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.Application of optimized hippocampus-avoidance prophylactic cranial irradiation in limited-stage small cell lung cancer
Tianyou ZHAN ; Lei DENG ; Wenqing WANG ; Tao ZHANG ; Nan BI ; Jianyang WANG ; Xin WANG ; Wenyang LIU ; Yirui ZHAI ; Zefen XIAO ; Jima LYU ; Qinfu FENG ; Dongfu CHEN ; Ye-Xiong LI ; Zongmei ZHOU
Chinese Journal of Radiation Oncology 2024;33(3):205-211
Objective:To analyze the treatment efficacy, safety and dose parameters of optimized hippocampus-avoidance prophylactic cranial irradiation (HA-PCI) in limited-stage small cell lung cancer (LS-SCLC) and explore the corresponding dosimetric parameters under the condition of narrowing the hippocampus avoidance region as hippocampus region plus 2 mm in three dimensions.Methods:Clinical data of patients with LS-SCLC receiving HA-PCI (hippocampus avoidance region defined as hippocampus region plus 2 mm in three dimensions) in Cancer Hospital Chinese Academy of Medical Sciences from August 2014 to June 2020 were retrospectively analyzed. Dose parameters of HA-PCI and adverse events were analyzed using descriptive statistics analysis. Changes of neurocognitive function, such as mini-mental state examination (MMSE) and Hopkins verbal learning test-revised (HVLT-R) scores, were evaluated by analysis of variance and Kruskal-Wallis H test. Overall survival (OS), progression-free survival (PFS) and intracranial PFS (iPFS) were calculated using Kaplan-Meier method. The cumulative incidence of local-regional recurrence (LRR), extracranial distant metastases (EDM), and locoregional recurrence (LR) were investigated under competing risk analysis. Results:A total of 112 patients were included, the median follow-up time was 50 months (95% CI: 45.61-54.38). The median volume of hippocampus was 4.85 ml (range: 2.65-8.34 ml), with the average dose ≤9 Gy in 106 patients (94.6%), ≤8 Gy in 92 patients (82.1%). The median volume of hippocampus avoidance area was 15.00 ml (range: 8.61-28.06 ml), with the average dose ≤12 Gy in 109 patients (97.3%), ≤10 Gy in 101 patients (90.2%). The 2-year cumulative LRR, EDM, LR rates were 16.9%, 23.2% and 28.5%, respectively. The 5-year cumulative LRR, EDM, LR rates were 23.2%, 26.9% and 33.3%, respectively. The 2-year iPFS, PFS and OS rates were 66.1% (95% CI: 57.9%-75.4%), 53.6% (95% CI: 45.1%-63.7%) and 80.4% (95% CI: 73.3%-88.1%), respectively. The most common grade I-Ⅱ adverse events were nausea (33.9%) and dizziness (31.3%), and only 1 patient developed grade Ⅲ nausea and dizziness. MMSE ( n=57) and HVLT-R tests ( n=56) showed no significant decline. Conclusions:Optimized HA-PCI can achieve similar dose limitation with favorable efficacy and light toxicity. No significant decline is observed in short-term neurocognitive function in evaluable patients.
3.Retrospective analysis of 62 cases who received clinical application of artificial temporomandibular joint
Peng WANG ; Yao LIU ; Nan JIANG ; Ruiye BI ; Pinyin CAO ; Wenli ZHAO ; Mingjun REN ; Songsong ZHU
Chinese Journal of Stomatology 2024;59(10):1014-1018
Objective:To conduct a retrospective study on the treatment outcomes of patients who underwent artificial temporomandibular joint (TMJ) replacement surgery and to evaluate the effectiveness of artificial TMJ treatment.Methods:This study selected 62 patients who received standard Biomet artificial TMJ treatment at Department of Orthognathic and TMJ Surgery, West China Hospital of Stomatology, Sichuan University from May 2010 to September 2023 as the study subjects. Among them, there were 15 male patients and 47 female patients. The average age was 33.5 years old(ranging from 18 to 67 years). This study statistically analyzed postoperative indicators, including maximum mouth opening, forward jaw movement, lateral movement, postoperative pain scores, and patient satisfaction.Results:This study included a total of 62 patients with 99 TMJ joints. No infections occurred postoperatively. The average follow-up period was 33.7 months (ranging from 7 to 170 months). At 6 months postoperatively, the mean mouth opening was (36.1±6.2) mm, lateral movement was (2.1±0.9) mm, and forward jaw movement was (1.0±0.9) mm. The pain visual analog scale score at 6 months postoperatively was (2.8±0.6), and patient satisfaction with the surgery was (8.8±1.1). Spiral CT scans conducted after surgery showed no joint dislocation or migration, and the artificial joint remained stable during the follow-up period.Conclusions:Artificial TMJ replacement is a valuable method for effectively restoring TMJ structure and essential functions related to mouth opening and chewing. It is worthy of promotion as a reconstructive approach for the temporomandibular joint
4.Tildrakizumab for moderate-to-severe plaque psoriasis in Chinese patients: A 12-week randomized placebo-controlled phase III trial with long-term extension
Chen YU ; Songmei GENG ; Bin YANG ; Yunhua DENG ; Fuqiu LI ; Xiaojing KANG ; Mingye BI ; Furen ZHANG ; Yi ZHAO ; Weili PAN ; Zhongwei TIAN ; Jinhua XU ; Zhenghua ZHANG ; Nan YU ; Xinsuo DUAN ; Shuping GUO ; Qing SUN ; Weiquan LI ; Juan TAO ; Zhijun LIU ; Yuanyuan YIN ; Gang WANG
Chinese Medical Journal 2024;137(10):1190-1198
Background::There is a need for effective and safe therapies for psoriasis that provide sustained benefits. The aim of this study was to assess the efficacy and safety of tildrakizumab, an anti-interleukin-23p19 monoclonal antibody, for treating moderate-to-severe plaque psoriasis in Chinese patients.Methods::In this multi-center, double-blind, phase III trial, patients with moderate-to-severe plaque psoriasis were enrolled and randomly assigned (1:1) to receive subcutaneous tildrakizumab 100 mg or placebo at weeks 0 and 4. Patients initially assigned to placebo were switched to receive tildrakizumab at weeks 12, 16, and every 12 weeks thereafter. Patients in the tildrakizumab group continued with tildrakizumab at week 16, and every 12 weeks until week 52. The primary endpoint was the Psoriasis Area and Severity Index (PASI 75) response rate at week 12.Results::At week 12, tildrakizumab demonstrated significantly higher PASI 75 response rates (66.4% [73/110] vs. 12.7% [14/110]; difference, 51.4% [95% confidence interval (CI), 40.72, 62.13]; P <0.001) and Physician’s Global Assessment (60.9% [67/110] vs. 10.0% [11/110]; difference, 49.1% [95% CI, 38.64, 59.62]; P <0.001) compared to placebo. PASI 75 response continued to improve over time in both tildrakizumab and placebo-switching to tildrakizumab groups, reaching maximal efficacy after 28 weeks (86.8% [92/106] vs. 82.4% [89/108]) and maintained up to 52 weeks (91.3% [95/104] vs. 87.4% [90/103]). Most treatment-emergent adverse events were mild and not related to tildrakizumab. Conclusion::Tildrakizumab demonstrated durable efficacy through week 52 and was well tolerated in Chinese patients with moderate-to-severe plaque psoriasis.Trial registration::ClinicalTrials.gov, NCT05108766.
5.Impact of pancreatic and biliary stent on post-endoscopic papillectomy complications: A single-center retrospective study
Nan RU ; Ningli CHAI ; Bo ZHANG ; Longsong LI ; Yawei BI ; Enqiang LINGHU
Chinese Medical Journal 2024;137(17):2111-2118
Background::Endoscopic papillectomy (EP) is recommended as the first-line therapy for ampullary tumors, despite a relatively high incidence of complications. Pancreatic and/or biliary stents are placed at the endoscopist’s discretion to prevent post-EP complications. The present study aimed to evaluate the efficacy of different stents.Methods::A total of 117 patients who underwent EP and met the criteria between June 2006 and October 2022 were enrolled in the study. These patients were divided into a pancreatic stent group (PS group, n = 47), a biliary stent group (BS group, n = 38), and a two-stent group (PBS [PS and BS] group, n = 32). Relevant clinical data were collected and compared among the three groups. Multivariate logistic analyses were performed to explore risk factors for post-EP complications. Results::The incidence of all complications was 37.6% (44/117). Pancreatitis and hemorrhage were the two most common complications with incidence rates of 14.5% (17/117) and 17.9% (21/117). The incidence rates of post-EP pancreatitis were 10.6% (5/47), 23.7% (9/38), and 9.4% (3/32) in the PS group, BS group, and PBS group, respectively, with no significant differences. There were also no significant differences in other complications among the three groups. Age (odds ratio [OR]: 0.95; 95% confidence interval [CI]: 0.91-0.99; P = 0.022) was independently associated with post-EP pancreatitis while tumor size (OR: 1.66; 95% CI: 1.06-2.60; P = 0.028) was independently associated with post-EP hemorrhage. Conclusions::While pancreatic stenting is the first choice to prevent post-EP pancreatitis, biliary stenting could also be considered as a substitute for patients with difficulties in pancreatic cannulation. Two-stent (biliary and pancreatic stent) placement is unnecessary unless it is required due to other concerns.
6.Distribution and prognosis analysis of TCM syndromes elements in elderly patients with sepsis and septic shock
Fuyao NAN ; Caijun WU ; Junxi LIU ; Xiang JI ; Yuanzhen JIAN ; Lan LI ; Wei BI
International Journal of Traditional Chinese Medicine 2024;46(9):1113-1120
Objective:To analyze the distribution pattern of TCM syndrome elements in elderly patients with sepsis and septic shock, as well as the relationship between TCM syndrome elements, Sepsis Sequential Organ Failure Score (SOFA), Acute Physiology and Chronic Health Score Ⅱ (APACHE Ⅱ), and short-term mortality prognosis.Methods:A retrospective analysis was conducted on the clinical data of 58 patients treated in the Emergency Department and ICU of Dongzhimen Hospital of Beijing University of Chinese Medicine and the Third Affiliated Hospital of Beijing University of Chinese Medicine from January 1, 2021, to May 1, 2022. The patients were divided into a sepsis group of 38 cases and a septic shock group of 20 cases based on disease type. Basic information, TCM syndromes, SOFA score, and APACHE Ⅱ score of the two groups were collected. The survival and death statuses of the two groups within 28 days of admission were separately analyzed. Association rule analysis was used to investigate the distribution pattern of TCM syndromes in patients, and logistic regression analysis was performed to explore the relationship between TCM syndromes, SOFA score, APACHE Ⅱ score, and death prognosis.Results:In the sepsis group, the main TCM syndromes included yin deficiency, lung, phlegm, qi deficiency, blood stasis, heat, and yang deficiency; while in the septic shock group, the main TCM syndromes were yin deficiency, lung, yang deficiency, and qi deficiency. Multifactor logistic regression analysis showed that in the sepsis group, liver syndromes [ OR (95% CI)=0.080 (0.011, 0.578), P=0.012], meridians and collaterals [ OR (95% CI)=0.088 (0.011, 0.718), P=0.024], SOFA score [ OR (95% CI)=0.524 (0.310, 0.886), P=0.016], and APACHE Ⅱ score [ OR (95% CI)=0.426 (0.186, 0.977), P=0.044] were independent influencing factors for patient mortality prognosis. In the septic shock group, phlegm [ OR (95% CI)=0.014 (0.001, 0.267), P=0.005], meridians and collaterals [ OR (95% CI)=0.041 (0.003, 0.618), P=0.021], yang deficiency [ OR (95% CI)=0.028 (0.002, 0.427), P=0.010], SOFA score [ OR (95% CI)=0.543 (0.310, 0.950), P=0.032], and APACHE Ⅱ score [ OR (95% CI)=0.633 (0.408, 0.985), P=0.042] were independent influencing factors for patient mortality prognosis. Conclusions:The sepsis group mainly exhibits a mixture of deficiency and excess, while the septic shock group predominantly shows deficiency. Qi deficiency and yin deficiency are consistent throughout the disease progression. Meridians and collaterals, high SOFA score, and high APACHE Ⅱ score in elderly patients with sepsis and septic shock may indicate a poorer prognosis.
7.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]
8.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.
9.Advances on T cells related biomarkers of tumor immune microenvironment in non-small cell lung cancer
Chinese Journal of Radiation Oncology 2024;33(10):971-977
Immune checkpoint inhibitors (ICI) have recently revolutionized the treatment of non-small cell lung cancer (NSCLC). Tumor immune microenvironment (TIME), composed of immune inflammatory cells and related cytokines, is a key region regulated by ICI. The characteristics and dynamic changes of T cells within TIME are closely correlated with the therapeutic effect of ICI. In recent years, efforts have been devoted to exploring the potential biomarkers of T cells in NSCLC. In this review, advances in the phenotypes of TIME, T cell related biomarkers from tumor tissues and peripheral blood, and influencing factors were summarized.

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