1.Mechanism of Tumor T Cell Exhaustion from Perspective of ''Sanjiao-Yingwei'' Qi Transformation Malfunction
Xinhao TANG ; Bowen CHU ; Yuanyuan QIN ; Yeling LIU ; Xinyan SHU ; Mianhua WU ; Gang YIN ; Jianguo DAI
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(5):176-185
In order to promote the innovative application of Sanjiao theory and Yingwei theory, this paper tries to apply the ''Sanjiao-Yingwei'' Qi transformation theory to the treatment of tumor diseases, integrating it with T cell exhaustion mechanism to elaborate on its scientific connotation and using network pharmacology and bioinformatics to elucidate the correlation between the anti-tumor mechanism of ''Sanjiao-Yingwei'' Qi transformation and T cell exhaustion. The ''Sanjiao-Yingwei'' Qi transformation function is closely related to the immunometabolic ability of the human body, and the ''Sanjiao-Yingwei'' Qi transformation system constitutes the immunometabolic exchange system within and outside the cellular environment. Cancer toxicity is generated by the fuzzy Sanjiao Qi, and the long-term fuzzy Sanjiao Qi is the primary factor leading to T cell exhaustion, which is related to the long-term activation of T cell receptors by the high tumor antigen load in the tumor microenvironment. Qi transformation malfunction of the Sanjiao produces phlegm and collects stasis, which contributes to T cell exhaustion and is correlated with nutrient deprivation, lipid accumulation, and high lactate levels in the immunosuppressed tumor microenvironment, as well as with the release of transforming growth factor-β and upregulated expression of programmed death receptor-1 by tumor-associated fibroblasts and platelets in the tumor microenvironment. Ying and Wei damage due to Sanjiao Qi transformation malfunction is similar to the abnormal manifestations such as progressive loss of exhausted T cell effector function and disturbance of cellular energy metabolism. Guizhi decoction, Shengming decoction, and Wendan decoction can correct T cell exhaustion and exert anti-tumor effects through multi-target and multi-pathways by regulating ''Sanjiao-Yingwei'' Qi transformation, and hypoxia inducible factor-1α (HIF-1α) may be one of the main pathways to correct T cell exhaustion. It was found that HIF-1α may be one of the important prognostic indicators in common tumors by bioinformatics. The use of the ''Sanjiao-Yingwei'' Qi transformation method may play an important part in improving the prognosis of tumor patients in clinical practice.
2.Effects of motivational enhancement group intervention on relapse tendency and self-esteem of male recovering amphetamine addicts
Yuanyuan WU ; Kunli WU ; Xiong ZHANG ; Na ZHAO ; Li WU ; Shu TAN ; Wensa YIN
Chinese Mental Health Journal 2024;38(12):1028-1033
Objective:To explore the effect of motivational enhancement group intervention conducted by nur-ses on the motivation of self-improvement,relapse tendency and self-esteem in the recovering male amphetamine addicts.Methods:Ninety-eight recovering male amphetamine addicts in the Compulsory Detoxification Center were randomly divided into control group(n=54)and motivational enhancement group(n=44).The addicts in the con-trol group received routine education while those in the motivational enhancement group received routine education combined with a 12-week motivational enhancement group intervention conducted by nurses.The Stages of Change Readiness and Treatment Eagerness Scale(SOCRATES),Relapse Tendency Questionnaire,and Rosenberg Self-es-teem Scale(RSES-T)were applied to measure the effect,before and after the intervention.Results:In both two groups,the scores of RSEST,questionnaire of relapse tendency,and self-confidence of detoxification were lower af-ter 12-week intervention than at the baseline(Ps<0.05).After 12-week intervention,all the above scores were lower in the motivational enhancement group than in the control group(Ps<0.05).Conclusion:Compared with routine education,the motivational enhancement group intervention conducted by nurses may be more effective to improve their self-confidence in drug rehabilitation and prevention of relapse in recovering male amphetamine ad-dicts,however,the improvement on self-esteem is limited.
3.Efficacy and safety of omalizumab in the treatment of chronic urticaria in children: a retrospective study
Shuzhen YUE ; Ye SHU ; Yangyang LUO ; Keyao LI ; Yuanyuan ZHANG ; Jianping TANG ; Zhu WEI
Chinese Journal of Dermatology 2024;57(4):354-358
Objective:To evaluate the efficacy and safety of omalizumab in the treatment of chronic urticaria in children.Methods:A retrospective study was conducted. Patients with chronic urticaria were collected from the Department of Dermatology, Hunan Children′s Hospital from January to December 2021, and divided into a control group and a combination group according to different medication regimens. The patients in the combination group received subcutaneous injections of omalizumab (150 mg, once every 4 weeks) combined with conventional-dosage antihistamines, while the patients in the control group were only treated with double-dosage or multiple types of antihistamines. The course of treatment was 3 to 6 months. The clinical efficacy and adverse reactions were evaluated at 3, 6, and 12 months after the start of treatment, and the recurrence was evaluated at 3 and 6 months after the end of treatment.Results:A total of 46 children with chronic urticaria were collected. There were 23 children (13 males and 10 females) in the combination group, aged from 6 to 17 years and including 16 aged from 6 to 12 years and 7 aged from 13 to 17 years; according to the total serum IgE levels before treatment, the patients in the combination group were divided into an increased IgE subgroup (11 cases) and a normal IgE subgroup (12 cases). In the control group, there were 13 males and 10 females, aged from 6.33 to 16 years and including 15 aged from 6 to 12 years and 8 aged from 13 to 17 years. At 3, 6, and 12 months after the start of treatment, the response rates in the combination group were all 86.96% (20/23), which were all significantly higher than those in the control group (52.17% [12/23], 56.52% [13/23], 56.52% [13/23], P = 0.010, 0.022, 0.022, respectively). In the combination group, the response rates at 3, 6, and 12 months after the start of treatment were all 14/16 in the children aged 6 to 12 years and 6/7 in those aged 13 to 17 years, and there were no significant differences between the two age groups (all χ2 = 0.01, P = 0.907) ; in the control group, the response rates were 5/15, 6/15 and 5/15 respectively in the children aged 6 to 12 years, which were all significantly lower than those in the combination group ( P = 0.002, 0.006, 0.006, respectively). In the combination group, the response rates at 3, 6, and 12 months after the start of treatment were all 9/11 in the increased IgE subgroup and 11/12 in the normal IgE subgroup, and there were no significant differences between the two subgroups (all P = 0.484). During the treatment, no serious adverse reactions were observed in the combination group or control group, and mild somnolence only occurred in 2 children in the control group. At 3 months after the end of treatment, no recurrence was observed in 16 patients in the combination group, 2 out of 6 patients experienced recurrence in the control group, and the recurrence rate was lower in the combination group than in the control group ( P = 0.030) ; at 6 months after the end of treatment, no recurrence was observed in 16 patients in the combination group, 3 out of 6 patients experienced recurrence in the control group, and the recurrence rate was lower in the combination group than in the control group ( P = 0.022) . Conclusion:Omalizumab combined with conventional-dosage antihistamines could improve the clinical efficacy and reduce the recurrence rate in the treatment of chronic urticaria in children, with few adverse reactions.
4.Research on fungal culturomics based on different universal media
ZHANG Shu ; ZHOU Mengshi ; LI Rui ; GENG Yuanyuan ; ZHAO Fei ; HE Lihua ; GONG Jie
China Tropical Medicine 2023;23(8):783-
Abstract: Objective To screen out a more universally applicable culture medium for the isolation and culturing of pathogenic fungi through comparing the performance of various universal fungal culture media, to optimize the fungal culturomics technique, and to better apply it to the culturomics research of pathogenic fungi. Methods Multiple common fungal culture media Sabouraud dextrose agar (SDA), potato dextrose agar (PDA), modified Dixon (mDixon), modified LeemingNotman agar (MLNA), etc., and a new pan-fungal medium (PF) were used to culture 40 strains of common pathogenic fungi to determine the growth states of strains under different conditions. Based on that, PF, SDA, PDA, mDixon and MLNA, a total of 5 culture media, were used to isolate and culture a simulated sample (suspension of Candida albicans and Aspergillus fumigatus), 10 human samples (4 fecal samples and 6 vaginal secretion samples) and 3 environmental samples. Results The positive growth rates of 40 strains of pathogenic fungi in the 7 media were as follows: PDA 95.0% (38/40), SDA 95.0% (38/40), BHI 95.0% (38/40), YPD 90.0% (36/40), mDixon 95.0% (38/40), MLNA 87.5% (35/40), PF 100.0% (40/40). For the simulated samples, PF could effectively promote the self-limited growth of filamentous fungi, performing better in isolation and culture. For the human samples and environmental samples, PF showed the same versatility as SDA and PDA. Conclusions In the isolation and culturing of pathogenic fungi, PF medium can effectively isolate and culture most fungal species. Meanwhile, PF can make the fast-growing fungi show self-limited growth and clear edges, and not easy to cross-contamination, which indicates it is conducive to the isolation and identification of single colonies. PF medium outperforms other common media in isolating strains from unknown samples in culturomics, which illustrates PF medium can be effectively used for the study of
fungal culturomics.
5.High-frequency oscillations analysis in stereotactic electroencephalogram guided radiofrequency thermocoagulation in treating refractory epilepsy
Zhichuang QU ; Xin CHEN ; Juan LUO ; Yuanyuan ZHANG ; Sixun YU ; Haifeng SHU
Chinese Journal of Neuromedicine 2023;22(6):585-591
Objective:To explore the clinical application values of radiofrequency thermocoagulation (RF-TC) based on stereotactic electroencephalogram (SEEG) high-frequency oscillations (HFOs) analysis in patients with refractory epilepsy.Methods:Fourteen patients with refractory epilepsy treated with SEEG-guided RF-TC were selected from Department of Neurosurgery, PLA Western Theater Command General Hospital from August 2019 to December 2021. Automatic detection algorithm of Matlab was used to calculate the HFOs incidence in each montage, and the fitting curves of HFOs incidences were used to formulate the threshold of HFOs and delimit the HFOs regions (ripples and fast ripples). These patients were divided into non-seizure group and seizure group according to the prognoses 3 and 6 months after RF-TC. At the last follow-up, these patients were divided into good prognosis group and poor prognosis group according to Engel grading; the differences of ripple thermocoagulation rate and fast ripple thermocoagulation rate between the 2 groups were compared.Results:A total of 7,332 ripples and 1,144 fast ripples were detected in SEEG data from 14 patients. Six months after surgery, neurological dysfunction incidence was 14.3%, without permanent neurological dysfunction, intracranial infection, intracranial hemorrhage, or electrode equipment failure. Within 3 months of RF-TC, seizure-free rate was 71.4% (10/14), and fast ripple thermocoagulation rate in non-seizure group was significantly higher than that in seizure group ( P<0.05); within 6 months of RF-TC, seizure-free rate was 57.1% (8/14), and ripple thermocoagulation rate in non-seizure group was significantly higher than that in seizure group ( P<0.05). At last follow-up, 6 patients had good prognosis and 8 patients had poor prognosis; the ripple thermocoagulation rate in good prognosis group was significantly higher than that in poor prognosis ( P<0.05). Conclusions:HFOs can assist in designating epileptogenic regions. Patients with wider range of thermocoagulation ripples or fast ripples will have better short-term efficacy; patients with wider range ofthermocoagulation ripples will have better prognosis.
6.Analysis of public health risks associated with pathogenic fungi in China
Jie GONG ; Yuanyuan GENG ; Shu ZHANG ; Wei LIU ; Weiwei WU ; Ruoyu LI ; Jianzhong ZHANG
Chinese Journal of Epidemiology 2023;44(12):1977-1983
At present, the public health risks caused by pathogenic fungi are greater in China and have attracted great attention from disease control departments. Due to the difficulty in diagnosing fungal infections, the public health risk of pathogenic fungi is currently hidden in the unexplained pneumonia/encephalitis/fever syndrome and is not effectively appreciated. From the public health perspective, the mainly focused fungal pathogens include highly pathogenic fungi (including dimorphic fungi and dematiaceous fungi), pathogenic fungi that cause regional aggregation infections, and drug-resistant pathogenic fungi. However, due to the lack of systematic monitoring data, the disease burden related to pathogenic fungi cannot be accurately quantified and evaluated. Therefore, to effectively reduce the serious harm of fungal infections to the public, systematic monitoring of pathogenic fungi should be carried out nationally.
7.Drug discovery of sclerostin inhibitors.
Sifan YU ; Dijie LI ; Ning ZHANG ; Shuaijian NI ; Meiheng SUN ; Luyao WANG ; Huan XIAO ; Dingdong LIU ; Jin LIU ; Yuanyuan YU ; Zongkang ZHANG ; Samuel Tin Yui YEUNG ; Shu ZHANG ; Aiping LU ; Zhenlin ZHANG ; Baoting ZHANG ; Ge ZHANG
Acta Pharmaceutica Sinica B 2022;12(5):2150-2170
Sclerostin, a protein secreted from osteocytes, negatively regulates the WNT signaling pathway by binding to the LRP5/6 co-receptors and further inhibits bone formation and promotes bone resorption. Sclerostin contributes to musculoskeletal system-related diseases, making it a promising therapeutic target for the treatment of WNT-related bone diseases. Additionally, emerging evidence indicates that sclerostin contributes to the development of cancers, obesity, and diabetes, suggesting that it may be a promising therapeutic target for these diseases. Notably, cardiovascular diseases are related to the protective role of sclerostin. In this review, we summarize three distinct types of inhibitors targeting sclerostin, monoclonal antibodies, aptamers, and small-molecule inhibitors, from which monoclonal antibodies have been developed. As the first-in-class sclerostin inhibitor approved by the U.S. FDA, the monoclonal antibody romosozumab has demonstrated excellent effectiveness in the treatment of postmenopausal osteoporosis; however, it conferred high cardiovascular risk in clinical trials. Furthermore, romosozumab could only be administered by injection, which may cause compliance issues for patients who prefer oral therapy. Considering these above safety and compliance concerns, we therefore present relevant discussion and offer perspectives on the development of next-generation sclerostin inhibitors by following several ways, such as concomitant medication, artificial intelligence-based strategy, druggable modification, and bispecific inhibitors strategy.
8.Research progress of human cytomegalovirus in escaping from the host interferon response
Chinese Journal of Applied Clinical Pediatrics 2022;37(11):878-880
The human cytomegalovirus (HCMV) infection is widespread in the world, which mainly affects people with an insufficient immunity.Interferon is an important member involved in the innate immune, which is of great significance in the early antiviral response.Owing to the huge genome, HCMV expresses various proteins that resist the host immune response effectively.Moreover, HCMV also exploits host cells to resist the immune response of interferon, thus escaping from the host immune response and establishing a latent infection.This study aims to review the research progress of HCMV in escaping from the host interferon response.
9.Experience and influencing factors of endoscopic retrograde cholangiopancreatography intubation in children
Shizhen ZHOU ; Hao WENG ; Mingzhe WENG ; Yijun SHU ; Yuanyuan YE ; Wenjie ZHANG ; Xuefeng WANG
Chinese Journal of Digestive Endoscopy 2022;39(3):203-208
Objective:To report pediatric endoscopic retrograde cholangiopancreatography (ERCP) intubation techniques and to analyze the influencing factors of pediatric ERCP in China.Methods:Retrospective analysis was performed on 90 cases of pediatric and adult ERCP operations respectively at Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from January 2016 to June 2020. The anatomic data, intubation time, and endoscopic intubation measures were reviewed. The anatomic differences in duodenal papilla between the children and adults were analyzed to find the factors affecting ERCP intubation time in children.Results:There were 88 cases of successful infantile intubation with the success rate of 97.8%, and 90 cases of successful adult intubation with the success rate of 100.0%. The intubation time in the pediatric group was 187±67 s, and that in the adult group was 247±86 s with significant difference ( t=5.220, P<0.001). The duodenal diameter of pediatric patients was 3.38±1.57 cm, and that of adult patients was 5.94±1.87 cm with significant difference ( t=9.832, P<0.001). The horizontal distance from the duodenal bulb to the papilla in pediatric patients was 2.44±1.15 cm, which was significantly shorter than 4.22±1.43 cm in adult patients ( t=9.077, P<0.001). Most duodenal papillae in children were hemispherical [flat 26.1% (23/88), hemispherical 51.1% (45/88), cylindrical 22.7% (20/88)], while most of those in the adult patients were cylindrical [flat 9.1% (8/88), hemispherical 23.9% (21/88), cylindrical 67.0% (59/88)]. The factors influencing the intubation time of ERCP in children by univariate analysis included the shape of duodenal papilla, duodenal papilla hardness, visual region, distance from junction of duodenal bulb and descending part to duodenal papilla, distance from duodenal papilla to endoscope, and degree of incising. Conclusion:Shorter and stiffer duodenal papillae in children with normal papilla orientation are associated with shorter intubation time. These indicators are favorable factors for intubation.
10.Risk factors for central lymph nodes more than 5 involved in papillary thyroid microcarcinoma with cN0
Ping YU ; Chang DENG ; Daixing HU ; Chun HUANG ; Yuanyuan WANG ; Xiujie SHU ; Xinliang SU
Chinese Journal of Endocrine Surgery 2022;16(4):426-430
Objective:To analyze the risk factors of the number of central lymph node metastasis (CLNM) >5 in papillary thyroid microcarcinoma (PTMC) with clinical lymph node negative (cN0) .Methods:A total of 1567 cases of unilateral cN0 PTMC patients undergoing surgery at Endocrine and Breast Surgery Department of the First Affiliated Hospital of Chongqing Medical University from Jan. 2013 to Dec. 2018 were analyzed retrospectively. There were 405 cases of male and 1162 cases of female among them. According to the CLNM, they were divided into 0-5 and ≥5 groups. Clinicopathological characteristics of two groups were compared with Chi-square test and χ 2 test, et al. Results:The case of CLNM>5 involved was 4.1% (65/1567) .Univariate analysis showed that male, age ≤50 years old, tumor diameter> 8 mm, multifocal cancer all were related to CLNM>5 involved ( P<0.05) , multivariate logistic regression analysis found that male ( OR=1.886, P=0.017) , age ≤50 years ( OR=3.778, P=0.002) , tumor diameter>8 mm ( OR=2.483, P<0.001) and multifocal cancer ( OR=2.362, P=0.005) were independent risk factors for CLNM>5. Subgroup analysis showed that the number of Delphian lymph nodes metastasis≥1 ( OR=13.475, P<0.001) , pretracheal lymph nodes metastasis≥2 ( OR=41.695, P<0.001) , and Delphian+pretracheal lymph nodes metastasis≥2 ( OR=28.750, P<0.001) were also independent risk factors for CLNM>5. Conclusions:Unilateral PTMC patients who are male and age ≤50 years old with tumor diameter>8 mm, multifocal cancer have higher risk of central lymph nodes more than 5 involved, surgical treatment and prophylactic central neck dissection are recommended to such patients instead of long-term follow-up observation.Total thyroidectomy should be selected appropriately according to the intraoperative situation.

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