5) ECG and imaging findings: ECG showed ST-T changes in 33 cases, and abnormal Q waves, and arrhythmias in the remaining patients; echocardiography indicated coronary artery aneurysm with thrombosis in 27 cases, reduced left ventricular ejection fraction in 18 cases, abnormal wall motion in 15 cases, and ventricular aneurysm in 3 cases. Thirty-seven patients underwent coronary angiography and (or) multi-slice spiral CT angiography, with 39 occluded vessels and 3 severe stenosis (≥75%), all of which were caused by giant aneurism with thrombus formation. (6) Treatment of MI: of the 32 patients with acute MI, 9 patients received successful cardiopulmonary resuscitation, 7 patients received intravenous thrombolysis, and 1 patient underwent percutaneous coronary balloon angioplasty. All of these patients received dual antiplatelet drugs and low-molecular-weight heparin at therapeutic doses following MI treatment. Sixteen patients received coronary artery bypass graft (CABG) treatment, all of which were successful. (7) Outcomes: the follow-up time was 994 (215, 1 832) d. Thirty-one patients showed improvement, 5 patients experienced disease progression or no change, 1 patient died, and 4 patients were lost to follow-up.Conclusions:MI in children with CAL after KD often occurs within 1 year after the onset of KD. MI can present with atypical clinical symptoms in children. CABG is the main treatment option in children severe CAL after KD who developed MI.

Objective To construct the performance evaluation index system of specialist cooperation alliance in hos-pital-community in order to scientifically evaluate the effect of the construction of the specialist cooperation alliance.Methods By searching literature related to the construction of specialized league,sort out national and local policy documents,and the"structure-process-result"model was adopted to initially construct the index system.The ex-pert letter consultation form of the indicator system was formed through the discussion of the special group,two rounds of Delphi expert consultation were carried out to determine the evaluation indicator system,and the weight coefficient of each indicator was determined by the simultaneous application of analytic hierarchy process.Results The effective recovery rates of the two rounds of questionnaire were 84.62％and 100.00％,respectively.The positive de-gree of experts was high,and the average authority degree of experts was 0.864.The importance,operability,sen-sitivity Kendall's W coefficient and x2 test value of all indexes were P＜0.05.Finally,an evaluation index system covering 9 first-level indicators and 25 second-level indicators was established.Conclusion The constructed perfor-mance evaluation index is scientific and reliable.The practical application shows that it can be used as a tool to evalu-ate the effect of integrated,continuous and collaborative health service delivery in hospital-community.

Objective To construct the performance evaluation index system of specialist cooperation alliance in hos-pital-community in order to scientifically evaluate the effect of the construction of the specialist cooperation alliance.Methods By searching literature related to the construction of specialized league,sort out national and local policy documents,and the"structure-process-result"model was adopted to initially construct the index system.The ex-pert letter consultation form of the indicator system was formed through the discussion of the special group,two rounds of Delphi expert consultation were carried out to determine the evaluation indicator system,and the weight coefficient of each indicator was determined by the simultaneous application of analytic hierarchy process.Results The effective recovery rates of the two rounds of questionnaire were 84.62％and 100.00％,respectively.The positive de-gree of experts was high,and the average authority degree of experts was 0.864.The importance,operability,sen-sitivity Kendall's W coefficient and x2 test value of all indexes were P＜0.05.Finally,an evaluation index system covering 9 first-level indicators and 25 second-level indicators was established.Conclusion The constructed perfor-mance evaluation index is scientific and reliable.The practical application shows that it can be used as a tool to evalu-ate the effect of integrated,continuous and collaborative health service delivery in hospital-community.

Objective:To analyze the clinical characteristics,diagnosis and treatment of pediatric myocardial infarction (MI) patients with coronary artery lesions (CAL) after Kawasaki disease (KD).Methods:Clinical data including baseline characteristics, KD and CAL information, clinical symptoms at MI onset, electrocardiogram (ECG) and imaging findings, MI treatment, and clinical outcomes of 41 MI patients with CAL after KD admitted to the Children′s Hospital of Fudan University from January 2017 to August 2024 were analyzed retrospectively.Results:(1) Demographic characteristics: a total of 41 patients were included (36 males and 5 females). The age at MI was 4.6 (2.3, 5.7) years, and time from KD onset to MI was 397 (50, 1 095) d. (2) Treatment of acute KD: only 15 patients (37%) received standard initial treatment within 10 days of KD onset with intravenous immunoglobulin 2 g/kg. The other 26 cases (63%) received non-standard treatment or no treatment. (3) Treatment of CAL before MI: the time from KD onset to CAL was 14 (10, 116) d, with CAL not identified before MI onset in 15 patients. Among the 26 cases diagnosed with CAL prior to MI, 9 cases received only single or dual antiplatelet drug, of which 7 cases received oral dipyridamole. The remaining 16 cases received antiplatelet drug combined with warfarin, but only 1 case achieved the target international standardized ratio of 1.5-2.5. Out of all 41 cases, only 1 case (2%) received standard antithrombotic treatment before MI onset. (4) Clinical symptoms of MI: at MI onset, 32 patients presented with different clinical symptoms, with typical MI symptoms such as chest tightness, chest pain, precordial discomfort in 18 cases, and cardiopulmonary arrest accompanied by syncope or convulsions in 10 cases. Other non-specific symptoms included abdominal pain, nausea, vomiting and pallor. Nine patients were asymptomatic and were found to have silent MI on follow-up. (5) ECG and imaging findings: ECG showed ST-T changes in 33 cases, and abnormal Q waves, and arrhythmias in the remaining patients; echocardiography indicated coronary artery aneurysm with thrombosis in 27 cases, reduced left ventricular ejection fraction in 18 cases, abnormal wall motion in 15 cases, and ventricular aneurysm in 3 cases. Thirty-seven patients underwent coronary angiography and (or) multi-slice spiral CT angiography, with 39 occluded vessels and 3 severe stenosis (≥75%), all of which were caused by giant aneurism with thrombus formation. (6) Treatment of MI: of the 32 patients with acute MI, 9 patients received successful cardiopulmonary resuscitation, 7 patients received intravenous thrombolysis, and 1 patient underwent percutaneous coronary balloon angioplasty. All of these patients received dual antiplatelet drugs and low-molecular-weight heparin at therapeutic doses following MI treatment. Sixteen patients received coronary artery bypass graft (CABG) treatment, all of which were successful. (7) Outcomes: the follow-up time was 994 (215, 1 832) d. Thirty-one patients showed improvement, 5 patients experienced disease progression or no change, 1 patient died, and 4 patients were lost to follow-up.Conclusions:MI in children with CAL after KD often occurs within 1 year after the onset of KD. MI can present with atypical clinical symptoms in children. CABG is the main treatment option in children severe CAL after KD who developed MI.

Objective To analyze the spatio-temporal characteristics and influencing factors of local hospitalization proportion in 57 counties of Guangdong Province.Methods Using local hospitalization proportion and related indicators in 57 counties of Guangdong Province from 2016 to 2019,temporal trend analysis and spatial autocorrelation analy-sis were used to analyze the spatiotemporal characteristics.Bayesian spatio-temporal model was used to explore in-fluencing factors of local hospitalization proportion.Results The local hospitalization proportion in Guangdong Province rose from 79.8%in 2016 to 84.1%in 2019,showing an increasing trend and the overall characteristics of"high in the west and low in the east".The global and local spatial autocorrelation results show that there is a spatial correla-tion in the local hospitalization proportion within the counties of Guangdong Province,and spatial aggregation has formed in some areas.There is a"high"aggregation in western Guangdong,and a"low"aggregation in eastern Guangdong Province.The Bayesian spatio-temporal model shows that the number of people with a bachelor's de-gree or above per 1 000 population and the CMI of county hospitals had an effect on the local hospitalization propor-tion(P＜0.05).Conclusion Guangdong Province can improve the medical service capacity of county hospitals sub-stantially and introduce or train high-quality talents through multiple measures,and continue to improve the local hospitalization proportion.

As a supplement to randomized controlled trials， observational studies can provide evidence for the effectiveness of traditional Chinese medicine （TCM） treatment measures. They can also study influencing factors of diseases， etiology， and prognosis. However， there is a confounding effect due to the lack of randomization， which seriously affects the causal inference between the study factors and the outcome， resulting in confounding bias. Therefore， identifying and controlling confounding factors are key issues to be addressed in TCM observational studies. According to the causal network and the characteristics of TCM theory， confounding factors can be categorized into measured and unmeasured confounding factors. In addition， attention must be paid to identifying confounding factors and intermediate variables， as well as the interaction between confounding factors and study factors. For methods of controlling confounding factors， measured confounding factors can be controlled by stratification， multifactor analysis， propensity scores， and disease risk scores. Unmeasured and unknown confounding factors can be corrected using instrumental variable methods， difference-in-difference methods， and correction for underlying event rate ratios. Correcting and controlling confounding factors can ensure a balance between groups， and confounding bias can be reduced. In addition， methods such as sensitivity analysis and determination of interactions make the control of confounding factors more comprehensive. Due to the unique characteristics of TCM， observational studies of TCM face unique challenges in identifying and controlling confounding factors， including the ever-changing TCM treatment measures received by patients， the often-overlooked confounding effects in the four diagnostic information of TCM， and the lack of objective criteria for TCM evidence-based diagnosis. Some scholars have already conducted innovative explorations to address these issues， providing a methodological basis for conducting higher-quality TCM observational studies， so as to obtain more rigorous real-world evidence of TCM and gradually develop quality evaluation criteria for OS that are consistent with the characteristics of TCM.

【Objective】 To evaluate the screening efficacy and practical value of the portable microfluidic biochemical analyzer in the detection of blood donors before blood donation. 【Methods】 Blood donor samples, clinical blood samples and constant quality control products were collected. Referring to the documents of ISO15189 and National Health Industry Standard, the precision and accuracy of hemoglobin (Hb) and alanine aminotransferase (ALT) were verified and compared with other detection systems. 【Results】 The MS200 biochemistry instrument has an intra-batch precision of 1.40% to 1.46%, inter-batch precision of 1.91% to 1.94%, and correctness bias of -0.9% to -1.3% for Hb test, and an intra-batch precision of 3.77% to 4.86%, inter-batch precision of 4.92% to 6.02%, and correctness bias of -3.0% to -4.8% for ALT test, which were within the range of quality requirements of industry standard. Comparison of Hb test results between MS200 biochemistry and Hb201 analyser on 1 189 peripheral blood samples from donors showed no statistically significant difference (P>0.05). 65 samples showed positive correlation between MS200 biochemistry and XS-900i automated hematology analyzer on Hb test results (R²=0.986, P=0.000). Correlation analysis of all the results of ALT detection by MS200 biochemical analyzer and AU480 biochemical analyzer in 1 065 samples showed a positive correlation (R²=0.965, P=0.000). The elevated ALT samples did not affect the Hb test results, and the samples with abnormal Hb value did not affect the ALT test results, with no interference between the two items in the detection. 【Conclusion】 The MS200 biochemical analyzer based on microfluidic technology has reliable methodological performance and can meet the need of pre-donation testing.

Objective:To analyze the distribution of clopidogrel metabolism-related gene variability in Kawasaki disease (KD) children with coronary artery lesions (CAL) across different age groups and the impact of genetic variability on the efficacy of clopidogrel antiplatelet therapy.Methods:A retrospective cohort study was conducted. Clinical data were collected from 46 KD children with CAL who were hospitalized in the Cardiovascular Center of Children′s Hospital of Fudan University between January 2021 and August 2022 and were treated with clopidogrel, including gender, age, body mass index, course of KD, CAL severity grade, and baseline platelet count. According to their age, the children were divided into ≥2-year-old group and <2-year-old group. Their platelet responsiveness was assessed by adenosine diphosphate-induced platelet inhibition rate (ADPi) calculated via thromboelastography, and children were categorized into high on-treatment platelet reactivity (HTPR) and normal on-treatment platelet reactivity (NTPR) groups. Genotypes of CYP2C19, PON1 and ABCB1 were detected. The t test, one-way analysis of variance and Chi-square test were used for intergroup comparison. Results:Among the 46 KD children with CAL, 34 were male and 12 were female; 37 were ≥2-year-old and 9 were <2-year-old; 25 cases were in the HTPR group and 21 cases were in the NTPR group, with 19 HTPR and 18 NTPR in the ≥2-year-old group, and 6 HTPR and 3 NTPR in the <2-year-old group. Genetic analysis showed that 92 alleles among the 46 children, with frequencies of CYP2C19*1, CYP2C19*2, CYP2C19*3, CYP2C19*17, PON1 192Q, PON1 192R, ABCB1 3435C, ABCB1 3435T at 59% (54/92), 32% (29/92), 9% (8/92), 1% (1/92), 36% (36/92), 64% (59/92), 63% (58/92) and 37% (34/92), respectively. Analysis of the impact of genotype on ADPi revealed that in children aged ≥2 years, those with CYP2C19*1/*3 genotype had significantly lower ADPi than those with CYP2C19*1/*1 genotype ((34±15)% vs. (61±29)%, t=2.18, P=0.036). There were also no significant difference in ADPi among children with PON1 192Q homozygous, PON1 192R heterozygote and PON1 192R homozygous genotypes ((40±22)% vs. (52±33)% vs. (65±27)%, F=2.17, P=0.130), or among those with ABCB1 3435C homozygous, ABCB1 3435T heterozygote and ABCB1 3435T homozygous genotypes ((55±34)% vs. (60±27)% vs. (49±24)%, F=0.33, P=0.719). In <2-year-old group, there were no significant differences in ADPi across CYP2C19*1/*1, CYP2C19*1/*2 and CYP2C19*2*2 genotypes ((40±20)% vs. (53±37)% vs. (34±16)%, F=0.37, P>0.05). There were no significant differences in ADPi across CYP2C19*1/*1 and CYP2C19*1/*3 genotypes ((44±27)% vs. (42±20)%, t=0.08, P>0.05). There were no significant differences in ADPi across PON1 192Q homozygous, PON1 192R heterozygote and PON1 192R homozygous genotypes (45% vs. (55±27)% vs. (24±5)%, F=1.83, P>0.05). There were no significant differences in ADPi across ABCB1 3435C homozygous, ABCB1 3435T heterozygote and ABCB1 3435T homozygous genotypes ((36±16)% vs. (50±35)% vs. 45%, F=0.29, P>0.05). The risk analysis of HTPR in different genotypes revealed that in children aged ≥2 years, carrying at least 1 or 2 loss-of-function alleles of CYP2C19 was a risk factor for HTPR ( OR=4.69, 10.00, 95% CI 1.11-19.83, 0.84-119.32, P=0.033, 0.046, respectively), and PON1 192R homozygosity and carrying at least one PON1 192R allele were protective factors against HTPR ( OR=0.08, 0.13, 95% CI 0.01-0.86, 0.01-1.19, P=0.019, 0.043, respectively). Conclusion:KD children aged ≥2 years carrying CYP2C19 loss-of-function alleles and PON1 192Q are more likely to develop HTPR.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been reapproved for heart failure (HF) therapy in patients with and without diabetes. However, the initial glucose-lowering indication of SGLT2i has impeded their uses in cardiovascular clinical practice. A challenge of SGLT2i then becomes how to separate their anti-HF activity from glucose-lowering side-effect. To address this issue, we conducted structural repurposing of EMPA, a representative SGLT2 inhibitor, to strengthen anti-HF activity and reduce the SGLT2-inhibitory activity according to structural basis of inhibition of SGLT2. Compared to EMPA, the optimal derivative JX01, which was produced by methylation of C2-OH of the glucose ring, exhibited weaker SGLT2-inhibitory activity (IC₅₀ > 100 nmol/L), and lower glycosuria and glucose-lowering side-effect, better NHE1-inhibitory activity and cardioprotective effect in HF mice. Furthermore, JX01 showed good safety profiles in respect of single-dose/repeat-dose toxicity and hERG activity, and good pharmacokinetic properties in both mouse and rat species. Collectively, the present study provided a paradigm of drug repurposing to discover novel anti-HF drugs, and indirectly demonstrated that SGLT2-independent molecular mechanisms play an important role in cardioprotective effects of SGLT2 inhibitors.