1.Mechanism of Qinggan Jianpi Huoxue Prescription Against Hepatic Fibrosis via FoxO1 Mediated Regulation of Glycolytic Metabolic Reprogramming of Hepatic Stellate Cells
Fuzhen PAN ; Meng ZHU ; Chuanjian SHI ; Shiqiang XU ; Ding LIU ; Jinfang ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(18):98-107
ObjectiveTo investigate the mechanism of Qinggan Jianpi Houxue prescription against hepatic fibrosis in mice using metabolomics. MethodsA hepatic fibrosis mouse model was established by intraperitoneal injection of 20% carbon tetrachloride (CCl4, diluted with olive oil at a ratio of 4∶1) at a dose of 2.5 mL·kg-1 for 4 weeks. A total of 54 C57BL/6J mice were randomly divided into the blank control group, model group, Qinggan Jianpi Houxue prescription high-dose group (47.32 g·kg-1), medium-dose group (23.66 g·kg-1), low-dose group (11.83 g·kg-1), and Biejiajian pill group (1.365 g·kg-1), with 9 mice in each group. Concurrently with modeling, each administration group received the corresponding dose continuously for 4 weeks, once daily. After 4 weeks, liver tissues and blood samples were collected for liver function and hepatic pathological examinations. Non-targeted metabolomics was employed to detect hepatic metabolites. Principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were performed to explore the metabolites and their involved metabolic pathways in the liver tissues of mice in the blank control group, model group and Qinggan Jianpi Houxue prescription high-dose group. Western blot validation was conducted at both the cellular and animal levels. ResultsCompared with the blank control group, the model group showed significantly increased levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) (P<0.01), along with increased inflammatory cell infiltration, and formation of fibrous septa. The predominantly enriched pathway was the forkhead box O (FoxO) signaling pathway. Compared with the model group, the Qinggan Jianpi Huoxue prescription high-dose group exhibited significantly decreased ALT and AST levels (P<0.01). In all administration groups of Qinggan Jianpi Huoxue prescription, inflammatory cell infiltration was reduced, fibrous septa were narrowed and diminished, collagen fibers were reduced, and the collagen area was significantly decreased. Non-targeted metabolomics identified 79 differential metabolites, among which 49 were up-regulated and 30 down-regulated, primarily enriched in the tricarboxylic acid (TCA) cycle and pyruvate metabolism pathways. Western blot results demonstrated that, compared with the blank control group, the model group exhibited significantly upregulated protein expressions of α-smooth muscle actin (α-SMA), lactate dehydrogenase A (LDHA), FoxO1, pyruvate kinase M2 (PKM2), hexokinase 2 (HK2), and phosphofructokinase 1 (PFK1) in liver tissues (P<0.05, P<0.01). In hepatic stellate cells, the glucose concentration increased, and the protein expression of α-SMA, LDHA, FoxO1, PKM2, glucose transporter 1 (GLUT1), and PFK1 were significantly up-regulated (P<0.05, P<0.01). Conversely, compared with the model group, the Qinggan Jianpi Huoxue prescription high-dose group showed significantly downregulated protein expression of α-SMA, LDHA, FoxO1, PKM2, HK2, and PFK1 in liver tissues (P<0.05, P<0.01). In hepatic stellate cells, the glucose concentration decreased, and the protein expression of α-SMA, LDHA, FoxO1, PKM2, GLUT1, and PFK1 were significantly down-regulated (P<0.05, P<0.01). ConclusionQinggan Jianpi Huoxue prescription can alleviate the pathological progression of hepatic fibrosis in mice, potentially by regulating the TCA cycle and pyruvate metabolism through FoxO1, and by modulating glycolytic metabolic reprogramming in hepatic stellate cells, thereby promoting liver tissue repair.
2.The role and mechanism of innate immune cells in Mycobacterium tuberculosis infection
Jiaojiao WEI ; Yu PANG ; Fuzhen ZHANG ; Ling LI
Chinese Journal of Microbiology and Immunology 2025;45(7):605-610
Tuberculosis is a infectious disease caused by Mycobacterium tuberculosis( Mtb), which seriously threatens human health. Innate immune cells can synergistically resist the invasion of Mtb by phagocytosing pathogens, releasing inflammatory cytokines, and activating other immune cells, playing a crucial role in the host′s defense against Mtb infection. A comprehensive and in-depth understanding of the role of innate immune cells in Mtb infection will help reveal the complexity of immune response and understand the mechanism of early elimination of Mtb and immune escape of Mtb, and provide new ideas and strategies for the prevention and treatment of tuberculosis. This article will provide an overview of the research progress on the mechanisms of several important innate immune cells, including macrophages, neutrophils, natural killer cells, dendritic cells, and constant natural killer T cells, in Mtb infection.
3.Incidence and spatiotemporal clustering of hepatitis B in China, 2006-2020
Lei WANG ; Na LIU ; Hong YANG ; Fuzhen WANG ; Guomin ZHANG ; Huaqing WANG
Chinese Journal of Epidemiology 2025;46(3):410-417
Objective:To analyze the incidence and spatiotemporal clustering of hepatitis B in China from 2006 to 2020 and provide reference for hepatitis B prevention and control.Methods:The incidence data of hepatitis B in 31 provinces (autonomous regions and municipalities) from 2006 to 2020 were collected from National Notifiable Infectious Disease Reporting System of China Information System for Disease Control and Prevention. The incidence trend analysis was conducted by using software Joinpoint 5.0.2, and the spatiotemporal scan analysis was performed by using software SaTScan 10.1.2.Results:From 2006 to 2020, a total of 1 049 546 cases of acute hepatitis B were reported in China. The average annual reported incidence rate was 5.17/100 000. The reported incidence rate showed a decreasing trend during this period. The incidence decreased from 3.00/100 000 to 0.41/100 000 in age group 0-14 years, from 14.15/100 000 to 3.44/100 000 in age group 15-34 years, and from 6.87/100 000 to 3.72/100 000 in age group ≥35 years, the differences were all significant (all P<0.001). From 2006 to 2020, a total of 10 732 017 cases of chronic hepatitis B were reported in China. The average annual reported incidence rate was 52.85/100 000. The reported incidence of chronic hepatitis B varied in different age groups, which decreased from 11.38/100 000 to 2.18/100 000 in age group 0-14 years, and from 73.17/100 000 to 61.40/100 000 in age group 15-34 years, while increased from 48.07/100 000 to 90.75/100 000 in age group ≥35 years, the differences were all significant (all P<0.05). Spatiotemporal scan analysis indicated that the age of reported acute hepatitis B cases became older over time, and the regions with high-incidence gradually shifted from western China to southwestern China. The overall reported incidence of chronic hepatitis B in those aged ≥35 years showed an upward trend, and the regions with high-incidence were mainly found in coastal area in southeastern China and in southwestern China. Conclusions:From 2006 to 2020, the overall reported incidence of acute hepatitis B in China showed a continuous downward trend, while the reported incidence of chronic hepatitis B in those aged ≥35 years showed an upward trend. It indicated that the need to improve the diagnosis and treatment of chronic hepatitis B in adults in coastal area in southeastern China and southwestern China.
4.Genomic characterization and evolutionary analysis of hepatitis B virus subgenotype D3 in China in 2020
Hui XIANG ; Shuang ZHANG ; Feng WANG ; Feng QIU ; Fuzhen WANG ; Liping SHEN ; Qiudong SU
Chinese Journal of Experimental and Clinical Virology 2025;39(1):62-68
Objective:To analyze the genetic characteristics and evolutionary origin of hepatitis B virus (HBV) subgenotype D3 in China in 2020.Methods:Serum samples and demographic details from patients infected with HBV D3 subgenotype were collected. HBV genomic sequences were obtained by nested PCR amplification and subsequent sequencing. Phylogenetic analysis, nucleotide homology, amino acid mutation and evolution rate of the S protein were conducted by comparing with reference sequence using bioinformatics tools.Results:The complete HBV gene sequences of 14 samples of D3 subtype HBV were obtained. Compared with 97 reference sequences, it was found that the sequences with the highest homology were from India, Mongolia, Iran and China, with the homology ranging from 96.0% to 97.9%. Mutations of 24 amino acids were found in 14 strains of D3 subtype. Among them, T131A, Y134F and T140I were associated with immune escape-related mutations. The genetic diversity of HBV D3 subtype increased slowly before 1975, remained relatively constant from 1975 to 2000, and began to decline after 2000. Evolutionary rate analysis showed that samples QGLD D3-02 and 03 originated from a common ancestor with the Iranian reference strain in 1872, and the other 12 samples QGLD D3-04-17 originated from a common ancestor with the Mongolian reference strain in 1843.Conclusions:The gene sequence of HBV D3 subtype in China had the highest homology with reference sequences from India, Iran, Mongolia and China. Evolutionary rate analysis revealed that 14 cases of HBV D3 subtype originated from a common ancestor with reference strains from Mongolia and Iran, which enriched the sequence and evolution information of HBV D3 subtype and provided a reference basis for the molecular epidemiological study of HBV.
5.Role of DHA in long-term cognitive impairment after multiple sevoflurane anesthesia in newborn mice
Sufang JIANG ; Jiaqi LI ; Tianyu CAO ; Jiaqi YUE ; Lichao DI ; Shizhao WANG ; Fuzhen ZHANG ; Rongtian KANG ; Huan CHEN ; Huixian CUI ; Sha LI ; Lining HUANG
Chinese Journal of Anesthesiology 2025;45(5):559-563
Objective:To evaluate the role of docosahexaenoic acid (DHA) in long-term cognitive impairment after multiple sevoflurane anesthesia in newborn mice.Methods:Clean-grade healthy male C57BL/6 mice, aged 6 days, were used in this study. Ten mice were divided into 2 groups ( n=5 each) by the random number table method: control group (group C) and sevoflurane group (group S). The animals inhaled 3% sevoflurane for 2 h at 6, 7 and 8 days after birth. The DHA content was detected by ultra-high performance liquid chromatography-mass spectrometry at 9 days of age. Fifty-two mice were selected and divided into 4 groups ( n=13 each) by a random number table method: control+ normal saline group (group C+ S), sevoflurane anesthesia + normal saline group (group S+ S), control+ DHA group (group C+ D), and sevoflurane anesthesia+ DHA group (group S+ D). The sevoflurane anesthesia method was the same as the one mentioned above. DHA 50 mg/kg was administered by intragastric gavage from postnatal days 6-19 (at 6, 7 and 8 days after birth, 2 h before anesthesia) in C+ D and S+ D groups. The equal volume of normal saline was given instead in C+ S group and S+ S group. The novel object recognition test was conducted at 37 days of age, and the Morris water maze test was performed at 42 days of age. The corpus callosum and hippocampal tissues were isolated at 47 days of age for examination of the ultrastructure of myelin (with a transmission electron microscope) and for determination of the expression of myelin basic protein (MBP) in hippocampal tissues (by Western blot). The G-ratio was calculated. Results:Compared with group C, the content of DHA in hippocampal tissues was significantly decreased in group S ( P<0.05). Compared with group C+ S, the discrimination index was significantly decreased, the percentage of duration of staying at the target platform quadrant and the number of crossing the original platform were decreased, the expression of MBP was down-regulated, and the G-ratio in the original platform and hippocampus was increased in S+ S group ( P<0.05). Compared with group S+ S, the discrimination index was significantly increased, the percentage of duration of staying at the target platform quadrant and the number of crossing the original platform were increased, the expression of MBP was up-regulated, and the G-ratio in the original platform and hippocampus was decreased in S+ D group ( P<0.05). Conclusions:The mechanism of long-term cognitive impairment following multiple sevoflurane anesthesia may be related to a decrease in the content of DHA, which subsequently leads to myelin structural damage in neonatal mice.
6.Incidence and spatiotemporal clustering of hepatitis B in China, 2006-2020
Lei WANG ; Na LIU ; Hong YANG ; Fuzhen WANG ; Guomin ZHANG ; Huaqing WANG
Chinese Journal of Epidemiology 2025;46(3):410-417
Objective:To analyze the incidence and spatiotemporal clustering of hepatitis B in China from 2006 to 2020 and provide reference for hepatitis B prevention and control.Methods:The incidence data of hepatitis B in 31 provinces (autonomous regions and municipalities) from 2006 to 2020 were collected from National Notifiable Infectious Disease Reporting System of China Information System for Disease Control and Prevention. The incidence trend analysis was conducted by using software Joinpoint 5.0.2, and the spatiotemporal scan analysis was performed by using software SaTScan 10.1.2.Results:From 2006 to 2020, a total of 1 049 546 cases of acute hepatitis B were reported in China. The average annual reported incidence rate was 5.17/100 000. The reported incidence rate showed a decreasing trend during this period. The incidence decreased from 3.00/100 000 to 0.41/100 000 in age group 0-14 years, from 14.15/100 000 to 3.44/100 000 in age group 15-34 years, and from 6.87/100 000 to 3.72/100 000 in age group ≥35 years, the differences were all significant (all P<0.001). From 2006 to 2020, a total of 10 732 017 cases of chronic hepatitis B were reported in China. The average annual reported incidence rate was 52.85/100 000. The reported incidence of chronic hepatitis B varied in different age groups, which decreased from 11.38/100 000 to 2.18/100 000 in age group 0-14 years, and from 73.17/100 000 to 61.40/100 000 in age group 15-34 years, while increased from 48.07/100 000 to 90.75/100 000 in age group ≥35 years, the differences were all significant (all P<0.05). Spatiotemporal scan analysis indicated that the age of reported acute hepatitis B cases became older over time, and the regions with high-incidence gradually shifted from western China to southwestern China. The overall reported incidence of chronic hepatitis B in those aged ≥35 years showed an upward trend, and the regions with high-incidence were mainly found in coastal area in southeastern China and in southwestern China. Conclusions:From 2006 to 2020, the overall reported incidence of acute hepatitis B in China showed a continuous downward trend, while the reported incidence of chronic hepatitis B in those aged ≥35 years showed an upward trend. It indicated that the need to improve the diagnosis and treatment of chronic hepatitis B in adults in coastal area in southeastern China and southwestern China.
7.Role of DHA in long-term cognitive impairment after multiple sevoflurane anesthesia in newborn mice
Sufang JIANG ; Jiaqi LI ; Tianyu CAO ; Jiaqi YUE ; Lichao DI ; Shizhao WANG ; Fuzhen ZHANG ; Rongtian KANG ; Huan CHEN ; Huixian CUI ; Sha LI ; Lining HUANG
Chinese Journal of Anesthesiology 2025;45(5):559-563
Objective:To evaluate the role of docosahexaenoic acid (DHA) in long-term cognitive impairment after multiple sevoflurane anesthesia in newborn mice.Methods:Clean-grade healthy male C57BL/6 mice, aged 6 days, were used in this study. Ten mice were divided into 2 groups ( n=5 each) by the random number table method: control group (group C) and sevoflurane group (group S). The animals inhaled 3% sevoflurane for 2 h at 6, 7 and 8 days after birth. The DHA content was detected by ultra-high performance liquid chromatography-mass spectrometry at 9 days of age. Fifty-two mice were selected and divided into 4 groups ( n=13 each) by a random number table method: control+ normal saline group (group C+ S), sevoflurane anesthesia + normal saline group (group S+ S), control+ DHA group (group C+ D), and sevoflurane anesthesia+ DHA group (group S+ D). The sevoflurane anesthesia method was the same as the one mentioned above. DHA 50 mg/kg was administered by intragastric gavage from postnatal days 6-19 (at 6, 7 and 8 days after birth, 2 h before anesthesia) in C+ D and S+ D groups. The equal volume of normal saline was given instead in C+ S group and S+ S group. The novel object recognition test was conducted at 37 days of age, and the Morris water maze test was performed at 42 days of age. The corpus callosum and hippocampal tissues were isolated at 47 days of age for examination of the ultrastructure of myelin (with a transmission electron microscope) and for determination of the expression of myelin basic protein (MBP) in hippocampal tissues (by Western blot). The G-ratio was calculated. Results:Compared with group C, the content of DHA in hippocampal tissues was significantly decreased in group S ( P<0.05). Compared with group C+ S, the discrimination index was significantly decreased, the percentage of duration of staying at the target platform quadrant and the number of crossing the original platform were decreased, the expression of MBP was down-regulated, and the G-ratio in the original platform and hippocampus was increased in S+ S group ( P<0.05). Compared with group S+ S, the discrimination index was significantly increased, the percentage of duration of staying at the target platform quadrant and the number of crossing the original platform were increased, the expression of MBP was up-regulated, and the G-ratio in the original platform and hippocampus was decreased in S+ D group ( P<0.05). Conclusions:The mechanism of long-term cognitive impairment following multiple sevoflurane anesthesia may be related to a decrease in the content of DHA, which subsequently leads to myelin structural damage in neonatal mice.
8.The role and mechanism of innate immune cells in Mycobacterium tuberculosis infection
Jiaojiao WEI ; Yu PANG ; Fuzhen ZHANG ; Ling LI
Chinese Journal of Microbiology and Immunology 2025;45(7):605-610
Tuberculosis is a infectious disease caused by Mycobacterium tuberculosis( Mtb), which seriously threatens human health. Innate immune cells can synergistically resist the invasion of Mtb by phagocytosing pathogens, releasing inflammatory cytokines, and activating other immune cells, playing a crucial role in the host′s defense against Mtb infection. A comprehensive and in-depth understanding of the role of innate immune cells in Mtb infection will help reveal the complexity of immune response and understand the mechanism of early elimination of Mtb and immune escape of Mtb, and provide new ideas and strategies for the prevention and treatment of tuberculosis. This article will provide an overview of the research progress on the mechanisms of several important innate immune cells, including macrophages, neutrophils, natural killer cells, dendritic cells, and constant natural killer T cells, in Mtb infection.
9.Genomic characterization and evolutionary analysis of hepatitis B virus subgenotype D3 in China in 2020
Hui XIANG ; Shuang ZHANG ; Feng WANG ; Feng QIU ; Fuzhen WANG ; Liping SHEN ; Qiudong SU
Chinese Journal of Experimental and Clinical Virology 2025;39(1):62-68
Objective:To analyze the genetic characteristics and evolutionary origin of hepatitis B virus (HBV) subgenotype D3 in China in 2020.Methods:Serum samples and demographic details from patients infected with HBV D3 subgenotype were collected. HBV genomic sequences were obtained by nested PCR amplification and subsequent sequencing. Phylogenetic analysis, nucleotide homology, amino acid mutation and evolution rate of the S protein were conducted by comparing with reference sequence using bioinformatics tools.Results:The complete HBV gene sequences of 14 samples of D3 subtype HBV were obtained. Compared with 97 reference sequences, it was found that the sequences with the highest homology were from India, Mongolia, Iran and China, with the homology ranging from 96.0% to 97.9%. Mutations of 24 amino acids were found in 14 strains of D3 subtype. Among them, T131A, Y134F and T140I were associated with immune escape-related mutations. The genetic diversity of HBV D3 subtype increased slowly before 1975, remained relatively constant from 1975 to 2000, and began to decline after 2000. Evolutionary rate analysis showed that samples QGLD D3-02 and 03 originated from a common ancestor with the Iranian reference strain in 1872, and the other 12 samples QGLD D3-04-17 originated from a common ancestor with the Mongolian reference strain in 1843.Conclusions:The gene sequence of HBV D3 subtype in China had the highest homology with reference sequences from India, Iran, Mongolia and China. Evolutionary rate analysis revealed that 14 cases of HBV D3 subtype originated from a common ancestor with reference strains from Mongolia and Iran, which enriched the sequence and evolution information of HBV D3 subtype and provided a reference basis for the molecular epidemiological study of HBV.
10.Effect of residual corneal astigmatism on visual acuity of patients undergoing regional refractive intraocular lens implantation
Xiaoting MA ; Kejun LI ; Zhihua ZHAO ; Yin ZHANG ; Yinghua DU ; Fuzhen LIANG
Recent Advances in Ophthalmology 2024;44(1):43-47
Objective To investigate the effect of residual corneal astigmatism on visual acuity after regional refrac-tive intraocular lens(IOL)implantation.Methods A retrospective cohort study was conducted.The medical records and follow-up data of 73 eyes of 57 cataract patients who underwent ultrasound emulsification cataract extraction combined with LENTIS Comfort LS-313 MF15 IOL implantation in the Ophthalmology Department of the Hebei General Hospital from June 2020 to March 2022 were collected.These patients were grouped according to postoperative residual corneal astigmatism:32 patients(40 eyes)with a residual corneal astigmatism of 0.75(exclusive)-1.50 D were taken as the experimental group,and 25 patients(33 eyes)with a residual corneal astigmatism ≤0.75 D were taken as the control group.The uncor-rected distance visual acuity(5 m),uncorrected intermediate visual acuity(80 cm),uncorrected near visual acuity(40 cm),out-of-focus curve,objective visual quality,subjective visual quality,satisfaction degree and lens removal rate of pa-tients in the two groups were recorded 6 months postoperatively.Results The postoperative uncorrected distance visual acuity(logMAR)was 0.10(0.00,0.22),the uncorrected intermediate visual acuity(logMAR)was 0.00(0.00,0.10),and the uncorrected near visual acuity(logMAR)was 0.20(0.10,0.30)and 0.20(0.10,0.20)in the experimental and control groups,with no statistically significant differences(all P>0.05).The postoperative out-of-focus curves showed that the distance visual acuity of patients with additional spherical equivalent refraction ranged from+2.00 D to-4.00 D in the two groups had no statistically significant difference(all P>0.05).There were statistically significant differences in to-tal aberration,coma aberration,modulation transfer function and Strehl ratio in the objective visual quality of patients after surgery(all P<0.05),and there was no statistically significant difference in the total higher-order aberration,spherical ab-erration and cloverleaf aberration(all P>0.05).There was no statistically significant difference in the subjective visual quality,satisfaction degree and lens removal rate in the two groups(all P>0.05).Conclusion Residual corneal astig-matism of 0.75 D to 1.50 D after LENTIS Comfort LS-313 MF15 IOL implantation has no effect on higher-order aberration,spherical aberration,and cloverleaf aberration in subjective and objective visual quality,and has an impact on total aberra-tion,coma aberration,modulation transfer function and Strehl ratio in objective visual quality.

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