1.Clinical observation of Zhengxintai granules in the treatment of microvascular angina for acute ST-segment elevation myocardial infarction patients with qi deficiency and blood stasis syndrome after PCI
Wenhui MA ; Ying ZHANG ; Lei LIU ; Xiuyan YU ; Yali CHEN ; Liming CHEN
China Pharmacy 2026;37(15):2023-2029
OBJECTIVE To investigate the clinical efficacy and safety of Zhengxintai granules as in the treatment of microvascular angina (MVA) following percutaneous coronary intervention (PCI) in patients with acute ST-segment elevation myocardial infarction (STEMI) and qi deficiency and blood stasis syndrome. METHODS Patients with STEMI and qi deficiency and blood stasis syndrome who underwent PCI and developed MVA and were admitted to the Jinan Fourth People’s Hospital (Jinan Cardiovascular Hospital) from March 2022 to March 2025 were selected, they were randomly divided into the control group and the observation group according to a random number table, with 76 cases in each group. Patients in the control group received conventional Western medicine treatment combined with a placebo, while patients in the observation group received Zhengxintai granules (5 mg per dose, three times daily, for 8 weeks) in addition to conventional Western medicine treatment. The clinical efficacy [including the total effective rate of traditional Chinese medicine (TCM) syndrome improvement and the total effective rates of Western clinical efficacy] was compared between the two groups. The following indicators were detected before and after treatment: TCM syndrome scores, angina pectoris episodes [daily attack frequency, duration per attack, Visual Analogue Scale (VAS) score], cardiac function indicators [lactate dehydrogenase (LDH), N-terminal pro-B-type natriuretic peptide (NT-proBNP), left ventricular end-diastolic dimension (LVEDD), left ventricular end-systolic dimension (LVESD), left ventricular ejection fraction (LVEF), cardiac output (CO), fractional shortening (FS)], coagulation function indicators [thrombin time (TT), prothrombin time (PT), fibrinogen (FIB)], fibrinolytic marker (D-dimer), vascular endothelial function indicators [vascular endothelial growth factor (VEGF), nitric oxide (NO), endothelin-1 (ET-1)] and myocardial microcirculation hemodynamic indicators [end-diastolic velocity (EDV), peak systolic velocity (PSV), resistance index (RI), pulsatility index (PI)]. The quality of life [Seattle Angina Questionnaire (SAQ) score] and the incidence of adverse reactions were also compared between the two groups. RESULTS There was no patient dropout during the entire course of the study. The total effective rates of improvement in TCM syndromes and the total effective rates of Western clinical efficacy in the observation group were significantly higher than those in the control group (93.42% vs. 82.89%, 94.74% vs. 84.21%, P<0.05). Before the treatment, the comparison of each examination indicator between the two groups showed no statistically significant differences (P>0.05). Compared with before treatment, the TCM syndrome scores, the number of daily angina pectoris attacks and the duration of each attack, the VAS scores, LDH, NT-proBNP, FIB, D-dimer, ET-1 levels, LVEDD, LVESD, RI and PI after treatment in both groups were significantly reduced, shortened or decreased (P<0.05); VEGF and NO levels, LVEF, CO, FS, TT, PT, EDV, PSV, and the standard scores of five dimensions including angina pectoris stability, as well as the total scores of SAQ, all significantly increased or prolonged (P<0.05). Furthermore, the improvements in the aforementioned indicators (except for LVEF) in the observation group were significantly greater than those in the control group (P<0.05). There was no statistically significant difference in the total incidence of adverse reactions between the two groups (P>0.05). CONCLUSIONS Zhengxintai granules, when used as an adjunct to conventional Western medicine, can significantly alleviate the related symptoms of MVA in STEMI patients with qi deficiency and blood stasis syndrome after PCI, repair damaged cardiac function, restore the balance of the coagulation-fibrinolysis system, improve vascular endothelial function and myocardial microcirculation perfusion, and significantly enhance the quality of life of patients
2.Mechanism of Action of Kaixinsan in Ameliorating Alzheimer's Disease
Xiaoming HE ; Xiaotong WANG ; Dongyu MIN ; Xinxin WANG ; Meijia CHENG ; Yongming LIU ; Yetao JU ; Yali YANG ; Changbin YUAN ; Changyang YU ; Li ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(1):20-29
ObjectiveTo investigate the mechanism of action of Kaixinsan in the treatment of Alzheimer's disease (AD) based on network pharmacology, molecular docking, and animal experimental validation. MethodsThe Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) and the Encyclopedia of Traditional Chinese Medicine(ETCM) databases were used to obtain the active ingredients and targets of Kaixinsan. GeneCards, Online Mendelian Inheritance in Man(OMIM), TTD, PharmGKB, and DrugBank databases were used to obtain the relevant targets of AD. The intersection (common targets) of the active ingredient targets of Kaixinsan and the relevant targets of AD was taken, and the network interaction analysis of the common targets was carried out in the STRING database to construct a protein-protein interaction(PPI) network. The CytoNCA plugin within Cytoscape was used to screen out the core targets, and the Metascape platform was used to perform gene ontology(GO) functional enrichment analysis and Kyoto encyclopedia of genes and genomes(KEGG) pathway enrichment analysis. The “drug-active ingredient-target” interaction network was constructed with the help of Cytoscape 3.8.2, and AutoDock Vina was used for molecular docking. Scopolamine (SCOP) was utilized for modeling and injected intraperitoneally once daily. Thirty-two male C57/BL6 mice were randomly divided into blank control (CON) group (0.9% NaCl, n=8), model (SCOP) group (3 mg·kg-1·d-1, n=8), positive control group (3 mg·kg-1·d-1 of SCOP+3 mg·kg-1·d-1 of Donepezil, n=8), and Kaixinsan group (3 mg·kg-1·d-1 of SCOP+6.5 g·kg-1·d-1 of Kaixinsan, n=8). Mice in each group were administered with 0.9% NaCl, Kaixinsan, or Donepezil by gavage twice a day for 14 days. Morris water maze experiment was used to observe the learning memory ability of mice. Hematoxylin-eosin (HE) staining method was used to observe the pathological changes in the CA1 area of the mouse hippocampus. Enzyme linked immunosorbent assay(ELISA) was used to determine the serum acetylcholine (ACh) and acetylcholinesterase (AChE) contents of mice. Western blot method was used to detect the protein expression levels of signal transducer and activator of transcription 3(STAT3) and nuclear transcription factor(NF)-κB p65 in the hippocampus of mice. ResultsA total of 73 active ingredients of Kaixinsan were obtained, and 578 potential targets (common targets) of Kaixinsan for the treatment of AD were screened out. Key active ingredients included kaempferol, gijugliflozin, etc.. Potential core targets were STAT3, NF-κB p65, et al. GO functional enrichment analysis obtained 3 124 biological functions, 254 cellular building blocks, and 461 molecular functions. KEGG pathway enrichment obtained 248 pathways, mainly involving cancer-related pathways, TRP pathway, cyclic adenosine monophosphate(cAMP) pathway, and NF-κB pathway. Molecular docking showed that the binding of the key active ingredients to the target targets was more stable. Morris water maze experiment indicated that Kaixinsan could improve the learning memory ability of SCOP-induced mice. HE staining and ELISA results showed that Kaixinsan had an ameliorating effect on central nerve injury in mice. Western blot test indicated that Kaixinsan had a down-regulating effect on the levels of NF-κB p65 phosphorylation and STAT3 phosphorylation in the hippocampal tissue of mice in the SCOP model. ConclusionKaixinsan can improve the cognitive impairment function in SCOP model mice and may reduce hippocampal neuronal damage and thus play a therapeutic role in the treatment of AD by regulating NF-κB p65, STAT3, and other targets involved in the NF-κB signaling pathway.
3.Optimal regimen screening of acupuncture and moxibustion for obstructive sleep apnea hypopnea syndrome.
Yuqiang SONG ; Yuanbo FU ; Sanfeng SUN ; Yali WEN ; Yinxia LIU ; Jie SUN ; Xin DU ; Xueting ZHANG ; Linbo SHEN ; Baijie LI ; Han YU ; Qingdai LI
Chinese Acupuncture & Moxibustion 2025;45(2):242-248
OBJECTIVE:
To screen the optimal regimen of acupuncture and moxibustion for obstructive sleep apnea hypopnea syndrome (OSAHS), so as to provide the evidences for clinical decision-making.
METHODS:
From 7 databases in Chinese and English i.e. the Full-Text Database of China Journal Network (CNKI), Wanfang Data Knowledge Service Platform (Wanfang), VIP Information Chinese Journal Service Platform (VIP), Chinese Biomedical Literature Database (SinoMed), PubMed, Web of Science (WOS) and Cochrane Library, randomized controlled trial (RCT) articals of OSAHS treated with acupuncture and moxibustion were searched. The quality of evidence was evaluated with the modified Jadad scale, the evaluation index was established and the optimal regimen of acupuncture and moxibustion for OSAHS was screened by multi-index decision analysis.
RESULTS:
A total of 10 RCTs were included, and the filiform needling therapy was optimal in treatment of OSAHS. The acupoints included Lianquan (CV23), Danzhong (CV17), Zhongwan (CV12), and bilateral Kongzui (LU6), Pishu (BL20), Fenglong (ST40), Zusanli (ST36), Yinlingquan (SP9) and Zhaohai (KI6). Zusanli (ST36) received the reinforcing method, Pishu (BL20) and Fenglong (ST40) were stimulated with the reducing technique, and the rest acupoints with the uniform reinforcing-reducing. Each acupoint was manually manipulated once every 10 min during the needle retention for 30 min. Acupuncture was delivered once a day, 5 times a week and for consecutive 4 weeks. Among the included literature, the severity of disease was not reported in detail, the filiform needling was the dominant intervention, the local acupoints such as Lianquan (CV23) and Panglianquan (Extra) were mainly selected. The apnea-hypopnea index and the minimum oxygen saturation were taken as the evaluation indexes, and the effect was evaluated in reference to the generally accepted standards. The attention to safety evaluation was insufficient, the report on methodology was not adequate and the quality was low.
CONCLUSION
Filiform needling is the dominant therapy of acupuncture and moxibustion for OSAHS, and the local acupoints are considered specially. But the quality of clinical research should be improved.
Humans
;
Moxibustion
;
Acupuncture Therapy
;
Sleep Apnea, Obstructive/therapy*
;
Acupuncture Points
;
Randomized Controlled Trials as Topic
4.Research progress on ferritinophagy in cancer intervention
Weihua ZHENG ; Zihang WANG ; Long XUA ; Caiyan AN ; Yali YAN ; Yu ZHANG ; Hongquan WANG ; Junjing ZHANG
Chinese Journal of Hepatobiliary Surgery 2025;31(7):549-552
Ferroptosis is an iron-dependent cell death modality triggered by the accumulation of lipid peroxides and is closely linked to tumor pathogenesis. Ferritinophagy refers to the selective autophagic degradation of ferritin, releasing intracellular stored iron to maintain iron metabolic homeostasis. This process is also significantly associated with tumor-targeted interventions. This review systematically elucidates the mechanisms of ferroptosis and ferritinophagy, their roles in tumor progression, and the therapeutic potential of pharmacologically induced ferritinophagy in anticancer strategies.
5.Analysis of the safety of dinutuximab β for the treatment of neuroblastoma
Anle SHEN ; Yali HAN ; Liting YU ; An'an ZHANG ; Jie ZHAO ; Qiushi YANG ; Haonan LI ; Zhiling LI ; Yijin GAO
Journal of Chongqing Medical University 2025;50(8):1042-1046
Objective:To analyze the clinical characteristics of adverse reactions caused by dinutuximab β for the treatment of neuro-blastoma(NB)in China and to provide safety evidence for the rational use of dinutuximab β in clinical practice.Methods:Clinical data were retrospectively collected from 16 pediatric patients with NB who had been treated with dinutuximab β at Shanghai Children's Medical Center Affiliated to Shanghai Jiao Tong University School of Medicine from January 2022 to November 2023,and the adverse reactions caused by dinutuximab β were summarized and analyzed.Results:The male-to-female ratio was 5:3 among the 16 children with NB.The retroperitoneum was the main initial site of involvement,accounting for 75%.Thirteen(81.25%)patients had high-risk NB.The adverse reactions caused by dinutuximab β mainly included decreased hemoglobin,fever,vomiting,and diarrhea.The inci-dence of adverse reactions was highest in the first course of treatment,and the median time of adverse reactions was 2-5 days.Conclu-sion:Targeted monitoring should be carried out at an early stage during dinutuximab β administration.Adverse reactions should be de-tected and managed early to ensure the safety of medication for children.
6.Qualitative study on neurosurgical nurses′ experience of lack of perioperative nursing for intracranial tumors patients
Xuerui YANG ; Yuxin ZHAN ; Pei WANG ; Yali WAN ; Jiaohua YU
Chinese Journal of Practical Nursing 2025;41(4):310-315
Objective:To deeply understand the experience of neurosurgery nurses on the lack of perioperative nursing for intracranial tumors patients, so as to provide reference for reducing the lack of nursing and improving the quality of nursing and patients′ medical experience.Methods:From December 2023 to February 2024, the neurosurgical nurses of Union Hospital, Tongji Medical College, Huazhong University of Science and Technology were selected by the purpose sampling method with maximum differentiation. Semi-structured interviews were conducted with phenomenological research methods. The interview data were transcribed, coded, categorized and described.Results:A total of 17 neurosurgical nurses were enrolled, including 6 males and 11 females, aged 24-45(33.29 ± 6.74) years. Three themes of perioperative nursing lack experience of neurosurgery nurses were obtained, including nursing lack experience (lack of safety nursing, lack of timely nursing, lack of high efficiency nursing, lack of effectiveness nursing, lack of fair nursing, and lack of patient-centered), the physical and mental effects of nursing lack on nurses (impacts of lack of nursing on nurses′ physiology and psychology), and reasons for lack of nursing (personnel, equipment, materials, organization management, environment).Conclusions:Neurosurgical nurses lack of perioperative nursing for patients with intracranial tumor, which has a certain impact on the physical and mental health of nurses, suggesting that neurosurgical nurses should attach great importance to the lack of nursing for patients with intracranial tumor and formulate a scientific and effective management system.
7.Analysis of factors related to quality of life in patients undergoing total knee arthroplasty at 6 months af-ter surgery and construction of a nomogram prediction model
Tianyang XING ; Yali LIU ; Bin YU
Chinese Journal of Rehabilitation Medicine 2025;40(9):1366-1372
Objective:To explore the risk factors of quality of life(QoL)being below normal levels in patients undergo-ing total knee arthroplasty(TKA)at 6 months after surgery,and to construct a nomogram prediction model.Method:Two-hundred and sixty-seven patients who underwent TKA at Qingdao Hospital,University of Health and Rehabilitation Sciences(Qingdao Municipal Hospital)from April 2021 to October 2022 were selected.Clini-cal data were collected on admission and within 6 months after surgery.According to the QoL assessment at 6 months after surgery,they were divided into a high-quality group(n=136)and a non-high-quality group(n=131).LASSO regression was used to screen the predictors,and multivariate Logistic regression was established to construct the predictive model of QoL of TKA patients at 6 months after surgery.Receiver operating character-istic curve(ROC curve),calibration curve and decision curve were drawn to evaluate its predictive value.Result:A total of 131(49.06%)patients had lower QoL than normal 6 months after TKA.LASSO regression selected age,surgical side,education level,duration of knee osteoarthritis(KOA),perioperative recovery,and visual analog scale(VAS)during preoperative rest as predictors.Multivariate logistic regression analysis showed that age(OR,1.08;95%CI,1.01-1.15),duration of KOA(OR,1.13;95%CI,1.05-1.22),VAS during preoperative rest(OR,1.94;95%CI,1.20-3.15),and perioperative rehabilitation(OR,0.42;95%CI,0.18-0.97)were independent risk factors for lower than normal QoL in TKA patients at 6 months after surgery(P<0.05).Statistically significant indicators in multivariate logistic regression analysis were includ-ed in the nomogram model,which underwent internal validation.The area under the ROC curve was 0.829(95%CI,0.779-0.879),indicating good predictive ability of the model.The calibration curve showed good consistency between the predicted probability and the actual probability.The decision curve analysis showed that this model is clinically applicable.Conclusion:Age,duration of KOA,VAS during preoperative rest,and perioperative rehabilitation are indepen-dent predictors of lower-than-normal QoL in TKA patients at 6 months after surgery,and the nomogram mod-el based on the above indicators had good predictive performance.
8.Role of NLRP3 inflammasome-mediated microglia activation in myocardial ischaemia-reperfusion-induced brain injury in mice
Hu CHENG ; Xiao CHENG ; Xueyan LI ; Yasen YALI ; Jianjiang WU ; Long YANG ; Wenbin YU ; Kuo ZHU ; Jiang WANG
Chinese Journal of Anesthesiology 2025;45(7):827-833
Objective:To evaluate the role of NOD-like receptor protein 3 (NLRP3) inflammasome-mediated microglia activation in myocardial ischaemia-reperfusion-induced brain injury in mice.Methods:Fifty-two SPF healthy male wild-type C57BL/6 mice and 52 NLRP3 -/- mice, aged 8-10 weeks, were divided into 4 groups ( n=26 each) using a random number table method: wild type sham operation group (W-S group), wild type myocardial ischemia-reperfusion group (W-IR group), NLRP3 -/- sham operation group (NLRP3 -/--S group), and NLRP3 -/- myocardial ischemia-reperfusion group (NLRP3 -/--IR group). The myocardial ischemia-reperfusion-induced brain injury model was established by ligating the left anterior descending coronary artery for 45 min followed by 24 h of reperfusion in anesthetized mice. The cognitive function was evaluated using the modified Morris water maze test at 24 h of reperfusion. The mice were sacrificed after blood specimens were collected, and brain tissues were obtained for measurement of the blood-brain barrier permeability and water content, for microscopic examination of the pathological changes of brain tissues, and for determination of serum S-100β protein and neuron-specific enolase (NSE) concentrations, contents of interleukin-1 beta (IL-1β), IL-6 and tumor necrosis factor-alpha (TNF-α) in hippocampal tissues (by enzyme-linked immunosorbent assay), expression of NLRP3, apoptosis-associated speck-like protein (ASC), cleaved cysteine aspartate protease 1 (cleaved-caspase-1), gasdermin D (GSDMD), ionized calcium-binding adapter molecule 1 (Iba-1), and occludin in hippocampal tissues (by immunofluorescence and/or Western blot). The apoptosis rate of neurons and density of dendritic spine were calculated. Results:Compared with sham operation group, the escape latency was significantly prolonged, the number of crossing the original platform was decreased, and the time spent in the target quadrant was shortened, the concentrations of serum S-100β protein and NSE were increased, the blood-brain barrier permeability and brain water content were increased, the dendritic spine density in the hippocampal CA1 area was decreased, the contents of IL-1β, IL-6 and TNF-α were increased, the expression of NLRP3, ASC, cleaved-caspase-1, GSDMD and Iba-1 was up-regulated, and the expression of occludin was down-regulated ( P<0.05), and the pathological injury to brain tissues was found in ischemia-reperfusion group. Compared with W-IR group, the escape latency was significantly shortened, the number of crossing the original platform was increased, and the time spent in the target quadrant was prolonged, the concentrations of serum S-100β protein and NSE were decreased, the blood-brain barrier permeability and brain water content were decreased, the dendritic spine density in the hippocampal CA1 area was increased, the contents of IL-1β, IL-6 and TNF-α were decreased, the expression of NLRP3, ASC, cleaved-caspase-1, GSDMD and Iba-1 was down-regulated, and the expression of occludin was up-regulated ( P<0.05), and the pathological injury to brain tissues was alleviated in NLRP3 -/--IR group. Conclusions:NLRP3 inflammasome-mediated microglia activation is involved in myocardial ischaemia-reperfusion-induced brain injury in mice.
9.Preliminary efficacy and safety analysis of modified SIOPEL-4 protocol for newly diagnosed pediatric hepatoblastoma with lung metastases
Jiaxin PENG ; Can HUANG ; An'an ZHANG ; Yali HAN ; Haishan RUAN ; Xiaoxia WANG ; Min XU ; Yuan XIN ; Liting YU ; Zhibao LYU ; Mingxuan FENG ; Shayi JIANG ; Yijin GAO
Chinese Journal of Pediatrics 2025;63(12):1343-1348
Objective:To assess the preliminary efficacy and safety of modified Société Internationale d′Oncologie Pédiatrique Epithelial Liver Tumor Study Group (SIOPEL)-4 protocol for pediatric hepatoblastoma (HB) with lung metastases.Methods:This prospective cohort study enrolled 27 newly diagnosed pediatric HB with lung metastases who received the modified SIOPEL-4 protocol at Shanghai Children′s Medical Center, Shanghai Jiao Tong University School of Medicine, and Shanghai Children′s Hospital between January 2020 to December 2023. Clinical characteristics, lung response rates to induction chemotherapy, treatment outcomes, prognostic factors and sever chemotherapy toxicities at different stages were analyzed. Survival analysis was performed by Kaplan-Meier method. Univariate prognostic analysis was conducted by Log-Rank test.Results:Of the 27 patients, there were 17 males and 10 females, with the age of 21 (15, 33) months. During the follow-up of 31 (12, 45) months for 17 continuous complete remission patients, 4 cases disease progression (2 cases death) and 6 cases relapse were observed. The 2-year event free survival (EFS) and overall survival (OS) rate was (58±11)% and (89±7)%, respectively. All the 27 patients had response to block 1-3 induction chemotherapy (cisplatin+doxorubicin), with 14 cases (52%) achieving complete response and 13 cases (48%) achieving partial response of lung metastatic lesions, the 2-year EFS rate was (81±12)% and (34±14)%, respectively ( χ 2=6.76, P=0.009), the 2-year OS rate was 100% and (79±13)%, respectively ( χ2=2.12, P=0.145). Patients with caudate lobe tumors or ≥10 pulmonary metastatic nodules had significantly lower EFS rates ( χ2=5.36, 7.84, P=0.021, 0.005, respectively). The incidence of grade 3/4 neutropenia after block 1-3 induction chemotherapy, CD (carboplatin+doxorubicin), and VI (vincristine+irinotecan) consolidation chemotherapy was 90% (73/81), 75% (58/77), and 31% (11/35), respectively. The incidence of grade 3/4 thrombocytopenia was 77% (62/81), 69% (53/77), and 14% (5/35), respectively. The incidence of grade 3/4 infections was 64% (52/81), 25% (19/77), and 20% (7/35), respectively. The differences between the groups were statistically significant ( χ2=43.51, 42.69, 33.00, all P<0.001). Two patients (10%) of the 20 evaluable patients for ototoxicity occurred grade 3 and higher hearing impairment, with 1 patient requiring a hearing aid. Conclusions:The modified SIOPEL-4 regimen shows good preliminary efficacy and safety in treating pediatric HB with lung metastases. The prognosis for patients with residual lesions in the lungs after induction chemotherapy needs to be improved. Attention should be given to the ototoxicity induced by high-dose cisplatin chemotherapy.
10.Latent profile analysis and nursing implications of social alienation in colorectal cancer patients
Xiaoxia YANG ; Zifu YU ; Fang WANG ; Yali HOU ; Lijing ZHU ; Liming LÜ
Chinese Journal of Nursing 2025;60(20):2499-2506
Objective To analyze the latent classes of social alienation in colorectal cancer patients and further explore the influencing factors and cumulative effects of risk factors across different classes,thereby providing a reference for individualized interventions.Methods Convenience sampling was used to select colorectal cancer patients hospitalized in the gastrointestinal surgery and oncology departments of 3 tertiary-level hospitals in Shandong Province from January to June 2023 as the study subjects.A questionnaire survey was conducted using the General Information Questionnaire,Social Avoidance Scale,Social Anxiety Scale,UCLA Loneliness Scale,Sense of Coherence Scale,Family Cohesion Scale,and Social Support Rating Scale.Data analysis was performed using latent profile analysis and multivariate logistic regression analysis.Results A total of 292 questionnaires were distributed,with 270 valid responses collected,yielding a response rate of 92.47%.The results of the latent profile analysis indicated that social alienation among colorectal cancer patients could be categorized into 3 latent groups:the"low alienation group"(42.59%),the"high alienation-high social avoidance group"(14.08%),and the"moderate alienation-high social anxiety group"(43.33%).Results of logistic regression analysis revealed that employment status,stoma status,metastasis,sense of coherence,family cohesion,and social support were influencing factors across different categories.Moreover,a cumulative effect of sense of coherence,family cohesion,and social support on distinct categories was observed(P<0.05).Conclusion Social alienation among colorectal cancer patients exhibits group heterogeneity.Healthcare professionals should identify the characteristic differences among patients,prioritise those with multiple risk factors,and develop targeted intervention measures to help them better integrate into society.

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