1.Development and validation of a nutrition-related genetic-clinical-radiological nomogram associated with behavioral and psychological symptoms in Alzheimer’s disease
Jiwei JIANG ; Yaou LIU ; Anxin WANG ; Zhizheng ZHUO ; Hanping SHI ; Xiaoli ZHANG ; Wenyi LI ; Mengfan SUN ; Shirui JIANG ; Yanli WANG ; Xinying ZOU ; Yuan ZHANG ; Ziyan JIA ; Jun XU
Chinese Medical Journal 2024;137(18):2202-2212
Background::Few evidence is available in the early prediction models of behavioral and psychological symptoms of dementia (BPSD) in Alzheimer’s disease (AD). This study aimed to develop and validate a novel genetic-clinical-radiological nomogram for evaluating BPSD in patients with AD and explore its underlying nutritional mechanism.Methods::This retrospective study included 165 patients with AD from the Chinese Imaging, Biomarkers, and Lifestyle (CIBL) cohort between June 1, 2021, and March 31, 2022. Data on demographics, neuropsychological assessments, single-nucleotide polymorphisms of AD risk genes, and regional brain volumes were collected. A multivariate logistic regression model identified BPSD-associated factors, for subsequently constructing a diagnostic nomogram. This nomogram was internally validated through 1000-bootstrap resampling and externally validated using a time-series split based on the CIBL cohort data between June 1, 2022, and February 1, 2023. Area under receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA) were used to assess the discrimination, calibration, and clinical applicability of the nomogram.Results::Factors independently associated with BPSD were: CETP rs1800775 (odds ratio [OR] = 4.137, 95% confidence interval [CI]: 1.276-13.415, P = 0.018), decreased Mini Nutritional Assessment score (OR = 0.187, 95% CI: 0.086-0.405, P <0.001), increased caregiver burden inventory score (OR = 8.993, 95% CI: 3.830-21.119, P <0.001), and decreased brain stem volume (OR = 0.006, 95% CI: 0.001-0.191, P = 0.004). These variables were incorporated into the nomogram. The area under the ROC curve was 0.925 (95% CI: 0.884-0.967, P <0.001) in the internal validation and 0.791 (95% CI: 0.686-0.895, P <0.001) in the external validation. The calibration plots showed favorable consistency between the prediction of nomogram and actual observations, and the DCA showed that the model was clinically useful in both validations. Conclusion::A novel nomogram was established and validated based on lipid metabolism-related genes, nutritional status, and brain stem volumes, which may allow patients with AD to benefit from early triage and more intensive monitoring of BPSD.Registration::Chictr.org.cn, ChiCTR2100049131.
2.Strolling through the glorious years of Alveolar Surgery, bravely stepping onto the path of practice and innovation
Yiming WANG ; Yang XUE ; Jihong ZHAO ; Jian PAN ; Duohong ZOU ; Nianhui CUI ; Wei ZHANG ; Qizhang WANG ; Zhizheng LI ; Yuqiong ZHOU ; Kaijin HU
Chinese Journal of Stomatology 2024;59(4):301-311
This article summarizes and organizes relevant publications in journals, along with a review of medical history, systematically summarizing the development process of dental alveolar surgery in China. The initial establishment phase (1935—1952) marked the starting point of Chinese Alveolar Surgery. Despite the impact of wars, it laid the foundation for subsequent research and practice. During the early development phase (1953—1966), the "Chinese Journal of Stomatology" was founded, which promoted the development of Alveolar Surgery. Research focused on tooth extraction methods and complications. Tooth Transplantation and Preprosthetic Surgery gradually began to take off. The stagnant phase (1967—1977) occurred due to the interruption of international exchanges, leading to an almost complete halt in the development of Alveolar Surgery. Entering the rapid catch-up phase (1978—1985), Alveolar Surgery scholars in China began striving to overcome the stagnation of the previous decade. While some progress was made, no significant innovative achievements emerged. In the scientific development phase (1986—2010), clinical research, basic experiments, and paper writing in modern Chinese Alveolar Surgery began to adhere to scientific standards with the rise of experimental medicine. The exploration and innovation stage (2011—2023) is the current development phase, during which Chinese Aveolar Surgery has reached its peak, making substantial progress in technology, clinical practices, and basic research, gradually reaching or even surpassing international advanced levels. Looking back at the development history in China, we can find the wisdom and hard work of the older generation of Alveolar Surgery scholars. However, contemporary challenges and issues, such as standardizing technology, promoting clinical practices, and talent cultivation, need to be addressed by present-day Alveolar Surgery professionals as they forge ahead.
3.Effect of residual dental follicle after removal of impacted mandibular third molars on the periodontal health of adjacent second molars
Tingting LI ; Chaofan WANG ; Yu CAI ; Zhizheng LI ; Jihong ZHAO
Chinese Journal of Stomatology 2024;59(8):784-790
Objective:To investigate whether residual dental follicles in the alveolar socket after extraction of impacted mandibular third molars affect the periodontal health of adjacent mandibular second molars, in order to provide clinical reference for the management of residual dental follicles after third molar extraction.Methods:A total of 82 patients who underwent bilateral impacted mandibular third molar extraction at the Department of Oral Surgery, School and Hospital of Stomatology Wuhan University, from November 1, 2020, to November 30, 2022, were included in the study. Using a self-controlled method, each patient′s bilateral mandibular third molars were randomly divided into two groups: Group A underwent third molar extraction with thorough removal of residual dental follicle tissue, while Group B underwent third molar extraction without any treatment of the remaining dental follicle tissue. Operation time and adverse reactions were recorded. Clinical and radiographic examinations were performed at 6-month follow-up to evaluate the periodontal parameters and alveolar bone height of the bilateral mandibular second molars, and differences between the two groups were compared.Results:All patients had successful bilateral mandibular third molar extractions, and no serious complications occurred intraoperatively or postoperatively. There were no statistically significant differences in surgical time, postoperative pain, or facial swelling between the two groups ( P>0.05). At the 6-month follow-up, the probing depth on the distal aspect of the mandibular second molars in Group A [2.67 (2.00, 3.67) mm] was significantly less than that in Group B [4.00 (3.00, 5.00) mm] ( Z=-6.55, P<0.001). The clinical attachment loss on the distal aspect of the mandibular second molars in Group A [1.00 (0.00, 3.00) mm] was less than that in Group B [3.00 (2.00, 5.00) mm] ( Z=-5.99, P<0.001). The distance from the alveolar crest to the cementoenamel junction on the distal aspect of the mandibular second molars in Group A [(1.86±1.34) mm] was less than that in Group B [(3.04± 1.89) mm] ( t=-6.87, P<0.001). In patients aged≥20 years, the probability of recovery of alveolar bone height to normal level on the distal aspect of the mandibular second molars in Group A [42.3% (11/26)] was significantly higher than that in Group B [0 (0/26)] ( P<0.01), while there was no statistically significant difference between Group A [63.3% (19/30)] and Group B [46.7% (14/20)] in patients aged<20 years ( P>0.05). Conclusions:Residual dental follicles in the alveolar socket after extraction of impacted mandibular third molars adversely affect the periodontal health of adjacent teeth. Thorough removal of residual dental follicles during impacted mandibular third molar extraction is beneficial for the postoperative recovery of alveolar bone height of the distal aspect of the mandibular second molars, especially in patients aged≥20 years.
4.GRADE Clinical Study Evidence Evaluation and Expert Consensus on Antihypertensive Chinese Patent Medicines Combined with Western Medicines for Treatment of Hypertension
Liangyu CUI ; Yukun LI ; Tianyue JING ; Yu WANG ; Cong REN ; Tong YIN ; Zhiwei ZHAO ; Jiaheng WANG ; Chenge SUN ; Dasheng LIU ; Zhizheng XING ; Xuejie HAN ; Liying WANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(10):106-115
ObjectiveTo evaluate the quality of research and evidence related to antihypertensive Chinese patent medicines combined with western medicines for the treatment of hypertension, synthesize and update the evidence, form expert consensus, and provide evidence for clinical decision-making. MethodThe databases of China National Knowledge Infrastructure (CNKI), WanFang Data Knowledge Service Platform (WanFang), Vip Chinese Science and Technology Journal Database (VIP), Chinese Biomedical Literature Service System (Sinomed), National Library of Medicine (PubMed), Cochrane Library, Web of Science, and US Clinical Trials Registry were searched for randomized controlled trials of antihypertensive Chinese medicine combined with western medicine for the treatment of hypertension from database construction to July 31, 2022. The quality of the literature was evaluated using the bias risk assessment tool in Cochrane Handbook 6.3. Evidence synthesis of main outcome indicators was performed using R software. The Grading of Recommendations Assessment, Development, and Evaluation profiler (GRADEprofiler) 3.6 was employed to evaluate the quality of evidence. Expert consensus was formed based on the Delphi method after two rounds of voting. Result64 pieces of literature were included, and the results of literature quality evaluation and risk of bias showed that 70.31% (45/64) of the studies indicated some risks, and 29.69% (19/64) indicated high risks. Compared with conventional western medicines, the combination of Chinese patent medicines with western medicines can significantly lower systolic pressure (SBP) and diastolic pressure (DBP), increase the effective rate of antihypertensive, reduce the incidence of adverse reactions, endothelin-1, and traditional Chinese medicine syndrome scores. Egger's test showed that Songling Xuemaikang capsules reduced SBP and DBP. Tianma Gouteng granules reduced SBP and DBP and increased the effective rate of antihypertensive, and Xinmaitong capsules reduced SBP and increased the effective rate of antihypertensive, without significant publication bias. Songling Xuemaikang capsules increased the effective rate of antihypertensive, and Xinmaitong capsules decreased DBP, with significant publication bias. The results of the GRADE evidence quality evaluation showed that most evidence was at grades B and C. Finally, four strong recommendations and 14 weak recommendations were formed. ConclusionCompared with conventional western medicines for the treatment of hypertension, antihypertensive Chinese patent medicines combined with western medicines have advantages in reducing blood pressure and improving drug use safety, but they are mostly weak recommendations in terms of efficacy, and more high-quality evidence is needed.
5.Comparison between laparoscopic-assisted natural orifice specimen extraction surgery and conventional laparoscopic surgery for left colorectal cancer: 5-year follow-up results of a randomized controlled study
Zhizheng CHEN ; Zhijie DING ; Zhenfa WANG ; Shuzhen XU ; Shifeng ZHANG ; Sibo YUAN ; Feng YAN ; Guoyan LIU ; Xingfeng QIU ; Jianchun CAI
Chinese Journal of Gastrointestinal Surgery 2023;26(8):768-772
Objective:To evaluate the long-term efficacy of laparoscopic-assisted natural orifice specimen extraction surgery (NOSES) colectomy using Cai tube for treating left-sided colorectal cancer.Methods:This was a randomized controlled trial. Inclusion criteria were as follows: preoperative pathological diagnosis of left-sided colorectal adenocarcinoma (rectal, sigmoid colon, descending colon, or left transverse colon cancer with the caudad margin ≥8 cm from the anal margin); preoperative abdominal and pelvic computed tomography (or magnetic resonance imaging) showing maximum tumor diameter <4.5 cm; and BMI <30 kg/m 2. Patients with synchronous multiple primary cancers or recurrent cancers, a history of neoadjuvant chemoradiotherapy, preoperative evidence of significant local infiltration, distant metastasis, or complications such as intestinal obstruction and intestinal perforation, or who were not otherwise considered suitable for laparoscopic surgery were excluded. A random number table was used to randomize sequential patients to NOSES surgery using Cai tube (non-assisted incision anal sleeve: patent number ZL201410168748.2) (NOSES group) or traditional laparoscopic-assisted surgery (CLS group). Relevant clinical data of the two groups of patients were analyzed, the main outcomes being disease-free survival, overall survival, overall recurrence rate, and local recurrence rate 5 years after surgery. Results:Patients in both study groups completed the surgery successfully with no requirement for additional surgery. After mean 70 (7–83) months postoperative follow-up, the 5-year overall postoperative survival in the NOSES and CLS groups was 90.0% and 83.3%, respectively ( P=0.455); disease free survival was 90.0% and 83.3%, respectively ( P=0.455); overall recurrence rate 6.6% and 10.0%, respectively ( P=0.625); and local recurrence rate both were 3.3% ( P=0.990), respectively. None of these differences was statistically significant. Conclusions:NOSES and CLS have similar long-term efficacy, and NOSES deserves to be used in clinical practice.
6.Comparison between laparoscopic-assisted natural orifice specimen extraction surgery and conventional laparoscopic surgery for left colorectal cancer: 5-year follow-up results of a randomized controlled study
Zhizheng CHEN ; Zhijie DING ; Zhenfa WANG ; Shuzhen XU ; Shifeng ZHANG ; Sibo YUAN ; Feng YAN ; Guoyan LIU ; Xingfeng QIU ; Jianchun CAI
Chinese Journal of Gastrointestinal Surgery 2023;26(8):768-772
Objective:To evaluate the long-term efficacy of laparoscopic-assisted natural orifice specimen extraction surgery (NOSES) colectomy using Cai tube for treating left-sided colorectal cancer.Methods:This was a randomized controlled trial. Inclusion criteria were as follows: preoperative pathological diagnosis of left-sided colorectal adenocarcinoma (rectal, sigmoid colon, descending colon, or left transverse colon cancer with the caudad margin ≥8 cm from the anal margin); preoperative abdominal and pelvic computed tomography (or magnetic resonance imaging) showing maximum tumor diameter <4.5 cm; and BMI <30 kg/m 2. Patients with synchronous multiple primary cancers or recurrent cancers, a history of neoadjuvant chemoradiotherapy, preoperative evidence of significant local infiltration, distant metastasis, or complications such as intestinal obstruction and intestinal perforation, or who were not otherwise considered suitable for laparoscopic surgery were excluded. A random number table was used to randomize sequential patients to NOSES surgery using Cai tube (non-assisted incision anal sleeve: patent number ZL201410168748.2) (NOSES group) or traditional laparoscopic-assisted surgery (CLS group). Relevant clinical data of the two groups of patients were analyzed, the main outcomes being disease-free survival, overall survival, overall recurrence rate, and local recurrence rate 5 years after surgery. Results:Patients in both study groups completed the surgery successfully with no requirement for additional surgery. After mean 70 (7–83) months postoperative follow-up, the 5-year overall postoperative survival in the NOSES and CLS groups was 90.0% and 83.3%, respectively ( P=0.455); disease free survival was 90.0% and 83.3%, respectively ( P=0.455); overall recurrence rate 6.6% and 10.0%, respectively ( P=0.625); and local recurrence rate both were 3.3% ( P=0.990), respectively. None of these differences was statistically significant. Conclusions:NOSES and CLS have similar long-term efficacy, and NOSES deserves to be used in clinical practice.
7.Quantitative magnetic susceptibility imaging sequence for intracranial inflammation in patients with optic neuromyelitis
Xinli WANG ; Ning FENG ; Ningning WANG ; Zhizheng ZHUO ; Haoxiao CHANG ; Ai GUO ; Decai TIAN ; Xiaodong ZHU
Chinese Journal of Postgraduates of Medicine 2023;46(8):679-683
Objective:To identify the potential intracranial inflammation in neuromyelitis optica spectrum disorders(NMOSD) patients without supratentorial MRI lesions using quantitative susceptibility mapping (QSM).Methods:Seventy NMOSD patients and 35 age- and gender-matched healthy controls (NC) underwent QSM, 3D-T 1, diffusion MRI from Beijing Tiantan Hospital during June 2019 to June 2021. Susceptibility was compared among NMOSD patients with acute attack (ANMOSD), NMOSD patients in chronic phase (CNMOSD) and NC. The correlation between susceptibility in several brain regions and the cerebrospinal fluid levels of inflammatory makers were analyzed. Results:NMOSD patients showed different susceptibility in several brain regions including bilateral hippocampus, precuneus, right cuneus, putamen, superior parietal and inferior temporal ( P<0.001) and the posr-hoc showed it is higher than normal. Compared to CNMOSD patients, the ANMOSD patients showed increased susceptibility in the cuneus (0.009 ± 0.004 vs. 0.005 ± 0.004, P<0.05). There was significant positive correlations between susceptibility and CSF levels of sTREM2 which reflect the active of microglial cells ( r = 0.494, P<0.05). Conclusions:Despite the absence of supratentorial lesions on MRI, increased susceptibility suggests underlying inflammation in the cerebral cortex in both patients with ANMOSD and CNMOSD, and some of them are obviously related to inflammatory markers in CSF. QSM sequence can be used to explore the potential inflammation in NMOSD patients without obvious supratentorial lesions.
8.A multicenter study of brain T 2WI lesions radiomics machine learning models distinguishing multiple sclerosis and neuromyelitis optica spectrum disorder
Ting HE ; Yi MAO ; Zhi ZHANG ; Zhizheng ZHUO ; Yunyun DUAN ; Lin WU ; Yuxin LI ; Ningnannan ZHANG ; Xuemei HAN ; Yanyan ZHU ; Yao WANG ; Xiao LIANG ; Yongmei LI ; Haiqing LI ; Fuqing ZHOU ; Ya′ou LIU
Chinese Journal of Radiology 2022;56(12):1332-1338
Objective:To investigate the efficacy of a machine learning model based on radiomics of brain lesions on T 2WI in differentiating multiple sclerosis (MS) from neuromyelitis optica spectrum disorders (NMOSD). Methods:Totally 223 MS and NMOSD patients who were treated from January 2009 to September 2018 in Beijing Tiantan Hospital Affiliated to Capital Medical University, Donghu Branch of the First Affiliated Hospital of Nanchang University, Tianjin Medical University General Hospital, and Xuanwu Hospital of Capital Medical University were analyzed retrospectively, and according to the proportion of 7∶3, 223 patients were completely randomly divided into training set (156 cases) and test set (67 cases). A total of 74 patients with MS and NMOSD who were treated in Huashan Hospital Affiliated to Fudan University and China-Japan Friendship Hospital of Jilin University from January 2009 to September 2018 and in Xianghu Branch of the First Affiliated Hospital of Nanchang University from March 2020 to September 2021 were collected as an independent external validation set. All patients underwent brain cross-sectional MR T 2WI, radiomics features were extracted from T 2WI, and features were selected by max-relevance and min-redundancy and least absolute shrinkage and selection operator algorithms. Then various machine learning classifier models (logistic regression, decision tree, AdaBoost, random forest or support vector machine) were constructed to differentiate MS from NMOSD. The area under curve (AUC) of receiver operating characteristics was used to evaluate the performance of each classifier model in the training set, test set and external validation set. Results:Based on multi-center T 2WI, a total of 11 radiomics features related to the discrimination between MS and NMOSD were extracted and classifier models were constructed. Among them, the random forest model had the best efficiency in distinguishing MS from NMOSD, and its AUC values for distinguishing MS from NMOSD in the training set, test set and external validation set were 1.000, 0.944 and 0.902, with specificity of 100%, 76.9% and 86.0%, and sensitivity of 100%, 92.1% and 79.7%, respectively. Conclusion:The random forest model based on the radiomic features of T 2WI of brain lesions can effectively distinguish MS from NMOSD.
9.Clinical research on rhubarb powder modulated by different excipients to intervene solid constipation in cancer patients undergoing chemotherapy
Kun WANG ; Yanli HOU ; Hong JU ; Zhiqiang SONG ; Zhizheng ZHAO
Chinese Journal of Modern Nursing 2022;28(35):4954-4958
Objective:To explore the effects of different excipients and rhubarb powder in interfering with TCM solid constipation in cancer patients undergoing chemotherapy.Methods:Totally 120 tumor patients who developed solid constipation after chemotherapy during hospitalization from May 2019 to May 2021 in the Department of Oncology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences by convenience sampling and divided into an observation group and a control group according to the random number table, with 60 cases in each group. On the basis of the routine treatment and nursing protocol, patients in the control group received acupoint sticking with Kaisailu and rhubarb powder, and patients in the observation group were treated with sesame oil and rhubarb powder for acupoint sticking. The effective rate of treatment, the score of Cleveland Constipation Score (CCS), and the incidence of adverse reactions were compared between the two groups.Results:After the intervention, the total effective rate in the observation group was higher than in the control group, the CCS score and the incidence of adverse reactions were lower than those of the control group, with statistically significant differences ( P<0.05) . Conclusions:Acupoint sticking of rhubarb prepared with sesame oil can better relieve chemotherapy-induced constipation than that prepared with Kaisailu, and the adverse reactions rate is low.
10.Development of the triazole-fused pyrimidine derivatives as highly potent and reversible inhibitors of histone lysine specific demethylase 1 (LSD1/KDM1A).
Zhonghua LI ; Lina DING ; Zhongrui LI ; Zhizheng WANG ; Fengzhi SUO ; Dandan SHEN ; Taoqian ZHAO ; Xudong SUN ; Junwei WANG ; Ying LIU ; Liying MA ; Bing ZHAO ; Pengfei GENG ; Bin YU ; Yichao ZHENG ; Hongmin LIU
Acta Pharmaceutica Sinica B 2019;9(4):794-808
Histone lysine specific demethylase 1 (LSD1) has been recognized as an important modulator in post-translational process in epigenetics. Dysregulation of LSD1 has been implicated in the development of various cancers. Herein, we report the discovery of the hit compound (IC = 3.93 μmol/L) and further medicinal chemistry efforts, leading to the generation of compound (IC = 49 nmol/L, and = 16 nmol/L), which inhibited LSD1 reversibly and competitively with H3K4me2, and was selective to LSD1 over MAO-A/B. Docking studies were performed to rationalize the potency of compound . Compound also showed strong antiproliferative activity against four leukemia cell lines (OCL-AML3, K562, THP-1 and U937) as well as the lymphoma cell line Raji with the IC values of 1.79, 1.30, 0.45, 1.22 and 1.40 μmol/L, respectively. In THP-1 cell line, significantly inhibited colony formation and caused remarkable morphological changes. Compound induced expression of CD86 and CD11b in THP-1 cells, confirming its cellular activity and ability of inducing differentiation. The findings further indicate that targeting LSD1 is a promising strategy for AML treatment, the triazole-fused pyrimidine derivatives are new scaffolds for the development of LSD1/KDM1A inhibitors.

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