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.
2.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*
3.Research on dynamic monitoring of drug consumption based on statistical process control
Yang CHEN ; Chonghui DAN ; Meiling XU ; Xiao CHEN ; Ying LIU ; Xiaoyuan ZHENG
China Pharmacy 2024;35(19):2328-2334
OBJECTIVE To investigate a method for dynamic monitoring of drug consumption (DMDC) based on statistical process control (SPC), aiming to improve the macro-supervisory capacity in the process of drug utilization. METHODS The lists of key monitoring drug varieties in our hospital were established based on drug cost and relevant national documents. Monthly consumption data of key monitoring drug varieties in the entire hospital, outpatient pharmacy and inpatient pharmacy were taken as monitoring objects,and the DMDC model was established using SPC’s X control chart, moving range control chart, and exponentially weighted moving-average control chart, monitoring from three dimensions: single-month consumption, range variation, and consumption trend. Rosuvastatin, metoprolol and meropenem were taken as examples to demonstrate the monitoring capabilities of the DMDC model. RESULTS Lists of key monitoring drug varieties were established for entire hospital, outpatient pharmacy and inpatient pharmacy, containing 203, 167 and 200 varieties, respectively. After excluding drug varieties that could not be modeled and for which modeling failed, 179, 116 and 172 DMDC models were successfully established for these three drug consumption areas, respectively. During the first four months of 2024, these three groups of model separately warned 54, 32 and 62 drug varieties. The DMDC model successfully monitored the monthly consumption of drugs,such as rosuvastatin throughout the hospital, metoprolol in outpatient pharmacy, and meropenem in inpatient pharmacy. Compared with the previously used floating rate ranking method in our hospital, the application of the DMDC model significantly improved the scope and depth of drug monitoring, with the monitored drug varieties greatly expanded from about 50 to 179, and the monitoring dimensions increased from a single dimension to three. CONCLUSIONS The DMDC model based on SPC is effective and feasible,suitable for monitoring drug varieties with stable monthly consumption.
4.The Correlation between Tooth Brushing Frequency and Blood Indicators in Adolescents: A Cross-sectional Observational Study
Xu ZHANG ; Hanze DU ; Wenhao ZHAI ; Shuaihua SONG ; Xiaoyuan GUO ; Linlin WEN ; Lei HUANG ; Shi CHEN ; Daowei LI ; Hui PAN
Medical Journal of Peking Union Medical College Hospital 2024;15(4):960-967
To analyze the effects of tooth brushing frequency on blood indicators among adolescents and to preliminarily explore the effects of tooth brushing frequency on general health. Using convenience sampling method, the study included the students of class 2021 of Jining No. 7 Middle School and student athletes from the Jining Sports Training Center. Univariate and multivariate linear regression analyses were used to investigate the correlation between tooth brushing frequency and blood indicators such as eosinophil percentage (EOS%), eosinophil count (EOS#), basophil percentage (BAS%), basophil count (BAS#), superoxide dismutase (SOD), insulin-like growth factor 1 (IGF-1) and uric acid (UA). A total of 305 students were included (167 from Jining No. 7 Middle School, 138 from Jining Sports Training Centre), with 192 (62.95%) males and 113 (37.05%) females. They were divided into three groups based on daily teeth brushing frequency: ≤1 time (40.33%, 123/305), 2 times (53.77%, 164/305), and ≥3 times (5.90%, 18/305).Univariate linear regression analysis showed that brushing twice daily was negatively correlated with EOS%, EOS#, BAS%, and BAS#(all The adolescent tooth brushing frequency correlates with several blood indicators affecting general health, suggesting that there may be a potential association between oral health and general health.
5.Effects of Electroacupuncture on Urodynamics and Expression of ERK/CREB/Bcl-2 Pathway in Spinal Cord of Rats with Neurogenic Bladder after Suprasacral Spinal Cord Injury
Ming XU ; Kun AI ; Yue ZHUO ; Qiong LIU ; Xiaomeng LIU ; Ya LI ; Xiaoyuan LUO ; Hong ZHANG
Chinese Journal of Information on Traditional Chinese Medicine 2024;31(4):100-105
Objective To observe the effects of electroacupuncture at"Ciliao","Zhongji","Sanyinjiao"and"Dazhui"on urodynamics and expression of ERK/CREB/Bcl-2 pathway in spinal cord tissue of neurogenic bladder rats after suprasacral spinal cord injury.Methods Sixty female SD rats randomly selected 24 and divided into blank group and sham-operation group(12 rats in each group),the remaining 36 rats were subjected to surgical modeling.After modeling,rats were randomly divided into the model group and the electroacupuncture group,with 12 rats in each group.The electroacupuncture group received unilateral electroacupuncture stimulation at acupoints"Ciliao","Zhongji","Sanyinjiao",and"Dazhui"for 30 minutes each time,once a day,for 7 consecutive days.After administration,urodynamic testing was performed,HE staining was used to observe the morphology of bladder detrusor tissue,TUNEL method was used to detected apoptosis in spinal cord tissue,Western blot was used to detected expressions of p-ERK1/2,p-CREB,p-p90Rsk,CRE,Bcl-2,and Bax proteins in spinal cord tissue.Results Compared with the sham-operation group,the basal pressure,maximum pressure,and leakage point pressure of the bladder in the model group increased significantly(P<0.01),while the maximum capacity and compliance of the bladder decreased significantly(P<0.01);the structure of bladder smooth muscle cells was severely damaged and disorderly arranged,accompanied by a large amount of inflammatory cell infiltration;the apoptosis rate of spinal cord tissue cells significantly increased(P<0.01),and the expressions of p-ERK1/2,p-p90Rsk,p-CREB,CRE,and Bcl-2 proteins in spinal cord tissue were significantly decreased,while the expression of Bax protein significantly increased(P<0.01).Compared with the model group,the basal pressure,maximum pressure,and leakage point pressure of the bladder in the electroacupuncture group decreased significantly(P<0.05),while the maximum capacity and compliance of the bladder increased significantly(P<0.05,P<0.01);the integrity of bladder smooth muscle cells was enhanced,the degree of cell edema was reduced,and inflammatory cell infiltration was reduced;the apoptosis rate of spinal cord tissue cells was significantly reduced(P<0.05),and the expressions of p-ERK1/2,p-p90Rsk,p-CREB,CRE,and Bcl-2 proteins in spinal cord tissue significantly increased,while the expression of Bax protein was significantly decreased(P<0.05,P<0.01).Conclusion Electroacupuncture can promote the repair of bladder detrusor tissue in rats with neurogenic bladder model after suprasacral spinal cord injury,increase the maximum capacity and compliance of the bladder,alleviate the high pressure state in the bladder,and its mechanism is related to activating the ERK/CREB/Bcl-2 pathway,reducing secondary apoptosis of damaged neurons,effectively improving bladder innervation,and protecting bladder function.
6.Application progress of Evans blue modified radiopharmaceuticals for theranostics
Guochang WANG ; Pengfei XU ; Jingjing ZHANG ; Xiaoyuan CHEN
Chinese Journal of Nuclear Medicine and Molecular Imaging 2024;44(1):35-40
Theranostics in nuclear medicine is an important direction for the precision medicine. Radionuclide therapy based on small molecules/peptides often requires high doses. Improving the utilization efficiency of radionuclides, optimizing the pharmacokinetics of radionuclide therapeutic molecular probes as well as increasing the target to non-target ratio have become the international hot frontiers in the field of radiotheranostics. Evans blue (EB) motif uses endogenous albumin as a reversible carrier, and the small molecule and polypeptide structure modified based on EB can effectively extend the half-life in the blood and substantially increase the uptake, accumulation and retention of radiopharmaceuticals in target lesions, and thereby enhance the therapeutic effect and reduce the dosage of nuclides. This article focuses on the research of EB modified radiopharmaceuticals for theranostics.
7.Abnormal liver biochemical parameters in pregnancy during the epidemic of coronavirus disease 2019
Binbin LIU ; Wen GAO ; Xiaoyuan XU ; Jianxiang LIU
Journal of Clinical Hepatology 2024;40(1):104-109
ObjectiveTo investigate the differences in abnormal liver biochemical parameters in pregnant patients during the epidemic or non-epidemic period of coronavirus disease 2019 (COVID-19). MethodsA retrospective analysis was performed for 539 pregnant women who were discharged from Department of Obstetrics, Peking University First Hospital, from October 2017 to March 2022 and had at least one abnormal liver biochemical parameter among alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT), total bilirubin (TBil), and total bile acid. The patients in the epidemic period of COVID-19 and those in the non-epidemic period of COVID-19 were compared in terms of etiology, coagulation parameters, aminotransferases, bile acid, and renal function. The independent samples t-test was used for comparison of continuous data between two groups, and the chi-square test was used for comparison of categorical data between two groups. ResultsAmong the patients discharged from Department of Obstetrics during the non-epidemic period of COVID-19, 262 had abnormal liver biochemical parameters, accounting for 1.46%, while 277 patients had abnormal liver biochemical parameters during the epidemic period of COVID-19, accounting for 1.73% among the patients discharged from Department of Obstetrics during the same period of time, and there was a significant difference between these two groups (χ2=3.947, P=0.047). The etiological analysis of the patients with abnormal liver biochemical parameters during the two periods showed that there was no difference in the proportion of patients with four pregnancy-specific liver diseases (hyperemesis gravidarum, preeclampsia and eclampsia, intrahepatic cholestasis of pregnancy, and acute fatty liver of pregnancy). As for the patients with abnormal liver biochemical parameters in pregnancy, there was no significant difference in the proportion of patients with normal creatinine and stimated glomerular filtration rate (eGFR) between the epidemic period and the non-epidemic period (86.78% vs 87.90%, χ2=0.141, P=0.708). The patients with ALT≥5×upper limit of normal accounted for 7.94% in the epidemic period of COVID-19 and 9.54% in the non-epidemic period (χ2=0.433, P=0.511), and the patients with severe cholestasis accounted for 7.75% in the epidemic period of COVID-19 and 9.27% in the non-epidemic period (χ2=0.392, P=0.531). The proportion of patients with obstetric bleeding during the epidemic period of COVID-19 was significantly lower than that during the non-epidemic period (14.61% vs 24.19%, χ2=489.334, P<0.001). ConclusionThere is no difference in the proportion of patients with pregnancy-specific liver diseases among the patients with abnormal liver biochemical parameters in pregnancy between the epidemic period and the non-epidemic period of COVID-19, and there is no change in the proportion of patients with normal creatinine and eGFR among these patients in the epidemic period of COVID-19.
8.Pay attention to the diagnosis and treatment of "easily neglected" complications in liver cirrhosis
Jinghang XU ; Yanyan YU ; Xiaoyuan XU
Chinese Journal of Hepatology 2024;32(6):481-483
Managing cirrhosis complications is an important measure for improving patients' clinical outcomes. Therefore, in order to provide a complete disease assessment and comprehensive treatment, improve quality of life, and improve the prognosis for patients with cirrhosis, it is necessary to pay attention to complications such as thrombocytopenia and portal vein thrombosis in addition to common or severe complications such as ascites, esophagogastric variceal bleeding, hepatic encephalopathy, and hepatorenal syndrome. The relevant concept that an effective albumin concentration is more helpful in predicting the cirrhosis outcome is gradually being accepted; however, the detection method still needs further standardization and commercialization.
9.An analysis of related factors in thrombocytopenia combined with cirrhosis: a cross-sectional study of 2 517 cases
Ming HE ; Yanan FAN ; Zhengqing BA ; Tongtong JI ; Duanmin ZHANG ; Yanyan YU ; Xiaoyuan XU ; Jinghang XU
Chinese Journal of Hepatology 2024;32(6):508-516
Objective:To explore the related factors of thrombocytopenia (TCP) occurrence in patients with cirrhosis.Methods:A cross-sectional study was conducted. Inpatients with an initial diagnosis of cirrhosis at Peking University First Hospital from January 1, 2010 to December 31, 2020 were included. Clinical data such as demographic characteristics, etiology of cirrhosis, complications of cirrhosis, laboratory indicators, Child-Pugh grade, invasive procedures, and mortality during hospitalization were collected. A logistic regression model was used to explore the related factors of TCP occurrence in patients with cirrhosis. Categorical variables were compared by the χ2 test. The inter-group comparison was performed using continuous variables, a t-test, one-way analysis of variance (ANOVA), or a nonparametric test. Results:There were a total of 2 592 cases of cirrhosis. 75 cases with incomplete clinical data were excluded. 2 517 cases were included for analysis. The median age was 58 (50, 67) years. Males accounted for 64%. 1 435 cases (57.0%) developed TCP, and 434 cases (17.2%) had grade 3-4 TCP. Gender, primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), and concomitant esophagogastric varices (EGV) were the major factors associated with TCP. Females were more prone to combine with TCP ( OR=1.32, 95% CI: 1.12-1.56, P=0.001). Patients combined with EGV ( OR=3.09, 95% CI: 2.63-3.65, P<0.001) were more prone to develop TCP, which was associated with the increased incidence of hypersplenism ( P<0.001). Patients with PBC ( OR=0.64, 95% CI: 0.50-0.82, P<0.001) and PSC ( OR=0.23, 95% CI: 0.06-0.65, P=0.010) were less prone to develop TCP, which was due to the shorter prothrombin time and better coagulation function of PBC patients ( P<0.001), and the lower proportion of hypersplenism in combined PSC patients ( P=0.004). Patients with TCP and grade 3-4 TCP had a higher rate of hemostatic procedures ( P<0.05), but a lower rate of liver biopsy ( P<0.05). Patients with grade 3-4 TCP had a higher nosocomial mortality rate compared to those without ( P=0.004). Conclusion:TCP is common in patients with cirrhosis. However, TCP occurrence is higher in female patients with EGV and lower in patients combined with PBC and PSC. TCP affects invasive procedures and is associated with adverse outcomes.
10.Clinical effect of modified vertical rectus abdominis myocutaneous flap in repairing skin and soft tissue defects after abdominoperineal resection for rectal cancer
Mitao HUANG ; Zhan QU ; Pengfei LIANG ; Weidong LIU ; Zhiyou HE ; Xu CUI ; Le GUO ; Jie CHEN ; Mengjuan LI ; Xiaoyuan HUANG ; Pihong ZHANG
Chinese Journal of Burns 2024;40(1):57-63
Objective:To investigate the clinical effect of the modified vertical rectus abdominis myocutaneous flap in repairing the skin and soft tissue defect after abdominoperineal resection for rectal cancer.Methods:This study was a retrospective observational study. From June 2019 to July 2022, five male patients with low rectal cancer who were conformed to the inclusion criteria were admitted to the Department of Basic Surgery of Xiangya Hospital of Central South University, with ages ranging from 65 to 70 years and the sizes of the perianal skin ulcers ranging from 5 cm×4 cm to 11 cm×9 cm, and all of them underwent abdominoperineal resection. The secondary skin and soft tissue defects in the perineum with an area of 8 cm×6 cm-14 cm×12 cm (with the depth of pelvic floor dead space being 10-15 cm) were repaired intraoperatively with transplantation of modified vertical rectus abdominis myocutaneous flaps with the skin area being 9 cm×7 cm-16 cm×12 cm, the volume of the muscle being 18 cm×10 cm×5 cm-20 cm×12 cm×5 cm, and the vessel pedicle being 18-20 cm in length. During the operation, most of the anterior sheath of the rectus abdominis muscle was retained, the flap was transferred to the recipient area through the abdominal cavity, the remaining anterior sheaths of the rectus abdominis muscle on both sides of the donor area were repeatedly folded and sutured, the free edge of the transverse fascia of the abdomen was sutured with the anterior sheath of the rectus abdominis muscle, and the donor area skin was directly sutured. After the operation, the survival of the transplanted myocutaneous flap was observed. The occurrence of complications in the perineal recipient area was recorded within 2 weeks after the operation. The recovery of the perineal recipient area and the abdominal donor area was observed during follow-up, and the occurrence of complications in the donor area of the abdomen as well as the recurrence of tumors and metastasis were recorded.Results:All transplanted myocutaneous flaps in 5 patients survived after surgery. One patient had dehiscence of the incision in the perineal recipient area 2 days after surgery, which healed after 7 d with intermittent dressing changes and routine vacuum sealing drainage treatment. In the other 4 patients, no complications such as incisional rupture, incisional infection, or fat liquefaction occurred in the perineal recipient area within 2 weeks after surgery. Follow-up for 6-12 months after discharge showed that the skin of the perineal recipient area had good color, texture, and elasticity, and was not bloated in appearance; linear scars were left in the perineal recipient area and the abdominal donor area without obvious scar hyperplasia or hyperpigmentation; no complications such as incisional rupture, incisional infection, intestinal adhesion, intestinal obstruction, or weakening of the abdominal wall strength occurred in the abdominal donor area, and the abdominal appearance was good with no localized bulge or formation of abdominal hernia; there was no local recurrence of tumor or metastasis in any patient.Conclusions:The surgical approach of using the modified vertical rectus abdominis myocutaneous flap to repair the skin and soft tissue defects after abdominoperineal resection for rectal cancer is relatively simple in operation, can achieve good postoperative appearances of the donor and recipient areas with few complications, and is worthy of clinical promotion.

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