ObjectiveTo investigate the mechanism by which adrenoceptor alpha 2A (Adra2a) regulates lipopolysaccharide (LPS)-induced inflammation in primary hepatocytes from lipopolysaccharide-binding protein (LBP) knockout mice (Lbp^-/-). MethodsPrimary hepatocytes from C57BL/6J and Lbp^-/- mice were isolated using a two-step perfusion method. An in vitro inflammatory model was established by LPS stimulation, and an in vivo inflammatory mouse model was established by intraperitoneal injection of LPS. The in vitro experiments were grouped as follows: Control group, LPS group, BRL+LPS group, OE-NC+LPS group, and OE-Adra2a+LPS group. The Control group served as the blank control. The LPS group involved stimulating primary hepatocytes with LPS. The BRL+LPS group involved pretreating primary hepatocytes with BRL-44408 maleate followed by LPS stimulation. The OE-NC+LPS group involved transfecting primary hepatocytes with an empty vector followed by LPS stimulation. The OE-Adra2a+LPS group involved transfecting primary hepatocytes with a lentivirus overexpressing Adra2a, followed by LPS stimulation. The in vivo experimental groups were divided into Control', LPS', BRL+LPS', OE-NC+LPS', and OE-Adra2a+LPS' groups. The Control' group served as the blank control. The LPS' group received intraperitoneal injection of LPS. The BRL+LPS' group received intraperitoneal injection of BRL-44408 maleate for pretreatment, followed by LPS injection. The OE-NC+LPS' group received intraperitoneal injection of empty vector for pretreatment, followed by LPS injection. The OE-Adra2a+LPS' group received intraperitoneal injection of a lentivirus overexpressing Adra2a for pretreatment, followed by LPS injection. Cell viability after Adra2a inhibition and overexpression was assessed via the Cell Counting Kit-8 (CCK-8) assay. RT-qPCR measured changes in gene expression levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) after Adra2a inhibition and overexpression. Western blotting was performed to detect Adra2a protein expression and phosphorylation levels of extracellular signal-regulated kinase 1/2 (ERK1/2), p38 mitogen-activated protein kinase, and c-Jun N-terminal kinase (JNK) following LPS stimulation. ResultsIn vitro experiments revealed that LPS stimulation significantly decreased Adra2a protein expression in primary hepatocytes from C57BL/6J mice compared to the Control group (P<0.05), whereas it increased in primary hepatocytes from Lbp^-/- mice (P<0.001). Compared to the LPS group, the BRL+LPS group exhibited significantly increased cell viability (P<0.01), reduced TNF-α, IL-6, and IL-1β gene transcription levels (P<0.01, P<0.001, P<0.001), and decreased phosphorylation levels of MAPK signaling pathway-related proteins ERK1/2, p38, and JNK (P<0.01, P<0.001, P<0.001). Compared with the OE-NC+LPS group, the OE-Adra2a+LPS group showed significantly decreased cell viability (P<0.001), increased gene transcription levels of TNF-α, IL-6, and IL-1β genes (P<0.001, P<0.01, P<0.001), and elevated phosphorylation levels of MAPK signaling pathway-related proteins ERK1/2, p38, and JNK (P<0.001, P<0.01, P<0.001). In vivo experiments showed that, compared with the LPS' group, the BRL+LPS' group exhibited significantly reduced phosphorylation levels of MAPK signaling pathway-related proteins ERK1/2, p38, and JNK (P<0.001, P<0.01, P<0.01). In the OE-Adra2a+LPS' group, the phosphorylation levels of ERK1/2, p38, and JNK were significantly elevated compared to the OE-NC+LPS' group (P<0.01, P<0.001, P<0.01). ConclusionLPS stimulation can cause a significant increase in Adra2a protein expression in primary hepatocytes of Lbp^-/- mice. Adra2a protein can regulate the level of LPS-induced inflammation in primary hepatocytes of Lbp^-/- mice through the MAPK signaling pathway.

This study aimed to explore the effects and mechanisms of total extracts from Anthriscus sylvestris on pulmonary hypertension in rats. Sixty male SD rats were divided into normal(NC) group, model(M) group, positive drug sildenafil(Y) group, low-dose A. sylvestris(ES-L) group, medium-dose A. sylvestris(ES-M) group, and high-dose A. sylvestris(ES-H) group. On day 1, rats were intraperitoneally injected with monocrotaline(60 mg·kg~(-1)) to induce pulmonary hypertension, and the rat model was established on day 28. From days 15 to 28, intragastric administration of the respective treatments was performed. After modeling and treatment, small animal echocardiography was used to detect the right heart function of the rats. Arterial blood gas was measured using a blood gas analyzer. Hematoxylin and eosin(HE) staining and Masson staining were performed to observe cardiopulmonary pathological damage. Flow cytometry was used to detect apoptosis in the lung and myocardial tissues and reactive oxygen species(ROS) levels. Western blot was applied to detect the expression levels of transforming growth factor-β1(TGF-β1), phosphorylated mothers against decapentaplegic homolog 3(p-Smad3), Smad3, tissue plasminogen activator(t-PA), and plasminogen activator inhibitor-1(PAI-1) in lung tissue. A blood routine analyzer was used to measure inflammatory immune cell levels in the blood. Enzyme-linked immunosorbent assay(ELISA) was used to detect the expression levels of P-selectin and thromboxane A2(TXA2) in plasma. The results showed that, compared with the NC group, right heart hypertrophy index, right ventricular free wall thickness, right heart internal diameter, partial carbon dioxide pressure(PaCO_2), apoptosis in cardiopulmonary tissue, and ROS levels were significantly increased in the M group. In contrast, the ratio of pulmonary blood flow acceleration time(PAT)/ejection time(PET), right cardiac output, change rate of right ventricular systolic area, systolic displacement of the tricuspid ring, oxygen partial pressure(PaO_2), and blood oxygen saturation(SaO_2) were significantly decreased in the M group. After administration of the total extract of A. sylvestris, right heart function and blood gas levels were significantly improved, while apoptosis in cardiopulmonary tissue and ROS levels significantly decreased. Further testing revealed that the total extract of A. sylvestris significantly decreased the levels of interleukin-1β(IL-1β), interleukin-6(IL-6), and PAI-1 proteins in lung tissue, while increasing the expression of t-PA. Additionally, the extract reduced the levels of inflammatory cells such as leukocytes, lymphocytes, granulocytes, and monocytes in the blood, as well as the levels of P-selectin and TXA2 in plasma. Metabolomics results showed that the total extract of A. sylvestris significantly affected metabolic pathways, including arginine biosynthesis, tyrosine metabolism, and taurine and hypotaurine metabolism. In conclusion, the total extract of A. sylvestris may exert an anti-pulmonary hypertension effect by inhibiting the TGF-β1/Smad3 signaling pathway, thereby alleviating immune-inflammatory responses and thrombosis.
Animals ; Male ; Smad3 Protein/metabolism* ; Transforming Growth Factor beta1/metabolism* ; Rats, Sprague-Dawley ; Rats ; Signal Transduction/drug effects* ; Hypertension, Pulmonary/genetics* ; Thrombosis/immunology* ; Drugs, Chinese Herbal/administration & dosage* ; Humans ; Apoptosis/drug effects*

Objective To investigate the role of cholinergic receptor muscarinic 3(Chrm3)in regulating lipopolysaccharide(LPS)-induced inflammation in peritoneal macrophages in lipopolysaccharide binding protein(LBP)-knockout(Lbp-/-)mice.Methods Peritoneal macrophages were isolated from wild-type and Lbp-/-mice to establish an LPS-induced inflammation model.Chrm3 expression in Lbp-/-mouse peritoneal macrophages was inhibited by 1,1-dimethyl-4-diphenylacetoxypiperidinium iodide(4-damp)and small interfering(siRNA)and Chrm3 overexpression was achieved by lentivirus transfection.For 4-damp inhibition,cells were divided into control,LPS,and inhibitor groups,and for siRNA transfection,cells were divided into control,LPS,si-normal control group,and si-Chrm3 groups.For overexpression,cells were divided into control,LPS,negative control,and overexpression groups.Changes in Chrm3 in response to LPS stimulation were verified by Western blot.The effects of 4-damp,si-Chrm3,and lentivirus on cell inflammation and survival were confirmed by Cell Counting Kit-8,quantitative polymerase chain reaction,and Western blot assays.Results Chrm3 protein expression was significantly elevated in Lbp-/-peritoneal macrophages post-LPS stimulation(P＜0.001),whereas there was no notable change in wild-type cells.The cell survival rate was significantly increased in the 4-damp and si-Chrm3 groups(P＜0.05,P＜0.01),and cell survival was significantly reduced in the overexpression group(P＜0.01).Furthermore,4-damp and si-Chrm3 significantly reduced expression levels of the inflammatory factors tumor necrosis factor(TNF)-α,interleukin(IL)-1β,IL-6(P＜0.01,P＜0.001),and phospho-extracellular signal-regulated kinase(p-ERK)(P＜0.01,P＜0.001),which are associated with cell damage and inflammation.In contrast,TNF-α,IL-1β,IL-6(P＜0.001),and p-ERK protein(P＜0.001)were significantly elevated in the overexpression group.Conclusions LPS stimulation upregulated the expression of Chrm3 and proinflammatory cytokines in Lbp-/-peritoneal macrophages.Specific downregulation of Chrm3 by 4-damp and si-Chrm3 significantly decreased LPS-induced proinflammatory cytokines in Lbp-/-peritoneal macrophages,while upregulation of Chrm3 using overexpressing lentivirus significantly elevated the expression of related inflammatory factors.Chrm3 is implicated in the regulation of the LPS-induced inflammation response in peritoneal macrophages in Lbp-/-mice.

In recent years， hyperuricemia （HUA） has shown a rapidly increasing incidence and tends to occur in increasingly young people， with a wide range of cardiac， renal， joint， and cancerous hazards and all-cause mortality associations. Western medicine treatment has limitations such as large liver and kidney damage， medication restriction， and easy recurrence. The intestine is the major extra-renal excretion pathway for uric acid （UA）， and the intestinal microecology can be regulated to promote UA degradation. It offers great potential to develop UA-lowering strategies that target the intestinal microecology， which are promising to provide safer and more effective therapeutic approaches. Traditional Chinese medicine （TCM） can treat HUA via multiple targets and multiple pathways from a holistic view， with low toxicity and side effects. Studies have shown that intestinal microecology is a crucial target for TCM in the treatment of HUA. However， its specific mechanism of action has not been fully elucidated. Focusing on the key role of intestinal microecology in HUA， this review explores the relationship between intestinal microecology and HUA in terms of intestinal flora， intestinal metabolites， intestinal UA transporters， and intestinal barriers. Furthermore， we summarize the research progress in TCM treatment of HUA by targeting the intestinal microecology， with the aim of providing references for the development of TCM intervention strategies for HUA and the direction of future research.

Osteoporosis(OP) is a senile bone disease characterized by an imbalance between bone remodeling and bone formation. Targeting pathogenesis of kidney deficiency, spleen deficiency, and blood stasis, Bushen Jianpi Huoxue Decoction has a significant effect on the treatment of OP by tonifying kidney, invigorating spleen, and activating blood circulation. MicroRNA(miRNA) and the anti-apoptotic protein B-cell lymphoma-2-like protein 1(BCL2L1) are closely related to bone cell metabolism. Therefore, in this study, the binding of miR-140-5p to BCL2L1 was detected by dual luciferase assay and polymerase chain reaction(PCR). After silencing or overexpressing miR-140-5p, the apoptosis, autophagy, and osteogenic function of human fetal osteoblast cell line 1.19(HFOB1.19) were observed by flow cytometry and Western blot. Bushen Jianpi Huoxue Decoction-containing serum was prepared by intragastric administration of Bushen Jianpi Huoxue Decoction in rats. Different concentrations of Bushen Jianpi Huoxue Decoction-containing serum were used to treat HFOB1.19 with or without miR-140-5p mimic. The expression of osteogenic proteins in each group was observed, and the role of miR-140-5p/BCL2L1 in apoptosis and autophagy of HFOB1.19 was studied, along with the effect of Bushen Jianpi Huoxue Decoction on these processes. As indicated by the dual luciferase assay, miR-140-5p bound to BCL2L1. Flow cytometry and Western blot showed that miR-140-5p promoted apoptosis and inhibited autophagy in HFOB1.19. After intervention with high, medium, and low doses of Bushen Jianpi Huoxue Decoction-medicated serum, compared with the miR-140-5p NC group, the expression of osteocalcin(OCN), osteopontin(OPN), Runt-related transcription factor 2(RUNX2), and transforming growth factor beta 1(TGF-β1) decreased in the miR-140-5p mimic group, while the expression of bone morphogenetic protein 2(BMP2) showed no significant difference under high-dose intervention. Therefore, miR-140-5p/BCL2L1 can promote apoptosis and inhibit autophagy in HFOB1.19. Bushen Jianpi Huoxue Decoction can affect the osteogenic effect of miR-140-5p through BMP2.
MicroRNAs/metabolism* ; Autophagy/drug effects* ; Apoptosis/drug effects* ; Humans ; Drugs, Chinese Herbal/administration & dosage* ; Animals ; Cell Line ; bcl-X Protein/metabolism* ; Osteoblasts/metabolism* ; Rats ; Osteoporosis/physiopathology* ; Male ; Rats, Sprague-Dawley ; Osteogenesis/drug effects*

Objective To investigate the screening results and factors affecting abnormal detection rates among high-risk groups of esophageal cancer and to explore effective intervention measures. Methods We investigated and collected the information on gender, education level, age, marital status, symptoms of reflux esophagitis (heartburn, acid reflux, belching, hiccup, foreign body sensation in the pharynx, and difficulty swallowing), consumption of pickled vegetables, salt use, and esophageal cancer incidence of villagers in a natural village in Wenfeng District, Anyang City, Henan Province. Changes in reflux esophagitis symptoms in the high-incidence area of esophageal cancer before and after 16 years were observed, and the relationship of such changes with esophageal cancer was analyzed. Results In 2008, 711 cases were epidemiologically investigated, including 213 cases with one of the symptoms of reflux esophagitis such as heartburn, acid reflux, belching, hiccups, foreign body sensation in the pharynx, and difficulty swallowing (sorted in accordance with the abovementioned symptoms; if there are multiple symptoms, then the former is taken); 55 cases with at least two related symptoms, among which the most symptom was heartburn in 108 cases (15.1%); followed by acid reflux, belching, etc. In 2024, the same group of people was investigated, and eight people were missing because of relocation. A total of 703 people were successfully investigated, of which 189 cases (26.8%) had one of the symptoms of reflux esophagitis, such as heartburn (sorted in accordance with relevant symptoms, if there are multiple symptoms, then the former will be selected); 167 cases (23.7%) had at least two related symptoms, among which the most symptom was heartburn in 139 cases (19.7%); followed by acid reflux. Over 16 years, among the 703 people investigated, 45 cases had esophageal cancer and they had one or more of the abovementioned symptoms. No significant differences in the reflux esophagitis-like symptoms were found between 2008 and 2024 (P=0.26); no significant differences in the composition of reflux esophagitis-like symptoms were found between 2008 and 2024 (P=0.299). Conclusion The detection rate of reflux esophagitis-related symptoms in the population in a high-risk area of esophageal cancer has not decreased in the past 16 years, and the high-risk factors still exist. Esophageal cancer is closely related to reflux esophagitis, and clinical practice can provide early diagnosis and treatment for high-risk population.

Objective To investigate the role of cholinergic receptor muscarinic 3(Chrm3)in regulating lipopolysaccharide(LPS)-induced inflammation in peritoneal macrophages in lipopolysaccharide binding protein(LBP)-knockout(Lbp-/-)mice.Methods Peritoneal macrophages were isolated from wild-type and Lbp-/-mice to establish an LPS-induced inflammation model.Chrm3 expression in Lbp-/-mouse peritoneal macrophages was inhibited by 1,1-dimethyl-4-diphenylacetoxypiperidinium iodide(4-damp)and small interfering(siRNA)and Chrm3 overexpression was achieved by lentivirus transfection.For 4-damp inhibition,cells were divided into control,LPS,and inhibitor groups,and for siRNA transfection,cells were divided into control,LPS,si-normal control group,and si-Chrm3 groups.For overexpression,cells were divided into control,LPS,negative control,and overexpression groups.Changes in Chrm3 in response to LPS stimulation were verified by Western blot.The effects of 4-damp,si-Chrm3,and lentivirus on cell inflammation and survival were confirmed by Cell Counting Kit-8,quantitative polymerase chain reaction,and Western blot assays.Results Chrm3 protein expression was significantly elevated in Lbp-/-peritoneal macrophages post-LPS stimulation(P＜0.001),whereas there was no notable change in wild-type cells.The cell survival rate was significantly increased in the 4-damp and si-Chrm3 groups(P＜0.05,P＜0.01),and cell survival was significantly reduced in the overexpression group(P＜0.01).Furthermore,4-damp and si-Chrm3 significantly reduced expression levels of the inflammatory factors tumor necrosis factor(TNF)-α,interleukin(IL)-1β,IL-6(P＜0.01,P＜0.001),and phospho-extracellular signal-regulated kinase(p-ERK)(P＜0.01,P＜0.001),which are associated with cell damage and inflammation.In contrast,TNF-α,IL-1β,IL-6(P＜0.001),and p-ERK protein(P＜0.001)were significantly elevated in the overexpression group.Conclusions LPS stimulation upregulated the expression of Chrm3 and proinflammatory cytokines in Lbp-/-peritoneal macrophages.Specific downregulation of Chrm3 by 4-damp and si-Chrm3 significantly decreased LPS-induced proinflammatory cytokines in Lbp-/-peritoneal macrophages,while upregulation of Chrm3 using overexpressing lentivirus significantly elevated the expression of related inflammatory factors.Chrm3 is implicated in the regulation of the LPS-induced inflammation response in peritoneal macrophages in Lbp-/-mice.

Objective:To evaluate the efficacy and safety of endoscopic variceal ligation (EVL) of esophageal varices combined with endoscopic variceal intensive ligation (EVIL) of gastric varices for gastroesophageal variceal bleeding with liver cirrhosis under non-emergency settings.Methods:Data of 643 consecutive patients with gastroesophageal variceal bleeding due to liver cirrhosis admitted to the Department of Gastroenterology, Henan Provincial People's Hospital from January 2017 to March 2023 were included in the retrospective study. A total of 192 patients were included after excluding 451 patients. One hundred and forty-nine patients who underwent EVL of esophageal varices combined with EVIL of gastric varices were enrolled into the EVIL group, while 43 patients who underwent EVL of esophageal varices combined with endoscopic tissue adhesive injection (ETAI) of gastric varices were enrolled into the ETAI group. The endoscopic treatment success rate, esophageal variceal ligations number, operation time of endoscopic treatment, hospitalization time, rebleeding rate, mortality and the incidence of adverse events were compared between the two groups.Results:Compared with the ETAI group, the EVIL group exhibited significantly higher endoscopic treatment success rate [100.0% (149/149) VS 95.3% (41/43), P=0.049], slightly greater esophageal variceal ligations number [8 (6, 11) rings VS 7 (6, 9) rings, Z=-1.29, P=0.196], shorter operation time of endoscopic treatment [27.0 (20.5, 34.0) min VS 36.0 (21.0, 51.0) min, Z=-2.30, P=0.021], and significantly shorter hospitalization time [10 (7, 13) d VS 13 (9, 15) d, Z=-3.02, P=0.003]. The rebleeding rate within 24, 72, 120 hours after the operation, early, delayed and total rebleeding in the EVIL group were 0.0% (0/149), 0.0% (0/149), 0.7% (1/149), 2.0% (3/149), 12.8% (19/149) and 14.8% (22/149) respectively, and 4.7% (2/43) ( P=0.049), 9.3% (4/43) ( P=0.002), 9.3% (4/43) ( χ2=6.69, P=0.010), 4.7% (2/43) ( χ2=0.17, P=0.679), 30.2% (13/43) ( χ2=7.34, P=0.007) and 44.2% (19/43) ( χ2=17.20, P<0.001) in the ETAI group, respectively. No death related to rebleeding occurred within 6 weeks after the operation in 2 groups. The mortality related to rebleeding within 1 year after the operation and during the follow-up period in the EVIL group were 1.3% (2/149) and 3.4% (5/149) respectively, and 0.0% (0/43) ( P=1.000) and 2.3% (1/43) ( χ2=0.02, P=0.876) in the ETAI group, respectively. The incidences of fever, chest pain, nausea or vomiting in the EVIL group were 12.1% (18/149), 14.1% (21/149) and 13.4% (20/149) respectively, and 11.6% (5/43) ( χ2=0.01, P=0.936), 16.3% (7/43) ( χ2=0.13, P=0.721) and 18.6% (8/43) ( χ2=0.72, P=0.396) in the ETAI group, respectively. Two patients (1.3%) in the EVIL group had gastric variceal ring loss. Ectopic embolism occurred in 1 patient (2.3%) in the ETAI group. Conclusion:For patients with gastroesophageal variceal bleeding due to liver cirrhosis who are suitable for non-emergency endoscopic treatment, EVL of esophageal varices combined with EVIL of gastric varices is also safe, and more effective than EVL of esophageal varices combined with ETAI of gastric varices. This approach offers improved treatment success rate, reduced operation and hospitalization time, lower rebleeding rates, and decreased rebleeding-related mortality.

Objective:To evaluate the efficacy and safety of endoscopic variceal ligation (EVL) of esophageal varices combined with endoscopic variceal intensive ligation (EVIL) of gastric varices for gastroesophageal variceal bleeding with liver cirrhosis under non-emergency settings.Methods:Data of 643 consecutive patients with gastroesophageal variceal bleeding due to liver cirrhosis admitted to the Department of Gastroenterology, Henan Provincial People's Hospital from January 2017 to March 2023 were included in the retrospective study. A total of 192 patients were included after excluding 451 patients. One hundred and forty-nine patients who underwent EVL of esophageal varices combined with EVIL of gastric varices were enrolled into the EVIL group, while 43 patients who underwent EVL of esophageal varices combined with endoscopic tissue adhesive injection (ETAI) of gastric varices were enrolled into the ETAI group. The endoscopic treatment success rate, esophageal variceal ligations number, operation time of endoscopic treatment, hospitalization time, rebleeding rate, mortality and the incidence of adverse events were compared between the two groups.Results:Compared with the ETAI group, the EVIL group exhibited significantly higher endoscopic treatment success rate [100.0% (149/149) VS 95.3% (41/43), P=0.049], slightly greater esophageal variceal ligations number [8 (6, 11) rings VS 7 (6, 9) rings, Z=-1.29, P=0.196], shorter operation time of endoscopic treatment [27.0 (20.5, 34.0) min VS 36.0 (21.0, 51.0) min, Z=-2.30, P=0.021], and significantly shorter hospitalization time [10 (7, 13) d VS 13 (9, 15) d, Z=-3.02, P=0.003]. The rebleeding rate within 24, 72, 120 hours after the operation, early, delayed and total rebleeding in the EVIL group were 0.0% (0/149), 0.0% (0/149), 0.7% (1/149), 2.0% (3/149), 12.8% (19/149) and 14.8% (22/149) respectively, and 4.7% (2/43) ( P=0.049), 9.3% (4/43) ( P=0.002), 9.3% (4/43) ( χ2=6.69, P=0.010), 4.7% (2/43) ( χ2=0.17, P=0.679), 30.2% (13/43) ( χ2=7.34, P=0.007) and 44.2% (19/43) ( χ2=17.20, P<0.001) in the ETAI group, respectively. No death related to rebleeding occurred within 6 weeks after the operation in 2 groups. The mortality related to rebleeding within 1 year after the operation and during the follow-up period in the EVIL group were 1.3% (2/149) and 3.4% (5/149) respectively, and 0.0% (0/43) ( P=1.000) and 2.3% (1/43) ( χ2=0.02, P=0.876) in the ETAI group, respectively. The incidences of fever, chest pain, nausea or vomiting in the EVIL group were 12.1% (18/149), 14.1% (21/149) and 13.4% (20/149) respectively, and 11.6% (5/43) ( χ2=0.01, P=0.936), 16.3% (7/43) ( χ2=0.13, P=0.721) and 18.6% (8/43) ( χ2=0.72, P=0.396) in the ETAI group, respectively. Two patients (1.3%) in the EVIL group had gastric variceal ring loss. Ectopic embolism occurred in 1 patient (2.3%) in the ETAI group. Conclusion:For patients with gastroesophageal variceal bleeding due to liver cirrhosis who are suitable for non-emergency endoscopic treatment, EVL of esophageal varices combined with EVIL of gastric varices is also safe, and more effective than EVL of esophageal varices combined with ETAI of gastric varices. This approach offers improved treatment success rate, reduced operation and hospitalization time, lower rebleeding rates, and decreased rebleeding-related mortality.

Tic disorder is a neurodevelopmental disorder that occurs in children or adolescents, often attracting the attention of others due to involuntary, repetitive, and non-rhythmic tics, and drug therapy often causes negative emotions in children and their families due to its significant adverse reactions, poor compliance, and tendency of recurrence after drug withdrawal. In recent years, comprehensive behavioral intervention has shown great potential as a safe and effective treatment modality for tic disorders, with few adverse reactions. This article reviews the advances in the application of comprehensive behavioral intervention for tic disorder in China and abroad in the past 5 years, in order to provide a reference for clinical application.
Humans ; Tic Disorders/therapy* ; Behavior Therapy/methods*