1.Challenges and strategies for clinical treatment of low-level viremia in chronic hepatitis B patients
Huilin GAN ; Cuicui SHI ; Guangming LI
Journal of Clinical Hepatology 2025;41(4):736-741
Hepatitis B virus (HBV) infection is a global public health issue, affecting the health of 250 million people worldwide. Despite the significant progress in antiviral therapy for HBV, some patients still experience low-level viremia (LLV) after receiving antiviral therapy and fail to achieve viral clearance, with an HBV DNA load remaining at a relatively low level of 20 — 2 000 IU/mL. LLV is often caused by multiple factors such as the high stability of the virus, the difficulty in clearing the virus with antiviral drugs, host immune factors, and drug resistance, which increase the difficulties in antiviral therapy. In addition, LLV can also cause liver damage, which may eventually progress to severe outcomes such as hepatocellular carcinoma. This article reviews LLV in hepatitis B in terms of diagnosis, influencing factors, clinical significance, and treatment strategies.
2.Research progress of HGF/c-Met signaling pathway in oral squamous cell carcinoma
SHI Jiafan ; GONG Lingling ; SUN Mingze ; LIU Lulu ; ZHANG Huilin ; LI Ming
Journal of Prevention and Treatment for Stomatological Diseases 2025;33(8):709-718
Oral squamous cell carcinoma (OSCC) is a malignant tumor that seriously threatens human health. Its typical biological characteristics include strong local invasiveness, high lymph node metastasis rate, and high recurrence rate after treatment. Hepatocyte growth factor (HGF), cellular-mesenchymal to epithelial transition factor (c-Met), and the HGF/c-Met signaling pathway are involved in the regulation of the occurrence and development of OSCC. HGF and c-Met proteins are overexpressed in OSCC, and multiple studies have suggested that they are significantly associated with the malignant characteristics of tumors and poor prognosis. Furthermore, the abnormal activation of the HGF/c-Met signaling pathway (driven by HGF-dependent autocrine/paracrine or non-dependent mechanisms such as MET gene mutations, amplification, fusion, and protein overexpression) can synergistically promote tumor cell invasion, metastasis, and angiogenesis by activating downstream signaling pathways. However, HGF/c-Met can also mediate immune escape by promoting lactate secretion increase, inducing programmed death ligand 1 (PD-L1) expression upregulation, activating and expanding myeloid-derived suppressor cells, and promoting the proliferation of regulatory T cells (Tregs). In addition, the crosstalk between the HGF/c-Met signaling pathway and key pathways such as phosphatidylinositide 3-kinases (PI3K)/protein kinase B (AKT), epidermal growth factor receptor (EGFR), Janus kinase (JAK)/signal transducer and activator of transcription (STAT3), and non-coding RNAs can also promote tumor progression. Currently, three types of targeted drugs have been developed targeting the HGF/c-Met pathway: HGF monoclonal antibody, c-Met monoclonal antibody, and tyrosine kinase inhibitors. Some of these drugs have entered clinical trials. However, the emergence of drug resistance during treatment, especially the bidirectional compensatory activation of alternative signaling pathways such as EGFR, has become a major challenge in clinical practice. This article aims to provide an in-depth analysis of the mechanism of action of the HGF/c-Met pathway in OSCC and its interaction with other pathways, and to review the current research status of existing therapeutic drugs. The aim is to provide an important theoretical basis for developing more effective combined treatment strategies and achieving individualized precise treatment, ultimately improving the clinical prognosis and quality of life of patients.
3.Research progress on barriers to clinical application of evidence in nursing
Funa YANG ; Xiaoxia XU ; Hongying SHI ; Eva Ho Ka Yan ; Ping ZHU ; Huilin WANG
Chinese Journal of Nursing 2024;59(18):2290-2296
As an integral part of worldwide healthcare,nursing still has a big task to make in conducting implementation research.Addressing the pressing challenges of closing the gap between evidence and nursing practice,and effectively disseminating and applying evidence within the nursing discipline,remains a top priority.This paper presents a compilation of the status of evidence implementation in clinical nursing from an implementation science perspective,including the theoretical framework of barriers to evidence implementation,common research methodologies,and research progress of related factors in the field of nursing.The goal of this work is to bring more insights to further advance the implementation of evidence in nursing.
4.Pathological Mechanism of Diabetes Based on NF-κB Signaling Pathway and Traditional Chinese Medicine Intervention: A Review
Menglu WANG ; Lu SHI ; Changhao HE ; Yongcheng AN ; Yinglan LYU ; Chen WANG ; Huimin LI ; Huilin ZHANG ; Yan HUANG ; Wanxin FU ; Ziyi SHAN ; Baosheng ZHAO
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(5):246-255
As people's living standards improve, the development trend of diabetes has gradually become severe. Diabetes is a chronic inflammatory disease associated with abnormal expression of nuclear factor-kappa B (NF-κB) in patients. NF-κB exists in various tissue cells and participates in the regulation of a variety of genes related to immune function and inflammation. Varieties of factors can activate NF-κB when the body is stimulated by external factors, so as to produce inflammation and other reactions. Previous studies on NF-κB mainly focus on cancer, and the pathological mechanism of the treatment of diabetes by related signaling pathways and the progress of traditional Chinese medicine (TCM) treatment have not been systematically elaborated on. By referring to the relevant literature in China and abroad, it was found that NF-κB is not isolated in the development and progression of diabetes but is associated with signal molecules related to inflammation, oxidative stress, and energy metabolism, and it is involved in mediating inflammation, pancreatic β cell apoptosis, insulin signal transduction, and other physiological functions. Therefore, blocking the transmission of NF-κB signaling pathway is beneficial to the treatment of diabetes. At present, Western medicine for the treatment of diabetes mainly includes oral hypoglycemic drugs and insulin injections, but the adverse reactions are obvious. TCM has been characterized by multi-target, extensive action, and excellent curative effects in the treatment of diabetes. TCM and its compounds with functions of tonifying Qi and promoting blood circulation, regulating qi and eliminating phlegm, clearing heat and detoxifying, and nourishing Yin and moistening dryness can effectively intervene in the abnormal expression of NF-κB signaling pathway in vivo through anti-inflammatory effects. In this paper, the association between NF-κB signaling pathway and diabetes was summarized, and the modern research progress of TCM intervention of NF-κB signaling pathway in the treatment of diabetes in the past five years was reviewed, so as to lay a laboratory foundation for the study of a new pathological mechanism of diabetes based on NF-κB signaling pathway and provide new targets and research direction for the prevention and treatment of diabetes and development of related TCM.
5.Analysis of the current situation of defect of vertebral column among primary, middle, and high school students in Minhang District, Shanghai
Yan HAN ; Yuhuan HU ; Xiaosa WEN ; Huilin XU ; Fangjia YING ; Yujie WANG ; Jiamin CAO ; Qi GUO ; Huijing SHI
Shanghai Journal of Preventive Medicine 2024;36(6):574-578
ObjectiveTo investigate the general situation of defect of vertebral column among primary and middle school students in Minhang District of Shanghai and analyze the related factors, to provide a scientific basis for prevention and treatment. MethodsFrom September to October 2022, a total of 5 715 students were selected from two primary schools, two middle schools, and two high schools in Minhang District for physical examinations and screening for defect of vertebral column. ResultsTotally 219 students had defect of vertebral column, accounting for 3.83% of the sampled population. Anteroposterior spinal abnormalities were found in 4 individuals, accounting for 0.07%, and 218 students had scoliosis, accounting for 3.81%. The detection rate of defect of vertebral column was higher in girls (6.27%) than that in boys (1.51%), and higher in high school students (10.74%) than in primary school students (1.31%) and middle school students (10.97%). Students who are mildly underweight (5.95%) and who are moderately to severely underweight (7.46%) had a higher detection rate of defect of vertebral column than those with normal weight (4.54%), overweight (2.83%), and obesity (1.60%). The detection rate among students with poor vision (4.32%) was significantly higher than those with normal vision (2.24%), with all differences statistically significant (all P<0.05). ConclusionThe positive rate of defect of vertebral column in primary and middle school students in Minhang District, Shanghai is nearly 4%, with most cases being scoliosis. Factors such as being female, increasing age, being underweight, and poor vision are associated with a higher probability of detecting defect of vertebral column.
6.Rutin Promotes Browning of 3T3-L1 Preadipocytes and Its Mechanism
Yinglan LYU ; Long CHENG ; Lu SHI ; Hongyu DAI ; Yuhui DUAN ; Yongcheng AN ; Huimin LI ; Chen WANG ; Changhao HE ; Yan HUANG ; Huilin ZHANG ; Wanxin FU ; Yanyan MENG ; Baosheng ZHAO
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(5):137-143
ObjectiveTo investigate the effect of rutin on the browning of 3T3-L1 preadipocytes and the mechanism. MethodCell counting kit-8 (CCK-8) assay was used to detect the effect of different concentration of rutin (3.125, 6.25, 12.5, 25, 50, 100, 200 μmol·L-1) on 3T3-L1 cell activity, and Western blot to examine the effect of rutin (12.5, 25, 50 μmol·L-1) on the expression of thermogenesis-associated proteins uncoupling protein 1 (UCP1), PR domain containing 16 (PRDM16) and peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) in adipocytes. After the optimal concentration of rutin was determined, the effect of rutin on lipid droplet formation in adipocytes was observed based on oil red O staining, and the expression of nuclear respiratory factor 1 (NRF1), nuclear respiratory factor 2 (NRF2) and mitochondrial transcription factor A (TFAM), which were the landmark proteins of mitochondrial biosynthesis, was detected by Western blot. ResultCompared with the blank group, 200 μmol·L-1 rutin inhibited 3T3-L1 cell activity (P<0.01). Compared with the blank group, at the concentration of 12.5, 25, 50 μmol·L-1 rutin significantly promoted the expression of thermogenesis-associated proteins (UCP1, PRDM16, and PGC-1α) (P<0.01), which was determined as the optimal concentration. Compared with the blank group, 50 μmol·L-1 rutin significantly increased the immunofluorescence intensity of mitochondrial UCP1 protein in 3T3-L1 cells (P<0.01) and the expression of the markers of mitochondrial biosynthesis (NRF1, NRF2, and TFAM) (P<0.01). In addition, 50 μmol·L-1 rutin significantly inhibited lipid droplet formation of 3T3-L1 adipocytes (P<0.01). ConclusionRutin inhibited lipid droplet deposition in 3T3-L1 adipocytes and increased the expression of thermogenesis-related proteins (UCP1, PRDM16, and PGC-1α) and markers of mitochondrial biosynthesis (NRF1, NRF2, and TFAM), thereby inducing the browning of 3T3-L1 adipocytes. This lays a basis for the development of drugs that safely regulate the browning of white cells.
7.Treatment of cement dislodgement after vertebral augmentation
Linlin ZHANG ; Minfeng GAN ; Jinhui SHI ; Peng YANG ; Shaofeng YANG ; Mo ZHU ; Yunxia TAO ; Huilin YANG
Chinese Journal of Orthopaedic Trauma 2023;25(1):19-24
Objective:To analyze the clinical efficacy of treatment of cement dislodgement after vertebral augmentation for osteoporotic vertebral fractures.Methods:A retrospective study was conducted to analyze the data of 13 patients who had been treated at Department of Orthopaedics, The First Affiliated Hospital of Soochow University for cement dislodgement after vertebral augmentation for osteoporotic vertebral fractures from July 2013 to July 2022. There were 4 males and 9 females, with an average age of (76.5±8.6) years and a T value of bone mineral density of -3.3±0.6. By the CT and MRI features of cement dislodgement, their conditions fell in 4 types: cement loosening in situ (4 cases), anterior cement moving (6 cases), anterior cement moving with posterior bone mass moving (2 cases), and posterior cement moving (1 case). They were treated by percutaneous vertebroplasty (3 cases), pedicle screw fixation combined with bone graft fusion and decompression (7 cases), and conservative therapy (3 cases). The curative effects for surgical patients were evaluated by comparing their visual analogue scale (VAS), Oswestry dysfunction index (ODI) and cobb angle of kyphosis at preoperation, 1 week and 1 month postoperation, and the last follow-up, and Frankel grading for nerve injury as well. The curative effects for patients undergoing conservative treatment were evaluated by observing their symptoms.Results:This cohort was followed up for 7 (5, 12) months after treatment. The VAS scores [5.0 (4.0, 5.0) points, 3.0 (2.0, 3.0) points, and 3.0 (2.0, 3.0) points] in the 10 surgical patients at 1 week and 1 month postoperation and the last follow-up were significantly improved compared with the preoperative value [8.5 (8.0, 9.0) points] ( P<0.05); the VAS scores at 1 month postoperation and the last follow-up were also significantly improved compared with that at 1 week postoperation ( P < 0.05), but there was no significant difference between the last follow-up and 1 month postoperation ( P > 0.05). The ODIs (50.6%±4.2%, 37.8%±4.5%, and 29.3%±5.6%) in the 10 surgical patients at 1 week and 1 month postoperation and the last follow-up were significantly improved compared with the preoperative value (93.2%±3.6%), showing significant differences in pairwise comparisons ( P<0.05). The cobb angles [10.0 (9.0, 11.0)°, 9.0 (9.0, 11.0)°, and 10.0 (9.0, 12.0)°] in the 10 surgical patients at 1 week and 1 month postoperation and the last follow-up were significantly improved compared with the preoperative value [12.5 (11.0, 14.0)°] ( P<0.05) , but there was no statistically significant difference between the time points after operation ( P>0.05). The Frankel grading was significantly improved in the 6 patients with nerve injury after operation. Of the 3 patients undergoing conservative treatment, the symptoms were cured in one, showed no change during follow-up in one, and aggravated in one. Conclusion:Surgical treatment can significantly relieve pain, improve spinal dysfunction and repair nerve injury in patients with bone cement dislodgement after vertebral augmentation.
8.Mulberry leaf flavonoids activate BAT and induce browning of WAT to improve type 2 diabetes via regulating the AMPK/SIRT1/PGC-1α signaling pathway.
Long CHENG ; Lu SHI ; Changhao HE ; Chen WANG ; Yinglan LV ; Huimin LI ; Yongcheng AN ; Yuhui DUAN ; Hongyu DAI ; Huilin ZHANG ; Yan HUANG ; Wanxin FU ; Weiguang SUN ; Baosheng ZHAO
Chinese Journal of Natural Medicines (English Ed.) 2023;21(11):812-829
Mulberry (Morus alba L.) leaf is a well-established traditional Chinese botanical and culinary resource. It has found widespread application in the management of diabetes. The bioactive constituents of mulberry leaf, specifically mulberry leaf flavonoids (MLFs), exhibit pronounced potential in the amelioration of type 2 diabetes (T2D). This potential is attributed to their ability to safeguard pancreatic β cells, enhance insulin resistance, and inhibit α-glucosidase activity. Our antecedent research findings underscore the substantial therapeutic efficacy of MLFs in treating T2D. However, the precise mechanistic underpinnings of MLF's anti-T2D effects remain the subject of inquiry. Activation of brown/beige adipocytes is a novel and promising strategy for T2D treatment. In the present study, our primary objective was to elucidate the impact of MLFs on adipose tissue browning in db/db mice and 3T3-L1 cells and elucidate its underlying mechanism. The results manifested that MLFs reduced body weight and food intake, alleviated hepatic steatosis, improved insulin sensitivity, and increased lipolysis and thermogenesis in db/db mice. Moreover, MLFs activated brown adipose tissue (BAT) and induced the browning of inguinal white adipose tissue (IWAT) and 3T3-L1 adipocytes by increasing the expressions of brown adipocyte marker genes and proteins such as uncoupling protein 1 (UCP1) and beige adipocyte marker genes such as transmembrane protein 26 (Tmem26), thereby promoting mitochondrial biogenesis. Mechanistically, MLFs facilitated the activation of BAT and the induction of WAT browning to ameliorate T2D primarily through the activation of AMP-activated protein kinase (AMPK)/sirtuin 1 (SIRT1)/peroxisome proliferator-activated receptor-gamma coactivator 1α (PGC-1α) signaling pathway. These findings highlight the unique capacity of MLF to counteract T2D by enhancing BAT activation and inducing browning of IWAT, thereby ameliorating glucose and lipid metabolism disorders. As such, MLFs emerge as a prospective and innovative browning agent for the treatment of T2D.
Mice
;
Animals
;
Adipose Tissue, Brown
;
Sirtuin 1/pharmacology*
;
Diabetes Mellitus, Type 2/metabolism*
;
AMP-Activated Protein Kinases/metabolism*
;
Morus/metabolism*
;
Flavonoids/metabolism*
;
Prospective Studies
;
Signal Transduction
;
Adipose Tissue, White
;
Plant Leaves
;
Uncoupling Protein 1/metabolism*
;
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism*
9.Analysis of parainfluenza virus infection in acute respiratory tract infection adult cases in Shanghai, 2015-2021
Qi QIU ; Huanyu WU ; Huilin SHI ; Hao PAN ; Chenyan JIANG ; Zheng TENG ; Jiajing LIU ; Yaxu ZHENG ; Jian CHEN
Chinese Journal of Epidemiology 2023;44(10):1628-1633
Objective:To study the infection status and epidemiological characteristics of parainfluenza virus (PIV) in acute respiratory tract infection adult cases in Shanghai from 2015 to 2021, and to provide a scientific basis for preventing and controlling PIV.Methods:Acute respiratory tract infections were collected from 13 hospitals in Shanghai from 2015 to 2021. Relevant information was registered, and respiratory specimens were sampled to detect respiratory pathogens by multiplex PCR.Results:A total of 5 104 adult acute respiratory tract infection cases were included; the overall positive rate of the respiratory pathogens was 29.37% (1 499/5 104). The positive rate of PIV was 2.61% (133/5 104), compared with 2.32% (55/2 369) and 2.85% (78/2 735) in influenza-like cases (ILI) and severe acute respiratory infection (SARI) cases, respectively. Among them, PIV3 accounted for the highest proportion (62.41%, 83/133), followed by PIV1 (18.80%, 25/133), PIV2 (9.77%, 13/133), and PIV4 (9.02%, 12/133). The incidence of PIV-positive cases was mainly distributed in the first and second quarters, accounting for 62.41% (83/133). The difference in the incidence in each quarter was significant ( χ2=24.78, P<0.001). Mixed infection accounted for 18.80% (25/133) of 133 PIV-positive cases, the mixed infection rates of ILI and SARI were 18.18% (10/55) and 19.23% (15/78), respectively, and the main mixed pathogen of PIV was coronavirus 229E. Conclusions:There are a certain proportion of PIV-positive acute respiratory tract infection cases in Shanghai. It is necessary to strengthen the etiological surveillance in acute respiratory tract infection cases, especially the mixed infection of PIV and other pathogens.
10.Total Flavonoids of Mulberry Leaves Improves Liver Lipid Metabolism in Type 2 Diabetic Rats by Regulating PPAR-α/CPT-1 Pathway
Yuhui DUAN ; Hongyu DAI ; Yongcheng AN ; Long CHENG ; Lu SHI ; Huimin LI ; Chen WANG ; Yinglan LYU ; Changhao HE ; Huilin ZHANG ; Yan HUANG ; Wanxin FU ; Yanyan MENG ; Baosheng ZHAO
Chinese Journal of Experimental Traditional Medical Formulae 2022;28(15):61-69
ObjectiveTo investigate the medicinal effect of total flavonoids of mulberry leaves on regulating liver lipid metabolism disorder in diabetes mellitus type 2 (T2DM) rats, and the mechanism based on liver peroxidase proliferators activate receptors-α (PPAR-α) and carnitine palmityl transferase-1 (CPT-1) proteins. MethodTotal flavonoids of mulberry leaves were extracted and purified by ethanol extraction + macroporous resin purification and then identified. T2DM rat model was induced by high fat diet (HFD) + streptozocin(STZ)method. Rats with blood glucose ≥ 11.1 mmol·L-1 were divided into three administration groups with the high dose (300 mg·kg-1), medium dose (150 mg·kg-1), and low dose (75 mg·kg-1) of total flavonoids of mulberry leaves for 8 weeks, respectively, to observe the weight and blood glucose of the rats. The pathological changes of rat livers were observed by hematoxylin-eosin (HE) staining. Biochemical method was used to detect the levels of total cholesterol (TC), triglyceride (TG), low density lipoprotein-cholesterol (LDL-C), and high density lipoprotein-cholesterol (HDL-C) of blood lipid metabolism in rats. The messenger ribonucleic acid (mRNA) and protein expressions of PPAR-α and CPT-1 were determined by real-time quantitative polymerase chain reaction (Real-time PCR) and Western blot. ResultAfter 8 weeks of intervention of total flavonoids of mulberry leaves, compared with the control group, the food intake, liver index, and fasting blood glucose of rats in the model group increased significantly (P<0.01). Compared with the model group, the food intake, fasting blood glucose, and liver index of rats in the administration groups decreased significantly (P<0.01). The results of HE staining showed that the liver tissue structure of rats in the control group was complete and there was no obvious abnormality. The model group showed vacuolar degeneration and inflammatory infiltration of hepatocytes of rats. There was no obvious abnormality in the liver structure of rats in the administration groups. The results of blood lipid showed that compared with the control group, the levels of TC, TG, and LDL-C increased significantly (P<0.01), but the level of HDL-C decreased significantly (P<0.01) in the model group. Compared with the model group, the levels of TC, TG, and LDL-C decreased significantly (P<0.05, P<0.01), whereas the level of HDL-C increased significantly (P<0.01) in the administration groups. The results of Real-time PCR showed that compared with the control group, the mRNA expression of PPAR-α and CPT-1 of rats in the model group decreased significantly (P<0.01). Compared with the model group, the mRNA expressions of PPAR-α and CPT-1 of rats in the high-dose group increased significantly (P<0.01). The results of Western blot showed that compared with the control group, the protein expressions of PPAR-α and CPT-1 of rats in the model group decreased significantly (P<0.01). Compared with the model group, the protein expressions of PPAR-α and CPT-1 of rats in the high-dose group increased significantly (P<0.05, P<0.01). ConclusionTotal flavonoids of mulberry leaves can effectively reduce blood glucose and improve liver lipid metabolism disorder in T2DM rats. The total flavonoids of mulberry leaves could regulate lipid metabolism and play a hypoglycemic role by activating and regulating PPAR-α and CPT-1 proteins and promoting oxidative decomposition of fatty acids.


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