1.miR-4645-5p regulates malignant biological behavior of esophageal cancer cells by targeting MUC16
Zhen ZHOU ; Linna JIANG ; Peng HE ; Feng YIN ; Ping WEI ; Xin AN ; Xianghong LI
International Journal of Laboratory Medicine 2024;45(1):54-59
Objective To investigate the effect of microRNA(miR)-4645-5p on the proliferation,invasion and epithelial-mesenchymal transition of esophageal cancer cells by targeting mucin 16(MUC16)and its mo-lecular mechanism.Methods The expression of miR-4645-5p in esophageal cancer tissues was analyzed online by TCGA database.The expression level of miR-4645-5p in esophageal cancer cell lines was analyzed by fluo-rescent real-time fluorescence quantitative polymerase chain reaction(qPCR).KYSE-30 cells were transfected with miR-4645-5p mimic and negative control mimic by lipofection technology,and were divided into miR-4645-5p group and control mimic group.The proliferation ability,migration ability and invasion ability of transfected KYSE-30 cells were analyzed by CCK-8 method,scratch test and Transwell test respectively.The target gene of miR-4645-5p was predicted by the bioinformatics website,and the binding of miR-4645-5p to the target gene was detected by the dual-luciferase reporter gene assay.The expression level of MUC16 mR-NA was detected by qPCR,and the protein expression levels of MUC16,transcription factor-1(ZEB-1),zonal atresia protein(ZO-1),tight junction protein-1(Claudin-1)and α-smooth muscle actin(α-SMA)were detected by Western blotting.Results The expression level of miR-4645-5p in esophageal cancer tissues was signifi-cantly lower than that in adjacent tissues(P<0.01).Compared with HET-1 A,the expression of miR-4645-5p was lower in esophageal cancer cell lines(P<0.05).After overexpression of miR-4645-5p,the proliferation a-bility of KYSE-30 cells was significantly reduced(P<0.05),the migration ability was significantly reduced(P<0.01)and the invasion ability was significantly reduced(P<0.01).miR-4645-5p targeted and negatively regulated the expression of MUC16 mRNA(P<0.01).After overexpression of miR-4645-5p,the protein ex-pression levels of MUC16,ZEB-1 and α-SMA were all down-regulated,and the protein expression levels of ZO-1 and Claudin-1 were up-regulated.Conclusion miR-4645-5p regulates the malignant biological behavior of esophageal cancer KYSE-30 cells by targeting MUC16.
2.Polycystin-2 Ion Channel Function and Pathogenesis in Autosomal Dominant Polycystic Kidney
Kai WANG ; Yuan HUANG ; Ce-Fan ZHOU ; Jing-Feng TANG ; Xing-Zhen CHEN
Progress in Biochemistry and Biophysics 2024;51(1):47-58
Polycystin-2 (also known as PC2, TRPP2, PKD2) is a major contributor to the underlying etiology of autosomal dominant polycystic kidney disease (ADPKD), which is the most prevalent monogenic kidney disease in the world. As a transient receptor potential (TRP) channel protein, PC2 exhibits cation-permeable, Ca2+-dependent channel properties, and plays a crucial role in maintaining normal Ca2+ signaling in systemic physiology, particularly in ADPKD chronic kidney disease. Structurally, PC2 protein consists of six transmembrane structural domains (S1-S6), a polycystin-specific “tetragonal opening for polycystins” (TOP) domain located between the S1 and S2 transmembrane structures, and cytoplasmic N- and C-termini. Although the cytoplasmic N-terminus and C-terminus of PC2 may not be significant in the gating of PC2 channels, there is still much protein structural information that needs to be thoroughly investigated, including the regulation of channel function and the assembly of homotetrameric ion channels. This is further supported by the presence of human disease-associated mutation sites on the PC2 structure. Moreover, PC2 synthesized in the endoplasmic reticulum is enriched in specific subcellular localization via membrane transport and can assemble itself into homotetrameric ion channels, as well as form heterotrimeric receptor-ion channel complexes with other proteins. These complexes are involved in a wide range of physiological functions, including the regulation of mechanosensation, cell polarity, cell proliferation, and apoptosis. In particular, PC2 assembles with chaperone proteins to form polycystic protein complexes that affect Ca2+ transport in cell membranes, cilia, endoplasmic reticulum, and mitochondria, and are involved in activating cell fate-related signaling pathways, particularly cell differentiation, proliferation, survival, and apoptosis, and more recently, autophagy. This leads to a shift of cystic cells from a normal uptake, quiescent state to a pathologically secreted, proliferative state. In conclusion, the complex structural and functional roles of PC2 highlight its critical importance in the pathogenesis of ADPKD, making it a promising target for therapeutic intervention.
3.Clinical trial of Morinda officinalis oligosaccharides in the continuation treatment of adults with mild and moderate depression
Shu-Zhe ZHOU ; Zu-Cheng HAN ; Xiu-Zhen WANG ; Yan-Qing CHEN ; Ya-Ling HU ; Xue-Qin YU ; Bin-Hong WANG ; Guo-Zhen FAN ; Hong SANG ; Ying HAI ; Zhi-Jie JIA ; Zhan-Min WANG ; Yan WEI ; Jian-Guo ZHU ; Xue-Qin SONG ; Zhi-Dong LIU ; Li KUANG ; Hong-Ming WANG ; Feng TIAN ; Yu-Xin LI ; Ling ZHANG ; Hai LIN ; Bin WU ; Chao-Ying WANG ; Chang LIU ; Jia-Fan SUN ; Shao-Xiao YAN ; Jun LIU ; Shou-Fu XIE ; Mao-Sheng FANG ; Wei-Feng MI ; Hong-Yan ZHANG
The Chinese Journal of Clinical Pharmacology 2024;40(6):815-819
Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P<0.05).After continuation treatment,the remission rate was 54.59%(202 cases/370 cases),and the recurrence rate was 6.49%(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35%(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.
4.Determination of lacidipine in Beagle dog plasma by UHPLC-MS/MS method
Yan-Yan WANG ; Yi-Hong JIANG ; Xiao-Ying ZHAO ; Zhen-Yu ZHOU ; Xiao-Hong LI ; Cheng-Da YAN ; Feng QIN
The Chinese Journal of Clinical Pharmacology 2024;40(20):3038-3041
Objective To establish an ultra high performance liquid chromatography-tandem mass spectrometry method for the determination of lacidipine in plasma of beagle dogs was established.Methods It was pretreated by protein precipitation method and the internal standard was nimodipine.Chromatographic column:ACQUITYUPLC? BEH C8(2.1 mm x50.0 mm,1.7 μm),mobile phase:100%water containing 5 mmol·L-1 ammonium acetate-100%acetonitrile,flow rate:0.7 mL·min-1,column temperature:40 ℃,automatic injector temperature:4 ℃,injection volume:20 μL.Electrospray ionization source,positive ion mode,multi-reaction monitoring.The specificity,residual effect,standard curve and quantitative lower limit,precision and recovery,matrix effect and stability of the method were investigated.Results Lacidipine has a good linear relationship in the range of 0.10-50.0 ng·mL-1,r=0.996 6,the lower limit of quantification was 0.10 ng·mL-1.The specificity was good.The intra-and inter-relative standard deviation was less than 12%.The extraction recovery was higher than 80%,and the stability was good.Conclusion The method has the advantages of high sensitivity,simple operation and short analysis time,and was suitable for the pharmacokinetic study of lacidipine in Beagle dog plasma.
5.Secondary metabolites and their α-glucosidase inhibitory activity of endophyte fungi from Orixa japonica
Pei-Feng ZHOU ; Yong-Zhong LU ; Xiao-Jie WANG ; Yan LI ; Zhen ZHANG
Chinese Traditional Patent Medicine 2024;46(2):478-483
AIM To identify the endophytic fungus G-(JK)-2 from Orixa japonica Thunb.and to study its secondary metabolites and their α-glucosidase inhibitory activities.METHODS Through the ITS sequence,the evolutionary tree that identifies the endophytic fungus G-(JK)-2 was established.Then 45 days rice solid medium of endophytic fungus G-(JK)-2 was extracted by methanol,and then by ethyl acetate.The ethyl acetate extract was separated and purified by silica gel chromatography,Sephadex LH-20,and semi-preparative HPLC.The structures of obtained compounds were identified by physicochemical properties and spectral data.Their α-glucosidase inhibitory activities were evaluated by PNPG method.RESULTS The endophytic fungus G-(JK)-2 from O.japonica was identified as Fusarium nematophilum.Thirteen compounds were isolated and identified as p-hydroxybenzaldehyde(G1),4-hydroxyacetophenone(G2),anhydromevalonolactone(G3),flazine(G4),salicylic acid(G5),p-hydroxybenzoic acid(G6),di-(2-ethylhexyl)-phthalate(G7),terephthalic acid bis(2-ethyl-hexyl)ester(G8),thymine(G9),uridine(G10),adenosine(G11),2′-deoxyuridine(G12),nicotinic acid(G13).The inhibitory effect of each compound on α-glucosidase was in sequence of G4>G11>G10>G13>G12.CONCLUSION All compounds are first isolated from the endophytic fungi of the O.japonica,and G10,G11,G13 are first isolated from the endophytic fungi of Fusarium.G4 and G11 have mild inhibition to α-glucosidase.
6.Expert consensus on the diagnosis and treatment of osteoporotic proximal humeral fracture with integrated traditional Chinese and Western medicine (version 2024)
Xiao CHEN ; Hao ZHANG ; Man WANG ; Guangchao WANG ; Jin CUI ; Wencai ZHANG ; Fengjin ZHOU ; Qiang YANG ; Guohui LIU ; Zhongmin SHI ; Lili YANG ; Zhiwei WANG ; Guixin SUN ; Biao CHENG ; Ming CAI ; Haodong LIN ; Hongxing SHEN ; Hao SHEN ; Yunfei ZHANG ; Fuxin WEI ; Feng NIU ; Chao FANG ; Huiwen CHEN ; Shaojun SONG ; Yong WANG ; Jun LIN ; Yuhai MA ; Wei CHEN ; Nan CHEN ; Zhiyong HOU ; Xin WANG ; Aiyuan WANG ; Zhen GENG ; Kainan LI ; Dongliang WANG ; Fanfu FANG ; Jiacan SU
Chinese Journal of Trauma 2024;40(3):193-205
Osteoporotic proximal humeral fracture (OPHF) is one of the common osteoporotic fractures in the aged, with an incidence only lower than vertebral compression fracture, hip fracture, and distal radius fracture. OPHF, secondary to osteoporosis and characterized by poor bone quality, comminuted fracture pattern, slow healing, and severely impaired shoulder joint function, poses a big challenge to the current clinical diagnosis and treatment. In the field of diagnosis, treatment, and rehabilitation of OPHF, traditional Chinese and Western medicine have accumulated rich experience and evidence from evidence-based medicine and achieved favorable outcomes. However, there is still a lack of guidance from a relevant consensus as to how to integrate the advantages of the two medical systems and achieve the integrated diagnosis and treatment. To promote the diagnosis and treatment of OPHF with integrated traditional Chinese and Western medicine, relevant experts from Orthopedic Expert Committee of Geriatric Branch of Chinese Association of Gerontology and Geriatrics, Youth Osteoporosis Group of Orthopedic Branch of Chinese Medical Association, Osteoporosis Group of Orthopedic Surgeon Branch of Chinese Medical Doctor Association, and Osteoporosis Committee of Shanghai Association of Integrated Traditional Chinese and Western Medicine have been organized to formulate Expert consensus on the diagnosis and treatment of osteoporotic proximal humeral fracture with integrated traditional Chinese and Western medicine ( version 2024) by searching related literatures and based on the evidences from evidence-based medicine. This consensus consists of 13 recommendations about the diagnosis, treatment and rehabilitation of OPHF with integrated traditional Chinese medicine and Western medicine, aimed at standardizing, systematizing, and personalizing the diagnosis and treatment of OPHF with integrated traditional Chinse and Western medicine to improve the patients ′ function.
7.Research on sperm morphological classification based on convolutional neural network
Dian YU ; Feng-Ya LU ; Zhen-Sheng ZHONG ; Yi WANG ; Jin-Hua ZHOU
Chinese Medical Equipment Journal 2024;45(10):7-13
Objective To propose a sperm classification model based on convolutional neural network to enhance the accuracy of sperm morphological classification.Methods A FT-EfficientNet model was constructed using EfficientNetB0 as the base model,which was fine-tuned by data preprocessing enhancement,transfer learning and cosine decay.Classification experi-ments were performed on the sperm public datasets SCIAN-Morpho and HuSHeM,and the datasets were segmented and vali-dated using 5-fold cross-validation.The classification results by the FT-EfficientNet model were compared with those by the cascade ensemble of support vector machines(CE-SVM)model,the adaptive patch-based dictionary learning(APDL)model,fine tuning of visual geometry group(FT-VGG)model,morphological classification of human sperm heads(MH-HSH)model and transfer learning(TL)model.Ablation experiments were performed in the SCIAN-Morpho dataset to verify the effect of different fine-tuning methods on the model.Results The FT-EfficientNet model proposed had the accuracy,precision and F1 score on the SCIAN-Morpho validation set being 64.1%,63.8%and 64.8%,respectively,which were better than CE-SVM,APDL,FT-VGG and MC-HSH models.The recall rate of the model proposed(65.2%)was slightly lower than that of MC-HSH model(68.0%).The accuracy,precision,F1 score and recall rate on the HuSHeM validation set was 95.4%,95.8%,95.4%and 96.0%,respectively,which were slightly lower than those of TL model while better than those of CE-SVM,APDL,FT-VGG and MC-HSH models.Ablation experiments showed the FT-EfficientNet model behaved the best in fine-tuning.Conclusion The sperm classification model based on convolutional neural network facilitates sperm morphology classification with high accuracy and performance.[Chinese Medical Equipment Journal,2024,45(10):7-13]
8.Exploration of index system for localized computer screening and diagnosis system for mild cognitive impairment in elderly population in somewhere of Chengdu
Gui ZHOU ; Dejun LUO ; Zhen ZENG ; Jiangcuo LUO ; Shu YAN ; Yongxue YANG ; Wen HE ; Lei FENG
Chongqing Medicine 2024;53(20):3150-3155
Objective To understand the prevalence status quo of mild cognitive impairment(MCI)in the elderly people by conducting the investigation on the elderly people in somewhere,and to explore the influ-encing factors of MCI in the elderly people to provide reference for constructing the MCI localized computer screening and diagnosis system in the elderly.Methods A multi-stage sampling method was used to deter-mine the survey population.The self-made questionnaires,mini mental state examination(MMSE),geriatric depression screening scale(GDS-15),geriatric anxiety screening scale,geriatric psychiatric symptoms scale,and daily living ability scale were used to collect or evaluate basic information,cognitive impairment,depres-sion,anxiety,psychiatric symptoms,and daily living ability of elderly people from March 5,2022 to July 22,2022.The index system affecting MCI was screened by the receiver operating characteristic(ROC)curve and unconditional binary logistic regression,and the localized computer screening diagnosis system was construc-ted.Results A total of 1 004 elderly individuals were surveyed,among them there were 262 cases(26.1%)of MCI,194 cases(19.3%)of anxious state,21 cases(2.1%)of depression,313 cases(31.2%)of psychotic symptoms and 32 cases(3.2%)of impaired ability of activities of daily living(ADL).The ROC curve analysis showed that the area under the curves(AUC)of depression,anxiety and psychotic symptoms for predicting MCI in elderly individuals were 0.640,0.645,and 0.586,respectively.AUC of anxiety combined with depres-sion(anxiety+depression),depression+psychotic symptoms,anxiety+psychotic symptoms and depression+anxiety+psychotic symptoms were 0.676,0.652,0.645 and 0.676,respectively.The multivariate analysis found that the age,whether or not anyone close to you died in the last two years,ability of activities of daily living,anxiety degree,whether or not having psychotic symptoms,education level,whether or not having joint habitation with the family members and suffering from multiple chronic diseases were the influencing factors of MCI.Conclusion The age,education level,death of close persons in the past two years,ability to live daily life,depression,and psychotic symptoms could serve as the indicators system of the MCI localized computer screening and diagnosis system.
9.Leukocyte cell-derived chemotaxin 2(LECT2)regulates liver ischemia-reperfusion injury
Dong MENG-QI ; Xie YUAN ; Tang ZHI-LIANG ; Zhao XUE-WEN ; Lin FU-ZHEN ; Zhang GUANG-YU ; Huang ZHI-HAO ; Liu ZHI-MIN ; Lin YUAN ; Liu FENG-YONG ; Zhou WEI-JIE
Liver Research 2024;8(3):165-171
Background and aim:Hepatic ischemia-reperfusion injury(IRI)is a significant challenge in liver trans-plantation,trauma,hypovolemic shock,and hepatectomy,with limited effective interventions available.This study aimed to investigate the role of leukocyte cell-derived chemotaxin 2(LECT2)in hepatic IRI and assess the therapeutic potential of Lect2-short hairpin RNA(shRNA)delivered through adeno-associated virus(AAV)vectors. Materials and methods:This study analyzed human liver and serum samples from five patients under-going the Pringle maneuver.Lect2-knockout and C57BL/6J mice were used.Hepatic IRI was induced by clamping the hepatic pedicle.Treatments included recombinant human LECT2(rLECT2)and AAV-Lect2-shRNA.LECT2 expression levels and serum biomarkers including alanine aminotransferase(ALT),aspartate aminotransferase(AST),creatinine,and blood urea nitrogen(BUN)were measured.Histological analysis of liver necrosis and quantitative reverse-transcription polymerase chain reaction were performed. Results:Serum and liver LECT2 levels were elevated during hepatic IRI.Serum LECT2 protein and mRNA levels increased post reperfusion.Lect2-knockout mice had reduced weight loss;hepatic necrosis;and serum ALT,AST,creatinine,and BUN levels.rLECT2 treatment exacerbated weight loss,hepatic necrosis,and serum biomarkers(ALT,AST,creatinine,and BUN).AAV-Lect2-shRNA treatment significantly reduced weight loss,hepatic necrosis,and serum biomarkers(ALT,AST,creatinine,and BUN),indicating thera-peutic potential. Conclusions:Elevated LECT2 levels during hepatic IRI increased liver damage.Genetic knockout or shRNA-mediated knockdown of Lect2 reduced liver damage,indicating its therapeutic potential.AAV-mediated Lect2-shRNA delivery mitigated hepatic IRI,offering a potential new treatment strategy to enhance clinical outcomes for patients undergoing liver-related surgeries or trauma.
10.Application of metal cushion block combined with Jumbo cup in reconstruction of acetabular bone defect in revision of artificial hip joint
Feng-Zhen LI ; Wen-Teng SI ; Ai-Li TIAN ; Yu ZHOU ; Ming-Wei CHEN
China Journal of Orthopaedics and Traumatology 2024;37(5):464-469
Objective To investigate the application effect and imaging changes of metal cushion block combined with Jumbo cup in the reconstruction of acetabular bone defect after revision of artificial hip joint.Methods Retrospective analysis was made on the clinical data of 83 patients who underwent revision acetabular bone defect reconstruction of the artificial hip joint in our hospital from September 2019 to October 2021.They were divided into group A and group B according to different surgical methods.There were 42 patients in group A,including 26 males and 16 females,aged from 44 to 72 years old with an average of(60.57±4.62)years,who underwent revision with metal cushion block and Jumbo cup.There were 41 patients in group B,including 22 males and 19 females,aged from 42 to 71 years old with an average of(58.74±4.25)years,who under-went revision with metal cushion block and bone cement mortar cup.The operation related indexes,Harris hip function score and visual analogue scale(VAS)of pain before operation,1 month and 12 month after operation were compared between two groups.The results of X-ray imaging examination(hip rotation center height,acetabular abduction angle,femoral eccentricity and imaging standard qualification rate)before and 12 month after operation were evaluated,and the incidence of complica-tions was compared between two groups.Results There was no significant difference in operation time,intraoperative bleeding volume and postoperative drainage volume between two groups(P>0.05).Both groups were followed up for 12 to 36 months with an average of(25.36±3.59)months.The scores of pain,function,deformity and Harris'total score in the two groups at 1 month after operation were higher than those before operation(P<0.05),and the scores of pain,function,deformity,joint activ-ity and Harris'total score in two groups at 1 year after operation were higher than those before operation and 1 month after op-eration(P<0.05),and the above scores in group A were higher than those in group B at 1 year after operation(P<0.05).The VAS of two groups decreased successively at 1 month and 1 year after operation(P<0.05),but there was no significant differ-ence in both groups at each time point(P>0.05).The femoral eccentricity increased in both groups at 1 year after operation(P<0.05),and group A was higher than group B(P<0.05).The height of rotation center and acetabular abduction angle de-creased in both groups at 1 year after operation(P<0.05),and the height of rotation center in group A was lower than that in group B(P<0.05),but there was no significant difference in acetabular abduction angle between two groups(P>0.05).The imaging qualification rate of group A was higher than that of group B(P<0.05).There was no significant difference in the inci-dence of adverse reactions between two groups(P>0.05).Conclusion Metal cushion block combined with Jumbo cup in the treatment of acetabular bone defects can provide the hip joint function,and restore the hip joint rotation center,femoral eccen-tricity and acetabular abduction angle,with obvious clinical effect.

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