Objective To observe changes of white matter function in adolescent smoker(AS)with resting-state functional MRI(rs-fMRI)fractional amplitude of low-frequency fluctuation(fALFF)technique.Methods Forty-five adolescents(AS group)and 45 control subjects(control group)were prospectively enrolled,and brain rs-fMRI were acquired.Brain regions with fALFF being different between groups were observed,and the correlations with clinical indicators were analyzed.Results Compared with that in control group,fALFF of the right superior longitudinal fasciculus significantly elevated in AS group(FDR correct Q＜0.05),in which the peak of the cluster was positively correlated with score of Fagerstr?m test for nicotine dependence(FTND)(r=0.294,P=0.049).Conclusion White matter function changed in AS,presenting as significantly increased fALFF in right superior longitudinal fasciculus,which was positively correlated with nicotine dependence.

Objective To investigate the dynamic functional connectivity differences between insomnia patients and healthy controls in triple brain networks[the significant network(SN),the default mode network(DMN),and the executive control network(ECN)]using functional magnetic resonance imaging,and uncover their associations with cognitive ability.Methods Dynamic functional connectivity analysis was performed on functional magnetic resonance imaging data from 40 insomnia patients and 40 healthy controls.The changes in dynamic functional connectivity values were studied for SN,DMN,ECN[including the left executive control network(LECN)and the right executive control network(RECN)];the similarities and differences in time characteristic indicators such as time score,average dwell time,and conversion rate were explored;and their associations with clinical information were analyzed.Results The SN-LECN and DMN-RECN dynamic functional connectivity was significantly higher in insomnia patients than in healthy controls(P=0.013,0.047),while the RECN-LECN and RECN internal functional connectivity strength was lower in insomnia patients than in healthy controls(P<0.001).Additionally,the fractional time in state 2 in insomnia group was significantly higher than that in healthy controls(P<0.001),and it was positively correlated with the Pittsburgh sleep quality index(r=0.524,P=0.001).Conclusion Insomnia patients exhibit significant abnormalities in triple brain network dynamic functional connectivity,which may be related to abnormalities in cognitive control and sensory processing in insomnia patients.These findings provide a new perspective for further research on the neural mechanisms and potential intervention strategies for insomnia.

Objective To investigate the dynamic functional connectivity differences between insomnia patients and healthy controls in triple brain networks[the significant network(SN),the default mode network(DMN),and the executive control network(ECN)]using functional magnetic resonance imaging,and uncover their associations with cognitive ability.Methods Dynamic functional connectivity analysis was performed on functional magnetic resonance imaging data from 40 insomnia patients and 40 healthy controls.The changes in dynamic functional connectivity values were studied for SN,DMN,ECN[including the left executive control network(LECN)and the right executive control network(RECN)];the similarities and differences in time characteristic indicators such as time score,average dwell time,and conversion rate were explored;and their associations with clinical information were analyzed.Results The SN-LECN and DMN-RECN dynamic functional connectivity was significantly higher in insomnia patients than in healthy controls(P=0.013,0.047),while the RECN-LECN and RECN internal functional connectivity strength was lower in insomnia patients than in healthy controls(P<0.001).Additionally,the fractional time in state 2 in insomnia group was significantly higher than that in healthy controls(P<0.001),and it was positively correlated with the Pittsburgh sleep quality index(r=0.524,P=0.001).Conclusion Insomnia patients exhibit significant abnormalities in triple brain network dynamic functional connectivity,which may be related to abnormalities in cognitive control and sensory processing in insomnia patients.These findings provide a new perspective for further research on the neural mechanisms and potential intervention strategies for insomnia.

Volumes 9 and 10 of Sun Simiao's Supplement to Important Formulas Worth a Thousand Gold Pieces record part of Trea-tise on Cold Damage,which contain Sun Simiao's unique thoughts on six-meridian treatment.Sun Simiao's treatment of Taiyang me-ridian emphasizes the classification of prescriptions and syndromes,advocates the correct treatment methods,and establishes three guidelines;Yangming meridian emphasizes the differentiation of cold and heat syndromes;except Taiyang meridian,all meridians em-phasize the differentiation of outline syndromes.It has made important contributions to the inheritance and development of the six-me-ridian thought of Treatise on Cold Damage in later generations.

Objective To investigate the role of syntaxin 4(STX4)in endoplasmic reticulum(ER)-mitochondria corcinoma in ovarian cancer(OC)cells.Methods The differences in STX4 expression in the OC cell line SKOV-3 and normal ovarian epithe-lial cells HOSEpiC were analyzed by Western blot and real-time fluorescence quantitative polymerase chain reaction(qRT-PCR).SKOV-3 cell lines with stable knockdown of STX4 were constructed by lentiviral transfected cells,and the knockdown efficiency was verified by Western blot and qRT-PCR.The wound healing assay examined the changes in SKOV-3 migratory ability after STX4 knockdown,the Transwell assay examined the changes in SKOV-3 invasive ability after STX4 knockdown.The ER-mito-chondrial contact structure changes in SKOV-3 cells were visualized by transmission electron microscopy.Intracellular phospha-tidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin(PI3K/AKT/mTOR)pathway proteins and their phosphor-ylated proteins were measured at the protein level.Results Both Western blot and qRT-PCR results showed that the expression level of STX4 was significantly higher in SKOV-3 cells than in HOSEpiC cells,and the differences were statistically significant(t=7.86,9.27,all P<0.05).The knockdown efficiency was verified by Western blot and qRT-PCR.Subsequently,the results of the wound-healing assay indicated that the migratory ability of SKOV-3 cells was significantly inhibited upon STX4 knockdown.The results of the Transwell test showed that the invasive capacity of SKOV-3 cells was significantly reduced after STX4 knock-down(t=7.56,8.82,all P<0.05).Endoplasmic reticulum-mitochondrial contact structure was reduced in SKOV-3 cells with STX4 knockdown under TEM.Finally,no significant changes after STX4 knockdown in the overall levels of PI3K/AKT/mTOR pathway proteins in SKOV-3 cells(t=2.77,5.58,2.99,all P>0.05),but their phosphorylated proteins were significantlydecreased(t=4.42,5.01,5.58,all P>0.05).Conclusion STX4 promoted OC cell migration,invasion,and the formation of ER-mitochondrial contact structures through the activation of the PI3K/AKT/mTOR pathway through phosphorylation.

Objective:To analyze the infiltration of immune cells in different molecular subtypes of endometrial cancer(EC)at the protein level and explore the correlation between immune infiltration and clinicopathological features.Methods:Clinical data from 75 mismatch repair-deficient(MMR-D)EC cases and 74 mismatch re-pair-proficient(MMR-P)EC cases with comparable differentiation levels,diagnosed at Sichuan Provincial People's Hospital between January 2013 and January 2021,were selected.Molecular classification of EC was con-ducted according to the ProMisE standard.Immunohistochemistry(IHC)staining and fluorescent multiplexed im-munohistochemistry(F-mIHC)techniques were used to quantify the distribution of CD8+T cells,regulatory T cells(Tregs),and macrophages.The clinicopathological features and immune infiltration characteristics of different subtypes were investigated.Results:Among 149 samples,75 were MMR-D,8 were POLE-mutated(POLEmut),13 were p53-mutated(p53abn),and 53 were p53 wild-type(p53wt).The infiltration characteristics of CD8+T cells,Tregs,and macrophages were no statistically significant differences correlated with age and pathological stage(P>0.05).Among the molecular subtypes of EC,MMR-D tumors demonstrated a significantly higher densi-ty of CD8+T cells and Tregs compared to MMR-P tumors(P<0.05).Further comparison across the four EC mo-lecular subtypes revealed that the MMR-D subtype,which had a favorable prognosis,displayed a significantly high density of CD8+T cells compared to the p53abn subtype and the p53wt subtype(P<0.05).Additionally,the Tregs density of the MMR-D tumors was significantly higher than that of the p53wt tumors,in both the tumor area(P<0.05)and the stroma area(P<0.05).The POLEmut type tumors,which had the best prognosis,showed a high infiltration of CD8+T cells and Tregs cells compared to the p53abn and p53wt types,although there was no signifi-cant statistical difference(P>0.05).The p53wt subtype,which had a moderate prognosis,exhibited low density of CD8+T cells(P<0.05)and Tregs(tumor area,P<0.01,stroma area,P<0.05)compared to MMR-D tumors.The p53abn subtype,which was associated with the worst prognosis,exhibited higher infiltration of M2-like macro-phages than the MMR-D subtype(P<0.05)and the p53wt subtype(P<0.05)in tumor region,and lower CD8+T cell density than the MMR-D subtype(P<0.05).No significant statistical difference was observed in the density of M1-like macrophages across the four molecular subtypes in either the tumor or stroma areae(P>0.05).Conclu-sions:There was no statistically significant relation found between infiltration characteristics of immune cells and clinicopathological features.The types and distribution of infiltrated immune cells were different across these EC molecular subtypes.This indicated that ECs with different molecular subtype exhibited different features of immune infiltration which is closely associated with patient prognosis.

Objective To investigate the role of syntaxin 4(STX4)in endoplasmic reticulum(ER)-mitochondria corcinoma in ovarian cancer(OC)cells.Methods The differences in STX4 expression in the OC cell line SKOV-3 and normal ovarian epithe-lial cells HOSEpiC were analyzed by Western blot and real-time fluorescence quantitative polymerase chain reaction(qRT-PCR).SKOV-3 cell lines with stable knockdown of STX4 were constructed by lentiviral transfected cells,and the knockdown efficiency was verified by Western blot and qRT-PCR.The wound healing assay examined the changes in SKOV-3 migratory ability after STX4 knockdown,the Transwell assay examined the changes in SKOV-3 invasive ability after STX4 knockdown.The ER-mito-chondrial contact structure changes in SKOV-3 cells were visualized by transmission electron microscopy.Intracellular phospha-tidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin(PI3K/AKT/mTOR)pathway proteins and their phosphor-ylated proteins were measured at the protein level.Results Both Western blot and qRT-PCR results showed that the expression level of STX4 was significantly higher in SKOV-3 cells than in HOSEpiC cells,and the differences were statistically significant(t=7.86,9.27,all P<0.05).The knockdown efficiency was verified by Western blot and qRT-PCR.Subsequently,the results of the wound-healing assay indicated that the migratory ability of SKOV-3 cells was significantly inhibited upon STX4 knockdown.The results of the Transwell test showed that the invasive capacity of SKOV-3 cells was significantly reduced after STX4 knock-down(t=7.56,8.82,all P<0.05).Endoplasmic reticulum-mitochondrial contact structure was reduced in SKOV-3 cells with STX4 knockdown under TEM.Finally,no significant changes after STX4 knockdown in the overall levels of PI3K/AKT/mTOR pathway proteins in SKOV-3 cells(t=2.77,5.58,2.99,all P>0.05),but their phosphorylated proteins were significantlydecreased(t=4.42,5.01,5.58,all P>0.05).Conclusion STX4 promoted OC cell migration,invasion,and the formation of ER-mitochondrial contact structures through the activation of the PI3K/AKT/mTOR pathway through phosphorylation.

The pathological changes of myocardial infarction （MI） are mainly characterized by progressive myocardial ischemic necrosis， decline in cardiac diastolic function， thinning of the ventricular wall， and enlargement of the ventricles. The clinical manifestations include myocardial ischemia， heart failure， arrhythmia， shock， and even sudden cardiac death， rendering MI one of the most perilous cardiovascular diseases. Currently， the clinical treatment for MI primarily involves interventional procedures and drug therapy. However， due to their significant side effects and high complication rates associated with these treatments， they fail to ensure a satisfactory quality of life and long-term prognosis for patients. On the other hand， traditional Chinese medicine has demonstrated remarkable potential in improving patient prognosis while reducing side effects. Research has elucidated that various signaling pathways such as nuclear transcription factor-κB （NF-κB）， adenosine 5̒-monophosphate-activated protein kinase （AMPK）， transforming growth factor-β （TGF-β）/Smads， mitogen-activated protein kinase （MAPK）， Wnt/β-catenin （β-catenin）， and phosphatidylinositol 3-kinase （PI3K）/protein kinase B（Akt） play crucial roles in regulating the occurrence and development of MI. Effectively modulating these signaling pathways through its therapeutic interventions， traditional Chinese medicine can enhance MI management by inhibiting apoptosis， providing anti-inflammatory properties， alleviating oxidative stress levels， and resisting myocardial ischemia. Due to its notable efficacy and favorable safety， it has become an area of focus in clinical practice.

Objective:To analyze the infiltration of immune cells in different molecular subtypes of endometrial cancer(EC)at the protein level and explore the correlation between immune infiltration and clinicopathological features.Methods:Clinical data from 75 mismatch repair-deficient(MMR-D)EC cases and 74 mismatch re-pair-proficient(MMR-P)EC cases with comparable differentiation levels,diagnosed at Sichuan Provincial People's Hospital between January 2013 and January 2021,were selected.Molecular classification of EC was con-ducted according to the ProMisE standard.Immunohistochemistry(IHC)staining and fluorescent multiplexed im-munohistochemistry(F-mIHC)techniques were used to quantify the distribution of CD8+T cells,regulatory T cells(Tregs),and macrophages.The clinicopathological features and immune infiltration characteristics of different subtypes were investigated.Results:Among 149 samples,75 were MMR-D,8 were POLE-mutated(POLEmut),13 were p53-mutated(p53abn),and 53 were p53 wild-type(p53wt).The infiltration characteristics of CD8+T cells,Tregs,and macrophages were no statistically significant differences correlated with age and pathological stage(P>0.05).Among the molecular subtypes of EC,MMR-D tumors demonstrated a significantly higher densi-ty of CD8+T cells and Tregs compared to MMR-P tumors(P<0.05).Further comparison across the four EC mo-lecular subtypes revealed that the MMR-D subtype,which had a favorable prognosis,displayed a significantly high density of CD8+T cells compared to the p53abn subtype and the p53wt subtype(P<0.05).Additionally,the Tregs density of the MMR-D tumors was significantly higher than that of the p53wt tumors,in both the tumor area(P<0.05)and the stroma area(P<0.05).The POLEmut type tumors,which had the best prognosis,showed a high infiltration of CD8+T cells and Tregs cells compared to the p53abn and p53wt types,although there was no signifi-cant statistical difference(P>0.05).The p53wt subtype,which had a moderate prognosis,exhibited low density of CD8+T cells(P<0.05)and Tregs(tumor area,P<0.01,stroma area,P<0.05)compared to MMR-D tumors.The p53abn subtype,which was associated with the worst prognosis,exhibited higher infiltration of M2-like macro-phages than the MMR-D subtype(P<0.05)and the p53wt subtype(P<0.05)in tumor region,and lower CD8+T cell density than the MMR-D subtype(P<0.05).No significant statistical difference was observed in the density of M1-like macrophages across the four molecular subtypes in either the tumor or stroma areae(P>0.05).Conclu-sions:There was no statistically significant relation found between infiltration characteristics of immune cells and clinicopathological features.The types and distribution of infiltrated immune cells were different across these EC molecular subtypes.This indicated that ECs with different molecular subtype exhibited different features of immune infiltration which is closely associated with patient prognosis.

OBJECTIVE To investigate the clinical efficacy of integrating pharmacists into family health teams （FHTs） for long-term medication therapeutical management （MTM） in stroke patients， and empirically evaluate the service model. METHODS A pharmacist team， jointly established by clinical and community pharmacists from the Affiliated Suzhou Hospital of Nanjing Medical University （hereinafter referred to as “our hospital”）， developed a pharmacist-supported MTM model integrated into FHTs. Using a prospective randomized controlled design， 170 stroke patients discharged from our hospital （July 2022-December 2023） and enrolled in FHTs at Suzhou Runda Community Hospital were randomly divided into trial group （88 cases） and control group （82 cases） according to random number table. The control group received routine FHTs care （without pharmacist involvement in the team collaboration）， while the trial group xhz8405@126.com received 12-month MTM services supported by pharmacists via an information platform. These services specifically included innovative interventions such as personalized medication regimen optimization based on the MTM framework， dynamic medication adherence management， medication safety monitoring， a home medication assessment system， and distinctive service offerings. Outcomes of the 2 grousp were compared before and after intervention， involving medication adherence （adherence rate， adherence score）， compliance rates for stroke recurrence risk factors [blood pressure， low-density lipoprotein cholesterol （LDL-C）]， and incidence of adverse drug reactions （ADR）. RESULTS After 12 months， the trial group exhibited significantly higher medication adherence rates， improved adherence scores， higher compliance rates for blood pressure and LDL-C targets compared to the control group （P＜0.05）. The incidence of ADR in the trial group （4.55%） was significantly lower than that in the control group （8.11%）， though the difference was not statistically significant （P＞ 0.05）. CONCLUSIONS Pharmacist involvement in FHTs to deliver MTM services significantly enhances medication adherence and optimizes risk factor for stroke recurrence， offering practical evidence for advancing pharmaceutical care in chronic disease management under the family doctor system.