By employing the analytic hierarchy process(AHP), the CRITIC method(a weight determination method based on indicator correlations), and the AHP-CRITIC hybrid weighting method, the weight coefficients of evaluation indicators were determined, followed by a comprehensive score comparison. The grey correlation analysis was then performed to analyze the results calculated using the hybrid weighting method. Subsequently, a backpropagation-artificial neural network(BP-ANN) model was constructed to predict the extraction process parameters and optimize the extraction process for Shenxiong Huanglian Jiedu Granules(SHJG). In the extraction process, an L_9(3~4) orthogonal experiment was designed to optimize three factors at three levels, including extraction frequency, water addition amount, and extraction time. The evaluation indicators included geniposide, berberine, ginsenoside Rg_1 + Re, ginsenoside Rb_1, ferulic acid, and extract yield. Finally, the optimal extraction results obtained by the orthogonal experiment, grey correlation analysis, and BP-ANN method were compared, and validation experiments were conducted. The results showed that the optimal extraction process involved two rounds of aqueous extraction, each lasting one hour; the first extraction used ten times the amount of added water, while the second extraction used eight times the amount. In the validation experiments, the average content of each indicator component was higher than the average content obtained in the orthogonal experiment, with a higher comprehensive score. The optimized extraction process parameters were reliable and stable, making them suitable for subsequent preparation process research.
Drugs, Chinese Herbal/analysis* ; Neural Networks, Computer

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

With the rapid development of the Internet,the problem of internet gaming disorder(IGD)among adolescents has gradually become prominent.IGD has caused serious harm to their physical and mental health,and it is difficult to withdraw and treat.In 2019,the World Health Organization(WHO)officially listed Gaming Disorder(GD)in the diagnostic category and included it in the 11th edition of the International Classification of Diseases.In China,the number of adolescent internet users has approached 200 million,and the number of IGD patients is relatively large.It is urgent to make breakthroughs in the cognition and treatment of IGD.Domestic and foreign studies have shown that IGD's physical and psychological harm to adolescents is related to the abnormal activation and functional connection damage of structures such as the prefrontal lobe,limbic system,and striatum,which in turn causes neurocognitive disorders,executive dysfunction,difficulty in emotional regulation,abnormal reward and punishment feedback,behavioral abnormalities and other functional disorders;therefore,this article aims to systematically review the research literature on IGD in recent years,and use neurophysiological imaging research method to sort out the changes in the brain structure and function of adolescents with IGD,in order to improve the understanding of the pathophysiology of the disease,and assist in further clinical diagnosis,treatment,application and research design.

ObjectiveTo investigate the mechanism by which Feixin decoction treats hypoxic pulmonary hypertension （HPH） by regulating the peroxisome proliferator-activated receptor gamma （PPARγ）/nuclear factor-kappa B （NF-κB）/NOD-like receptor pyrin domain containing 3 （NLRP3） signaling pathway. MethodsForty-eight male SD rats were randomly allocated into normal， hypoxia， and low-， medium- and high-dose （5.85， 11.7， 23.4 g·kg^-1， respectively） Feixin decoction groups， with 8 rats in each group. Except the normal group， the remaining five groups were placed in a hypoxia chamber with an oxygen concentration of （10.0±0.5）% for 8 h per day， 28 days， and administrated with corresponding drugs during the modeling process. After 4 weeks of treatment， echocardiographic parameters ［pulmonary artery acceleration time （PAT）， pulmonary artery ejection time （PET）， right ventricular anterior wall thickness （RVAWd）， and tricuspid annular plane systolic excursion （TAPSE）］ were measured for each group. The right ventricular systolic pressure （RVSP） was measured by the right heart catheterization method， and the right ventricular hypertrophy index （RVHI） was calculated by weighing the heart. The pathological changes in pulmonary arterioles were observed by hematoxylin-eosin staining. The co-localization of α-smooth muscle actin （α-SMA） with NLRP3， N-terminal gasdermin D （N-GSDMD）， and cysteinyl aspartate-specific proteinase-1 （Caspase-1） in pulmonary arteries was detected by immunofluorescence. The protein levels of PPARγ， NF-κB， NLRP3， apoptosis-associated speck-like protein containing a CARD （ASC）， N-GSDMD， interleukin-1β （IL-1β）， interleukin-18（IL-18）， and cleaved Caspase-1 in the lung tissue was determined by Western blot. The ultrastructural changes in pulmonary artery smooth muscle cells （PASMCs） were observed by transmission electron microscopy. ResultsCompared with the normal group， the hypoxia group showed increased RVSP and RVHI （P<0.01）， decreased right heart function （P<0.01）， increased pulmonary vascular remodeling （P<0.01）， increased co-localization of α-SMA with NLRP3， N-GSDMD， and Caspase-1 in pulmonary arterioles （P<0.01）， up-regulated protein levels of NF-κB， NLRP3， ASC， N-GSDMD， IL-1β， IL-18， and cleaved Caspase-1 in the lung tissue （P<0.05， P<0.01）， a down-regulated protein level of PPARγ （P<0.05， P<0.01）， and pyroptosis in PASMCs. Compared with the hypoxia group， Feixin decoction reduced RVSP and RVHI， improved the right heart function and ameliorated pulmonary vascular remodeling （P<0.05， P<0.01）， decreased the co-localization of α-SMA with NLRP3， N-GSDMD， and Caspase-1 （P<0.05， P<0.01）， down-regulated the protein levels of NF-κB， NLRP3， ASC， N-GSDMD， IL-1β， IL-18， and cleaved Caspase-1 in the lung tissue （P<0.05， P<0.01）， up-regulated the protein level of PPARγ （P<0.05， P<0.01）， and alleviated pyroptosis in PASMCs. ConclusionFeixin decoction can ameliorate pulmonary vascular remodeling and right heart dysfunction in chronically induced HPH rats by regulating pyroptosis in PASMCs through the PPARγ/NF-κB/NLRP3 pathway.

The development of Traditional Chinese Medicine(TCM)medical alliances plays a pivotal role in enhancing grassroots TCM service capabilities and meeting public demand for TCM healthcare.However,challenges persist in establishing these alliances,including insufficient Party leadership at primary TCM institutions and deficiencies in clinical services,talent de-velopment,and emergency care capacity.This study examines innovative Party building approaches in public hospitals within the new era context,analyzing practical cases of alliance development.Our findings demonstrate that integrating Party building into the governance structure of medical alliances not only strengthens Party leadership at primary TCM institutions but also significant-ly promotes TCM service development.Systematic analysis of case hospital practices reveals several key insights.Firstly,strengthening top-level design through Party committee leadership is crucial.Secondly,addressing the most pressing public healthcare concerns with genuine commitment forms the foundation.Thirdly,deep integration of Party building with core medical services represents the essential approach.Lastly,policy-responsive innovation based on consolidated achievements serves as the key driver.

Objective:To investigate the clinical characteristics and prognosis of patients with locally advanced or metastatic pulmonary neuroendocrine tumors(NETs).Methods:The clinical records of patients with locally advanced or metastatic pulmonary NETs in Peking Uni-versity Cancer Hospital&Institute were selected from January 2014 to June 2024.The clinical characteristics,treatment,and survival pro-gnosis were then analyzed.Results:There were 32 patients,of which 18 were male and 14 female.The median age was 56 years.Nine pa-tients had typical carcinoid and 23 had atypical carcinoid,with six in stage Ⅲ and 26 in stage Ⅳ.The common metastatic sites included the bones(18 cases),lungs(8 cases),pleura(7 cases),and liver(7 cases).The median length of the measurable primary tumor was 5.2 cm,which was mostly located centrally(22 cases).Five among the 16 patients who underwent somatostatin receptor(SSTR)imaging had high SSTR ex-pression.The initial symptoms mainly included respiratory symptoms,and none of them were combined with carcinoid syndrome.For the first-line treatment,19 patients were treated with chemotherapy,seven were treated with targeted therapy,four were treated with soma-tostatin analogs(SSAs),and two were treated with surgery.The best efficacy was evaluated as a partial response in one case(3.1%),stable disease in 23 cases(71.9%),and non-evaluable or unknown in eight cases(25%)in the first-line treatment.The median progression-free sur-vival(mPFS)of patients who received first-line treatment was 5.2 months(95%CI:0.0-13.9).The PFS of targeted therapy was the longest(11.0 months,95%CI:0.0-29.6),but there was no significant difference compared with the PFS of chemotherapy and SSA groups(P>0.05).The longest PFS(24.5 months,95%CI:0.0-58.7)was found in patients treated with chemotherapy combined with radiotherapy,but there was no significant difference compared to the PFS of the combined immunotherapy and combined anti-angiogenesis groups(P>0.05).The survival rates at 1,3,and 5 years were 79.1%,65.5%,and 58.9%,respectively.Cox regression analysis did not identify independent risk factors for prognosis.Conclusions:The initial symptoms of patients with locally advanced or metastatic NETs were mainly respiratory symp-toms but without specific manifestations.Some of them were accompanied by high SSTR expression,and there was generally no carcinoid syndrome.The first-line systemic therapy mainly included chemotherapy and target therapy,with relatively low objective response and high disease control rates.Targeted therapy and combined radiotherapy have longer PFS than that of chemotherapy.The overall survival of pa-tients with pulmonary NETs was good.

AIM:This study aims to investigate the effects of Feixin decoction(FXD)on pyroptosis of pulmo-nary artery smooth muscle cells(PASMCs)by modulating nuclear factor κB(NF-κB)/nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)pathway,and to explore how FXD attenuates hypoxic pulmonary hypertension(HPH)in mice.METHODS:A mouse model of HPH was established using the Sugen 5416 combined hypoxia(SuHx)method.Sixty C57BL/6 mice were randomly divided into 6 groups:control group,SuHx group,sildenafil group,and low-,medium-and high-dose FXD groups,with 10 mice in each group.Five weeks after treatment,echocardiographic pa-rameters,including pulmonary artery acceleration time(PAT),pulmonary artery ejection time(PET),right ventricular anterior wall thickness at diastole(RVAWd)and tricuspid annular plane systolic excursion(TAPSE),were measured.Right ventricular systolic pressure(RVSP)was assessed via right heart catheterization.Right ventricular hypertrophy in-dex(RVHI)was determined by weighing the hearts.Histological examination using HE staining was conducted to observe pathological changes in small pulmonary arteries and the right ventricle,while Masson staining was used to assess fibrosis in the right ventricular wall.Immunofluorescence staining was used to detect co-localized expression of α-smooth muscle actin(α-SMA)with NLRP3,N-terminal fragment of gasdermin D(N-GSDMD)and caspase-1 in the pulmonary arteries.Western blot analysis was conducted to measure the protein levels of NF-κB,p-NF-κB,NLRP3,apoptosis-associated speck-like protein containing a caspase recruitment domain(ASC),N-GSDMD,interleukin(IL)-1β,IL-18 and cleaved caspase-1 in lung tissues.Transmission electron microscopy was employed to observe the ultrastructure of PASMCs.RE-SULTS:Compared with control group,the mice in SuHx group exhibited elevated RVSP and RVHI(P＜0.01),de-creased right heart function(P＜0.01),increased right ventricular wall fibrosis,and pulmonary vascular remodeling(P＜0.01).There was also increased co-localized expression of α-SMA with NLRP3,N-GSDMD and caspase-1 in small pul-monary arteries(P＜0.01),as well as elevated levels of p-NF-κB,NLRP3,ASC,N-GSDMD,IL-1β,IL-18 and cleaved caspase-1 in lung tissues(P＜0.01),indicating induced pyroptosis of PASMCs.Compared with SuHx group,FXD treat-ment significantly reduced RVSP and RVHI,improved right ventricular function,and attenuated right ventricular wall fi-brosis and pulmonary vascular remodeling(P＜0.05 or P＜0.01).Treatment with FXD also decreased the co-localized ex-pression of α-SMA with NLRP3,N-GSDMD and caspase-1 in small pulmonary arteries(P＜0.05 or P＜0.01),and down-regulated the protein expression of p-NF-κB,NLRP3,ASC,N-GSDMD,IL-1β,IL-18 and cleaved caspase-1 in lung tis-sues(P＜0.05 or P＜0.01),thereby attenuating the pyroptosis of PASMCs.CONCLUSION:FXD attenuates pulmonary vascular remodeling and right ventricular dysfunction in a mouse model of HPH.This effect may be attributed to its inhibi-tion of NF-κB/NLRP3 pathway,which subsequently reduces the pyroptosis of PASMCs.

Objective:To investigate the clinical characteristics and prognosis of patients with locally advanced or metastatic pulmonary neuroendocrine tumors(NETs).Methods:The clinical records of patients with locally advanced or metastatic pulmonary NETs in Peking Uni-versity Cancer Hospital&Institute were selected from January 2014 to June 2024.The clinical characteristics,treatment,and survival pro-gnosis were then analyzed.Results:There were 32 patients,of which 18 were male and 14 female.The median age was 56 years.Nine pa-tients had typical carcinoid and 23 had atypical carcinoid,with six in stage Ⅲ and 26 in stage Ⅳ.The common metastatic sites included the bones(18 cases),lungs(8 cases),pleura(7 cases),and liver(7 cases).The median length of the measurable primary tumor was 5.2 cm,which was mostly located centrally(22 cases).Five among the 16 patients who underwent somatostatin receptor(SSTR)imaging had high SSTR ex-pression.The initial symptoms mainly included respiratory symptoms,and none of them were combined with carcinoid syndrome.For the first-line treatment,19 patients were treated with chemotherapy,seven were treated with targeted therapy,four were treated with soma-tostatin analogs(SSAs),and two were treated with surgery.The best efficacy was evaluated as a partial response in one case(3.1%),stable disease in 23 cases(71.9%),and non-evaluable or unknown in eight cases(25%)in the first-line treatment.The median progression-free sur-vival(mPFS)of patients who received first-line treatment was 5.2 months(95%CI:0.0-13.9).The PFS of targeted therapy was the longest(11.0 months,95%CI:0.0-29.6),but there was no significant difference compared with the PFS of chemotherapy and SSA groups(P>0.05).The longest PFS(24.5 months,95%CI:0.0-58.7)was found in patients treated with chemotherapy combined with radiotherapy,but there was no significant difference compared to the PFS of the combined immunotherapy and combined anti-angiogenesis groups(P>0.05).The survival rates at 1,3,and 5 years were 79.1%,65.5%,and 58.9%,respectively.Cox regression analysis did not identify independent risk factors for prognosis.Conclusions:The initial symptoms of patients with locally advanced or metastatic NETs were mainly respiratory symp-toms but without specific manifestations.Some of them were accompanied by high SSTR expression,and there was generally no carcinoid syndrome.The first-line systemic therapy mainly included chemotherapy and target therapy,with relatively low objective response and high disease control rates.Targeted therapy and combined radiotherapy have longer PFS than that of chemotherapy.The overall survival of pa-tients with pulmonary NETs was good.

The development of Traditional Chinese Medicine(TCM)medical alliances plays a pivotal role in enhancing grassroots TCM service capabilities and meeting public demand for TCM healthcare.However,challenges persist in establishing these alliances,including insufficient Party leadership at primary TCM institutions and deficiencies in clinical services,talent de-velopment,and emergency care capacity.This study examines innovative Party building approaches in public hospitals within the new era context,analyzing practical cases of alliance development.Our findings demonstrate that integrating Party building into the governance structure of medical alliances not only strengthens Party leadership at primary TCM institutions but also significant-ly promotes TCM service development.Systematic analysis of case hospital practices reveals several key insights.Firstly,strengthening top-level design through Party committee leadership is crucial.Secondly,addressing the most pressing public healthcare concerns with genuine commitment forms the foundation.Thirdly,deep integration of Party building with core medical services represents the essential approach.Lastly,policy-responsive innovation based on consolidated achievements serves as the key driver.

AIM:This study aims to investigate the effects of Feixin decoction(FXD)on pyroptosis of pulmo-nary artery smooth muscle cells(PASMCs)by modulating nuclear factor κB(NF-κB)/nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)pathway,and to explore how FXD attenuates hypoxic pulmonary hypertension(HPH)in mice.METHODS:A mouse model of HPH was established using the Sugen 5416 combined hypoxia(SuHx)method.Sixty C57BL/6 mice were randomly divided into 6 groups:control group,SuHx group,sildenafil group,and low-,medium-and high-dose FXD groups,with 10 mice in each group.Five weeks after treatment,echocardiographic pa-rameters,including pulmonary artery acceleration time(PAT),pulmonary artery ejection time(PET),right ventricular anterior wall thickness at diastole(RVAWd)and tricuspid annular plane systolic excursion(TAPSE),were measured.Right ventricular systolic pressure(RVSP)was assessed via right heart catheterization.Right ventricular hypertrophy in-dex(RVHI)was determined by weighing the hearts.Histological examination using HE staining was conducted to observe pathological changes in small pulmonary arteries and the right ventricle,while Masson staining was used to assess fibrosis in the right ventricular wall.Immunofluorescence staining was used to detect co-localized expression of α-smooth muscle actin(α-SMA)with NLRP3,N-terminal fragment of gasdermin D(N-GSDMD)and caspase-1 in the pulmonary arteries.Western blot analysis was conducted to measure the protein levels of NF-κB,p-NF-κB,NLRP3,apoptosis-associated speck-like protein containing a caspase recruitment domain(ASC),N-GSDMD,interleukin(IL)-1β,IL-18 and cleaved caspase-1 in lung tissues.Transmission electron microscopy was employed to observe the ultrastructure of PASMCs.RE-SULTS:Compared with control group,the mice in SuHx group exhibited elevated RVSP and RVHI(P＜0.01),de-creased right heart function(P＜0.01),increased right ventricular wall fibrosis,and pulmonary vascular remodeling(P＜0.01).There was also increased co-localized expression of α-SMA with NLRP3,N-GSDMD and caspase-1 in small pul-monary arteries(P＜0.01),as well as elevated levels of p-NF-κB,NLRP3,ASC,N-GSDMD,IL-1β,IL-18 and cleaved caspase-1 in lung tissues(P＜0.01),indicating induced pyroptosis of PASMCs.Compared with SuHx group,FXD treat-ment significantly reduced RVSP and RVHI,improved right ventricular function,and attenuated right ventricular wall fi-brosis and pulmonary vascular remodeling(P＜0.05 or P＜0.01).Treatment with FXD also decreased the co-localized ex-pression of α-SMA with NLRP3,N-GSDMD and caspase-1 in small pulmonary arteries(P＜0.05 or P＜0.01),and down-regulated the protein expression of p-NF-κB,NLRP3,ASC,N-GSDMD,IL-1β,IL-18 and cleaved caspase-1 in lung tis-sues(P＜0.05 or P＜0.01),thereby attenuating the pyroptosis of PASMCs.CONCLUSION:FXD attenuates pulmonary vascular remodeling and right ventricular dysfunction in a mouse model of HPH.This effect may be attributed to its inhibi-tion of NF-κB/NLRP3 pathway,which subsequently reduces the pyroptosis of PASMCs.