1.Herbal Textual Research on Bletillae Rhizoma in Famous Classical Formulas
Dan ZHAO ; Tao ZHOU ; Chaolei LUO ; Dewei GAN ; Lingling LIU ; Chuanzhi KANG ; Zhikun WU ; Xu LI ; Yan FU ; Guoqiong CAO ; Yongping ZHANG ; Chenghong XIAO ; Zhilai ZHAN
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(4):77-88
In order to provide basic information for the utilization and development of famous classical formulas containing Bletillae Rhizoma, this article systematically analyzes the historical evolution of the name, origin, harvesting and processing of Bletillae Rhizoma by reviewing the ancient materia medica, prescription books, medical books and modern literature. The research results showed that Baiji(白及) was the main name, some scholars took Baiji(白芨) as its main name, and there were many other names such as Baiji(白给), Baigen(白根), Baiji(白苙). The mainstream source of Bletillae Rhizoma was the tubers of Bletilla striata, and drying, large, white, solid, root-free and skin removed completely were the good quality standards. With the promotion of wild to cultivated medicinal materials, there were certain differences between their traits, and the quality evaluation indexes should be adjusted accordingly. The origin of records in the past dynasties was widely distributed, with Guizhou and Sichuan having high production and good quality in modern times. The harvesting period is mostly in spring and autumn, and harvested in autumn was better. The processing and processing technology is relatively simple, and it was used fresh or powdered in past dynasties, while it is mainly sliced for raw use in modern times. Based on the results, it is suggested that the tubers of Bletilla striata of Orchidaceae should be used in the famous classical formulas, and it should be uniformly written as Baiji(白及). And if the original formula indicates the requirement of processing, it should be operated according to the requirement, if the requirement of processing is not indicated, it can be used in raw form as medicine.
2.Preparation and characterization of curcumin nanomicelles and evaluation of in vitro hepatoprotective activity against alcohol liver disease
Luhui LI ; Guangping GENG ; Lei XU ; Zhikun ZHANG ; Xiaohui PU
China Pharmacy 2024;35(10):1203-1208
OBJECTIVE To prepare and characterize curcumin nanomicelles (hereinafter referred to as Cur/mPEG-PBLA micelles), and to evaluate the in vitro hepatoprotective activity against alcohol liver disease (ALD). METHODS Cur/mPEG-PBLA micelles were prepared with the dialysis method using methoxy-poly(ethylene glycol)-poly(β-benzyl-L-aspartate) (mPEG-PLGA) as the carrier. The appearance and microscopic morphology of Cur/mPEG-PBLA micelles were observed, and particle size, polydispersity index, Zeta potential, encapsulation efficiency and drug loading content were all detected. The in vitro release, pH stability, thermal stability, dilution stability, storage stability, plasma stability tests, and hemolysis experiments were all performed. The cell model of ALD was established with anhydrous ethanol intervention using human liver cancer cells and normal liver cells as objects, Cur reference solution as reference, to evaluate in vitro preventive and ameliorative effects of Cur/mPEG- PBLA micelles on ALD. RESULTS The prepared Cur/mPEG-PBLA micelles exhibited a pale-yellow milky light, with a spherical shape and uniform distribution. The average particle size was about 140 nm, and the polydispersity index was less than 0.3. Zeta potential was (-8.15±0.05) mV; the encapsulation efficiency was (73.26±3.16)%, and the drug loading content was (4.87± 0.42)%. The cumulative release of Cur reference substance was close to 80% at 10 h; the cumulative release of Cur/mPEG-PBLA micelles at 8 h was 28.94% and only 48.25% at 48 h. pH stability and thermal stability of Cur/mPEG-PBLA micelles were better than those of Cur reference solution; Cur/mPEG-PBLA micelles showed good dilution stability, storage stability and plasma stability, and would not cause hemolysis. Cur reference solution and Cur/mPEG-PBLA micelles had varying degrees of in vitro preventive and ameliorative effects on ALD in two types of cells; after 48 h of application, the above effects of Cur/mPEG-PBLA micelles were significantly better than those of Cur reference solution at the same mass concentration (P<0.05). CONCLUSIONS Cur/mPEG-PBLA micelles can improve pH stability and thermal stability of Cur, delayits degradation rate, and have better in vitro hepatoprotective activity against ALD.
3.Clinical Manifestations,Molecular Genetics and Gonadal Pathology of 416 Patients with Disorders of Sex Development:A Single-Center Cohort Study
Wanjun LIN ; Cuili LIANG ; Wen FU ; Liyu ZHANG ; Wei JIA ; Jinhua HU ; Wen ZHANG ; Yunting LIN ; Huilin NIU ; Liping FAN ; Zhikun LU ; Duan LI ; Zongcai LIU ; Huiying SHENG ; Xi YIN ; Xiaodan CHEN ; Guochang LIU ; Jing CHENG ; Li LIU
JOURNAL OF RARE DISEASES 2024;3(3):310-317
Objective To investigate the clinical manifestations,molecular genetics and gonadal pathol-ogy characteristics of patients with disorders of sex development(DSD),and to summarize the clinical experi-ence of identifying rare diseases from common symptoms.Methods The clinical data of 416 patients with DSD diagnosed and treated in the multidisciplinary center of DSD of Guangzhou Women and Children's Medical Cen-ter from May 2018 to August 2023 were retrospectively analyzed,summarized and discussed.Results Accord-ing to chromosome karyotype,416 cases of DSD were classified into three types:92 cases(22.1%)of abnormal sex chromosome karyotype,285 cases(68.5%)of 46,XY karyotype and 39 cases(9.4%)of 46,XX karyotype.Among the 92 patients with abnormal sex chromosome karyotype,59 cases were raised as males,18 cases(30.5%)complained of short penis with hypospadias and cryptorchidism.The most common karyotype was 45,X/46,XY(58 cases,63.0%).Among the 285 patients with 46,XY karyotype,238 cases were raised as males,and 63 cases(26.5%)complained of short penis and hypospadias;47 cases were raised as females,and 13 ca-ses(27.7%)complained of inguinal mass.A total of 216 patients with 46,XY karyotype were subjected to whole exome gene detection,and 155 cases(71.8%)were found to have molecular pathogenesis with the clinical phe-notype.Among the 39 patients with 46,XX karyotype,19 cases were raised as males,and 8 cases(42.1%)com-plained of short penis and hypospadias.In the 18 cases of gonad biopsy,17 cases showed testicular tissue in go-nads.Whole exome sequencing was performed in 14 cases.NR5A1 gene heterozygous mutation,SRY gene muta-tion and SOX3 gene mutation were found in 2 cases,respectively(14.3%).Twenty cases were raised as females,and 14 cases(70.0%)complained of clitoral hypertrophy.Gonad biopsy was performed in 8 cases,with 7 cases of ovotestis(87.5%)and 1 case of NR5A1 gene heterozygous mutation(14.3%).Conclusions The etiologies of DSD are complex and diverse,and the clinical manifestations are various,which can be manifested as hypospa-dias,micropenis,cryptorchidism and other common symptoms of the urinary system.Different etiologies have dif-ferent treatment options.Therefore,chromosome karyotype,molecular genetic testing and gonadal pathology can be used to clarify the cause of disease,especially for rare diseases,improve the detection rate,reduce the rate of missed diagnosis,and ensure reasonable treatment,especially sex selection.
4.Study on gene mutation characteristics and its correlation with immunological markers in small cell lung cancer
Xuanpeng WU ; Zhikun JIA ; Tao JIANG ; Fei XUE ; Guangjian ZHANG ; Junke FU ; Xi LIU ; Qifei WU
Journal of Clinical Surgery 2024;32(11):1162-1165
Objective To investigate the relationship between gene mutation characteristics and immunological markers in patients with small cell lung cancer.Methods From January 2019 to 2020,155 patients with small cell lung cancer were admitted.Gene mutations were detected in these patients using target gene capture and sequencing method.Moreover,the tumor mutational burden(TMB)and expression of PD-L1 in some patients were detected.Results A total of 326 gene mutations were detected in the patients,the most significant of which were TP53 and RB1.Among the 8 genes with mutation frequency higher than 15%,patients with KMT2D,KMT2C,FAT1 and NOTCH1 mutations had higher TMB than those without mutation,and the difference was statistically significant(P<0.05).Conclusion The most common mutated genes in patients with small cell lung cancer are TP53 and RB1.KMT2D,KMT2C,FAT1 and NOTCH1 may be potential markers for the efficacy of immunotherapy in small cell lung cancer.
5.Establishment of MRI classification for traumatic osteonecrosis of the femoral head and its correlation with femoral head collapse
Zhikun ZHUANG ; Ziqi LI ; Shihua GAO ; Hanglin QIU ; Zhiqing XU ; Zhibing GONG ; Qingwen ZHANG ; Zhaoke WU ; Wei HE
Chinese Journal of Orthopaedics 2024;44(13):881-888
Objective:To establish a classification system for the repair band in the subchondral bone origination point in MRI for traumatic osteonecrosis of the femoral head (ONFH) and preliminarily explore the correlation between this classification and the progression of femoral head collapse.Methods:A retrospective analysis was conducted on 73 cases of traumatic ON-FH treated at the Quanzhou Orthopedic-traumatological hospital from January 2000 to December 2019. Among them, there were 46 males and 27 females with an average age of 34.9±8.3 years (range 19-55 years). Clinical and radiological data such as age, gender, side, fracture classification, reduction quality, JIC classification, and bone repair band (BRB) classification were recorded. The progression of traumatic ONFH was assessed using the ARCO staging system, with stages IIIA and IIIB defined as mild collapse and progressive collapse, respectively. The BRB classification was established based on MRI findings, and the inter- and intra-observer consistency of the BRB classification was analyzed using Kappa test. The correlation between the BRB classification and progressive femoral head collapse was analyzed using the Kaplan-Meier survival curve and binary variable Cox regression analysis.Results:According to the BRB classification, 73 cases were divided into type 1 with superficial lesion in 38.4%, type 2 with uncertain lesion in 21.9%, and type 3 with extensive lesion in 39.7%. The inter-observer consistency Kappa value for the BRB classification was 0.798, and the intra-observer consistency Kappa value was 0.896, indicating a high level of consistency. A follow-up of 73 cases (54.8±34.9 months, range 24-165 months) showed a significant correlation between the BRB classification and ARCO staging at the last follow-up (χ 2=37.556, P<0.001), with progression to stages IIIA and IIIB as follows: type 1 had 3 and 1 cases, type 2 had 4 and 1 cases, and type 3 had 14 and 12 cases, respectively. Using the occurrence of progressive collapse (stage IIIB) as the endpoint, the risk of progression to stage IIIB for type 2 was not statistically different from type 1 [ HR=1.766, 95% CI (0.465, 6.702), P=0.403]; the risk of progression to stage IIIB for type 3 was significantly higher than for type 1 [ HR=15.126, 95% CI (4.708, 48.592), P<0.001]. Conclusion:The BRB classification is closely related to the progression of traumatic ONFH and is an independent risk factor for predicting the occurrence of progressive collapse; this classification is helpful for early diagnosis and predicting the progression of collapse and treatment plan decision-making.
6.Deciphering the placental abnormalities associated with somatic cell nuclear transfer at single-nucleus resolution.
Liyuan JIANG ; Xin WANG ; Leyun WANG ; Sinan MA ; Yali DING ; Chao LIU ; Siqi WANG ; Xuan SHAO ; Ying ZHANG ; Zhikun LI ; Wei LI ; Guihai FENG ; Qi ZHOU
Protein & Cell 2023;14(12):924-928
7.Oridonin restores hepatic lipid homeostasis in an LXRα-ATGL/EPT1 axis-dependent manner
Yulian CHEN ; Huanguo JIANG ; Zhikun ZHAN ; Jindi LU ; Tanwei GU ; Ping YU ; Weimin LIANG ; Xi ZHANG ; Shilong ZHONG ; Lan TANG
Journal of Pharmaceutical Analysis 2023;13(11):1281-1295
Hepatosteatosis is characterized by abnormal accumulation of triglycerides(TG),leading to prolonged and chronic inflammatory infiltration.To date,there is still a lack of effective and economical therapies for hepatosteatosis.Oridonin(ORI)is a major bioactive component extracted from the traditional Chinese medicinal herb Rabdosia rubescens.In this paper,we showed that ORI exerted significant protective ef-fects against hepatic steatosis,inflammation and fibrosis,which was dependent on LXRα signaling.It is reported that LXRα regulated lipid homeostasis between triglyceride(TG)and phosphatidylethanol-amine(PE)by promoting ATCL and EPT1 expression.Therefore,we implemented the lipidomic strategy and luciferase reporter assay to verify that ORI contributed to the homeostasis of lipids via the regulation of the ATGL gene associated with TG hydrolysis and the EPT1 gene related to PE synthesis in a LXRα-dependent manner,and the results showed the TG reduction and PE elevation.In detail,hepatic TG overload and lipotoxicity were reversed after ORI treatment by modulating the ATCL and EPT1 genes,respectively.Taken together,the data provide mechanistic insights to explain the bioactivity of ORI in attenuating TG accumulation and cytotoxicity and introduce exciting opportunities for developing novel natural activators of the LXRα-ATGL/EPT1 axis for pharmacologically treating hepatosteatosis and metabolic disorders.
8.The value of risk stratification of nomogram for post-mastectomy radiotherapy in patients with pT 1-2N 1M 0 breast cancer
Jie KONG ; Chao WEI ; Huina HAN ; Xue WANG ; Zimeng GAO ; Danyang WANG ; Jun ZHANG ; Zhikun LIU
Chinese Journal of Radiation Oncology 2023;32(9):812-819
Objective:To investigate the high-risk factors affecting the prognosis of patients with pT 1-2N 1M 0 after mastectomy, establish a nomogram prediction model, perform risk stratification, and screen the radiotherapy benefit populations. Methods:Clinical data of 936 patients with pT 1-2N 1M 0 breast cancer undergoing mastectomy in the Fourth Hospital of Hebei Medical University from January 2010 to December 2016 were retrospectively analyzed and 908 cases had complete follow-up data. They were divided into the radiotherapy (RT) group ( n=583) and non radiotherapy (NRT) group ( n=325) according to the radiotherapy. After propensity score matching (PSM) was performed 1 vs. 1, 298 cases were assigned into the RT group and 298 in the NRT group. Overall survival (OS) and disease-free survival (DFS) were compared between two groups using log-rank test. Nomogram prediction model was established, the survival differences were compared among different risk groups, and the radiotherapy benefit populations were screened. Results:Univariate analysis showed that the 5- and 8-year OS and DFS in the RT group were significantly better than those in the NRT group (both P<0.001). Multivariate analysis showed that age, tumor quadrant, number of lymph node metastases, T staging, and Ki-67 level were the independent prognostic factors for OS. Age, tumor quadrant, and T staging were the independent prognostic factors for DFS. The OS nomogram analysis showed that the OS of patients in the high-risk group was significantly improved by post-mastectomy radiotherapy (PMRT) ( P=0.001), while PMRT did not show an advantage in the low- and medium-risk groups ( P=0.057, P=0.099). The DFS nomogram analysis showed that DFS was significantly improved by PMRT in patients in the medium- and high-risk groups ( P=0.036, P=0.001), whereas the benefits from PMRT were not significant in the low-risk group ( P=0.475). Conclusions:For patients with pT 1-2N 1M 0 breast cancer after mastectomy, age ≤ 40 years, tumor located in the inner quadrant or central area, T 2 staging, 2-3 lymph node metastases, Ki-67>30% are the high-risk factors affecting clinical prognosis. The nomogram prediction model can screen the populations that can benefit from PMRT, providing reference for clinical decision-making.
9.Diagnostic value of two-dimensional ultrasound combined with volume contrast imaging and MRI in fetal corpus callosum dysplasia
Dexuan KONG ; Xiaoyan HE ; Huidong LI ; Zhikun ZHANG
International Journal of Biomedical Engineering 2022;45(5):414-418
Objective:To investigate the diagnostic value of two-dimensional ultrasound combined with volumetric contrast imaging (VCI) and magnetic resonance imaging (MRI) for the developmental abnormalities of the fetal corpus callosum.Methods:Seventy-three fetuses who underwent cranial MRI within 1 week after suspected fetal corpus callosum dysplasia on ultrasound and received a definitive diagnosis in the neonatal period were retrospectively recruited for the study. The fetal corpus callosum was observed in the transverse, coronal, and sagittal views of the fetus, and the hyaline septal cavity, lateral ventricle, third ventricle, and corpus callosum were observed in the MRI scan. The diagnostic results and sensitivity of two-dimensional ultrasound combined with volumetric contrast imaging and MRI were analyzed.Results:Neonatal imaging showed that among 73 fetuses, 32 had agenesis of the corpus callosum, 29 had hypoplasia of the corpus callosum, and 12 had normal development of the corpus callosum. The differences in diagnostic results and sensitivity between 2D ultrasound combined with volumetric contrast imaging and MRI testing for agenesis of the corpus callosum were not statistically significant (all P>0.05), and the differences in diagnostic results and sensitivity for hypoplasia of the corpus callosum were statistically significant ( P<0.05). Conclusions:Both 2D ultrasound combined with volumetric contrast imaging and MRI are of high value for the diagnosis of partial-type agenesis of the corpus callosum, but MRI is more advantageous for the diagnosis of agenesis of the corpus callosum, and MRI can be a useful supplement and verification tool for ultrasound to provide a more accurate clinical diagnosis.
10.Prognostic analysis of patients with brain metastases from non-small cell lung cancer treated with supplemental radiotherapy under different prognostic scores
Dongxing SHEN ; Zhikun LIU ; Zhensheng LI ; Huina HAN ; Yuguang SHANG ; Longyu ZHU ; Deyou KONG ; Andu ZHANG ; Jie KONG ; Jian ZHANG ; Fang YANG ; Fuyin QU ; Jun ZHANG
Chinese Journal of Radiation Oncology 2022;31(2):131-137
Objective:To analyze the prognosis and influencing factors of different radiotherapy modes in patients with brain metastases from non-small cell lung cancer (NSCLC), and to explore the best benefit population with radiotherapy boost under different prognostic scores.Methods:634 patients with brain metastasis from NSCLC admitted to the Fourth Hospital of Hebei Medical University from 2013 to 2015 were analyzed retrospectively. According to different radiotherapy modes, they were divided into three groups: no radiotherapy group ( n=330), whole-brain radiotherapy group (WBRT)( n=127) and whole-brain radiotherapy combined with boost group (WBRT+ boost)( n=177). The intracranial progression-free survival (iPFS) and overall survival (OS) were calculated by Kaplan-Meier method. The multivariate prognostic factors were analyzed by the Cox models. Results:The median iPFS and OS of all patients were 6.9 months and 9.0 months, respectively. In the no radiotherapy, WBRT and WBRT+ boost groups, the 1-year iPFS was 15.1%, 16.3% and 40.2%( P=0.002), and the 1-year OS was 33.7%, 38.2% and 48.1%( P<0.001), respectively. Multivariate survival analysis demonstrated that different radiotherapy modes were the independent factors affecting iPFS and OS. Subgroup analysis revealed that for patients with 1-3 brain metastases, the 1-year OS and iPFS in the WBRT+ boost group were better than those of WBRT alone ( P=0.026, P=0.044) when GPA score was 2.5-4.0; the 1-year OS and iPFSin the WBRT+ boost group were better than those of WBRT alone ( P=0.036, P=0.049) when there was no targeted therapy; for patients with ≥4 brain metastases, the 1-year iPFS in the WBRT+ boost group was better than that of WBRT alone ( P=0.019, P=0.012) when GPA score was 2.5-4.0 and there was no targeted therapy. When the GPA score was 0-2 or there was targeted therapy, the 1-year OS and iPFS in the WBRT+ boost group were better than those of WBRT alone, but the difference was not statistically significant (all P>0.05). Conclusions:Radiotherapy can significantly improve the iPFS and OS of NSCLC patients with brain metastases. When the number of brain metastases is 1-3, GPA score is 2.5-4.0 or no targeted therapy, boost may improve the iPFS and OS; when the number of brain metastases is more than 4, GPA score is 2.5-4.0 or no targeted therapy, boost may only bring iPFS benefit; when GPA score is 0-2 or targeted therapy, boost may not benefit significantly.

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