Drug-induced liver injury(DILI)is one of the major challenges in drug development and clinical practice,and effective prevention and con-trol measures remain lacking.Research has shown that DILI is primarily mediated by immune respons-es.Human leukocyte antigen(HLA)alleles are cur-rently the strongest genetic factors reported to be associated with DILI.Due to the low positive predic-tive value of HLA alleles,preemptive HLA genetic screening has limited clinical utility in preventing DILI.However,its high negative predictive value makes it valuable for DILI diagnosis and causality assessment.In recent years,polymorphisms in im-mune-related genes-such as those involved in anti-gen processing and presentation pathways,T-cell receptors,immunostimulatory molecules,and cyto-kines-have been found to be associated with DILI.Future studies combining these genes with HLA analysis may provide deeper mechanistic insights into DILI and facilitate their translational applica-tion in clinical practice,ultimately improving drug safety.

Drug-induced liver injury(DILI)is one of the major challenges in drug development and clinical practice,and effective prevention and con-trol measures remain lacking.Research has shown that DILI is primarily mediated by immune respons-es.Human leukocyte antigen(HLA)alleles are cur-rently the strongest genetic factors reported to be associated with DILI.Due to the low positive predic-tive value of HLA alleles,preemptive HLA genetic screening has limited clinical utility in preventing DILI.However,its high negative predictive value makes it valuable for DILI diagnosis and causality assessment.In recent years,polymorphisms in im-mune-related genes-such as those involved in anti-gen processing and presentation pathways,T-cell receptors,immunostimulatory molecules,and cyto-kines-have been found to be associated with DILI.Future studies combining these genes with HLA analysis may provide deeper mechanistic insights into DILI and facilitate their translational applica-tion in clinical practice,ultimately improving drug safety.

OBJECTIVE: To explore the effect of thoracic paravertebral anesthesia (TPVB) on prognosis of patients undergoing resection of lung cancer. METHODS: This study was conducted among the patients undergoing surgical resection of primary lung cancer under general anesthesia or TPVB combined with general anesthesia (TPVB+GA) between January, 2017 and May, 2018.The patients were enrolled in TPVB+GA group and GA group (control group) using a propensity score matching (PSM) method at the ratio of 1:2 based on their baseline characteristics.The clinical parameters, 5-year overall survival (OS), progression-free survival (PFS) and intraoperative dosage of opioids were compared between the two groups to assess the impact of TPVB on prognosis of the patients. RESULTS: Forty-seven patients were enrolled in TPVB+GA group and 94 in the control group.Kaplan-Meier survival analysis showed a significantly prolonged PFS in the patients with TPVB+GA (log-rank P=0.034), with an odds ratio (OR) of 0.45(95%CI: 0.33-0.89).Consistently, univariate and multivariate Cox regression analyses identified TPVB as an independent protective prognostic factor for patients with lung cancer resection (P=0.002, OR=0.33, 95%CI: 0.16-0.66).Cox regression analyses indicated that a lower intraoperative dose of remifentanil was significantly correlated with a longer PFS of the patients following lung cancer resection (P=0.017, OR=0.47, 95%CI: 0.25-0.87).Chi-square test confirmed that TPVB, but not general anesthesia, significantly reduced intraoperative dose of remifentanil, indicating a possible synergistic effect of TPVB with opioids to affect the survival of the patients. CONCLUSION TPVB can prolong the survival time and improve the prognosis of the patients undergoing surgical resection of lung cancer.
Humans ; Remifentanil ; Pain, Postoperative ; Nerve Block/methods* ; Analgesics, Opioid ; Prognosis ; Lung Neoplasms/surgery*

Objective: Due to genetic factors might increase the risk of depression, this study investigated the genetic risk factors of depression in Chinese Han population by analyzing the association between 13 candidate genes and depression. Methods: 439 depression patients and 464 healthy controls were included in this case-control study. Case group consisted of 158 males and 281 females, aged (29.84±14.91) years old, who were hospitalized in three departments of the affiliated Brain Hospital of Guangzhou Medical University including Affective Disorders Department, Adult Psychiatry Department and Geriatrics Department, from February 2020 to September 2021. The control group consisted of 196 males and 268 females, aged (30.65±12.63) years old. 20 loci of 13 candidate genes in all subjects were detected by MALDI-TOF mass spectrometry. Age difference was compared using the student's t-test, the distributions of gender and genotype were analyzed with Pearson's Chi-square test. The analyses of Hardy-Weinberg equilibrium, allele frequency and the genetic association of depression were conducted using the corresponding programs in PLINK software. Results: PLINK analysis showed that SCN2A rs17183814, ABCB1 rs1045642, CYP2C19*3 rs4986893 and NAT2*5A rs1799929 were associated with depression before Bonferroni correction (χ²=10.340, P=0.001; χ²=11.010, P=0.001; χ²=9.781, P=0.002; χ²=4.481, P=0.034). The frequencies of minor alleles of above loci in the control group were 12.07%, 43.64%, 2.59% and 3.88%, respectively. The frequencies of minor alleles of loci mentioned above in the case group were 17.43%, 35.99%, 5.47% and 6.04%, respectively. OR values were 1.538, 0.726, 2.178 and 1.592, respectively. After 1 000 000 permutation tests using Max(T) permutation procedure, the four loci were still statistically significant, the empirical P-value were 0.002, 0.001, 0.003 and 0.042, respectively. However, only three loci including SCN2A rs17183814, ABCB1 rs1045642 and CYP2C19 rs4986893 had statistical significance after Bonferroni correction, the adjusted P-value were 0.026, 0.018 and 0.035, respectively. Conclusion: SCN2A rs17183814, ABCB1 rs1045642 and CYP2C19*3 rs4986893 were associated with depression's susceptibility in Chinese Han population. The A allele of SCN2A rs17183814 and CYP2C19*3 rs4986893 were risk factors for depression, while the T allele of ABCB1 rs1045642 was a protective factor for depression.
ATP Binding Cassette Transporter, Subfamily B/genetics* ; Adolescent ; Adult ; Alleles ; Arylamine N-Acetyltransferase/genetics* ; Case-Control Studies ; Clopidogrel ; Cytochrome P-450 CYP2C19/genetics* ; Depressive Disorder, Major/genetics* ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Humans ; Male ; NAV1.2 Voltage-Gated Sodium Channel ; Polymorphism, Single Nucleotide ; Young Adult

Gut microbiota dysbiosis is a risk factor for colorectal cancer (CRC) in inflammatory bowel disease (IBD). In this study, the effects of Panax notoginseng saponins (PNS) on colitis-associated CRC progression were evaluated on an azoxymethane (AOM)/dextran sulfate sodium (DSS) mouse model. In vivo, PNS significantly relieved AOM/DSS-induced colon tumorigenesis and development by reducing the disease activity index (DAI) scores and colon tumor load. The 16S rRNA data of fecal samples showed that the microbiome community was obviously destructed, while PNS could recover the richness and diversity of gut microbiota. Especially, PNS could increase the abundance of Akkermansia spp. which was significantly decreased in model group and negatively correlated with the progression of CRC. Moreover, ginsenoside compound K (GC-K) was evaluated on the effects of human CRC cells, which was the main bio-transformed metabolite of PNS by gut microbiota. Our data showed that PNS played important role in the prevention of the progression of CRC, due to their regulation on the microbiome balance and microbial bio-converted product with anti-CRC activity.

Panax notoginseng saponins (PNS) are the major components of Panax notoginseng, with multiple pharmacological activities but poor oral bioavailability. PNS could be metabolized by gut microbiota in vitro, while the exact role of gut microbiota of PNS metabolism in vivo remains poorly understood. In this study, pseudo germ-free rat models were constructed by using broad-spectrum antibiotics to validate the gut microbiota-mediated transformation of PNS in vivo. Moreover, a high performance liquid chromatography-electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS) was developed for quantitative analysis of four metabolites of PNS, including ginsenoside F1 (GF1), ginsenoside Rh2 (GRh2), ginsenoside compound K (GCK) and protopanaxatriol (PPT). The results showed that the four metabolites could be detected in the control rat plasma, while they could not be determined in pseudo germ-free rat plasma. The results implied that PNS could not be biotransformed effectively when gut microbiota was disrupted. In conclusion, gut microbiota plays an important role in biotransformation of PNS into metabolites in vivo.
Animals ; Anti-Bacterial Agents ; pharmacology ; Biotransformation ; Chromatography, High Pressure Liquid ; Feces ; microbiology ; Gastrointestinal Microbiome ; drug effects ; physiology ; Ginsenosides ; blood ; Male ; Panax notoginseng ; chemistry ; Rats, Sprague-Dawley ; Sapogenins ; blood ; Saponins ; administration & dosage ; metabolism ; Tandem Mass Spectrometry

BACKGROUND: Proteomics is a well studied research method, but its application in the non-surgical treatment of lumbar intervertebral disc protrusion (LIDP) is little reported. OBJECTIVE: To screen the differentially expressed proteins in patients with LIDP but without blood stasis before and after non-surgical treatment by proteomics. METHODS: Sixty patients with LIDP but without blood stasis were selected, and treated with non-surgical treatment for 4 weeks. The differentially expressed proteins were screened and identified by iTRAQ combined with LC-MS/MS. The bioinformatics analysis of the identified proteins was carried out, and the curative effectiveness was investigated. RESULTS AND CONCLUSION: Compared with those before treatment, the Visual Analogue Scale scores were significantly (P ＜ 0.05), the Japanese Orthopedic Association scores were significantly increased decreased (P ＜ 0.05), and the excellent and good rate reached 95.0% post-treatment. A total of 300 differentially expressed proteins were screened and 25 significantly expressed proteins were identified (P ＜0.05). Bioinformatics analysis revealed that nine of the significantly expressed proteins were enriched to 15 KEGG signaling pathways. These results suggest that the use of Western medicine non-surgical treatment for the LIDP without blood stasis can achieve satisfactory results. Besides, complement C1qA, cDNA protein (FLJ60724), complement C4B frameshift mutation, cDNA protein (FLJ53025), mannose binding protein C, apolipoprotein B, hemoglobin α-1 globin chain variant, hemoglobin β subunit and cDNA protein (FLJ76254) may be the potential serum markers of the non-surgical treatment for the LIDP without non-blood stasis.

Objective To observe the clinical efficacy and safety of re-bamipide combined with rabeprazole sodium enteric -coated tablets in the treatment of chronic atrophic gastritis .Methods A total of 94 pa-tients with chronic atrophic gastritis were randomly divided into control and treatment groups with 47 cases per group.Control group was given riberazole 20 mg per time, qd, orally.Treatment group received rabe-prazole 0.1 g per time, tid, orally, on the basis of control group.Two groups were treated for 8 weeks. The clinical efficacy, pepsinogen (PG), endothelin (ET) and adverse drug reactions were compared be-tween two groups.Results After treatment, total effective rates of treat-ment and control groups were 93.62%( 44 cases/47 cases ) and 70.21%(33 cases/47 cases) with significant difference ( P<0.05 ) . After treatment, the main indexes of treatment and control groups were compared: PGⅠ were ( 127.38 ±13.96 ) and ( 103.84 ±13.58 ) μg· L-1, ET were (65.49 ±5.99 ) and ( 74.20 ±9.79 ) ng· L-1, there were statistically significant differences (all P<0.05).The adverse drug reactions of treatment group were liver dysfunction and skin rash , which in control group were diarrhea , rash and nausea and vomiting .The total incidence of adverse drug reactions were 6.38%and 14.89%without significant difference (P>0.05).Conclusion Rebamipide combined with rabeprazole sodium enteric-coated tablets has a definitive clinical efficacy in the treatment of chronic atrophic gastritis , which can effectively regulate the levels of PG and inhibit the expression of ET , without increasing the incidence of adverse drug reactions.

BACKGROUND: Percutaneous vertebroplasty (PVP) is usually used for osteoporotic thoracolumbar fractures,which has various advantages such as easy to operate, short operation time, less trauma, rapid recovery,analgesic effect and so on. But its application is restricted due to nerve compression symptoms and pulmonary embolism caused by bone cement leakage. Thereafter, how to reduce the leakage of bone cement is an issue of concern.OBJECTIVE: To investigate the relationship between the lumbar quantitative computed tomography (QCT) values and contrast agent dispersion in osteoporotic thoracolumbar fractures. METHODS: Sixty cases of osteoporotic thoracolumbar fractures undergoing PVP were enrolled, and received QCT examination before surgery, and contrast agent was injected intraoperatively. X-ray examination was conducted to detect the bone mineral density, contrast agent dispersion and leakage of bone cement, and the relationship between the lumbar QCT values and contrast agent dispersion as well as leakage of bone cement.RESULTS AND CONCLUSION: (1) There were 110 vertebral fractures, and 74 vertebrae with contrast agent diffusing more than vertebral midline, accounting for 67.3%. There was significant difference in the contrast agent dispersion among groups (P < 0.05). (2) The bone cement leakage showed no significant difference among groups after injected with bone cement by unilateral or bilateral approach (P > 0.05). (3) These results suggest that contrast agent dispersion in osteoporotic thoracolumbar fractures has a certain relationship with the lumbar QCT values, and lumbar QCT values with more contrast agent dispersion, but the lumbar QCT values have no correlation with bone cement leakage. Therefore, choosing a appropriate approach based on the QCT values and contrast agent dispersion can reduce leakage and improve the safety of PVP.

Objective: To evaluate the role of the serum testosterone level as an independent predictor of bone metastasis of prostate cancer. METHODS: This study included 165 male patients with prostate cancer confirmed by biopsy. The patients were aged 58－78 (66.6±5.3) years and none had received androgen-deprivation therapy, chemotherapy or radiotherapy previously. We obtained the baseline clinical data from the patients, including prostate biopsy Gleason scores and the levels of serum prostate-specific antigen (PSA), total testosterone (TT), luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol (E2), alkaline phosphatase (ALP) and prolactin. According to the results of bone scanning, we divided the patients into a bone metastasis and a non-bone metastasis group and screened out the differential factors by univariate analysis and the independent predictor of bone metastasis using the multivariate non-conditional logistic regression model. RESULTS: Univariate analysis showed no statistically significant differences between the bone metastasis and non-bone metastasis groups in age (P = 0.126) or the levels of serum LH (P = 0.930), FSH (P = 0.763) and E2 (P = 0.256), but that the former had remarkably higher Gleason scores (P < 0.01), total PSA (P <0.01) and ALP (P <0.01) but a lower TT level than the latter (P = 0.013). According to the results of multivariate logistic regression analysis, serum ALP (P <0.01, OR = 1.018 ［1.011－1.026］) and total PSA (P <0.01, OR = 1.029 ［1.015－1.044］) could be regarded as independent predictors of bone metastasis of prostate cancer but not low serum TT (P = 0.531, OR = 0.999 ［0.996－1.002］) or biopsy Gleason score (P = 0.898, OR = 0.787 ［0.412－1.9559］). CONCLUSIONS The low level of serum testosterone is closely associated with but not an independent predictor of bone metastasis of prostate cancer.
Aged ; Alkaline Phosphatase ; blood ; Antineoplastic Agents, Hormonal ; Biopsy ; Bone Neoplasms ; secondary ; Estradiol ; blood ; Follicle Stimulating Hormone ; blood ; Humans ; Logistic Models ; Luteinizing Hormone ; blood ; Male ; Middle Aged ; Neoplasm Grading ; Prolactin ; blood ; Prostate-Specific Antigen ; blood ; Prostatic Neoplasms ; blood ; pathology ; Retrospective Studies ; Testosterone ; blood ; deficiency