1.Safety, dosimetry, and efficacy of an optimized long-acting somatostatin analog for peptide receptor radionuclide therapy in metastatic neuroendocrine tumors: From preclinical testing to first-in-human study.
Wei GUO ; Xuejun WEN ; Yuhang CHEN ; Tianzhi ZHAO ; Jia LIU ; Yucen TAO ; Hao FU ; Hongjian WANG ; Weizhi XU ; Yizhen PANG ; Liang ZHAO ; Jingxiong HUANG ; Pengfei XU ; Zhide GUO ; Weibing MIAO ; Jingjing ZHANG ; Xiaoyuan CHEN ; Haojun CHEN
Acta Pharmaceutica Sinica B 2025;15(2):707-721
Peptide receptor radionuclide therapy (PRRT) with radiolabeled SSTR2 agonists is a treatment option that is highly effective in controlling metastatic and progressive neuroendocrine tumors (NETs). Previous studies have shown that an SSTR2 agonist combined with albumin binding moiety Evans blue (denoted as 177Lu-EB-TATE) is characterized by a higher tumor uptake and residence time in preclinical models and in patients with metastatic NETs. This study aimed to enhance the in vivo stability, pharmacokinetics, and pharmacodynamics of 177Lu-EB-TATE by replacing the maleimide-thiol group with a polyethylene glycol chain, resulting in a novel EB conjugated SSTR2-targeting radiopharmaceutical, 177Lu-LNC1010, for PRRT. In preclinical studies, 177Lu-LNC1010 exhibited good stability and SSTR2-binding affinity in AR42J tumor cells and enhanced uptake and prolonged retention in AR42J tumor xenografts. Thereafter, we presented the first-in-human dose escalation study of 177Lu-LNC1010 in patients with advanced/metastatic NETs. 177Lu-LNC1010 was well-tolerated by all patients, with minor adverse effects, and exhibited significant uptake and prolonged retention in tumor lesions, with higher tumor radiation doses than those of 177Lu-EB-TATE. Preliminary PRRT efficacy results showed an 83% disease control rate and a 42% overall response rate after two 177Lu-LNC1010 treatment cycles. These encouraging findings warrant further investigations through multicenter, prospective, and randomized controlled trials.
3.Expert consensus on the diagnosis and treatment of cemental tear.
Ye LIANG ; Hongrui LIU ; Chengjia XIE ; Yang YU ; Jinlong SHAO ; Chunxu LV ; Wenyan KANG ; Fuhua YAN ; Yaping PAN ; Faming CHEN ; Yan XU ; Zuomin WANG ; Yao SUN ; Ang LI ; Lili CHEN ; Qingxian LUAN ; Chuanjiang ZHAO ; Zhengguo CAO ; Yi LIU ; Jiang SUN ; Zhongchen SONG ; Lei ZHAO ; Li LIN ; Peihui DING ; Weilian SUN ; Jun WANG ; Jiang LIN ; Guangxun ZHU ; Qi ZHANG ; Lijun LUO ; Jiayin DENG ; Yihuai PAN ; Jin ZHAO ; Aimei SONG ; Hongmei GUO ; Jin ZHANG ; Pingping CUI ; Song GE ; Rui ZHANG ; Xiuyun REN ; Shengbin HUANG ; Xi WEI ; Lihong QIU ; Jing DENG ; Keqing PAN ; Dandan MA ; Hongyu ZHAO ; Dong CHEN ; Liangjun ZHONG ; Gang DING ; Wu CHEN ; Quanchen XU ; Xiaoyu SUN ; Lingqian DU ; Ling LI ; Yijia WANG ; Xiaoyuan LI ; Qiang CHEN ; Hui WANG ; Zheng ZHANG ; Mengmeng LIU ; Chengfei ZHANG ; Xuedong ZHOU ; Shaohua GE
International Journal of Oral Science 2025;17(1):61-61
Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans
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Dental Cementum/injuries*
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Consensus
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Diagnosis, Differential
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Cone-Beam Computed Tomography
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Tooth Fractures/therapy*
4.Multidimensional analysis of diagnosis and treatment status of chronic hepatitis B
Ying TAN ; Bo LI ; Aiqi LU ; Lihua LIN ; Xiaoyuan CHEN ; Jianping LI ; Yujuan GUAN
Chinese Journal of Experimental and Clinical Virology 2025;39(4):449-453
Objective:The aim was to analyze key indicators for the diagnosis and treatment of chronic hepatitis B(CHB),including virus detection rate,standardized treatment rate,and loss to follow-up rate,in order to provide a basis for optimizing diagnosis and treatment plans,improve the diagnosis and treatment level of CHB,and improve patient prognosis.Methods:Patients with CHB admitted to the Guangzhou Eighth People′s Hospital Affiliated to Guangzhou Medical University from January 2024 to January 2025 were enrolled. The datas were collected and organized using Excel. Statistical analysis was conducted using SPSS 26.0 software,with a focus on evaluating core indicators such as virus detection rate,standardized treatment rate,and loss to follow-up rate.Results:The positive rate of hepatitis B surface antigen(HBsAg)in non-specific patients was 28.95%,the antiviral treatment rate in specialized patients was 90.78%,and the standardized antiviral drug conversion treatment rate in low-level viremia(LLV)patients was 61.45%. The standardized antiviral drug conversion treatment rates for high-risk patients with combined kidney/bone injuries were 72.75% and 74.40%,respectively. The overall dropout rate was 10.47%,with a dropout rate of 13.80% for LLV patients.Conclusions:The antiviral treatment coverage rates in CHB patients were over 90%,but in certain groups(such as LLV patients and those with kidney or bone injuries),the standardized treatment rates were still low and loss to follow-up rates were high,suggesting the need to improve HBV screening,treatment for special populations,and patient adherence.
5.Effects of Sishen Pills on the Expression of TREK-1 Signaling Pathway in Rats of Irritable Bowel Syndrome with Diarrhea
Xiaoyuan LIN ; Shuangyang LUO ; Na DENG ; Xuting XIA ; Jiemin LIU ; Yujie LI
Chinese Journal of Information on Traditional Chinese Medicine 2025;32(10):94-99
Objective To observe the effect of Sishen Pills on the expression of TREK-1 signaling pathway in rats of irritable bowel syndrome with diarrhea(IBS-D);To explore its mechanism in treating IBS-D.Methods Ten SPF-grade SD rats were randomly selected as the normal group,and the remaining 30 rats were used to prepare the IBS-D rat model by senna gavage combined with water stress avoidance method,and then the modeled rats were randomly divided into the model group,Western medicine group(15.23 mg/kg pivoxyl bromide)and Chinese medicine group(7.32 g/kg Sishen Pills).The medication groups were gavaged by corresponding drugs,and the normal group and model group were given equal volume of pure water,once a day,for consecutive 14 d.The general state of the rats was observed,the contents of serum cyclic adenosine monophosphate(cAMP),protein kinase A(PKA)and phosphorylated extracellular signal-regulated kinase(p-ERK)were detected by ELISA,the positive expressions of biportal potassium channel TREK-1 and p-ERK in colonic tissue were detected by immunofluorescence,the expressions of cAMP,PKA and p-ERK protein were detected by Western blot.Results Compared with the normal group,the body mass of rats in the model group was significantly reduced,and loose stool rate significantly increased(P<0.01);the contents of cAMP,PKA and p-ERK in serum were significantly increased(P<0.05,P<0.01);the positive expression and protein expression of TREK-1 in colonic tissue were significantly reduced,while the positive expression of p-ERK significantly increased(P<0.01),and the expressions of cAMP and PKA proteins significantly increased(P<0.01).Compared with the model group,the body mass of rats in Chinese medince group significantly increased,and loose stool rate significantly decreased(P<0.01);the contents of cAMP,PKA and p-ERK in serum were significantly reduced(P<0.05,P<0.01);the positive expression and protein expression of TREK-1 in colonic tissue significantly increased(P<0.01),while the positive expression of p-ERK significantly decreased(P<0.05),and the expressions of cAMP and PKA proteins significantly decreased(P<0.01).Conclusion Sishen Pills may regulate intestinal motility by affecting the expression of the TREK-1 signaling pathway,thereby treating IBS-D.
6.Quality Control and Analysis of Treatment for Hospitalized Cancer Patients:Interview and Medical Records Study from Nine Hospitals in Beijing
Liting LU ; Yanping ZHOU ; Xiang WANG ; Xiaoyuan LI ; Xiaorong HOU ; Lidong ZHU ; Xiaohong XU ; Guibin SUN ; Ziyuan WANG ; Jieshi ZHANG ; Lin ZHAO ; Yi BA
Medical Journal of Peking Union Medical College Hospital 2025;16(2):399-405
Objective To analyze the current quality of treatment for hospitalized cancer patients in Bei-jing,identify major issues in treatment practices,and propose improvements.Methods Nine hospitals in Beijing were selected for examination.Expert on-site interviews and medical record sampling were conducted.The"Bei-jing Cancer Diagnosis and Treatment Quality Control Checklist"was used to assess the hardware,management,anti-cancer drug therapy,radiation therapy,and surgical treatment during cancer treatment at these hospitals from January to October 2023.The relevant problems were analyzed.Results Among the nine hospitals,two(22.2%)were equipped with laminar flow rooms,and three(33.3%)had intravenous drug preparation centers.In terms of institutional management,seven hospitals(77.8%)had standardized anti-cancer drug prescription authority management,eight(88.9%)had complete emergency plans,and five(55.6%)had oncology specialist pharmacists.Regarding anti-cancer drug therapy,the areas with higher completion rates included pathology diag-nosis support(97.6%),routine pre-treatment examinations(96.3%),adverse reaction evaluation(92.7%),discharge summaries(95.1%),and admission records(91.5%).However,the accuracy of tumor staging before treatment(70.7%)and the evaluation of therapeutic efficacy after drug treatment(76.9%)needed improvement.The oncology specialty significantly outperformed the non-oncology specialty in terms of the accuracy rate of TNM staging(86.0%vs.46.9%,P<0.001),the completeness of informed consent forms(100%vs.68.8%,P<0.001),the completeness of drug indication evaluation(96.0%vs.78.1%,P=0.025),the completeness of admission medical history records(98.0%vs.81.3%,P=0.008),the rationality of drug dosage(96.0%vs.75.0%,P=0.005),the rationality of drug infusion time(100%vs.62.5%,P<0.001),and the rationality of the order of drug infusion(100%vs.87.5%,P=0.010).Although the quality of radiation therapy was high,the subsequent evaluation of therapeutic efficacy(39.3%)requires enhancement.In surgical treatment,the preoper-ative pathology diagnosis support rate(78.1%)and the accuracy of tumor staging(37.5%)were relatively low,indicating issues with incomplete preoperative evaluation and the absence of multidisciplinary discussions.Conclusions There remains significant room for improvement in the quality of cancer treatment in China.It is recommended to standardize tumor staging assessment processes,strengthen entry assessments for non-oncology departments,promote the implementation of multidisciplinary treatment models,and establish a multi-department collaborative management model.Continuous monitoring of cancer diagnosis and treatment quality indicators is es-sential to promote ongoing improvements in cancer treatment quality.
7.Mechanism of Zuogui Jiangtang Jieyu Prescription Against Damage to Hippocampal Synaptic Microenvironment via Suppressing GluR2/Parkin Signal-mediated Mitophagy in Rats with Diabetes-related Depression
Jian LIU ; Lin LIU ; Xiaoyuan LIN ; Wei LI ; Yuhong WANG ; Hui YANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(1):104-112
ObjectiveTo reveal the mechanism of Zuogui Jiangtang Jieyu prescription against damage to hippocampal synaptic microenvironment via suppressing glutamate receptor 2 (GluR2)/Parkin signal-mediated mitophagy in rats with diabetes-related depression (DD). MethodsEighty male SD rats underwent adaptive feeding for 5 days before the study. Ten rats were randomly assigned to the normal group. The model of DD rats was established with the rest by 2-week high-fat diet + streptozotocin (STZ) tail intravenous injection + 28 days of chronic unpredictable mild stress (CUMS) combined with isolation. The rats were randomly divided into a normal group, a model group, a GluR2 blocker group (5 μg·kg-1), a GluR2 agonist group (10 μg·kg-1), a metformin + fluoxetine group (0.18 g·kg-1 metformin + 1.8 mg·kg-1 fluoxetine), and high- and low-dose Zuogui Jiangtang Jieyu prescription groups (20.52 and 10.26 g·kg-1, respectively). The rats in the GluR2 blocker group and the GluR2 agonist group were continuously injected with CNQX and Cl-HIBO in the dentate gyrus of the hippocampus once a week starting from stress modeling, respectively, while the metformin + fluoxetine group and the high- and low-dose Zuogui Jiangtang Jieyu prescription groups were continuously given intragastric administration for 28 d at the same time of stress modeling. Depression-like behavior was evaluated by open field and forced swimming experiments. The levels of serum insulin and adenosine triphosphate (ATP) in hippocampus were detected by biochemical analysis. The levels of 5-hydroxytryptamine (5-HT) and dopamine (DA) in hippocampus were detected by enzyme-linked immunosorbent assay (ELISA). The autophagosomes of hippocampal neurons were observed by transmission electron microscopy. The morphology and structure of dendrites and spines of hippocampal neurons were evaluated by Golgi staining. Western blot detected the expression levels of GluR2 and Parkin proteins in hippocampus. The expression levels of GluR2, Parkin, regulating synaptic membrane exocytosis protein 3 (RIMS3), and postsynaptic density protein 95 (PSD95) in the dentate gyrus of the hippocampus were detected by immunofluorescence. ResultsCompared with the normal group, the model group exhibited reduced total activity distance in the open field and increased immobility time in forced swimming (P<0.01), lowered levels of serum insulin and ATP, 5-HT, and DA in hippocampus (P<0.01), increased autophagosomes of hippocampal neurons, significantly damaged morphology and structure of dendrites and spines of hippocampal neurons, decreased expression levels of GluR2, RIMS3, and PSD95 in hippocampus, and an increased Parkin expression level (P<0.05, P<0.01). Compared with the model group, the GluR2 blocker group and the GluR2 agonist group showed aggravation and alleviation of the above abnormal changes, respectively (P<0.05, P<0.01). The above depression-like behavior was significantly improved in the high- and low-dose Zuogui Jiangtang Jieyu prescription groups to different degrees. Specifically, the two groups saw elevated levels of serum insulin and ATP, 5-HT, and DA in hippocampus (P<0.05, P<0.01), restrained increase in autophagosomes and damage to morphology and structure of dendrites and spines of hippocampal neurons, up-regulated protein expression levels of GluR2, RIMS3, and PSD95, and down-regulated Parkin expression level (P<0.05, P<0.01). ConclusionZuogui Jiangtong Jieyu prescription can ameliorate the mitophagy-mediated damage to hippocampal synaptic microenvironment in DD rats, the mechanism of which might be related to the regulation of GluR2/Parkin signaling pathway.
8.Characteristics and management of perioperative complications in laparoscopic surgery for colorectal cancer patients aged over 85 years
Ganbin LI ; Xiao ZHANG ; Xiaoyuan QIU ; Chentong WANG ; Lai XU ; Beizhan NIU ; Guannan ZHANG ; Junyang LU ; Bin WU ; Yi XIAO ; Guole LIN
Chinese Journal of Gastrointestinal Surgery 2025;28(4):368-373
Objective:To analyze the types and characteristics of post-operative complications in colorectal cancer patients aged over 85 years undergoing laparoscopic surgery, and to summarize peri-operative management strategies.Methods:This was an observational study. Inclusion criteria: pathologically confirmed adenocarcinoma; tumor located in ileocecum, ascending colon, transverse colon, descending colon, sigmoid colon, or rectum; undergoing laparoscopic radical resection for colorectal cancer; complete clinical data. Exclusion criteria included distant metastasis, synchronous resection of multiple primary cancers, simultaneous liver metastasis surgery, and follow-up duration <1 month. A retrospective analysis was conducted on 191 patients of colorectal cancer patients aged over 85 years who underwent laparoscopic radical surgery in the General Surgery Department at Peking Union Medical College Hospital from January 2019 to January 2024. Among 191 patients, 107 patients (56.0%) had colon cancer and 84 (44.0%) rectal cancer. All patients received "home-based prehabilitation" and post-operative "enhanced recovery after surgery" protocols. Patient characteristics, peri-operative complication types, treatments, and outcomes were analyzed.Results:Post-operative complications occurred in 97 patients (50.8%), including 53 colon cancer patients (54.6%) and 44 rectal cancer patients (45.4%). Comorbidities existed in 88 patients (90.7%), with 93 patients (95.9%) classified as ASA II-III pre-operatively and 86 (88.7%) having nutritional risks. Surgical procedures included Dixon procedure (38 patients, 39.2%), right hemicolectomy (33 patients, 34.0%), sigmoidectomy (10 patients, 10.3%), and 17 patients (17.5%) received prophylactic stomas. Complication types comprised non-anastomotic infections (38 patients, 19.9%), intestinal flora disorder (26 patients, 13.6%), anastomotic/wound/stoma-related complications (16 patients, 8.4%), thrombotic/hemorrhagic events (6 patients, 3.1%), and others (11 patients, 5.8%). By Clavien-Dindo classification: Grade I (12 patients, 6.3%), Grade II (69 patients, 36.1%), Grade III (12 patients, 6.3%), and Grade IV (4 patients, 2.1%). Except for 5 patients (2.6%) requiring unplanned re-operation, all complications resolved with conservative treatment. The median duration of post-operative hospitalization was 9.5 days (7–13).Conclusion:Non-anastomotic infections and intestinal flora disorder constitute predominant complications after laparoscopic surgery in colorectal cancer patients aged over 85 years, mostly manageable with conservative treatment. Strengthened peri-operative management incorporating pre-operative prehabilitation and post-operative enhanced recovery after surgery protocols is crucial for patients aged over 85 years.
9.Clinical characteristics and risk factors for anastomotic leakage after laparoscopic rectal cancer surgery in the setting of neoadjuvant therapy
Ganbin LI ; Xiao ZHANG ; Xiaoyuan QIU ; Chentong WANG ; Weijie CHEN ; Guannan ZHANG ; Beizhan NIU ; Lai XU ; Junyang LU ; Bin WU ; Yi XIAO ; Guole LIN
Chinese Journal of General Surgery 2025;40(2):108-113
Objective:To evaluate the clinical features and risk factors of anastomotic leakage (AL) in patients with locally advanced rectal cancer (LARC) receiving neoadjuvant chemoradiotherapy (nCRT) followed by laparoscopic radical resection and proctocol ostomy.Method:Clinicla data of LARC patients receiving neoadjuvant chemoradiotherapy followed by laparoscopic radical resection and proctocol ostomy admitted to Peking Union Medical College Hospital between Jan 2019 and Oct 2023 was enrolled. According to the occurrence of AL, patients were divided into AL group and non-AL group.Results:After propersity matching score(PSM), there were 40 patients (33.4%) and 80 patients (66.6%) in the AL and non-AL group, respectively. The first-onset symptoms of AL were abnormal character and color of the drainage (23 cases, 57.5%) and fever (14 cases, 35.0%). About 82.5% of the AL were graded as B,and all 36 patients (90.0%) were managed consveratively by fully drainage anti-infection therapy. Logistic regression analysis indicated that tumor circumferential range more than 1/2 cycle ( OR=5.95, 95% CI:2.12-1.67, P=0.004), male ( OR=4.28, 95% CI:1.22-15.00, P=0.023) and high-ligation of Inferior mesenteric artery ( OR=8.08, 95% CI:1.86-37.78, P=0.006) were independent risk factors of AL. Conclusions:In this series, grade-B AL ranks the top of the incidence, and all were cured by conservative therapy. Special attention should be paid to those patients with the characteristics of male, tumor circumferential range more than 1/2 cycle, and high-ligation of inferior mesenteric artery.
10.Association of tumor circumferential involvement range with neoadjuvant therapy efficacy and long-term outcomes in locally advanced rectal cancer
Ganbin LI ; Xiaoyuan QIU ; Xiao ZHANG ; Lai XU ; Beizhan NIU ; Guannan ZHANG ; Junyang LU ; Bin WU ; Yi XIAO ; Guole LIN
Chinese Journal of Oncology 2025;47(8):750-755
Objective:To detect the association of tumor circumferential involvement range (CIR) with neoadjuvant chemoradiotherapy (NCRT) efficacy and long-term survival outcomes in locally advanced rectal cancer (LARC) patients.Methods:Clinical data of 451 patients admitted to our hospital from January, 2018 to January, 2022 were retrospectively collected. According to the CIRs as determined by rectal magnetic resonance imaging, patients were divided into the High group (≥2/3 cycle, 270 patients) and the Low group (<2/3 cycle, 181 patients). The primary outcome was three-year disease-free survival. The baseline characteristics, pathological features, and survival outcomes were compared.Results:Compared to patients in the Low group, patients in the High group exhibited significantly larger tumor vertical diameters [(4.7±1.7) vs. (3.6±1.4)cm, P<0.001], higher rates of mrT4 stage (37.8% vs. 13.2%, P<0.001), and higher rates of positive mesorectal fascia (54.1% vs. 29.8%, P<0.001) and extramural vascular invasion (55.6% vs. 38.1%, P<0.001). Patients in the High group were mainly pT3-4 stages (46.7% vs. 30.9%, P=0.002), with significantly lower rates of pathological complete response (22.2% vs. 33.1%, P=0.010) , poorer tumor regression grades (48.9% vs. 60.8%, P=0.013), and higher rates of positive peripheral nerve invasion (11.5% vs. 5.5%, P=0.031), as compared to patients in the Low group. The median follow-up time was 40 months. About 11 (2.4%) and 48 patients (10.6%) experienced tumor local recurrence and distant metastasis, respectively. The recurrence rates were 2.2% and 2.6%, and the distant metastasis rates were 7.7% and 12.6%, respectively, in the Low group and the High group, with no statistical significance ( P=0.957, P=0.096). The three-year disease-free survival in the High group was significantly lower than that in the Low group (84.4% vs. 92.4%, P=0.014). Conclusions:The CIR is closely related to tumor burden, which can judge tumor response to NCRT, and is negatively related to survival prognosis. For patients who have more than a 2/3 cycle of CIR, intensified or consolidated treatments may be required to improve survival outcomes.

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