1.Expert consensus on neoadjuvant PD-1 inhibitors for locally advanced oral squamous cell carcinoma (2026)
LI Jinsong ; LIAO Guiqing ; LI Longjiang ; ZHANG Chenping ; SHANG Chenping ; ZHANG Jie ; ZHONG Laiping ; LIU Bing ; CHEN Gang ; WEI Jianhua ; JI Tong ; LI Chunjie ; LIN Lisong ; REN Guoxin ; LI Yi ; SHANG Wei ; HAN Bing ; JIANG Canhua ; ZHANG Sheng ; SONG Ming ; LIU Xuekui ; WANG Anxun ; LIU Shuguang ; CHEN Zhanhong ; WANG Youyuan ; LIN Zhaoyu ; LI Haigang ; DUAN Xiaohui ; YE Ling ; ZHENG Jun ; WANG Jun ; LV Xiaozhi ; ZHU Lijun ; CAO Haotian
Journal of Prevention and Treatment for Stomatological Diseases 2026;34(2):105-118
Oral squamous cell carcinoma (OSCC) is a common head and neck malignancy. Approximately 50% to 60% of patients with OSCC are diagnosed at a locally advanced stage (clinical staging III-IVa). Even with comprehensive and sequential treatment primarily based on surgery, the 5-year overall survival rate remains below 50%, and patients often suffer from postoperative functional impairments such as difficulties with speaking and swallowing. Programmed death receptor-1 (PD-1) inhibitors are increasingly used in the neoadjuvant treatment of locally advanced OSCC and have shown encouraging efficacy. However, clinical practice still faces key challenges, including the definition of indications, optimization of combination regimens, and standards for efficacy evaluation. Based on the latest research advances worldwide and the clinical experience of the expert group, this expert consensus systematically evaluates the application of PD-1 inhibitors in the neoadjuvant treatment of locally advanced OSCC, covering combination strategies, treatment cycles and surgical timing, efficacy assessment, use of biomarkers, management of special populations and immune related adverse events, principles for immunotherapy rechallenge, and function preservation strategies. After multiple rounds of panel discussion and through anonymous voting using the Delphi method, the following consensus statements have been formulated: 1) Neoadjuvant therapy with PD-1 inhibitors can be used preoperatively in patients with locally advanced OSCC. The preferred regimen is a PD-1 inhibitor combined with platinum based chemotherapy, administered for 2-3 cycles. 2) During the efficacy evaluation of neoadjuvant therapy, radiographic assessment should follow the dual criteria of Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and immune RECIST (iRECIST). After surgery, systematic pathological evaluation of both the primary lesion and regional lymph nodes is required. For combination chemotherapy regimens, PD-L1 expression and combined positive score need not be used as mandatory inclusion or exclusion criteria. 3) For special populations such as the elderly (≥ 70 years), individuals with stable HIV viral load, and carriers of chronic HBV/HCV, PD-1 inhibitors may be used cautiously under the guidance of a multidisciplinary team (MDT), with close monitoring for adverse events. 4) For patients with a poor response to neoadjuvant therapy, continuation of the original treatment regimen is not recommended; the subsequent treatment plan should be adjusted promptly after MDT assessment. Organ transplant recipients and patients with active autoimmune diseases are not recommended to receive neoadjuvant PD-1 inhibitor therapy due to the high risk of immune related activation. Rechallenge is generally not advised for patients who have experienced high risk immune related adverse events such as immune mediated myocarditis, neurotoxicity, or pneumonitis. 5) For patients with a good pathological response, individualized de escalation surgery and function preservation strategies can be explored. This consensus aims to promote the standardized, safe, and precise application of neoadjuvant PD-1 inhibitor strategies in the management of locally advanced OSCC patients.
2.Mechanistic Study on Tougu Xiaotong Capsules in Regulating PANoptosis to Delay Degeneration of Chondrocytes in Knee Osteoarthritis
Jinxia YE ; Yixin LIN ; Xiaoqing LEI ; Yanfeng HUANG ; Changlong FU ; Desen LI ; Wenyi WANG ; Lan WANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(8):149-161
ObjectiveTo investigate the effect of Tougu Xiaotong capsules (TGXTC) on the regulation of chondrocyte PANoptosis, delay of chondrocyte degeneration, and improvement of the symptoms in knee osteoarthritis (KOA). MethodsIn vivo experiments: 50 male C57BL/6 mice were randomly assigned into five groups (n=10 per group): sham operation group, model group, low-dose TGXTC group (7.2 g·kg-1), high-dose TGXTC group (14.4 g·kg-1), and diclofenac sodium group (0.05 g·kg-1). Except for the sham group, KOA models were established in all other groups using the modified Hulth method. Following successful model induction, the TGXTC groups received daily oral gavage of 7.2 or 14.4 g·kg-1 for 6 weeks, while the diclofenac sodium group received 0.05 g·kg-1 solution daily over the same duration. Model evaluation was performed using Lequesne MG score; micro-computed tomography (micro-CT) was used to scan the knee, hematoxylin-eosin (HE) staining and safranin O-fast green staining were used to observe the morphology of cartilage, transmission electron microscopy (TEM) was used to determine ultrastructural changes of PANoptosis. Multiple immunofluorescence (IF) co-localization assays was performed to detect the co-localization of cleaved Caspase-3, receptor-interacting protein 3 (RlPK3), and the N-terminal domain of gasdermin D (GSDMD-N) in cartilage tissue, while western blot was employed to detect the expression levels of cleaved Caspase-3, RIPK3, and GSDMD-N. In vitro experiments: The knee cartilages of 4-week-old SD rats were isolated, and a chondrocyte in vitro culture system was established through mechanical digestion with 0.2% type Ⅱ collagenase. Second-generation chondrocytes were divided into three groups: the control group, the model group (pretreated with 10 mg·L-1 lipopolysaccharide (LPS) for 24 h followed by treatment with 1 μmol·L-1 nigericin for 4 h), and the TGXTC treatment group (pretreated with 10 mg·L-1 LPS for 24 h, followed by exposure to 1 μmol·L-1 nigericin for 4 h and subsequently treated with 100 mg·L-1 TGXTC for an additional 24 h). The levels of reactive oxygen species (ROS), apoptosis, necroptosis, and pyroptosis of chondrocytes were evaluated via fluorescence microscopy following staining with ROS detection, AO/EB and YO-PRO-1/PI staining kits. Transmission electron microscopy was utilized to investigate the ultrastructural changes associated with PANoptosis in cartilage tissue of KOA mice. Inflammatory cytokine levels (IL-1β and IL-18) were measured using ELISA. Western blot was conducted to assess protein expressions related to PANoptosis, including cleaved Caspase-3, cleaved Caspase-8, RIPK3, ZBP1, GSDMD-N, and NLRP3. ResultsCompared with the sham group, the Lequesne MG scores were significantly up-regulated(P<0.01) in the model group, and the pathological changes of cartilage were significantly, with joint spaces narrower, osteophyte formation increased, secere abrasion of cartilage surface. Ultrastructural analysis revealed pronounced chondrocyte apoptosis, necroptosis, and pyroptosis, along with markedly elevated expression of cleaved Caspase-3, RlPK3, and GSDMD-N in cartilage tissue (P<0.01). In addition, The mean fluorescence intensities of ROS, orange-red fluorescence in AO/EB staining, green fluorescence and red fluorescence in YO-PRO-1/PI staining were increased of chondrocyte in the model group (P<0.01) . The levels of inflammatory factors IL-1β and IL-18 in the supernatant were increased (P<0.01). The expression of PANoptosis related proteins (cleaved Caspase-3, cleaved Caspase-8, RIPK3, ZBP1, GSDMD-N, and NLRP3) were also significantly upregulated(P<0.05). Compared to the model group, the TGXTC group demonstrated a significant improvement in various parameters of mice. These included a reduction in the Lequesne MG score, an increase in joint space, a decrease in osteophyte formation, diminished cartilage damage, reduced release of ROS, and alleviation of apoptotic, necroptotic, and pyroptotic processes in chondrocytes. Additionally, mitochondrial swelling and endoplasmic reticulum dilation were also mitigated. The levels of ROS as well as IL-1β and IL-18 were significantly decreased (P<0.05). Furthermore, the expression levels of proteins associated with PANoptosis in cartilage tissue showed marked reductions (P<0.05). Similar results were observed in chondrocytes: cleaved Caspase-3, cleaved Caspase-8, RIPK3, ZBP1, GSDMD-N, and NLRP3 exhibited significant decreases as well (P<0.05). ConclusionTGXTC may mitigate chondrocytes degeneration and alleviate KOA symptoms by reducing oxidative stress and suppressing the activation of PANoptosis pathways.
3.Mechanistic Study on Tougu Xiaotong Capsules in Regulating PANoptosis to Delay Degeneration of Chondrocytes in Knee Osteoarthritis
Jinxia YE ; Yixin LIN ; Xiaoqing LEI ; Yanfeng HUANG ; Changlong FU ; Desen LI ; Wenyi WANG ; Lan WANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(8):149-161
ObjectiveTo investigate the effect of Tougu Xiaotong capsules (TGXTC) on the regulation of chondrocyte PANoptosis, delay of chondrocyte degeneration, and improvement of the symptoms in knee osteoarthritis (KOA). MethodsIn vivo experiments: 50 male C57BL/6 mice were randomly assigned into five groups (n=10 per group): sham operation group, model group, low-dose TGXTC group (7.2 g·kg-1), high-dose TGXTC group (14.4 g·kg-1), and diclofenac sodium group (0.05 g·kg-1). Except for the sham group, KOA models were established in all other groups using the modified Hulth method. Following successful model induction, the TGXTC groups received daily oral gavage of 7.2 or 14.4 g·kg-1 for 6 weeks, while the diclofenac sodium group received 0.05 g·kg-1 solution daily over the same duration. Model evaluation was performed using Lequesne MG score; micro-computed tomography (micro-CT) was used to scan the knee, hematoxylin-eosin (HE) staining and safranin O-fast green staining were used to observe the morphology of cartilage, transmission electron microscopy (TEM) was used to determine ultrastructural changes of PANoptosis. Multiple immunofluorescence (IF) co-localization assays was performed to detect the co-localization of cleaved Caspase-3, receptor-interacting protein 3 (RlPK3), and the N-terminal domain of gasdermin D (GSDMD-N) in cartilage tissue, while western blot was employed to detect the expression levels of cleaved Caspase-3, RIPK3, and GSDMD-N. In vitro experiments: The knee cartilages of 4-week-old SD rats were isolated, and a chondrocyte in vitro culture system was established through mechanical digestion with 0.2% type Ⅱ collagenase. Second-generation chondrocytes were divided into three groups: the control group, the model group (pretreated with 10 mg·L-1 lipopolysaccharide (LPS) for 24 h followed by treatment with 1 μmol·L-1 nigericin for 4 h), and the TGXTC treatment group (pretreated with 10 mg·L-1 LPS for 24 h, followed by exposure to 1 μmol·L-1 nigericin for 4 h and subsequently treated with 100 mg·L-1 TGXTC for an additional 24 h). The levels of reactive oxygen species (ROS), apoptosis, necroptosis, and pyroptosis of chondrocytes were evaluated via fluorescence microscopy following staining with ROS detection, AO/EB and YO-PRO-1/PI staining kits. Transmission electron microscopy was utilized to investigate the ultrastructural changes associated with PANoptosis in cartilage tissue of KOA mice. Inflammatory cytokine levels (IL-1β and IL-18) were measured using ELISA. Western blot was conducted to assess protein expressions related to PANoptosis, including cleaved Caspase-3, cleaved Caspase-8, RIPK3, ZBP1, GSDMD-N, and NLRP3. ResultsCompared with the sham group, the Lequesne MG scores were significantly up-regulated(P<0.01) in the model group, and the pathological changes of cartilage were significantly, with joint spaces narrower, osteophyte formation increased, secere abrasion of cartilage surface. Ultrastructural analysis revealed pronounced chondrocyte apoptosis, necroptosis, and pyroptosis, along with markedly elevated expression of cleaved Caspase-3, RlPK3, and GSDMD-N in cartilage tissue (P<0.01). In addition, The mean fluorescence intensities of ROS, orange-red fluorescence in AO/EB staining, green fluorescence and red fluorescence in YO-PRO-1/PI staining were increased of chondrocyte in the model group (P<0.01) . The levels of inflammatory factors IL-1β and IL-18 in the supernatant were increased (P<0.01). The expression of PANoptosis related proteins (cleaved Caspase-3, cleaved Caspase-8, RIPK3, ZBP1, GSDMD-N, and NLRP3) were also significantly upregulated(P<0.05). Compared to the model group, the TGXTC group demonstrated a significant improvement in various parameters of mice. These included a reduction in the Lequesne MG score, an increase in joint space, a decrease in osteophyte formation, diminished cartilage damage, reduced release of ROS, and alleviation of apoptotic, necroptotic, and pyroptotic processes in chondrocytes. Additionally, mitochondrial swelling and endoplasmic reticulum dilation were also mitigated. The levels of ROS as well as IL-1β and IL-18 were significantly decreased (P<0.05). Furthermore, the expression levels of proteins associated with PANoptosis in cartilage tissue showed marked reductions (P<0.05). Similar results were observed in chondrocytes: cleaved Caspase-3, cleaved Caspase-8, RIPK3, ZBP1, GSDMD-N, and NLRP3 exhibited significant decreases as well (P<0.05). ConclusionTGXTC may mitigate chondrocytes degeneration and alleviate KOA symptoms by reducing oxidative stress and suppressing the activation of PANoptosis pathways.
4.The Neural Circuit Characteristics of Repetitive Transcranial Magnetic Stimulation Over The Dorsolateral Prefrontal Cortex for The Treatment of Migraine
Chen-Xia JIN ; Bo-Lin TAN ; Yang YE ; Ji-Qing HE ; Ling-Yan WANG ; Zhong-Ming GAO ; Yu-Jun WANG ; Hui-Li LIU ; Yong-Xing YAN ; Xian-Wei CHE
Progress in Biochemistry and Biophysics 2026;53(7):1953-1968
ObjectiveMigraine is a leading neurological disorder and the fourth most common cause of years lived with disability worldwide, affecting nearly 116 million individuals. Although pharmacological treatments are available, their efficacy is often limited by side effects and variable response rates. Repetitive transcranial magnetic stimulation (rTMS) over the dorsolateral prefrontal cortex (DLPFC) offers a safe, non-invasive alternative for migraine management. However, the neurophysiological mechanisms, particularly how rTMS modulates local cortical excitability and distributed pain-related circuits, remain poorly understood. Elucidating these mechanisms is essential for optimizing treatment protocols and improving clinical outcomes. MethodsThis study employed concurrent transcranial magnetic stimulation and electroencephalography (TMS-EEG) to investigate neuroplastic and neurocircuitry mechanisms of DLPFC-rTMS in migraine. Study 1 compared 30 migraineurs and 28 healthy controls to identify abnormalities in TMS-evoked potentials (TEPs) and significant current density (SCD) within sensory-discriminative regions including the primary somatosensory cortex (S1) and posterior insula (pINS), cognitive-affective regions including the anterior insula (aINS) and midcingulate cortex (MCC), and a descending modulatory region, the periaqueductal gray (PAG). Study 2 used a single-blind, crossover, sham-controlled design in 34 healthy participants. Each participant received both active (10 Hz, 80% RMT, 1 500 pulses) and sham DLPFC-rTMS in counterbalanced order. TMS-EEG and cold pain tolerance were assessed before and after each session. ResultsIn Study 1, migraineurs showed a significantly less negative N120 amplitude compared to healthy controls (P=0.027, Cohen’s d=0.60), indicating local intracortical disinhibition. No group differences were observed for N40, P60, or P180 components. At the source level, migraineurs exhibited significantly higher SCD in the S1, pINS, aINS, and MCC (allQ<0.05), but not in the ventroposterior thalamus (vpTHAL), mediodorsal thalamus (mdTHAL), or PAG. In Study 2, active rTMS significantly reduced SCD from pre- to post-stimulation in the S1, aINS, and MCC (all Q<0.05). Sham stimulation also reduced SCD in the S1 (Q<0.05) but not in the aINS or MCC. Although no significant group-level analgesic effect was observed between active and sham conditions (P=0.107), correlation analyses revealed that greater SCD reductions in the S1 and MCC were significantly associated with higher post-rTMS pain tolerance (R=-0.487 and -0.495, both Q<0.01) and larger improvements in pain tolerance(R=-0.487 and -0.451, both Q<0.05). No such correlations were found following sham stimulation, suggesting that the behavioural relevance of neural changes is specific to active rTMS. ConclusionThis study provides novel evidence that migraineurs exhibit both local neuroplastic abnormalities (reduced N120 amplitude) and hyperactivity in key pain-processing regions (S1, pINS, aINS, MCC). A single session of DLPFC-rTMS reduced hyperactivity in the aINS, MCC, and S1. Notably, greater reductions in the S1 and MCC were associated with improved pain tolerance. These findings identify distinct cortical circuitries, particularly within the cognitive-affective pain network, that may serve as potential biomarkers for optimizing rTMS treatment in migraine and other chronic pain conditions. Future studies should validate these results in patient populations experiencing spontaneous migraine attacks and explore multi-session or accelerated rTMS protocols.
5.Uptake of HIV-related health services among cross-border couples in Dehong Dai and Jingpo Autonomous Prefecture
Runhua YE ; Yuanyuan HAN ; Qunbo ZHOU ; Lin LI ; Yuecheng YANG ; Lifen XIANG ; Renhai TANG ; Jibao WANG ; Yingying DING ; Na HE ; Song DUAN
Shanghai Journal of Preventive Medicine 2026;38(8):614-619
ObjectiveTo investigate the current status of HIV-related health service uptake among cross-border couples (Chinese husbands and Myanmar wives) in Dehong Dai and Jingpo Autonomous Prefecture (hereinafter referred to as Dehong Prefecture), and to provide evidence for optimizing HIV prevention and control strategies in border areas. MethodsA cross-sectional survey was conducted from September 2022 to September 2023 among 14 662 cross-border couples (Chinese husbands and Myanmar wives) in Dehong Prefecture. Data on sociodemographic characteristics, HIV/AIDS knowledge awareness, and utilization of HIV-related health services within the past year were collected. Multivariable logistic regression was used to analyze factors associated with HIV testing uptake among husbands and wives. ResultsA total of 29 324 individuals (14 662 couples) were included. The overall awareness rate of HIV/AIDS was 82.09%, with the rate among husbands significantly higher than that among wives (85.17% vs. 79.01%, P<0.001). Overall, 94.98% of participants had received at least one HIV-related health service, and the HIV testing rate in the past year was 65.52%. Multivariable logistic regression analysis showed that, compared with participants married for 0‒3 years, those married for 4‒10 years and ≥11 years were more likely to have received HIV testing. The corresponding ORs were 1.344 (95%CI: 1.187‒1.521) and 1.381 (95%CI: 1.211‒1.574) among husbands, and 1.308 (95%CI: 1.155‒1.481) and 1.344 (95%CI: 1.178‒1.533) among wives, respectively. Compared with those holding a marriage certificate, those possessing a border marriage registration certificate were positively associated with HIV testing uptake, with ORs of 1.710 (95%CI: 1.575‒1.857) among husbands and 1.700 (95%CI: 1.565‒1.847) among wives. Compared with illiterate participants, those with primary school education showed lower testing rates, with ORs of 0.738 (95%CI: 0.650‒0.837) among husbands and 0.827 (95%CI: 0.766‒0.891) among wives. Additionally, a history of sexually transmitted diseases (OR=3.656, 95%CI: 1.243‒15.589) and participation in the New Rural Cooperative Medical Scheme (OR=1.51, 95%CI: 1.179‒1.935) were independently associated with higher testing rates among husbands. ConclusionThe overall utilization of HIV-related health services among cross-border couples in Dehong Prefecture is satisfactory, but significant gender disparities exist, with foreign wives showing lower rates of knowledge awareness and lower proportions obtaining such knowledge through certain channels compared with their Chinese husbands. Couples with shorter marriage duration, those with primary school education, and those not included in the border marriage registration system are vulnerable groups with lower HIV testing uptake. Future interventions should prioritize cross-border marriage families at the early stage of entry and in the newly married period. Based on the border marriage registration management system and primary healthcare networks, health education and HIV testing services targeting foreign spouses should be strengthened to improve service accessibility and equity.
6.Long-term Outcomes of Endoscopic Radiofrequency Ablation versus Endoscopic Submucosal Dissection for Widespread Superficial Esophageal Squamous Cell Neoplasia
Xin TANG ; Qian-Qian MENG ; Ye GAO ; Chu-Ting YU ; Yan-Rong ZHANG ; Yan BIAN ; Jin-Fang XU ; Lei XIN ; Wei WANG ; Han LIN ; Luo-Wei WANG
Gut and Liver 2025;19(2):198-206
Background/Aims:
Endoscopic radiofrequency ablation (ERFA) is a treatment option for superficial esophageal squamous cell neoplasia (ESCN), with a relatively low risk of stenosis; however, the long-term outcomes remain unclear. We aimed to compare the long-term outcomes of patients with widespread superficial ESCN who underwent endoscopic submucosal dissection (ESD) or ERFA.
Methods:
We retrospectively analyzed the clinical data of patients with superficial ESCN who underwent ESD or ERFA between January 2015 and December 2021. The primary outcome measure was recurrence-free survival.
Results:
Ninety-two and 33 patients with superficial ESCN underwent ESD and ERFA, respectively. The en bloc, R0, and curative resection rates for ESD were 100.0%, 90.2%, and 76.1%, respectively. At 12 months, the complete response rate was comparable between the two groups (94.6% vs 90.9%, p=0.748). During a median follow-up of 66 months, recurrence-free survival was significantly longer in the ESD group than in the ERFA group (p=0.004), while no significant differences in overall survival (p=0.845) and disease-specific survival (p=0.494) were observed.Preoperative diagnosis of intramucosal cancer (adjusted hazard ratio, 5.55; vs high-grade intraepithelial neoplasia) was an independent predictor of recurrence. Significantly fewer patients in the ERFA group experienced stenosis compare to ESD group (15.2% vs 38.0%, p=0.016).
Conclusions
The risk of recurrence was higher for ERFA than ESD for ESCN but overall survival was not affected. The risk of esophageal stenosis was significantly lower for patients who underwent ERFA.
7.High Expression of INF2 Predicts Poor Prognosis and Promotes Hepatocellular Carcinoma Progression
Hai-Biao WANG ; Man LIN ; Fu-Sang YE ; Jia-Xin SHI ; Hong LI ; Meng YE ; Jie WANG
Progress in Biochemistry and Biophysics 2025;52(1):194-208
ObjectiveINF2 is a member of the formins family. Abnormal expression and regulation of INF2 have been associated with the progression of various tumors, but the expression and role of INF2 in hepatocellular carcinoma (HCC) remain unclear. HCC is a highly lethal malignant tumor. Given the limitations of traditional treatments, this study explored the expression level, clinical value and potential mechanism of INF2 in HCC in order to seek new therapeutic targets. MethodsIn this study, we used public databases to analyze the expression of INF2 in pan-cancer and HCC, as well as the impact of INF2 expression levels on HCC prognosis. Quantitative real time polymerase chain reaction (RT-qPCR), Western blot, and immunohistochemistry were used to detect the expression level of INF2 in liver cancer cells and human HCC tissues. The correlation between INF2 expression and clinical pathological features was analyzed using public databases and clinical data of human HCC samples. Subsequently, the effects of INF2 expression on the biological function and Drp1 phosphorylation of liver cancer cells were elucidated through in vitro and in vivo experiments. Finally, the predictive value and potential mechanism of INF2 in HCC were further analyzed through database and immunohistochemical experiments. ResultsINF2 is aberrantly high expression in HCC samples and the high expression of INF2 is correlated with overall survival, liver cirrhosis and pathological differentiation of HCC patients. The expression level of INF2 has certain diagnostic value in predicting the prognosis and pathological differentiation of HCC. In vivo and in vitro HCC models, upregulated expression of INF2 triggers the proliferation and migration of the HCC cell, while knockdown of INF2 could counteract this effect. INF2 in liver cancer cells may affect mitochondrial division by inducing Drp1 phosphorylation and mediate immune escape by up-regulating PD-L1 expression, thus promoting tumor progression. ConclusionINF2 is highly expressed in HCC and is associated with poor prognosis. High expression of INF2 may promote HCC progression by inducing Drp1 phosphorylation and up-regulation of PD-L1 expression, and targeting INF2 may be beneficial for HCC patients with high expression of INF2.
8.Establishment and evaluation of a lipopolysaccharide-induced acute respiratory distress syndrome model in minipigs
Chuang-Ye WANG ; Ran WANG ; Jian ZHANG ; Ling-Xiao QIU ; Bin QING ; Heng YOU ; Jin-Cheng LIU ; Bin WANG ; Nan-Bo WANG ; Jia-Yu LI ; Xing LIU ; Shuang WANG ; Jin HU ; Jian WEN ; Quan LI ; Xiao-Ou HUANG ; Kun ZHAO ; Shuang-Lin LIU ; Gang LIU ; Mei-Ju WANG ; Qing XIANG ; Hong-Mei WU ; Xiao-Rong SUN ; Tao GU ; Dong ZHANG ; Qi LI ; Zhi XU
Medical Journal of Chinese People's Liberation Army 2025;50(9):1154-1161
Objective To establish a stable,reliable,and clinically relevant porcine model of endotoxin-induced acute respiratory distress syndrome(ARDS).Methods Ten 8-month-old male Bama minipigs were deeply sedated,followed by invasive mechanical ventilation and electrocardiographic monitoring.Lipopolysaccharide(LPS)was intravenously pumped at 600 μg/(kg·h)for 3 hours,then maintained at 15 μg/(kg·h)thereafter.Dynamic monitoring was performed at five time points after LPS injection(LPS 0,1,3,5,and 8 h),including arterial blood gas analysis and chest computed tomography(CT)scans.Pathological examination of lung tissues obtained via bronchoscopic biopsy(HE staining and transmission electron microscopy)was conducted.These indicators were comprehensively used to evaluate the success of the animal model.Results At 5 hours after LPS administration,8 minipigs developed symptoms such as skin cyanosis,elevated body temperature,and respiratory distress.The oxygenation index decreased to<300 mmHg.Chest CT scans showed diffuse pulmonary infiltrates.Histopathology revealed alveolar edema and hyaline membrane formation.Transmission electron microscopy demonstrated disruption of pulmonary blood-air barrier,depletion of lamellar bodies in type Ⅱ pneumocytes,inflammatory cell infiltration,and exudation of plasma proteins and fibrin.Compared with LPS 0 h,at LPS 8 h,the oxygenation index and arterial blood pH were significantly decreased(P<0.001),while blood lactic acid and serum potassium were significantly increased(P<0.05);serum calcium and base excess were significantly decreased(P<0.05),and the lung injury score based on HE-stained lung sections was significantly increased(P<0.01).Conclusion The porcine ARDS model established by continuous LPS injection can dynamically simulate the pathophysiological characteristics and typical pathological manifestations of clinical septic ARDS,making it an effective tool to study the pathogenesis,prevention,and treatment strategies of septic ARDS.
10.Role of radiotherapy in extensive-stage small cell lung cancer after durvalumab-based immunochemotherapy: A retrospective study.
Lingjuan CHEN ; Yi KONG ; Fan TONG ; Ruiguang ZHANG ; Peng DING ; Sheng ZHANG ; Ye WANG ; Rui ZHOU ; Xingxiang PU ; Bolin CHEN ; Fei LIANG ; Qiaoyun TAN ; Yu XU ; Lin WU ; Xiaorong DONG
Chinese Medical Journal 2025;138(17):2130-2138
BACKGROUND:
The purpose of this study was to evaluate the safety and efficacy of subsequent radiotherapy (RT) following first-line treatment with durvalumab plus chemotherapy in patients with extensive-stage small cell lung cancer (ES-SCLC).
METHODS:
A total of 122 patients with ES-SCLC from three hospitals during July 2019 to December 2021 were retrospectively analyzed. Inverse probability of treatment weighting (IPTW) analysis was performed to address potential confounding factors. The primary focus of our evaluation was to assess the impact of RT on progression-free survival (PFS) and overall survival (OS).
RESULTS:
After IPTW analysis, 49 patients received durvalumab plus platinum-etoposide (EP) chemotherapy followed by RT (Durva + EP + RT) and 72 patients received immunochemotherapy (Durva + EP). The median OS was 17.2 months vs . 12.3 months (hazard ratio [HR]: 0.38, 95% confidence interval [CI]: 0.17-0.85, P = 0.020), and the median PFS was 8.9 months vs . 5.9 months (HR: 0.56, 95% CI: 0.32-0.97, P = 0.030) in Durva + EP + RT and Durva + EP groups, respectively. Thoracic radiation therapy (TRT) resulted in longer OS (17.2 months vs . 14.7 months) and PFS (9.1 months vs . 7.2 months) compared to RT directed to other metastatic sites. Among patients with oligo-metastasis, RT also showed significant benefits, with a median OS of 17.4 months vs . 13.7 months and median PFS of 9.8 months vs . 5.9 months compared to no RT. Continuous durvalumab treatment beyond progression (TBP) prolonged OS compared to patients without TBP, in both the Durva + EP + RT (NA vs . 15.8 months, HR: 0.48, 95% CI: 0.14-1.63, P = 0.238) and Durva + EP groups (12.3 months vs . 4.3 months, HR: 0.29, 95% CI: 0.10-0.81, P = 0.018). Grade 3 or 4 adverse events occurred in 13 (26.5%) and 13 (18.1%) patients, respectively, in the two groups; pneumonitis was mostly low-grade.
CONCLUSION
Addition of RT after first-line immunochemotherapy significantly improved survival outcomes with manageable toxicity in ES-SCLC.
Humans
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Small Cell Lung Carcinoma/therapy*
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Retrospective Studies
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Male
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Female
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Middle Aged
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Lung Neoplasms/therapy*
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Aged
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Antibodies, Monoclonal/therapeutic use*
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Adult
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Immunotherapy/methods*
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Aged, 80 and over


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