1.Research progress on strategies to target intestinal microbiota to improve drug resistance in tumor immunotherapy
Hui-ling LI ; Bi-qing LIU ; Ying-nan FENG ; Xin HU ; Lan ZHANG ; Xian-zhe DONG
Acta Pharmaceutica Sinica 2025;60(2):260-268
A growing body of research points out that gut microbiota plays a key role in tumor immunotherapy. By optimizing the composition of intestinal microbiota, it is possible to effectively improve immunotherapy resistance and enhance its therapeutic effect. This article comprehensively analyzes the mechanism of intestinal microbiota influencing tumor immunotherapy resistance, expounds the current strategies for targeted regulation of intestinal microbiota, such as traditional Chinese medicine and plant components, fecal microbiota transplantation, probiotics, prebiotics and dietary therapy, and explores the potential mechanisms of these strategies to improve patients' resistance to tumor immunotherapy. At the same time, the article also briefly discusses the prospects and challenges of targeting intestinal microbiota to improve tumor immunotherapy resistance, which provides a reference for related research to help the strategy research of reversing tumor immunotherapy resistance.
2.mfat-1 gene therapy prevents and ameliorates multiple sclerosis in mice
Min-Yi TANG ; Xin-Yun BI ; Shuai WANG ; Chao-Feng XING ; Xiao-Li WU ; Zi-Jian ZHAO ; Fang-Hong LI
Chinese Pharmacological Bulletin 2024;40(10):1930-1936
Aim To investigate the preventive and therapeutic effects of the mfat-1 gene therapy on exper-imental autoimmune encephalomyelitis in mice.Meth-ods mfat-1 gene therapy was used to render the host endogenous capability of producing ω-3 PUFAs,con-comitantly reduce the levels of ω-6 PUFAs,and change the proportion of ω-3/ω-6 PUFAs.Then,the levels of PUFAs in blood were analyzed by gas chromatography.The neurological deficits in mice were evaluated by neurological dysfunction score.HE staining and LFB staining of mouse spinal cord slices were used to ob-serve central nervous system inflammation infiltration and demyelinating lesions.Flow cytometry microsphere microarray technology was used to detect the content of cytokines in serum.Results The mfat-1 gene therapy could significantly raise the proportion of ω-3/ω-6 PU-FAs(P<0.05),markedly delay the incubation period and peak period and reduce neurological dysfunction scores(P<0.05),and improve inflammation and de-myelination of spinal cords(P<0.05).It could also greatly increase the levels of IL-2,IFN-γ,IL-4 and IL-17 in serum(P<0.05).Conclusion The pro-portion of ω-3/ω-6 PUFAs in blood circulation en-hanced by mfat-1 gene therapy can effectively prevent and treat experimental autoimmune encephalomyelitis in mice.
3.Radiofrequency ablation on prosthetic valve for atrial tachycardia after transcatheter aortic valve replacement
Hong-Xiao LI ; Bi-Jun HUANG ; Lu-Xin WANG ; Xing-Xu WANG ; Yun-Kai WANG ; Xiao-Yan HE ; Jian-Qiang ZHANG
Chinese Journal of Interventional Cardiology 2024;32(4):232-235
Transcatheter aortic valve replacement(TAVR)has emerged as a promising therapeutic alternative for addressing aortic valve-related pathologies.However,the occurrence of rapid arrhythmias linked to TAVR procedures is progressively drawing scrutiny.Presently,pharmacologic interventions constitute the mainstay of managing atrial arrhythmias related to TAVR,while the potential of ablation as a viable treatment modality remains undefined.Notably,in cases where the arrhythmia's genesis is presumed to be intricately linked to the prosthetic valve,the practicality and safety of ablation procedures remain unverified.Our institution has successfully ventured into radiofrequency ablation for a distinctive patient presenting with this intricate condition,thereby tentatively affirming the efficacy and safety of catheter ablation administered on the surface of prosthetic valves.
4.Research progress of clinical symptoms and treatment of primary uveal mucosa-associated lymphoid tissue lymphoma
Xin CHEN ; Lili ZHANG ; Ting ZHANG ; Qian CHEN ; Yingwen BI ; Gezhi XU
Chinese Journal of Ocular Fundus Diseases 2024;40(8):656-662
Mucosa-associated lymphoid tissue (MALT) lymphoma is an indolent B cell derived non-Hodgkin's lymphoma. It is the main type of uveal lymphoma and is extremely rare. The pathogenesis of ocular MALT lymphoma remains unclear. It is now considered to be associated with many causes. The manifestations of primary uveal MALT lymphoma differ. So sometimes it is necessary to diagnose depending on diversity of auxiliary tests. Ultrasound examination shows typical low and homogeneous internal reflectivity, with blood flow signal. Optical coherence tomography, fundus imaging, fundus angiography, magnetic resonance imaging and positron emission tomography computerized tomography can assist diagnosing. Primary uveal MALT lymphoma is sensitive to radiation therapy, chemotherapy and biotherapy have positive influence too. The prognosis of uveal MALT lymphoma is good, but its early diagnosis is rather challenging. The nonspecific clinical manifestations and the rarity of the disease can confound the initial diagnosis, resulting in delayed treatments which may cause irreversible vision loss.
5.A multi-center epidemiological study on pneumococcal meningitis in children from 2019 to 2020
Cai-Yun WANG ; Hong-Mei XU ; Gang LIU ; Jing LIU ; Hui YU ; Bi-Quan CHEN ; Guo ZHENG ; Min SHU ; Li-Jun DU ; Zhi-Wei XU ; Li-Su HUANG ; Hai-Bo LI ; Dong WANG ; Song-Ting BAI ; Qing-Wen SHAN ; Chun-Hui ZHU ; Jian-Mei TIAN ; Jian-Hua HAO ; Ai-Wei LIN ; Dao-Jiong LIN ; Jin-Zhun WU ; Xin-Hua ZHANG ; Qing CAO ; Zhong-Bin TAO ; Yuan CHEN ; Guo-Long ZHU ; Ping XUE ; Zheng-Zhen TANG ; Xue-Wen SU ; Zheng-Hai QU ; Shi-Yong ZHAO ; Lin PANG ; Hui-Ling DENG ; Sai-Nan SHU ; Ying-Hu CHEN
Chinese Journal of Contemporary Pediatrics 2024;26(2):131-138
Objective To investigate the clinical characteristics and prognosis of pneumococcal meningitis(PM),and drug sensitivity of Streptococcus pneumoniae(SP)isolates in Chinese children.Methods A retrospective analysis was conducted on clinical information,laboratory data,and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country.Results Among the 160 children with PM,there were 103 males and 57 females.The age ranged from 15 days to 15 years,with 109 cases(68.1% )aged 3 months to under 3 years.SP strains were isolated from 95 cases(59.4% )in cerebrospinal fluid cultures and from 57 cases(35.6% )in blood cultures.The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87)and 27% (21/78),respectively.Fifty-five cases(34.4% )had one or more risk factors for purulent meningitis,113 cases(70.6% )had one or more extra-cranial infectious foci,and 18 cases(11.3% )had underlying diseases.The most common clinical symptoms were fever(147 cases,91.9% ),followed by lethargy(98 cases,61.3% )and vomiting(61 cases,38.1% ).Sixty-nine cases(43.1% )experienced intracranial complications during hospitalization,with subdural effusion and/or empyema being the most common complication[43 cases(26.9% )],followed by hydrocephalus in 24 cases(15.0% ),brain abscess in 23 cases(14.4% ),and cerebral hemorrhage in 8 cases(5.0% ).Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old,with rates of 91% (39/43)and 83% (20/24),respectively.SP strains exhibited complete sensitivity to vancomycin(100% ,75/75),linezolid(100% ,56/56),and meropenem(100% ,6/6).High sensitivity rates were also observed for levofloxacin(81% ,22/27),moxifloxacin(82% ,14/17),rifampicin(96% ,25/26),and chloramphenicol(91% ,21/23).However,low sensitivity rates were found for penicillin(16% ,11/68)and clindamycin(6% ,1/17),and SP strains were completely resistant to erythromycin(100% ,31/31).The rates of discharge with cure and improvement were 22.5% (36/160)and 66.2% (106/160),respectively,while 18 cases(11.3% )had adverse outcomes.Conclusions Pediatric PM is more common in children aged 3 months to under 3 years.Intracranial complications are more frequently observed in children under 1 year old.Fever is the most common clinical manifestation of PM,and subdural effusion/emphysema and hydrocephalus are the most frequent complications.Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates.Adverse outcomes can be noted in more than 10% of PM cases.SP strains are high sensitivity to vancomycin,linezolid,meropenem,levofloxacin,moxifloxacin,rifampicin,and chloramphenicol.[Chinese Journal of Contemporary Pediatrics,2024,26(2):131-138]
6.Treatment of ornithine transcarbamylase deficiency in a child with glyceryl phenylbutyrate
Fan YANG ; Li-Rui WANG ; Xin LI ; Jia-Yue HU ; Ling-Wen YING ; Bi-Yun FENG ; Yun-Yun LI ; Ka-Na LIN ; Jia-Xiao SHE ; Hao LI ; Guo-Ying CHANG ; Xiu-Min WANG
Chinese Journal of Contemporary Pediatrics 2024;26(5):512-517
Glyceryl phenylbutyrate(GPB)serves as a long-term management medication for Ornithine transcarbamylase deficiency(OTCD),effectively controlling hyperammonemia,but there is a lack of experience in using this medicine in China.This article retrospectively analyzes the case of a child diagnosed with OTCD at Shanghai Children's Medical Center,Shanghai Jiao Tong University School of Medicine,including a review of related literature.After diagnosis,the patient was treated with GPB,followed by efficacy follow-up and pharmacological monitoring.The 6-year and 6-month-old male patient exhibited poor speech development,disobedience,temper tantrums,and aggressive behavior.Blood ammonia levels peaked at 327 μmol/L;urine organic acid analysis indicated elevated uracil levels;cranial MRI showed extensive abnormal signals in both cerebral hemispheres.Genetic testing revealed de novo mutation in the OTC gene(c.241T>C,p.S81P).Blood ammonia levels were approximately 43,80,and 56 μmol/L at 1,2,and 3 months after starting GPB treatment,respectively.During treatment,blood ammonia was well-controlled without drug-related adverse effects.The patient showed improvement in developmental delays,obedience,temperament,and absence of aggressive behavior.
7.Efficacy and toxicity analysis of thoracic radiotherapy for extensive-stage small cell lung cancer patients after first-line chemoimmunotherapy
Chaonan ZHANG ; Wenqing WANG ; Zongmei ZHOU ; Lei DENG ; Nan BI ; Tao ZHANG ; Jianyang WANG ; Xin WANG ; Wenyang LIU ; Zefen XIAO ; Jima LYU ; Yirui ZHAI ; Qinfu FENG
Chinese Journal of Radiation Oncology 2024;33(8):703-710
Objective:To evaluate the safety and efficacy of thoracic radiotherapy (TRT) for extensive-stage small cell lung cancer (ES-SCLC) patients in the era of first-line chemoimmunotherapy.Methods:Medical records of 56 patients with ES-SCLC who received thoracic radiotherapy after first-line platinum-based chemotherapy plus immunotherapy in Cancer Hospital Chinese Academy of Medical Sciences from January 2018 to December 2021 were retrospectively analyzed. The control group was not established for clinical causes. The overall survival (OS), progression-free survival (PFS) and local recurrence-free survival (LRFS) were calculated using the Kaplan-Meier method. Univariate and multivariate analyses were employed to identify prognostic factors using the Cox proportional hazards model. The cumulative incidence of local regional recurrence (LRR) was estimated using the Fine-Grey competing risks regression model.Results:Among 56 patients in our cohort, 47 patients received consolidative TRT (cTRT) before progression and 9 patients received salvage TRT after progression. The median follow-up time was 21 months (95% CI=19.8-22.2 months), the median OS was not reached, the median PFS was 9 months (95% CI=7.0-13.0 months), and the 1-year and 18-month OS rates were 84.9%, 62.1%. In the cTRT group, the 1-year and 18-month OS rates were 84.1%, 64.5%, with the median PFS of 10 months; 1-year and 18-month LRFS rates were 73.6% and 66.0%, respectively; the cumulative incidence of LRR at 1-year and 2-year were 24.9% and 30.8%, respectively. No other 4-5 grade adverse events (AE) were reported except 6 patients presenting with 4 grade hematologic toxicities. Three grade radiation esophagitis occurred in 3 patients (5%). Ten patients (18%) developed 1-2 grade treatment-related pneumonitis, including 5 (9%) patients with immune related pneumonitis and 5 (9%) patients with radiation pneumonitis. Conclusion:The application of TRT after first-line chemoimmunotherapy is safe and may has potential survival benefit for patients with ES-SCLC.
8.Study on original identification of Rhei Radix et Rhizoma decoction pieces based on electronic sensory system and GC-IMS technology
Shuo YANG ; Zhongli XU ; Xinzhi ZHAO ; Dianhua SHI ; Yanpeng DAI ; Yu BI ; Yizhou XIN
China Pharmacy 2024;35(9):1076-1081
OBJECTIVE To investigate the variations in taste, aroma and volatile organic compounds of Rhei Radix et Rhizoma decoction pieces derived from different sources, and to identify their origins. METHODS The flavor, odor and volatile organic compounds of Rhei Radix et Rhizoma decoction pieces from different sources were compared and analyzed by using electronic tongue, electronic nose, and gas chromatography-ion mobility spectrometry (GC-IMS). Principal component analysis (PCA), partial least squares-discriminant analysis (PLS-DA), orthogonal partial least squares discriminant analysis (OPLS-DA) and Fisher discriminant analysis were employed to identify the origins of Rhei Radix et Rhizoma decoction pieces and establish the basis discrimination criteria. RESULTS The differences in taste of Rhei Radix et Rhizoma decoction pieces from 3 origins were primarily characterized by bitterness, astringency, and bitter-astringent aftertaste. In terms of smell, variations were mainly observed in inorganic sulfides, organic sulfides containing aromatic components, methane and other short-chain alkanes, alcohols, ethers, aldehydes and ketones, as well as nitrogen oxides. Differentially volatile organic compounds mainly consisted of alcohols, aldehydes and ketones. Furthermore, the samples from 8 batches could be effectively classified into 3 categories.Three types of Rhei Radix et Rhizoma decoction pieces can be effectivily identified based on the peak intensity ratio between volatile substances. For example, when the peak intensity of 2-acetylfuran was 3-19 times that of isobutyric acid [dimer], it was considered as Rheum officinale Baill. CONCLUSIONS The discriminant models established in this study, along with the criteria for determining the origins based on the peak intensity ofcharacteristic volatile compounds, can be utilized for the identification of Rhei Radix et Rhizoma decoction pieces.
9.Research progress of TRPV4 in ocular pathophysiological function
International Eye Science 2024;24(2):225-229
Transient receptor potential vanilloid receptor 4(TRPV4)is a non-selective cation channel responsible for sensing changes in cell swelling, temperature, mechanical stretch, shear stress and osmotic pressure by regulating transmembrane calcium signaling and thereby influencing gene expression, cell morphology, and cytoskeletal construction. TRPV4 is widely expressed throughout the body. Intraocularly, TRPV4 is functionally expressed in the cornea, lens, ciliary body, trabecular meshwork and retina. In this article, the expression and physiopathological functions of TRPV4 in various tissues of the eye were described. With the in-depth study of TRPV4 in ocular pathophysiological functions, TRPV4 may become a potential drug target in corneal injury repair, glaucoma and retinal angiogenesis, but further in-depth study is still needed.
10.A controlled clinical study of two types of thoracoscopic precision segmentectomy for determining interseg-mental plane
Da-Qing CHEN ; Bi-Cheng ZHAN ; Xin-Tao ZHOU ; Jian CHEN
Journal of Regional Anatomy and Operative Surgery 2024;33(3):264-267
Objective To compare the application effects of simple artery ligation and modified inflation-deflation method in determining the lung intersegment plane during thoracoscopic precision segmentectomy.Methods A total of 80 patients who underwent thoracoscopic precision segmentectomy in our hospital from August 2021 to February 2023 were prospectively included and divided into the observation group and the control group by random number table method,with 40 cases in each group.Patients in the observation group were determined the lung intersegment plane by simple artery ligation,while patients in the control group were determined the lung intersegment plane by modified inflation-deflation method.The perioperative related indexes,lung function indexes,postoperative complications and follow-up of patients between the two groups were compared.Results The operative time and blood loss of patients in the observation group were significantly shorter/lower than those in the control group(P<0.05).There was no significant difference in the time to reveal the interseg-mental planes, total drainage volume after operation, indwelling time of drainage tube, postoperative hospital stay or lung segmentectomy distribution of patients between the two groups (P>0. 05). The percentage of forced vital capacity to the predicted values (FVC%pred) and percentage of forced expiratory volume in 1 second to the predicted values (FEV1%pred) after operation of patients in the two groups were significantly decreased compared with those before operation (P<0. 05), and FVC%pred and FEV1%pred after operation of patients in the observation group were significantly higher than those in the control group (P<0. 05). There was no statistically significant difference in the occurrence of postoperative complications of patients between the two groups (P>0. 05). There was no death, local recurrence or distant metastasis occurred in all patients during follow-up. Conclusion Compared with the modified inflation-deflation method, the application of simple artery ligation to determine the intersegment plane during thoracoscopic precision segmentectomy has significant advantages such as simple operation, less injury, and less impact on the lung function of patients, which is a feasible and effective technique, with high safety.

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