1.Effectiveness of group skills training intervention on social ability of high functional autism spectrum disorder children
HU Shasha, ZHAO Xiao, ZHU Zhenzhen, LIU Xiaoli, WANG Rong, HU Zhenyu, ZHANG Wenwu
Chinese Journal of School Health 2025;46(2):167-171
Objective:
To evaluate the intervention efficacy of integrated group social skills training on social ability in school age patients with high functioning ASD, so as to provide a reference for improving social skills in children with high functioning ASD.
Methods:
From January 2021 to December 2023, 62 children aged 7-12 with high functioning ASD who visited the Children s Psychiatry Outpatient Department of the Affiliated Kangning Hospital of Ningbo University were recruited, and were randomly divided into a training ( n =31) and a control group ( n =31) by a random number table method. The training group received a 20 week structured group social training program (mental interpretation courses and social courses), while the control group received only conventional treatment. Chinese version of Griffith Empathy Measure Parent Ratings (GEM-PR) and Social Response Scale (SRS) were used to assess the symptoms of social deficits before and after treatment. Emotional face recognition tasks and eye movement trajectories were used to test the characteristics of social visual attention in children with ASD. Group comparison was conducted using t-test and Mann-Whitney U test.
Results:
At baseline, there were no significant differences in GEM-PR score ( t = -1.20 to -0.81), SRS score ( t =-0.36-1.75), emotional face recognition accuracy and reaction time ( t =-0.58-1.85), and eye movement trajectory ( U/t =-1.63-0.29) between the two group ( P >0.05). After intervention, the total GEM-PR score and empathic cognitive factor score of training group [18.00(10.00,24.00),9.00(8.00,13.00)] were significantly higher than those of the control group [12.00(-1.00,18.00),2.00(-2.00,7.00)], and the total SRS score and social cognition, social perception, social communication, social motivation (73.23±14.20, 16.16±2.72, 6.58±2.50, 24.29±5.61, 9.52±3.73) were significantly lower than those of the control group (95.26±15.29, 19.90±2.84, 12.58±2.49,31.94±6.38, 13.74±4.81) ( U/t =-2.38, -4.59; -5.88, -5.29, -9.47, -5.01, -3.87, P <0.05). The overall correct rate of emotional face recognition and the correct rate of angry, fearful and neutral faces recognition in the training group [(81.55±6.62)%,(76.86±12.06)%,(79.61±12.42)%,(94.27±6.26)%] were significantly higher than the control group [(70.55±13.82)%,(62.82±18.77)%,(67.18±18.85)%,(79.60±20.05)%], and the average reaction time [(2 226.70±274.43)ms] was lower than the control group [(2 417.27±324.10)ms] (t=4.00, 3.50, 3.07, 3.89, -2.42, P<0.05). The time to first eye gaze [764.74 (748.64, 793.73) ms] in the training group was significantly lower than that in the control group [810.92 (782.86, 877.42) ms], and the proportion of moderatetohigh intensity attention area in the face [(37.37±1.27)%] was significantly higher than that in the control group [(30.34±1.23)%] (U/t=3.44, 8.89, P<0.05).
Conclusion
Integrated group social training can significantly improve the social communication and empathy ability of high functioning ASD children, increase active attention and recognition ability of faces, and improve mental development of children with ASD.
2.Efficacy and Mechanism of Action of Ermiao Situ Decoction in Modulating JAK/STAT Pathway in Rats with Damp-heat Eczema
Kangning HAN ; Junjie HU ; Juan LI ; Min ZHANG ; Xian ZHOU ; Songlin LIU ; Xin CHEN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(9):37-47
ObjectiveUltra performance liquid chromatography-quadrupole-time of flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS) coupled with network pharmacology and molecular docking was utilized to explore the efficacy and mechanism of action of Ermiao Situ decoction on rats with damp-heat eczema. MethodsA rat model of damp-heat eczema was established by artificial climate chamber intervention combined with sensitization induction by dinitrochlorobenzene (DNCB), and it was randomly divided into the normal group, the model group, the medium- and high-dose groups of Ermiao Situ decoction (3.40 g·kg-1 and 6.80 g·kg-1), and the prednisone acetate group (2.51 mg·kg-1), with eight rats in each group, totalling 46 rats, of which six rats were tested with the drug-containing serum. The chemical analysis of drug-containing serum from rats was carried out by UPLC-Q-TOF-MS/MS, combined with network pharmacology for the prediction of key components, core targets, and signaling pathways, and molecular docking experiments were performed by CB-Dock2 online website. The pharmacological effects of Ermiao Situ decoction in the treatment of damp-heat eczema were investigated by epitaxial indexes combined with the pathologic tissue staining method. The serum levels of gastrin (GAS), interleukin-4 (IL-4), and interleukin-13 (IL-13) were measured by enzyme-linked immunosorbent assay (ELISA). Interleukin-6 (IL-6), Janus kinase 1 (JAK1), phosphorylated (p)-JAK1, signal transduction and activation of transcription factor 3 (STAT3), and p-STAT3 protein expression level was determined by Western bolt. ResultsA total of 19 active ingredients were detected in drug-containing serum samples of rats, which were predicted to act on 198 targets for the treatment of damp-heat eczema, among which the key ingredients included rhodopsin, huangpai alkaloids, and quercetin, and the main core targets included STAT3, tumor necrosis factor (TNF), and IL-6, which were mainly involved in the cancer signaling pathway, phosphatidylinositol 3-kinase (PI3K)/protein kinase (Akt) signaling pathway, T helper 17 (Th17) cell differentiation signaling pathway, and JAK/STAT signaling pathway. The molecular docking results suggested that the key components had strong binding activities with the core targets IL-6, JAK1, and STAT3 in the JAK/STAT signaling pathway. The results of animal experiments showed that compared with those in the normal group, rats in the model group were depressed. They had loose hair, loose stools, epidermal oozing, vesiculation, and generation of thick scabs in the form of scales, decreased body weight, increased anus temperature and water intake, and increased indexes of the spleen, thymus gland, and stomach (P<0.05, P<0.01), and the lesion tissue could be seen to be hyperkeratotic, with the aggregation of inflammatory cells and nonsignificant separation of epidermis and dermis. The gastric mucosa was thinned, deficient, and structurally disorganized, and obvious inflammatory cell aggregation was seen. The levels of GAS, IL-4, and IL-13 in serum were significantly reduced (P<0.05, P<0.01), and the protein expression levels of IL-6, JAK1, p-JAK1, and p-STAT3 in the lesion tissue were significantly increased (P<0.05, P<0.01). Compared with those in the model group, rats in each administration group had stable mental states, formed feces, a clean perianal area, and basically normal epidermis. Only a small amount of scaly scabs existed, and the rats had body weight increased, with decreased anal temperature and water intake, as well as decreased spleen, thymus, and gastric indexes (P<0.05, P<0.01). Epidermal thickness was decreased, and epidermal and dermal separation boundaries were obvious, but hyperkeratotic and accumulation of inflammatory cells could still be seen. The thickness of gastric mucosa increased, and the structure was restored to varying degrees. The levels of GAS, IL-4, and IL-13 content in the serum of rats were increased to varying degrees, and the protein expression levels of IL-6, JAK1, p-JAK1, and p-STAT3 in the dermal lesion tissue were significantly decreased (P<0.05, P<0.01). ConclusionErmiao Situ decoction may exert therapeutic effects on rats with damp-heat eczema by modulating the JAK/STAT signaling pathway.
3.Long-term survival of surgical versus non-surgical treatment for esophageal squamous cell carcinoma in patients ≥70 years: A retrospective cohort study
Kexun LI ; Changding LI ; Xin NIE ; Wenwu HE ; Chenghao WANG ; Kangning WANG ; Guangyuan LIU ; Junqiang CHEN ; Zefen XIAO ; Qiang FANG ; Yongtao HAN ; Lin PENG ; Qifeng WANG ; Xuefeng LENG
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2025;32(05):619-625
Objective To compare the long-term survival of elderly patients with esophageal squamous cell carcinoma (ESCC) treated with surgical versus non-surgical treatment. Methods A retrospective analysis was conducted on the clinical data of elderly patients aged ≥70 years with ESCC who underwent esophagectomy or radiotherapy/chemotherapy at Sichuan Cancer Hospital from January 2009 to September 2017. Patients were divided into a surgical group (S group) and a non-surgical group (NS group) according to the treatment method. The propensity score matching method was used to match the two groups of patients at a ratio of 1∶1, and the survival of the two groups before and after matching was analyzed. Results A total of 726 elderly patients with ESCC were included, including 552 males and 174 females, with 651 patients aged ≥70-80 years and 75 patients aged ≥80-90 years. There were 515 patients in the S group and 211 patients in the NS group. The median follow-up time was 60.8 months, and the median overall survival of the S group was 41.9 months [95%CI (35.2, 48.5)], while that of the NS group was only 24.0 months [95%CI (19.8, 28.3)]. The 1-, 3-, and 5-year overall survival rates of the S group were 84%, 54%, and 40%, respectively, while those of the NS group were 72%, 40%, and 30%, respectively [HR=0.689, 95%CI (0.559, 0.849), P<0.001]. After matching, 138 patients were included in each group, and there was no statistical difference in the overall survival between the two groups [HR=0.871, 95%CI (0.649, 1.167), P=0.352]. Conclusion Compared with conservative treatment, there is no significant difference in the long-term survival of elderly patients aged ≥70 years who undergo esophagectomy for ESCC. Neoadjuvant therapy combined with surgery is still an important choice to potentially improve the survival of elderly patients with ESCC.
4.Precise Magnetic Stimulation of the Paraventricular Nucleus Improves Sociability in a Mouse Model of ASD.
Sha LIU ; Quyang YANG ; Pengfei ZHU ; Xuan LIU ; Qingbo LU ; Jie YANG ; Jingyao GAO ; Hongbin HAN ; Zhijun ZHANG ; Ning GU ; Tao TAN ; Jianfei SUN
Neuroscience Bulletin 2025;41(10):1711-1728
Magnetic stimulation has made significant strides in the treatment of psychiatric disorders. Nonetheless, current magnetic stimulation techniques lack the precision to accurately modulate specific nuclei and cannot realize deep brain magnetic stimulation. To address this, we utilized superparamagnetic iron oxide nanoparticles as mediators to achieve precise targeting and penetration. We investigated the effects of magnetic fields with varying frequencies on neuronal activity and compared the activation effects on neurons using a 10-Hz precise magneto-stimulation system (pMSS) with repetitive transcranial magnetic stimulation in mice. Oxytocin levels, dendritic morphology and density, and mouse behavior were measured before and after pMSS intervention. Our findings suggest that pMSS can activate oxytocinergic neurons, leading to upregulation of oxytocin secretion and neurite outgrowth. As a result, sociability was rapidly improved after a one-week pMSS treatment regimen. These results demonstrate a promising magneto-stimulation method for regulating neuronal activity in deep brain nuclei and provide a promising therapeutic approach for autism spectrum disorder.
Animals
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Autism Spectrum Disorder/physiopathology*
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Paraventricular Hypothalamic Nucleus/physiology*
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Disease Models, Animal
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Transcranial Magnetic Stimulation/methods*
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Male
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Social Behavior
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Mice
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Oxytocin/metabolism*
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Mice, Inbred C57BL
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Neurons/physiology*
5.Research Progress on Signaling Pathways Related to Treatment of Diabetic Cognitive Dysfunction with Traditional Chinese Medicine: A Review
Xinrui LI ; Yuqing WANG ; Ming SU ; Xinru SUN ; Hui ZHANG ; Kangning XIAO ; Shanxin LIU ; Xinjun ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(19):225-232
Diabetic cognitive dysfunction (DCD) is one of the complications of diabetes, which is characterized by impaired brain structure and progressively decreased learning and memory ability. With the increasing incidence of diabetes worldwide, DCD has become a serious medical and social problem. However, its pathophysiological mechanisms are not well understood. The occurrence and development of DCD involve multiple pathological links and mechanisms, and the prevention and treatment require multi-link and multi-target therapeutic measures. At present, there is no specific drug to prevent or improve DCD. Hypoglycemic drugs such as metformin and vigagliptin or anti-dementia drug including Donepezil are commonly used in clinical treatment to delay the occurrence and progression of cognitive dysfunction, but these drugs have a single target and obvious side effects. Traditional Chinese medicine has a long history in the prevention and treatment of diabetes and central cognitive diseases, and it has many unique advantages such as multiple components, multiple targets, side effects, and low price. A large number of studies have confirmed that traditional Chinese medicine has a significant prevention and treatment effect on DCD, which can improve insulin resistance, synaptic dysfunction, inflammation, oxidative stress, endoplasmic reticulum stress, and neuronal apoptosis by regulating phosphatidylin-ositol 3-kinase (PI3K)/protein kinase B (Akt), advanced glycation end products (AGEs)/advanced glycation end products receptor (RAGE)/nuclear transcription factor-κB (NF-κB), NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome, and endoplasmic reticulum stress and nuclear factor E2 related factor 2 (Nrf2)/antioxidant response element (ARE) signaling pathways. This article reviewed the effects and related mechanisms of traditional Chinese medicine on DCD in recent years, so as to provide a reference for the prevention and treatment of DCD by traditional Chinese medicine.
6.Incidence of venous thromboembolism in esophageal cancer: a real-world study of 8 458 cases
Kunyi DU ; Xin NIE ; Kexun LI ; Changding LI ; Kun LIU ; Zhiyu LI ; Kunzhi LI ; Simiao LU ; Kunhan NI ; Wenwu HE ; Chenghao WANG ; Jialong LI ; Haojun LI ; Qiang ZHOU ; Kangning WANG ; Guangyuan LIU ; Wenguang XIAO ; Qiang FANG ; Qiuling SHI ; Yongtao HAN ; Lin PENG ; Xuefeng LENG
Chinese Journal of Digestive Surgery 2024;23(1):109-113
Objective:To investigate the incidence of venous thromboembolism (VTE) in patients with esophageal cancer (EC).Methods:The retrospective cohort study was conducted. The clinicopathological data of 8 458 EC patients who were admitted to Sichuan Cancer Hospital from January 2017 to December 2021 were collected. There were 6 923 males and 1 535 females, aged (64±9)years. There were 3 187 patients undergoing surgical treatment, and 5 271 cases undergoing non-surgical treatment. Observation indicators: (1) incidence of VTE in EC patients; (2) treatment and outcomes of patients with VTE. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed using the t test. Measurement data with skewed distribution were represented as M(range), and comparison between groups was analyzed using the nonparameter rank sum test. Count data were expressed as absolute numbers or percentages, and comparison between groups was analyzed using the chi-square test or Fisher exact probability. Comparison of ordinal data was analyzed using the nonparameter rank sum test. Results:(1) Incidence of VTE in EC patients. Of 8 458 EC patients, 175 cases developed VTE, with an incidence rate of 2.069%(175/8 458). Among 175 VTE patients, there were 164 cases of deep venous thrombosis (DVT), 4 cases of pulmonary embolism (PE), 7 cases of DVT and PE. There were 59 surgical patients and 116 non-surgical patients. There was no significant difference in thrombus type between surgical and non-surgical EC patients with VTE ( χ2=1.95, P>0.05). Of 3 187 surgical patients, the incidence of VTE was 1.851%(59/3 187), including an incidence of 0.157%(5/3 187) of PE. PE accounted for 8.475%(5/59) of surgical patients with VTE. Of 5 271 non-surgical patients, the incidence of VTE was 2.201%(116/5 271), including an incidence of 0.114%(6/5 271) of PE. PE accounted for 5.172%(6/116) of non-surgical patients with VTE. There was no significant difference in the incidence of VTE or PE between surgical patients and non-surgical patients ( χ2=1.20, 0.05, P>0.05). (2) Treatment and outcomes of patients with VTE. Among 175 EC patients with VTE, 163 cases underwent drug treatment, and 12 cases did not receive treatment. Among 163 cases with drug therapy, 158 cases underwent anticoagulant therapy, 5 cases were treated with thrombolysis. All the 163 patients were improved and discharged from hospital. Conclusions:The incidence of VTE in patients with EC is relatively low, as 2.069%. There is no significant difference in the incidence of VTE or thrombus type between surgical EC patients and non-surgical EC patients.
7.Improvement effect of down-regulation of miR-208a on 5-FU resistance in colorectal cancer cells through targeting SFRP1 for mediating Wnt signaling pathway
Bingbing HU ; Kangning LUO ; Su PENG ; Yuzhong ZHOU ; Maoliang CHEN ; Changhua LIU
Journal of Jilin University(Medicine Edition) 2024;50(4):947-955
Objective:To discuss the effect of downregulating microRNA-208a(miR-208a)on the resistance of the colorectal cancer cells to 5-fluorouracil(5-FU),and to clarify its related molecular mechanism.Methods:Real-time fluorescence quantitative PCR(RT-qPCR)method was used to detect the expression levels of miR-208a and secreted frizzled-related protein 1(SFRP1)mRNA in the 5-FU-resistant colorectal cancer cell line HT-29/5-FU and its parent HT-29 cells.The HT-29/5-FU cells were transfected with miR-208a inhibitor plasmid and its negative control plasmid(inhibitor-NC),and SFRP1 small interfering RNA(si-SFRP1)and its negative control plasmid(si-NC),either separately or in combination,followed by treatment with 5-FU.The cells were divided into inhibitor-NC group,miR-208a inhibitor group,miR-208a inhibitor+si-NC group,and miR-208a inhibitor+si-SFRP1 group.MTT assay was used to detect the proliferation activities of the cells and the resistance indexes were calculated;Annexin V-FITC/PI double staining and flow cytometry were used to detect the apoptotic rates of the cells after treated with different concentrations of 5-FU;Western blotting method was used to detect the expression levels of SFRP1,β-catenin,P-glycoprotein(P-gp),and ATP-binding cassette subfamily B member 1(ABCB1)proteins in the cells in various groups;dual-luciferase reporter gene assay was used to validate the targeting relationship between miR-208a and SFRP1.Results:Compared with HT-29 cells,the expression level of miR-208a in the HT-29/5-FU cells was increased(P<0.05),and the expression level of SFRP1 mRNA was decreased(P<0.05).Compared with inhibitor-NC group,the proliferation activity of the cells in miR-208a inhibitor group was decreased(P<0.05),the resistance index was decreased,the apoptotic rate was increased(P<0.05),and the expression levels of β-catenin,P-gp,and ABCB1 proteins in the cells were decreased(P<0.05).The dual-luciferase reporter gene assay results showed that SFRP1 was a target gene of miR-208a and miR-208a could negatively regulate the expression of SFRP1.Compared with miR-208a inhibitor+si-NC group,the proliferation activity of the cells in miR-208a inhibitor+si-SFRP1 group was increased(P<0.05),the resistance index was increased,the apoptotic rate was decreased(P<0.05),and the expression levels of β-catenin,P-gp,and ABCB1 proteins in the cells were increased(P<0.05).Conclusion:Downregulation of miR-208a can improve the resistance of the HT-29/5-FU cells to 5-FU by targeting and upregulating the SFRP1 expression,thereby inhibiting the transmission of the Wnt signaling pathway.
8. Application and prospect of drug discrimination in field of drug abuse
Dan FU ; Qing-Xiao HONG ; Jun GU ; Ze-Min XU ; Ding-Ding ZHUANG ; Wen-Jin XU ; Hui-Fen LIU ; Wen-Hua ZHOU
Chinese Pharmacological Bulletin 2023;39(9):1623-1627
Drug discrimination is a behavioral pharmacological technique to study the discriminative stimulus effects of drug. Currently drug discrimination has been widely used in preclinical drug development of CNS drugs, the most extensive of which is psychodependent research in the field of drug abuse. This review describes in general the basic principles of drug discrimination, preliminarily elaborates on the relevant characteristics and applications of the subjective effects, time-course effect, stereo specificity, individual differences, and receptor mechanisms, and its development prospects for hallucinogens and cannabis drugs are also presented.
9.Surgical treatment and prognosis analysis of thoracic esophageal squamous cell carcinoma: a report of 2 766 cases
Kunhan NI ; Changding LI ; Longlin JIANG ; Wenwu HE ; Chenghao WANG ; Kangning WANG ; Guangyuan LIU ; Lin PENG ; Qiang FANG ; Wenguang XIAO ; Liang QIAO ; Qifeng WANG ; Yongtao HAN ; Xuefeng LENG
Chinese Journal of Digestive Surgery 2023;22(10):1199-1204
Objective:To investigate the surgical treatment and prognosis of thoracic esophageal squamous cell carcinoma (ESCC).Methods:The retrospective cohort study was conducted. The clinicopathological data of 2 766 patients with thoracic ESCC who were admitted to Sichuan Cancer Hospital & Institute from January 2010 to December 2017 were collected. There were 2 256 males and 510 females, aged (62±8)years. All patients underwent surgical treatment. Observation indicators: (1) treatment; (2) postoperative complications; (3) postoperative survival. Measurement data with normal distribution were represented as Mean± SD. Measurement data with skewed distribution were represented as M( Q1, Q3). Count data were described as absolute numbers or percentages. The Kaplan-Meier method was used to draw survival curve and calculate survival rate, and the Log-Rank test was used for survival analysis. Result:(1) Treatment. Fifty-two of the 2 766 patients underwent neoadjuvant therapy. There were 1 444 patients undergoing open surgery, including 44 cases conversion to thoracotomy, and there were 1 322 patients undergoing minimally invasive esophagectomy. There were 1 991, 729 and 46 cases with McKeown, Ivor-Lewis and Sweet esophagectomy, respectively. One thousand two hundred and seventy-one of the 2 766 patients underwent postoperative adjuvant therapy. The number of lymph node metastases, the number of lymph node dissected, rate of R 0 resection, operation time of 2 766 patients were 2.1(0,3.0), 22±12, 94.722%(2 620/2 766), (237±66)minutes. (2) Postoperative complications. The overall incidence of postoperative complications was 25.850%(715/2 766). The top two postoperative complications were pneumonia and anastomotic fistula, with incidence rates of 8.604%(238/2766) and 7.484%(207/2766), respectively. One patient may have more than two kinds of postoperative complications. (3) Postoperative survival. The 1-, 3-and 5-year overall survival rates of 2 766 patients were 86.2%, 57.5% and 46.8%, respectively. Further analysis indicated that the 5-year overall survival rates of 510 female patients and 2 256 male patients were 62.0% and 43.3%, respectively, showing a significant difference between them ( χ2=48.94, P<0.05). The 5-year overall survival rates of 693 cases with upper thoracic ESCC, 1 479 cases with middle thoracic ESCC and 594 cases with lower thoracic ESCC were 49.5%, 46.7% and 44.1%, respectively, showing no significant difference among them ( χ2=3.21, P>0.05). The 5-year overall survival rates of 68 cases with stage 0 thoracic ESCC, 259 cases with stage Ⅰ esophageal ESCC, 885 cases with stage Ⅱ thoracic ESCC, 1 222 cases with stage Ⅲ thoracic ESCC, and 332 cases with stage Ⅳ thoracic ESCC were 95.6%, 76.4%, 61.4%, 35.6%, and 14.5%, respectively, showing a significant difference among them ( χ2=500.40, P<0.05). The 5-year overall survival rates of 1 444 patients undergoing open esophagectomy and 1 322 patients undergoing minimally invasive esophagectomy were 42.5% and 51.8%, respectively, showing a significant difference between them ( χ2=31.29, P<0.05). The 5-year overall survival rates of 1 991 cases undergoing McKeown esophagectomy, 729 cases undergoing Ivor-Lewis esophagectomy, and 46 cases undergoing Sweet esophagectomy were 49.5%, 41.2%, and 32.3%, respectively, showing a significant difference among them ( χ2=19.19, P<0.05). Conclusions:Compared with open esophagectomy, minimally invasive esophagectomy brings survival benefits to patients with thoracic esophageal ESCC. Among different esophagectomy methods, the McKeown esophagectomy has also brought survival benefits to patients with esophageal ESCC compared to the Ivor-Lewis esophagectomy and the Sweet esophagectomy.
10.Practical considerations in the pharmacological treatment of bipolar disorder
Sichuan Mental Health 2023;36(6):481-484
Bipolar disorder is one of the most common mood disorders characterized by an early age of onset and high prevalence rate, and patients tent to have poor prognosis due to high misdiagnosis rate and incomplete diagnosis rate. At present, existing pharmacological treatment for bipolar disorder remains highly variable. Therefore, this paper presents a review of indications of the medications, clinical therapeutic effect and adverse drug reactions, thus providing references for the pharmaceutical treatment of bipolar disorder.


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