Hepatocellular carcinoma （HCC） is a common tumor in the digestive tract， the formation mechanism of which remains to be fully elucidated. Although surgery， radiation， chemotherapy， targeted therapy， and immunotherapy have achieved significant results in the treatment of HCC， these methods are accompanied by a considerable number of adverse reactions and complications. In recent years， Chinese medicine has shown remarkable efficacy in the treatment of HCC， and both basic experiments and clinical studies have confirmed the effectiveness of Chinese medicine， which exerts therapeutic effects via multiple components and multiple targets. However， the pathogenesis of HCC is exceptionally complex and not fully understood， which means that studies remain to be carried out regarding the specific mechanism of Chinese medicine in preventing and treating HCC. Network pharmacology and molecular biology can be employed to decipher the mechanism of Chinese medicine in the treatment of diseases. Studies have shown that Chinese medicine can regulate various pathways such as the mitogen-activated protein kinase （MAPK）， phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt）， Hedgehog， Wnt/β-catenin， nuclear factor-κB （NF-κB）， Janus kinase 2/signal transducer and activator of transcription 3 （JAK2/STAT3）， and transforming growth factor-β （TGF-β）/Smad signaling pathways. Chinese medicine can exhibit its anti-HCC effects by inducing cell apoptosis， inhibiting cell proliferation and migration， and blocking the cell cycle via the above pathways. However， the specific mechanisms remain to be systematically studied. This study comprehensively reviews the regulatory effects of Chinese medicine on HCC-related signaling pathways to reveal the molecular mechanisms of Chinese medicine in the treatment of HCC. This view holds the promise of providing new targets， new perspectives， and new therapies for HCC treatment and advancing the modernization and development of Chinese medicine.

Hepatic fibrosis characterized by various chronic liver injuries can lead to abnormal activation of hepatic stellate cells， unbalanced production and degradation of extracellular matrix proteins， and excessive deposition that destroys the normal structure of the liver. The aggravated liver fibrosis can cause irreversible cirrhosis and hepatocellular carcinoma， becoming a great challenge to the global health. Ferroptosis is a new form of iron-dependent cell death discovered in recent years， which mainly involves abnormal iron metabolism， lipid peroxide accumulation， and weakening of the antioxidant defense system. A number of studies have reported that inducing ferroptosis in hepatic stellate cells or alleviating ferroptosis in the liver can ameliorate liver fibrosis and reduce liver injury. Chinese medicine widely applied in the treatment of chronic liver diseases has demonstrated good safety， wide therapeutic effects， and easy access compared with Western medicine. Therefore， The intervention of hepatic stellate cells or hepatic ferroptosis by Chinese medicine may be a new direction for the prevention and treatment of liver fibrosis in the future. This paper summarized the various regulatory mechanisms of ferroptosis and expounded how ferroptosis affected the progression of liver fibrosis， providing theoretical support for the prevention and treatment of liver fibrosis with Chinese medicine in the future.

OBJECTIVE: To investigate the correlation between single-nucleotide polymorphism (SNP) of ARID5B gene and resistance to methotrexate (MTX) in children with acute lymphoblastic leukemia (ALL). METHODS: A total of 144 children with ALL who were treated in General Hospital of Ningxia Medical University from January 2015 to November 2021 were enrolled and divided into MTX resistant group and non-MTX resistant group, with 72 cases in each group. Matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) technology was used to measure the SNP of ARID5B gene in all children and analyze its correlation with MTX resistant. RESULTS: There were no significant differences in the genotype and gene frequency of rs7923074, rs10821936, rs6479778, and rs2893881 between MTX resistant group and non-MTX resistant group (P>0.05). The frequency of C/C genotype in the MTX resistant group was significantly higher than that in the non-MTX resistant group, while the frequency of T/T genotype was opposite (P<0.05). The frequency of C allele in the MTX resistant group was significantly higher than that in the non-MTX resistant group, while the frequency of T allele was opposite (P<0.05). Multivariate logistic regression analysis showed that ARID5B gene rs4948488 TT genotype and T allele frequency were risk factors for MTX resistant in ALL children (P<0.05). CONCLUSION The SNP of ARID5B gene is associated with MTX resistant in ALL children.
Child ; Humans ; DNA-Binding Proteins/genetics* ; Gene Frequency ; Genotype ; Methotrexate ; Polymorphism, Single Nucleotide ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics* ; Transcription Factors/genetics* ; Drug Resistance, Neoplasm

OBJECTIVE: This study was aimed at investigating the carrier rate of, and molecular variation in, α- and β-globin gene mutations in Hunan Province. METHODS: We recruited 25,946 individuals attending premarital screening from 42 districts and counties in all 14 cities of Hunan Province. Hematological screening was performed, and molecular parameters were assessed. RESULTS: The overall carrier rate of thalassemia was 7.1%, including 4.83% for α-thalassemia, 2.15% for β-thalassemia, and 0.12% for both α- and β-thalassemia. The highest carrier rate of thalassemia was in Yongzhou (14.57%). The most abundant genotype of α-thalassemia and β-thalassemia was -α ^3.7/αα (50.23%) and β ^IVS-II-654/β ^N (28.23%), respectively. Four α-globin mutations [CD108 (ACC>AAC), CAP +29 (G>C), Hb Agrinio and Hb Cervantes] and six β-globin mutations [CAP +8 (C>T), IVS-II-848 (C>T), -56 (G>C), beta nt-77 (G>C), codon 20/21 (-TGGA) and Hb Knossos] had not previously been identified in China. Furthermore, this study provides the first report of the carrier rates of abnormal hemoglobin variants and α-globin triplication in Hunan Province, which were 0.49% and 1.99%, respectively. CONCLUSION Our study demonstrates the high complexity and diversity of thalassemia gene mutations in the Hunan population. The results should facilitate genetic counselling and the prevention of severe thalassemia in this region.
Humans ; beta-Thalassemia/genetics* ; alpha-Thalassemia/genetics* ; Hemoglobinopathies/genetics* ; China/epidemiology* ; High-Throughput Nucleotide Sequencing

AIM To prepare bergenin nanostructured lipid carriers,and to investigate their in vivo pharmacokinetics.METHODS The nanostructured lipid carriers were prepared by melting method.With solid lipid type,liquid lipid type,solid-liquid lipid ratio,lipid-drug ratio and poloxamer 188 concentration as influecing factors,encapsulation efficiency,drug loading and particle size as evaluation indices,the formulation was optimized by single factor test,after which the in vitro drug release was investigated,the stability was determined,and crystalline form analysis was performed.Eighteen rats were randomly assigned into three groups and given intragastric administration of the 0.5%CMC-Na suspensions of bergenin,physical mixture and bergenin solid dispersions(60 mg/kg),respectively,after which blood collection was made at 0.25,0.5,1,2,3,4,5,6,8,10,12 h,HPLC was adopted in the plasma concentration determination of bergenin,and main pharmacokinetic parameters were calculated.RESULTS The optimal formulation was determined to be glyceryl behenate as solid lipid,oleic acid as liquid lipid,4 ∶ 1 for solid-liquid lipid ratio,10 ∶ 1 as lipid-drug ratio 2.0%for poloxamer 188 concentration,the average concentration,drug loading,particle size and Zeta potential were(84.16±1.57)%,(7.73±0.27)%and(215.53±18.04)nm and-(37.56±2.03)mV,respectively.The nanostructured lipid carriers demonstrated the accumulative release rate of less than 50%within 240 min in simulated gastric fluid,which was 71.04%within 36 h in simulated intestinal fluid,along with good stability within 12 h in the latter.Bergenin existed in the nanostructured lipid carriers in an amorphous state.Compared with raw medicine and physical mixture,the nanostructured lipid carriers displayed prolonged tmax and t1/2(P<0.01),and increased Cmax,AUC0-t,AUC0-∞(P<0.01),whose relative bioavailability was enhanced to 6.08 times as compared with that of raw medicine.CONCLUSION Nanostructured lipid carriers can improve the stability and oral bioavailability of bergenin.

OBJECTIVE: To analyze the changes in psychological distress and quality of life of patients with advanced liver cancer after transformation therapy. METHODS: This study was conducted among 60 patients with advanced liver cancer undergoing transformation therapy from July, 2019 to March, 2022. Before and after 2-10 cycles of treatment, the patients were assessed for psychological distress and quality of life using a psychological stress thermometer and the Functional Assessment of Cancer Therapy-Hepatobiliary (FACT-Hep). RESULTS: The patients showed significantly lowered scores for psychological distress after transformation therapy (P < 0.01) with decreased psychological stress, emotional factors, tension, worry, sleep problems, memory decline and inattention, physical factors, pain, fatigue, eating problems and dyspepsia (P < 0.05). The total score of quality of life and the scores for physical status, social and family status, emotional status, functional status and hepatobiliary-specific items were all significantly lowered after the treatment (P < 0.05). CONCLUSION In patients with advanced liver cancer, the psychological distress involves mainly the emotional factors and physical factors. Transformation therapy can significantly relieve psychological distress of the patients and improve their quality of life.
Humans ; Quality of Life/psychology* ; Surveys and Questionnaires ; Psychological Distress ; Fatigue/psychology* ; Stress, Psychological ; Neoplasms ; Liver Neoplasms

Objective: Several COVID-19 patients have overlapping comorbidities. The independent role of each component contributing to the risk of COVID-19 is unknown, and how some non-cardiometabolic comorbidities affect the risk of COVID-19 remains unclear. Methods: A retrospective follow-up design was adopted. A total of 1,160 laboratory-confirmed patients were enrolled from nine provinces in China. Data on comorbidities were obtained from the patients' medical records. Multivariable logistic regression models were used to estimate the odds ratio ( Results: Overall, 158 (13.6%) patients were diagnosed with severe illness and 32 (2.7%) had unfavorable outcomes. Hypertension (2.87, 1.30-6.32), type 2 diabetes (T2DM) (3.57, 2.32-5.49), cardiovascular disease (CVD) (3.78, 1.81-7.89), fatty liver disease (7.53, 1.96-28.96), hyperlipidemia (2.15, 1.26-3.67), other lung diseases (6.00, 3.01-11.96), and electrolyte imbalance (10.40, 3.00-26.10) were independently linked to increased odds of being severely ill. T2DM (6.07, 2.89-12.75), CVD (8.47, 6.03-11.89), and electrolyte imbalance (19.44, 11.47-32.96) were also strong predictors of unfavorable outcomes. Women with comorbidities were more likely to have severe disease on admission (5.46, 3.25-9.19), while men with comorbidities were more likely to have unfavorable treatment outcomes (6.58, 1.46-29.64) within two weeks. Conclusion Besides hypertension, diabetes, and CVD, fatty liver disease, hyperlipidemia, other lung diseases, and electrolyte imbalance were independent risk factors for COVID-19 severity and poor treatment outcome. Women with comorbidities were more likely to have severe disease, while men with comorbidities were more likely to have unfavorable treatment outcomes.
Adult ; Aged ; COVID-19/virology* ; China/epidemiology* ; Comorbidity ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Severity of Illness Index ; Treatment Outcome

Excess accumulation of white adipose tissue (WAT) causes obesity which is an imbalance between energy intake and energy expenditure. Obesity is a serious concern because it has been the leading causes of death worldwide, including diabetes, stroke, heart disease and cancer. Therefore, uncovering the mechanism of obesity and discovering anti-obesity drugs are crucial to prevent obesity and its complications. Browning, inducing white adipose tissue to brown or beige (brite) fat which is brown-like fat emerging in WAT, becomes an appealing therapeutic strategy for obesity and metabolic disorders. Due to lack of efficacy or intolerable side-effects, the clinical trials that promote brown adipose tissue (BAT) thermogenesis and browning of WAT have not been successful in humans. Obviously, more specific means still need to be developed to activate browning of white adipose tissue. In this review, we summarized seven kinds of natural products (alkaloids, flavonoids, terpenoids, long chain fatty acids, phenolic acids, else and extract) promoting white adipose tissue browning which can ameliorate the metabolic disorders, including obesity, dislipidemia, insulin resistance and diabetes. Since natural products are important drug sources and the browning property plays a significant role in not only obesity treatment but also in type 2 diabetes (T2DM) improvement, natural products of inducing browning may be an irreplaceable drug discovery orientation for obesity, diabetes and even other metabolic disorders.

Hyperglycemia is the dominant phenotype of diabetes and the main contributor of diabetic complications. Puerarin is widely used in cardiovascular diseases and diabetic vascular complications. However, little is known about its direct effects on diabetes. The aim of our study is to investigate its antidiabetic effect in vivo and in vitro, and explore the underlying mechanism. We used type I diabetic mice induced by streptozotocin to observe the effects of puerarin on glucose metabolism. In addition, oxidative stress and hepatic mitochondrial respiratory activity were evaluated in type I diabetic mice. In vitro, glucose consumption in HepG2 cells was assayed along with the qPCR detection of glucogenesis genes expression. Moreover, ATP production was examined and phosphorylation of AMPK was determined using Western blot. Finally, the molecular docking was performed to predict the potential interaction of puerarin with AMPK utilizing program LibDock of Discovery Studio 2018 software. The results showed that puerarin improved HepG2 glucose consumption and upregulated the glucogenesis related genes expression. Also, puerarin lowered fasting and fed blood glucose with improvement of glucose tolerance in type I diabetic mice. Further mechanism investigation showed that puerarin suppressed oxidative stress and improved hepatic mitochondrial respiratory function with enhancing ATP production and activating phosphorylation of AMPK. Docking study showed that puerarin interacted with AMPK activate site and enhancing phosphorylation. Taken together, these findings indicated that puerarin exhibited the hypoglycemic effect through attenuating oxidative stress and improving mitochondrial function via AMPK regulation, which may serve as a potential therapeutic option for diabetes treatment.

Objective:To investigate the genetic characteristics of norovirus (NoV) in children with acute gastroenteritis in Shanghai.Methods:A total of 709 stool specimens were collected from outpatients with acute gastroenteritis in Children′s Hospital of Shanghai from October 2018 to September 2019. Real-time RT-PCR was used for qualitative detection of NoV, and RT-PCR was used to identify the genotypes of NoV with the primers of VP1 gene, RdRp region and RdRp-VP1 region. SPSS20.0 statistical software was used for data processing and bioinformatics software was used for homology, phylogenetic and recombination analysis of NoV gene sequences.Results:NoV was detected in 265 out of the 709 stool specimens with a positive rate of 37.4%. Sequence analysis of RdRp region and VP1 gene showed that seven different genotypes including GⅡ.P16-GⅡ.2, GⅡ.P12-GⅡ.3, GⅡ.Pe-GⅡ.4_Sydney 2012, GⅡ.P7-GⅡ.6, GⅡ.P8-GⅡ.8, GⅡ.P21-GⅡ.13 and GⅡ.P17-GⅡ.17 were detected from 111 NoV-positive specimens. The predominated genotype was GⅡ.P16-GⅡ.2 (30.6%, 34/111), followed by GⅡ.Pe-GⅡ.4_Sydney 2012 (27.0%, 30/111) and GⅡ.P12-GⅡ.3 (24.3%, 27/111). Two new NoV recombinant strains belonging to GⅡ.P21-GⅡ.13 genotype were identified and the recombination site was in the junction region of ORF1 and ORF2. NoV infection occurred every month, but the predominant genotype was different. No significant difference in the positive rates of NoV was found between male and female patients ( P=0.329). However, there were significant differences between different age groups ( P=0.011) and the children in the age groups of >11-12 years old and >2-3 years old had higher rates of NoV infection. Conclusions:The predominated recombinant NoV strains belonged to GⅡ.P16-GⅡ.2, GⅡ.Pe-GⅡ.4_Sydney 2012 and GⅡ.P12-GⅡ.3 genotypes, and two new recombinant NoV strains (GⅡ.P21-GⅡ.13) were found in Shanghai during October 2018 to September 2019. Gene sequencing across ORF1 and ORF2 was conducive to better understanding the NoV genotypes and recombination.