Inhibitory Effect of Sesquiterpenoid M36 from Myrrha on Growth of Human Hepatoma Cells / 中国实验方剂学杂志

ObjectiveThe antitumor activity of sesquiterpenoid M36 isolated from Myrrha against human hepatoma HepG2 cells was investigated in this study. MethodHepG2 cells were treated with M36 at different concentrations （0， 2， 4， 6， 8， 10 μmol·L-1）. Firstly， the effects of M36 on the proliferation of human hepatoma HepG2 cells were detected by methyl thiazolyl tetrazolium （MTT）， colony formation assay， and EdU proliferation assay. Hoechst staining， flow cytometry analysis， and Western blot were used to explore the effect of M36 on the apoptosis of human hepatoma HepG2 cells. Acridine orange staining and western blotting were used to examine the effect of M36 on autophagy in HepG2 cells. Finally， Western blot was used to detect protein expression of cancer-related signaling pathways. ResultCompared with the blank group， M36 treatment significantly inhibited the proliferation of human hepatoma HepG2 cells （P<0.01）， and the half inhibitory concentration （IC50） value of M36 for 48 h was 5.03 μmol·L-1， in a dose- and time-dependent manner. M36 was also able to induce apoptosis and autophagy in human hepatoma HepG2 cells. After treatment with 8 μmol·L-1 M36 for 48 hours， the apoptosis rate of HepG2 cells was （42.03±9.65）% （P<0.01）. Compared with the blank group， HepG2 cells treated with 4 and 8 μmol·L-1 M36 for 48 h had a significant increase in cleaved poly ADP-ribose polymerase （cleaved-PARP） protein levels （P<0.01）. Acridine orange staining showed that autophagy was significantly activated in HepG2 cells treated with 4 and 8 μmol·L-1 M36 for 48 h compared with the blank group （P<0.01）， which was further verified by the up-regulation of microtubule-associated protein 1 light chain 3 Ⅱ （LC3 Ⅱ）. Western blot results showed that compared with the blank group， the levels of phosphorylated extracellular regulated protein kinase （p-ERK）， phosphorylated p38 mitogen-activated protein kinase （p-p38 MAPK）， phosphorylated c-Jun N-terminal kinase （p-JNK）， and its downstream nuclear transcription factors c-Jun and p-c-Jun protein were significantly increased in M36 group （P<0.05， P<0.01）. The mechanism may be related to the up-regulation of MAPK signaling pathway. ConclusionThe sesquiterpenoid M36 isolated from Myrrha inhibits the proliferation of human hepatoma HepG2 cells and promotes apoptosis and autophagy， which may be related to the activation of the MAPK signaling pathway.

Anti-infection treatment and pharmaceutical care for a patient with severe pneumonia caused by Chlamydia psittaci / 中国药房

OBJECTIVE To provide ideas and reference for the anti-infection treatment and pharmaceutical care for severe pneumonia caused by Chlamydia psittaci. METHODS Clinical pharmacists participated in the whole process of the treatment for a patient with C. psittaci-induced severe pneumonia. According to the patient’s medical history， clinical symptoms and test results， clinical pharmacists assisted the physician to dynamically adjust the anti-infective scheme； for C. psittaci infection， the patient was treated with tigecycline combined with azithromycin successively， and other infection therapy plans were dynamically adjusted according to the results of pathogen examination. During the treatment， the patient suffered from suspicious adverse drug reactions such as prolonged QTc interval， elevated lipase and amylase； the clinical pharmacists conducted pharmaceutical care and put forward reasonable suggestions. RESULTS The physician adopted the pharmacists’ suggestion， and the patient was discharged after treatment. CONCLUSIONS For the treatment of severe pneumonia caused by C. psittaci， the characteristics of patients， drugs and pathogens should be taken into account to develop individualized anti-infective treatment. Tetracyclines and macrolides have a definite effect on C. psittaci infection， but attention should be paid to the possible ADR caused by drugs in clinical application.

Analysis of 111 cases of aristolochic acids nephropathy / 药学实践杂志

Objective To analyze the clinical characteristics and regularity of aristolochic acid nephropathy (AAN) induced by drugs containing aristolochic acid. Methods The clinical data of 111 patients with AAN induced by aristolochic acid were reviewed. The clinical features, medication and treatment of AAN were analyzed. Results Among 111 patients, there were more females than males (2.58∶1), 101 cases (90.99%) were over 50 years old； the mean age was (63.70±11.67) years old;the average duration of medication was (8.08±6.94) years. The drugs involved were Guanxinsuhe pill and Longdanxiegan pill in 106 cases (95.50%). Serum creatinine increased in 108 cases, urea nitrogen increased in 106 cases and hemoglobin decreased in 103 cases, most of which were hypogravity urine, mild to moderate proteinuria and occult blood. Ultrasonic examination revealed that the kidneys were damaged to varying degrees. Pathological biopsy of kidney showed renal tubular damage. Most patients had an insidious onset and varying degrees of progression, which were not proportional to the age and the duration of taking the medicine. In clinical, the renal function was progressively damaged, most of which were irreversible and with a poor prognosis. Conclusion Patients with renal impairment differed greatly individually, and the renal damage was not paralleled with the medication duration and dose of drugs containing aristolochic acid.AAN progressed rapidly, and the disease still progressed even after stopping taking drugs containing aristolochic acid. Strengthening pharmacovigilance, implementing early diagnosis and effective intervention could help to reduce the occurrence of AAN and attenuate its development.

Neonatal ureaplasma meningitis: a report of 2 cases and literature review / 中国新生儿科杂志

Objective:To study the clinical features and treatment strategy of neonatal ureaplasma meningitis.Methods:During 2021, the clinical data of 2 neonates with ureaplasma meningitis treated in Children's Hospital of Hunan Province were retrospectively analyzed. Literature on this subject were searched in the following databases: CNKI, Wanfang Database, Chinese Medical Journal Full-Text Database, CQVIP database, SinoMed, PubMed, Embase and Web of Science (up to March 2022). The key words included “infant”, “neonate”, “newborn”, “ureaplasma”, “mycoplasma urealytium”, “meningitis”, “central nervous system infection”, “brain”. The clinical data, treatment and prognosis of patients from the literature were summarized.Results:Case 1, female, gestational age(GA) 33 +3 weeks, intracranial hemorrhage (ICH) and ventricular dilatation were found on 2 d after birth. The cerebrospinal fluid (CSF) routine and biochemistry tests indicated meningitis, but the CSF culture was negative. No improvement after antibiotic treatment. CSF metagenomic next-generation sequencing (mNGS) and 23S rRNA showed Ureaplasma urealyticum on 30 d after birth. The patient was treated with doxycycline (DOX) for 21 d until mNGS turned negative and DOX was discontinued. However, the disease recurred 23 d later and erythromycin was added with DOX as combined therapy. The patient was followed up until 6 months without neurodevelopmental disabilities. Case 2, male, GA 26 weeks, ICH and ventricular dilatation were found on 10 d after birth. The CSF routine and biochemistry tests indicated meningitis, but the CSF culture was negative. No improvement after antibiotic treatment. CSF mNGS and 23S rRNA showed Ureaplasma parvum. The patient received erythromycin therapy for 32 d and had normal neurodevelopment at 5 months. According to the literature, 43 cases were reported including the 2 cases descirbed above, 17 cases were full-term infants and 26 cases were preterm infants. The median CSF leukocytes, glucose and proteins were 566 cells/mm 3, 0.2 mmol/L and 2.2 g/L. 27 cases were diagnosed based on CSF culture, 6 cases using mNGS, 4 cases with both CSF culture and PCR method and 6 cases with other methods. Macrolides alone were used in 14 cases, macrolides combined with another antibiotic were used in 8 cases, non-macrolide antibiotics were used in 9 cases and 12 cases didn't receive any anti-ureaplasma therapy. All 17 term infants survived, however, 8 cases with hydrocephalus. Among the 26 preterm infants, 8 patients died, 18 patients had periventricular-intraventricular hemorrhage and 15 patients had hydrocephalus. Conclusions:Neonatal ureaplasma meningitis has significantly lower CSF glucose level with hydrocephalus as the common complication. For intracranial infections of unknown etiology and no response to treatment, mNGS is helpful in determining the pathogen.Neonatal ureaplasma meningitis should be treated with macrolides alone or as add-on therapy.

Research on BHLHE40 targets HMGA2 to reduce the sensitivity of thyroid cancer cells to cisplatin through activating the oxidative phosphorylation pathway / 国际肿瘤学杂志

Objective:To explore whether BHLHE40 can affect the sensitivity of thyroid cancer (TC) cells to cisplatin by activating oxidative phosphorylation (OXPHOS) pathway by targeting high mobility group A2 (HMGA2) .Methods:The mRNA expression of HMGA2 and its upstream transcription factor BHLHE40 in TC tissues was analyzed by TCGA-THCA and hTFtarget online databases. The si-HMGA2, oe-HMGA2, oe-BHLHE40, negative control si-NC and oe-NC were transfected into TC cells (K1 and SW579) by liposome transfection method. The mRNA expression levels of BHLHE40 and HMGA2 in TC cells (SW579, FTC-133, and K1) and normal thyroid cells (Nthy ori3-1) were detected by real-time quantitative PCR (qRT-PCR). The cell viability was detected by MTT assay, the half inhibitory concentration (IC 50) value of cisplatin was calculated by CCK-8 assay, the apoptosis level was detected by flow cytometry, and the expression of OXPHOS complex was detected by Western blotting. Seahorse XFe 96 was used to analyze the oxygen consumption rate of the TC cells. Dual-luciferase assay and chromatin immunoprecipitation (ChIP) assay were used to analyze the binding relationship between BHLHE40 and HMGA2. Results:TCGA database results showed that the mRNA expression levels of HMGA2 and BHLHE40 in TC tissues (10.57±2.58, 13.89±1.13) were higher than those in normal thyroid tissues (4.82±1.69, 12.28±1.01), with statistically significant differences ( t=16.69, P<0.001; t=10.43, P<0.001). The results of qRT-PCR showed that the relative mRNA expression levels of HMGA2 in normal thyroid cells (Nthy ori3-1) and TC cells (SW579, FTC-133, and K1) were 1.00±0.13, 2.94±0.23, 4.71±0.41 and 6.29±0.49, while those of BHLHE40 were 1.00±0.12, 2.60±0.23, 3.39±0.35 and 6.18±0.51 respectively, both with statistically significant differences ( F=130.50, P<0.001; F=125.20, P<0.001). Further pairwise comparison showed that mRNA expression levels of HMGA2 and BHLHE40 in TC cells were significantly higher than those in normal thyroid cells (all P<0.001). According to MTT experimental results, si-HMGA2 treatment significantly reduced the cell viability of K1 cells compared to the si-NC group (all P<0.05). In addition, compared to the oe-NC group, oe-HMGA2 treatment significantly increased the cell viability of SW579 cells (all P<0.05). Compared to the oe-NC+DMSO group, the oe-HMGA2+DMSO group showed enhanced cell viability of SW579 cells, while the OXPHOS pathway inhibitor Gboxin was able to reverse the effect of overexpressing HMGA2 on cell viability (all P<0.05). The results of flow cytometry and CCK-8 experiments showed that compared to the si-NC group (apoptosis level: 6.19%±0.28%; cisplatin IC 50 value: 17.47 μmol/L), knocking down HMGA2 could increase the apoptosis level (11.96%±0.32%; t=19.17, P<0.001) and cisplatin sensitivity (IC 50 value: 1.49 μmol/L) of K1 cells. In addition, compared to the oe-NC group (apoptosis level: 9.98%±0.32%; cisplatin IC 50 value: 8.17 μmol/L), overexpressing HMGA2 significantly decreased the apoptosis level (4.32%±0.25%; t=19.65, P<0.001) and cisplatin sensitivity (IC 50 value: 34.95 μmol/L) of SW579 cells. The results of dual-luciferase assay showed that compared with the si-NC group, knocking down the expression of BHLHE40 in human kidney epithelial 293T cells significantly reduced the luciferase activity of wild-type HMGA2 (0.31±0.02 vs. 1.00±0.11; t=10.69, P=0.004). However, there was no significant effect on the luciferase activity of mutant-type HMGA2 (1.06±0.11 vs. 1.00±0.07; t=0.80, P=0.470). ChIP results showed that the mRNA expression level of HMGA2 in K1 cells was significantly increased in the anti-BHLHE40 group (6.57±0.62) compared with the IgG group (1.00±0.10; t=15.36, P<0.001). Compared to the oe-NC+DMSO group, the oe-HMGA2+DMSO group showed decreased apoptosis level ( P<0.05) and cisplatin sensitivity of SW579 cells, with a significant increase in the expression of OXPHOS complexes Ⅰ-Ⅴ and cellular oxygen consumption rates (all P<0.05). The effect of overexpressing HMGA2 was reversed by treatment with oe-HMGA2+Gboxin (all P<0.05). The recovery experiment showed that compared to the oe-NC+si-NC group, overexpression of BHLHE40 in SW579 cells increased cell viability and the expression of OXPHOS complexes Ⅰ-Ⅴ, while decreasing apoptosis levels and increasing cellular oxygen consumption rates and cisplatin IC 50 values (all P<0.05). However, simultaneous knockdown of HMGA2 reversed the effect of overexpressing BHLHE40 (all P<0.05) . Conclusion:BHLHE40 can activate the OXPHOS pathway by targeting and regulating the expression of HMGA2, thereby affecting the sensitivity of TC cells to cisplatin.

Expression of TPX2 in kidney renal clear cell carcinoma and its clinical significance / 国际肿瘤学杂志

Objective:To analyze the expression of targeting protein for Xklp2 (TPX2) in kidney renal clear cell carcinoma (KIRC) and its clinical significance.Methods:The postoperative tissue samples of 54 patients with KIRC admitted to the Department of Urology, the First Affiliated Hospital of Bengbu Medical College from July 2017 to June 2019 were collected. Immunohistochemistry was used to detect the protein expression of TPX2 in renal carcinoma and paracancerous tissues. The difference of TPX2 mRNA expression between KIRC tissues and normal tissues was analyzed by using the TIMER database, which verified the immunohistochemical results. The UALCAN database and the Kaplan-Meier plotter database were used to analyze the relationship between TPX2 mRNA expression and clinical stage, molecular subtypes, lymph node metastasis, and prognosis of patients with KIRC. The protein interaction network was constructed by STRING database to obtain TPX2-related proteins, and the genes corresponding to the related proteins were enriched for the KEGG pathway. The relationship between TPX2 expression and immune cell infiltration and the immune checkpoint was studied by using the TIMER database.Results:Immunohistochemical results showed that the positive expression rate of TPX2 protein was 48.15% (26/54) in cancer tissues, which was higher than that in paracancerous tissues (20.37%, 11/54) ( χ2=9.25, P=0.002). The results of bioinformatics analysis showed that TPX2 mRNA expression was significantly up-regulated in KIRC [cancer tissue: 1.89 (1.49, 2.42), normal tissue: 0.35 (0.24, 0.57), U=2 297.00, P<0.001]. The expression of TPX2 mRNA was related to the clinical stage ( χ2=34.36, P<0.001), molecular subtypes ( χ2=30.15, P<0.001), and lymph node metastasis status ( χ2=27.21, P<0.001) of KIRC patients. The 5-year survival rate (53.80%) in patients with high TPX2 expression was lower than that in patients with low TPX2 expression (74.40%, χ2=18.87, P<0.001). STRING database protein interaction network construction obtained 20 TPX2-related proteins, and the genes corresponding to the related proteins were enriched in the cell cycle. The expression of TPX2 was positively correlated with B cells ( r=0.30, P<0.001), CD8 + T cells ( r=0.23, P<0.001), CD4 + T cells ( r=0.18, P<0.001), macrophages ( r=0.20, P<0.001), neutrophils ( r=0.31, P<0.001), dendritic cells ( r=0.39, P<0.001) infiltration and most of its biomarkers (all P<0.05). It was positively correlated with immune checkpoint PD-1 ( r=0.31, P<0.001) and CTLA-4 ( r=0.27, P<0.001), but not correlated with PD-L1 ( r=0.07, P=0.146) . Conclusion:TPX2 is highly expressed in KIRC and is closely associated with poor prognosis. It is expected to be a new therapeutic target for KIRC.

Comparison of safety and efficacy of 7.5 Fr and 9.5 Fr flexible ureteroscopy in the primary treatment of upper urinary tract calculi with maximum diameter<1.5 cm / 国际外科学杂志

Objective:To compare the safety and efficacy of 7.5 Fr and 9.5 Fr flexible ureteroscopy in the primary treatment of upper urinary tract calculi with maximum diameter<1.5 cm.Methods:Using a prospective randomized controlled study method, 96 patients with upper urinary tract calculi with maximum diameter<1.5 cm admitted to the Department of Urology, Beijing Friendship Hospital, Capital Medical University from August 2020 to May 2022 were selected as the study subjects. The patients were divided into two groups by random number table method: the experimental group and the control group, with 48 patients in each group. The experimental group patients underwent 7.5 Fr flexible ureteroscopic lithotripsy, while the control group patients underwent 9.5 Fr flexible ureteroscopic lithotripsy. Collect preoperative, intraoperative, and postoperative data from these patients, including success rate of ureteral access sheath insertion, surgical time, lithotripsy time, stone-free rate, ureteral injury status, and complications status. The measurement data were expressed as mean±standard deviation ( ± s), Student- t test was used for comparison between groups; the Chi-square test was used for inter-group comparison of count data, and the Mann-Whitney U test was used for inter-group comparison of rank data. Results:The success rate of primary sheath insertion in the experimental group was 93.8% (45/48), and that in the control group was 79.2% (38/48), the difference between the two groups was statistically significant ( P<0.05). There were no statistically significant difference between the experimental group and the control group in terms of surgical time [(52.0±11.0) min vs (55.1±11.4) min, P>0.05] and lithotripsy time [(26.0±9.3) min vs (23.7±8.7) min, P>0.05]. At four weeks after surgery, the stone-free rate in the experimental group was 93.3% (42/45), while that in the control group was 97.4% (37/38), there was no statistically significant difference between the two groups ( P>0.05). In terms of the degree of ureteral injury, there were 17 patients had grade 0 injury, 27 patients had grade 1 injury, 4 patients had grade 2 injury, and no patient had grade 3 injury in the experimental group; there were 9 patients had grade 0 injury, 23 patients had grade 1 injury, 13 patients had grade 2 injury, and 3 patients had grade 3 injury in the control group; the difference between the two groups was statistically significant ( P<0.05). In terms of complications, there were 22 cases of hematuria, 9 cases of pain, 8 cases of bladder spasm, and 2 cases of mild fever in the experimental group; there were 24 cases of hematuria, 12 cases of pain, 9 cases of bladder spasm, and 1 case of mild fever in the control group; there was no statistically significant difference between the two groups ( P>0.05). Conclusion:The application of 7.5 Fr flexible ureteroscopy and 9.5 Fr flexible ureteroscopy in the primary treatment of upper urinary tract calculi with maximum diameter<1.5 cm can achieve good stone-free rates, but the 7.5 Fr flexible ureteroscopy has a higher success rate of sheath insertion and less damage to the ureter.

Expression and Significance of Lactate Dehydrogenase A in Renal Cell Carcinoma / 中山大学学报(医学科学版)

ObjectiveTo analyze the expression of Lactate dehydrogenase A（LDHA） in both renal cell carcinoma （RCC） tissue and RCC cell lines， and to investigate the impact of LDHA expression on the progression of RCC. MethodsFrom June 2018 to June 2022， totally 52 cases of RCC tissue samples and 49 cases of para-cancerous tissue samples were collected through surgical procedures from our hospital. LDHA expression was detected using immunohistochemistry （IHC）. The expression levels of LDHA in vitro were also detected in the normal human proximal tubule epithelial cell line HK-2 and renal cell carcinoma cell lines A498， Caki-2， ACHN， and 786-O by using qRT-PCR and Western blot. A recombinant plasmid carrying LDHA-shRNA was constructed and then transfected into 786-O cells to down-regulate the expression of LDHA. Tumor proliferative capacity was monitored using CCK-8 assay， clonal formation assay and EdU assessments. Additionally， cell glycolytic activity was assessed through glucose uptake assay， lactate secretion assay， and ECAR analysis. ResultsIHC analysis revealed significantly higher expression of LDHA in RCC tissue compared to adjacent tissues（P<0.05）. Furthermore， RCC tissues with higher TNM stage exhibited greater expression of LDHA than those with lower TNM stage （P<0.05）. The results of qRT-PCR and Western blot demonstrated that the expression of LDHA in each RCC cell line was significantly higher than that in HK-2（P<0.05）. After blocking the expression of LDHA in 786-O， there was a significant down-regulation of cell proliferation and glycolysis capacity （P<0.05）. ConclusionsThe expression of LDHA in RCC tissue and RCC cell lines is significantly overexpressed compared with normal one， particularly in those with higher TNM stage. Knockdown of the expression of LDHA significantly suppresses cell proliferation and aerobic glycolysis capacity in 786-O.

Comparison of safety and effectiveness of active migration technique and in situ lithotripsy technique in the treatment of 1-2 cm upper ureteral calculi by flexible ure-teroscopy / 北京大学学报(医学版)

OBJECTIVE@#To compare the safety and effectiveness of active migration technique and in situ lithotripsy technique in the treatment of 1-2 cm upper ureteral calculi by retrograde flexible ureteroscopy.@*METHODS@#A total of 90 patients with 1-2 cm upper ureteral calculi treated in the urology department of Beijing Friendship Hospital from August 2018 to August 2020 were selected as the subjects. The patients were divided into two groups using random number table: 45 patients in group A were treated with in situ lithotripsy and 45 patients in group B were treated with active migration technique. The active migration technique was to reposition the stones in the renal calyces convenient for lithotripsy with the help of body position change, water flow scouring, laser impact or basket displacement, and then conduct laser lithotripsy and stone extraction. The data of the patients before and after operation were collected and statistically analyzed.@*RESULTS@#The age of the patients in group A was (51.6±14.1) years, including 34 males and 11 females. The stone diameter was (1.48±0.24) cm, and the stone density was (897.8±175.9) Hu. The stones were located on the left in 26 cases and on the right in 19 cases. There were 8 cases with no hydronephrosis, 20 cases with grade Ⅰ hydronephrosis, 11 cases with grade Ⅱ hydronephrosis, and 6 cases with grade Ⅲ hydronephrosis. The age of the patients in group B was (51.8±13.7) years, including 30 males and 15 females. The stone diameter was (1.52±0.22) cm, and the stone density was (964.6±214.2) Hu. The stones were located on the left in 22 cases and on the right in 23 cases. There were 10 cases with no hydronephrosis, 23 cases with grade Ⅰ hydronephrosis, 8 cases with grade Ⅱ hydronephrosis, and 4 cases with grade Ⅲ hydronephrosis. There was no significant diffe-rence in general parameters and stone indexes between the two groups. The operation time of group A was (67.1±16.9) min and the lithotripsy time was (38.0±13.2) min. The operation time of group B was (72.2±14.8) min and the lithotripsy time was (40.6±12.6) min. There was no significant difference between the two groups. Four weeks after operation, the stone-free rate in group A was 86.7%, and in group B was 97.8%. There was no significant difference between the two groups. In terms of complications, 25 cases of hematuria, 16 cases of pain, 10 cases of bladder spasm and 4 cases of mild fever occurred in group A. There were 22 cases of hematuria, 13 cases of pain, 12 cases of bladder spasm and 2 cases of mild fever in group B. There was no significant difference between the two groups.@*CONCLUSION@#Active migration technique is safe and effective in the treatment of 1-2 cm upper ureteral calculi.

Progress in evaluating the risk of lymph node metastasis in early colorectal cancer / 中华胃肠外科杂志

Early colorectal cancers refer to invasive cancers that have infiltrated into the submucosa without invading muscularis propria, and approximately 10% of these patients have lymph node metastases that cannot be detected by conventional imaging. According to the guidelines of Chinese Society of Clinical Oncology (CSCO) Colorectal Cancer, early colorectal cancer cases with risk factors for lymph node metastasis (poor tumor differentiation, lymphovascular invasion, deep submucosal invasion and high-grade tumor budding) should receive salvage radical surgical resection; however, the specificity of this risk-stratification is inadequate, making most patients undergo unnecessary surgery. Firstly, this review focuses on the definition, oncological impact importance and controversy of the above "risk factors". Then, we introduce the progress of the risk stratification system for lymph node metastasis in early colorectal cancer, including the identification of new pathological risk factors, the construction of new risk quantitative models based on pathological risk factors, artificial intelligence and machine learning technology and the discovery of novel molecular markers associated with lymph node metastasis based on gene test or liquid biopsy. Aim to enhance clinicians' understanding of the risk assessment of lymph node metastasis in early colorectal cancer; we suggest to take the patient's personal situation, tumor location, anti-cancer intention and other factors into account to make individualized treatment strategies.

Macrophage heterogeneity role in NAFLD and NASH disease progression / 中华肝脏病杂志

Nonalcoholic fatty liver disease (NAFLD) is a type of metabolic stress liver injury that is closely associated with insulin resistance and genetic susceptibility. The continuum of liver injury in NAFLD can range from nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH) and even lead to cirrhosis and liver cancer. The pathogenesis of NAFLD is complicated. Pro-inflammatory cytokines, lipotoxicity, and gut bacterial metabolites play a key role in activating liver-resident macrophages (Kupffer cells, KCs) and recruiting circulating monocyte-derived macrophages (MoDMacs) to deposit fat in the liver. With the application of single-cell RNA-sequencing, significant heterogeneity in hepatic macrophages has been revealed, suggesting that KCs and MoDMacs located in the liver exert distinct functions in regulating liver inflammation and NASH progression. This study focuses on the role of macrophage heterogeneity in the development and occurrence of NAFLD and NASH, in view of the fact that innate immunity plays a key role in the development of NAFLD.

Clinical study on early predictors of concurrent bile duct injury following TACE in patients with liver cancer / 中华肝脏病杂志

Objective: To explore the predictive factors of concurrent bile duct injury following transcatheter arterial chemoembolization (TACE) in patients with hepatocellular carcinoma (HCC). Methods: A retrospective study was conducted on 483 HCC patients in relation to TACE postoperative complications. A total of 21 cases of bile duct injury were observed following the TACE procedure. Laboratory data, imaging data, and clinically relevant medical histories were recorded before and after one week following the TACE procedure and follow-up. The χ (2) test, or Fisher's exact probability method, was used for categorical variables. The mean of the two samples was compared using a paired t-test or Wilcoxon rank sum test. The comparison of multiple mean values was conducted using an analysis of variance. Results: Twenty-one cases with bile duct injury had intrahepatic bile duct dilatation, bile tumors, hilar biliary duct stenoses, and other manifestations. 14.3% (3/21) of patients showed linear high-density shadows along the bile duct on a plain CT scan, while 76.2% (16/21) of patients had ALP > 200 U/L one week following TACE procedure, and bile duct injury occurred in later follow-up. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and γ-glutamyl transferase (GGT) were significantly increased in all patients following TACE procedure (t = -2.721, P = 0.014; t = -2.674, P = 0.015; t = -3.079, P = 0.006; t = -3.377, P = 0.003, respectively). Conclusion: The deposition of iodized oil around the bile duct on plain CT scan presentation or the continuous increase of ALP (> 200 U/L) one week following TACE procedure has a certain predictive value for the later bile duct injury.

Application of different prognostic scores in liver transplantation decision-making for acute-on-chronic liver failure / 中华肝脏病杂志

Objective: To compare the impact of different prognostic scores in patients with acute-on-chronic liver failure (ACLF) in order to provide treatment guidance for liver transplantation. Methods: The information on inpatients with ACLF admitted at Beijing You'an Hospital Affiliated to Capital Medical University and the First Affiliated Hospital of Zhejiang University School of Medicine from January 2015 to October 2022 was collected retrospectively. ACLF patients were divided into liver transplantation and non-liver transplantation groups, and the two groups prognostic conditions were followed-up. Propensity score matching was carried out between the two groups on the basis of liver disease (non-cirrhosis, compensated cirrhosis, and decompensated cirrhosis), the model for end-stage liver disease incorporating serum sodium (MELD-Na), and ACLF classification as matching factors. The prognostic condition of the two groups after matching was compared. The difference in 1-year survival rate between the two groups was analyzed under different ACLF grades and MELD-Na scores. The independent sample t-test or rank sum test was used for inter-group comparison, and the χ (2) test was used for the comparison of count data between groups. Results: In total, 865 ACLF inpatients were collected over the study period. Of these, 291 had liver transplantation and 574 did not. The overall survival rates at 28, 90, and 360 days were 78%, 66%, and 62%, respectively. There were 270 cases of matched ACLF post-liver transplantation and 270 cases without ACLF, in accordance with a ratio of 1:1. At 28, 90, and 360 days, patients with non-liver transplantation had significantly lower survival rates (68%, 53%, and 49%) than patients with liver transplantation (87%, 87%, and 78%, respectively; P < 0.001). Patients were classified into four groups according to the ACLF classification criteria. Kaplan-Meier survival analysis showed that the survival rates of liver transplantation and non-liver transplantation patients in ACLF grade 0 were 77.2% and 69.4%, respectively, with no statistically significant difference (P = 0.168). The survival rate with an ACLF 1-3 grade was significantly higher in liver transplantation patients than that of non-liver transplantation patients (P < 0.05). Patients with ACLF grades 1, 2, and 3 had higher 1-year survival rates compared to non-liver transplant patients by 50.6%, 43.6%, and 61.7%, respectively. Patients were divided into four groups according to the MELD-Na score. Among the patients with a MELD-Na score of < 25, the 1-year survival rates for liver transplantation and non-liver transplantation were 78.2% and 74.0%, respectively, and the difference was not statistically significant (P = 0.149). However, among patients with MELD-Na scores of 25-30, 30-35, and≥35, the survival rate was significantly higher in liver transplantation than that of non-liver transplantation, and the 1-year survival rate increased by 36.4%, 54.9%, and 62.5%, respectively (P < 0.001). Further analysis of the prognosis of patients with different ACLF grades and MELD-Na scores showed that ACLF grades 0 or 1 and MELD-Na score of < 30 had no statistically significant difference in the 1-year survival rate between liver transplantation and non-liver transplantation (P > 0.05), but in patients with MELD-Na score≥30, the 1-year survival rate of liver transplantation was higher than that of non-liver transplantation patients (P < 0.05). In the ACLF grade 0 and MELD-Na score of≥30 group, the 1-year survival rates of liver transplantation and non-liver transplantation patients were 77.8% and 25.0% respectively (P < 0.05); while in the ACLF grade 1 and MELD-Na score of≥30 group, the 1-year survival rates of liver transplantation and non-liver transplantation patients were 100% and 20.0%, respectively (P < 0.01). Among patients with ACLF grade 2, the 1-year survival rate with MELD-Na score of < 25 in patients with liver transplantation was 73.9% and 61.6%, respectively, and the difference was not statistically significant (P > 0.05); while in the liver transplantation patients group with MELD-Na score of ≥25, the 1-year survival rate was 79.5%, 80.8%, and 75%, respectively, which was significantly higher than that of non-liver transplantation patients (36.6%, 27.6%, 15.0%) (P < 0.001). Among patients with ACLF grade 3, regardless of the MELD-Na score, the 1-year survival rate was significantly higher in liver transplantation patients than that of non-liver transplantation patients (P < 0.01). Additionally, among patients with non-liver transplantation with an ACLF grade 0~1 and a MELD-Na score of < 30 at admission, 99.4% survived 1 year and still had an ACLF grade 0-1 at discharge, while 70% of deaths progressed to ACLF grade 2-3. Conclusion: Both the MELD-Na score and the EASL-CLIF C ACLF classification are capable of guiding liver transplantation; however, no single model possesses a consistent and precise prediction ability. Therefore, the combined application of the two models is necessary for comprehensive and dynamic evaluation, but the clinical application is relatively complex. A simplified prognostic model and a risk assessment model will be required in the future to improve patient prognosis as well as the effectiveness and efficiency of liver transplantation.

Assessment of liver transplant benefit and a novel strategy for liver donor allocation in acute-on-chronic liver failure / 中华肝脏病杂志

Acute-on-chronic liver failure (ACLF) is a type of complex clinical syndrome that is mainly characterized by acute deterioration of liver function based on chronic liver disease, hepatic and extrahepatic organ failures, and a high short-term mortality rate. The comprehensive medical treatment efficacy of ACLF is currently limited; thus, liver transplantation is the only viable potential treatment method. However, considering the severe liver donor shortage, economic and social costs, as well as the differences in disease severity and prognosis of different disease courses, it is particularly important to accurately assess the benefits of liver transplantation in patients with ACLF. Early identification and prediction, timing, prognosis, and survival benefits are discussed here by combining the latest research findings so as to optimize the liver transplantation treatment strategy for ACLF.

Efficacy of high-dose dual therapy for Helicobacter pylori infection eradication in servicemen: a randomized controlled trial / 中华内科杂志

Objective: To assess the efficacy and cost-effectiveness of high-dose dual therapy compared with bismuth-containing quadruple therapy for treating Helicobacter pylori(H.pylori) infection in servicemen patients. Methods: A total of 160 H. pylori-infected, treatment-naive servicemen, including 74 men and 86 women, aged from 20 years to 74 years, with a mean (SD) age of 43 (13) years, tested in the First Center of Chinese PLA General Hospital from March 2022 to May 2022 were enrolled in this open-label, randomized controlled clinical trial. Patients were randomly allocated into 2 groups: the 14-day high-dose dual therapy group and the bismuth-containing quadruple therapy group. Eradication rates, adverse events, patient compliance, and drug costs were compared between the two groups. The t-test was used for continuous variables, and the Chi-square test for categorical variables. Results: No significant difference in H. pylori eradication rates were found between high-dose dual therapy and bismuth-containing quadruple therapy by ITT, mITT and PP analysis[ITT:90.0% (95%CI 81.2%-95.6%) vs. 87.5% (95%CI 78.2%-93.8%), χ2=0.25, P=0.617;mITT:93.5% (95%CI 85.5%-97.9%) vs. 93.3% (95%CI 85.1%-97.8%), χ2<0.01, P=1.000; PP: 93.5% (95%CI 85.5%-97.9%) vs. 94.5% (95%CI 86.6%-98.5%), χ2<0.01, P=1.000 ]. The dual therapy group exhibited significantly less overall side effects compared with the quadruple therapy group [21.8% (17/78) vs. 38.5% (30/78), χ2=5.15,P=0.023]. There were no significant differences in the compliance rates between the two groups [98.7%(77/78) vs. 94.9%(74/78), χ2=0.83,P=0.363]. The cost of medications in the dual therapy was 32.0% lower compared with that in the quadruple therapy (472.10 RMB vs. 693.94 RMB). Conclusions: The dual regimen has a favorable effect on the eradication of H. pylori infection in servicemen patients. Based on the ITT analysis, the eradication rate of the dual regimen is grade B (90%, good). Additionally, it exhibited a lower incidence of adverse events, better compliance and significantly reduced cost. The dual regimen is expected to be a new choice for the first-line treatment of H. pylori infection in servicemen but needs further evaluation.

Investigation of familial tendency of endometriosis / 中华妇产科杂志

Objective: To investigate the familial heritability of endometriosis and to compare the clinical characteristics of patients with or without a family history of endometriosis. Methods: From January 2020 to June 2022, 850 patients with endometriosis confirmed by laparotomy or laparoscopy in Peking University Third Hospital were included in this study. Clinical data were collected, family history was followed up, and the differences of clinical indicators between patients with and without family history of endometriosis were compared. Results: A total of 850 patients were enrolled, with an average age of (33.8±7.0) years old, 315 (37.1%, 315/850) patients in stage Ⅲ and 496 (58.4%, 496/850) patients in stage Ⅳ. There were 100 patients with family history of endometriosis, accounting for 11.8% (100/850). Most of the 113 relatives involved were mothers, daughters and sisters (76.1%, 86/113), 81.5% (22/27) of the second and third degree relatives were maternal relatives. The median ages of patients with and without family history of endometriosis were 30 and 33 years old respectively at the time of diagnosis. The unmarried rate of patients with family history was higher [42.0% (42/100) vs 26.3% (197/750)]. The percentage of dysmenorrhea patients with family history was higher [89.0% (89/100) vs 55.5% (416/750)]. The medians of dysmenorrhea score in patients with and without family history were 6 and 2, and the median durations of dysmenorrhea were 10 and 1 years. There were significant differences in age, marital status, percentage of dysmenorrhea, dysmenorrhea score and duration (all P<0.001). The median levels of serum cancer antigen (CA) 125 in patients with family history and patients without family history at the time of diagnosis were 57.5 and 46.9 kU/L respectively, with a statistically significant difference (P<0.05). However, there were no significant differences between the two groups in nationality, bady mass index, menarche age, menstrual cycle, menstrual period, menstrual volume, serum CA19-9 level, cyst location and size, stage, history of adverse pregnancy and childbirth, infertility, adenomyosis and deep infiltrating endometriosis (all P>0.05). By comparing the specific conditions of dysmenorrhea patients with and without family history of endometriosis, there were no significant differences between the two groups in terms of the age of onset of dysmenorrhea, duration of dysmenorrhea, primary and secondary dysmenorrhea, and progressive aggravation of dysmenorrhea (all P>0.05). The difference in the degree of dysmenorrhea in dysmenorrhea patients with family history of endometriosis was significant (P<0.001). Conclusions: The incidence of endometriosis has a familial tendency, and most of the involved relatives are the first degree relatives. Compared with patients without family history of endometriosis, endometriosis patients with family history are diagnosed at an earlier age, with higher percentage of dysmenorrhea, had more severe dysmenorrhea and higher serum CA125 level.

Analysis of tuberculosis epidemiological characteristics and drug resistance among the floating population in Beijing in 2019 / 中华流行病学杂志

Objective: To analyze the epidemic characteristics and drug resistance of pulmonary tuberculosis among the floating population in Beijing and to provide a scientific basis for formulating strategies for the prevention and control of tuberculosis among the floating population. Methods: Data of tuberculosis patients who were positive for Mycobacterium tuberculosis culture was collected from 16 districts and one municipal institution of tuberculosis control and prevention in Beijing in 2019. The strain samples were tested for drug sensitivity by the proportional method. According to household registration location, patients were divided into the floating population and Beijing registration. SPSS 19.0 software analyzed tuberculosis patients' epidemic characteristics and drug resistance in the floating population. Results: In 2019, there were 1 171 culture-positive tuberculosis patients in Beijing, among the floating population, 593 (50.64%) patients were identified, with a male-to-female sex ratio of 2.2∶1 (409∶184). Compared to patients under household registration as Beijing residents, a higher proportion of young adults aged 20-39 years (65.09%,386/593) were noticed, with 55.65% (330/593) reported from the urban areas and 96.80% (574/593) were reported the first time. The differences were statistically significant (all P<0.05). After completing the drug sensitivity test, 37 cases were with multiple drug-resistant tuberculosis, accounting for 6.24% (37/593). The rates of isoniazid resistance (42.11%,8/19) and multidrug resistance (21.05%,4/19) in floating population patients after retreatment were significantly higher than those in newly treated patients (11.67%, 67/574 and 5.75%, 33/574), and the differences were statistically significant (all P<0.05). Conclusions: Most patients with tuberculosis in the floating population in Beijing in 2019 were young males aged 20-39 years. The reporting areas were urban areas and the newly treated patients mainly. The patients with tuberculosis in the re-treated floating population were more likely to suffer from multidrug and drug resistance, which should be taken as the key population for prevention and control.

Knowledge, attitudes and practices regarding tuberculosis prevention and control:analysis of influencing factors of prevention and control behavior among college students in Wuhan, China / 中国学校卫生

Objective@#To determine the knowledge, attitudes and practices (KAP) regarding tuberculosis prevention and control among college students in Wuhan, China, while analyzing the factors affecting tuberculosis prevention behavior.@*Methods@#Referring to the National KAP Questionnaire for Tuberculosis Prevention and Control among College Students, which was designed by China Center for Disease Control and Prevention, 22 colleges and universities in Wuhan were selected using a judgment sampling method, and a questionnaire survey was carried out through the online questionnaire platform. The formation of tuberculosis prevention and control behavior among this population was analyzed by single factor and multi factor Logistic regression.@*Results@#The total awareness rate of KAP regarding tuberculosis prevention and control among college students in Wuhan was 79.69%; the awareness rate of core knowledge was 79.28%, and the passing rate was 92.46%. The correct attitude holding rate was 89.69%, while the passing rate was 90.56%. In respect to correct behavior, the formation rate was 72.11%, with a passing rate of 96.62%. The multivariate Logistic regression analysis showed that the following factors were more likely to promote tuberculosis prevention and control behaviors that met the target: female college students ( OR =1.86); college students whose father had a primary school education level, junior high school and equivalent, high school and equivalent, and junior high school students ( OR =2.94, 3.05, 3.17, 3.24 ); no history of tuberculosis ( OR =3.32); the passing knowledge of core knowledge ( OR =9.91), and the passing attitude holding score ( OR =7.35)( P <0.05).@*Conclusion@#The overall awareness rate of KAP regarding tuberculosis prevention and control among college students in Wuhan is acceptable,the mainly influenced factors are gender, history of tuberculosis, awareness rate of core knowledge about prevention and control, attitudes and cognition, and parents educational background.

Analysis of ethical review issues of informed consent form for clinical trials of registered anti-tumor drugs in our hospital / 中国药房

OBJECTIVE To promote the standardization and integrity of the informed consent form for clinical trials of registered anti-tumor drugs， and to protect the legitimate rights and interests of the subjects. METHODS The ethical review resolutions of clinical trial projects of registered anti-tumor drugs that were initially reviewed by the Ethics Committee of our hospital from July 1st， 2020 to July 1st， 2022 were summarized to statistically analyze the problematic items according to the “Quality Analysis Form of Informed Consent” prepared by our hospital. RESULTS Of the 316 clinical trials of registered anti- tumor drugs that were initially reviewed， 257 （81.3%） had problems with the contents of informed consent form， mainly domestic multi-center trials and phase Ⅲ trials. The main problems included the vague notification of the test fee bearer （68.5%）， the incomplete notification of the test content （59.1%）， the insufficient notification of rights and interests and risks （58.4%）， the insufficient notification of personal information protection （56.0%）， and the nonstandard expression of the informed consent form （52.5%）. CONCLUSIONS There is still a gap between the informed consent form of the clinical trials of registered anti-tumor drugs in our hospital and the requirements of the new version of Good Clinical Practice for Drugs （GCP）. The parties involved in the test can take a number of measures to improve the standardization and integrity of the informed consent form， and the research team should design the informed consent form in strict accordance with the requirements of the new GCP and pay attention to the comprehensive notification about the test. The Ethics Committee can provide the sponsor and researcher with the template of informed consent form and the key points of writing， continue to strengthen the examination ability， improve the examination quality， and effectively protect the safety and interests of the subjects.

Therapeutic Effect of Canagliflozin on Nephrotic Syndrome and Its Ultrasonic Evaluation / 中山大学学报(医学科学版)

ObjectiveTo investigate the therapeutic effect of antidiabetic drug canagliflozin （CGLZ） on adriamycin-induced nephrotic syndrome （NS） in rats， and the evaluation of contrast-enhanced ultrasound （CEUS） combined with color Doppler flow imaging （CDFI） during the treatment. MethodsA total of 56 male SD rats were randomly divided into normal group （NG）， model group （MG）， prednisone （PAT） group （PG）， low-dose single CGLZ group （LSCG）， high-dose single CGLZ group （HSCG）， low-dose CGLZ + PAT group （LUCG） and high-dose CGLZ + PAT group （HUCG）， with 8 rats in each group. The NS model in rats was induced by injecting adriamycin twice into the tail vein， and then the NS rats were treated by intragastric administration daily for 6 weeks with reference of PAT. Twenty-four hour urine total protein （24 h-UTP） was assessed one day before the start of oral administration and at the end of 2， 4 and 6 weeks after oral administration， respectively. CDFI and CEUS were performed on the right renal artery at the end of 6 weeks after oral administration， and the blood of abdominal aorta was taken for serological test the next day. ResultsCompared with those detection index of NG rats， the 24-hour UTP of MG rats increased （P＜0.01）， the serum ALB decreased and TG， TC， LDL increased （P＜0.01）， and CDFI shows that RRCT was thinner （P＜0.01） and the renal artery blood flow indicators RA-PI， RA-RI， RA-S/D all increased （P＜0.05）， and CEUS image shows that the TIC curve parameters TTP， AT， AUC all increased and DPI decrease in MG rats （P＜0.01）. After drug treatment， compared with those detection index of MG rats， 24 h-UTP decrease in LSCG after 2 weeks （P＜0.01）， and decrease significantly in all drug groups after 6 weeks （P＜0.01）； the serological test results show that the serum ALB in all CGLZ groups increased （P＜0.05）， TG decrease in LSCG （P＜0.01）， TC and LDL also decrease in LUCG after 6 weeks （P＜0.05）； CDFI shows that the RRCT thinning degree in all CGLZ is reduced （P＜0.01）， and the RA-PI in LSCG， RA-RI in PG， and RA-S/D in PG， LSCG， HSCG and LUCG rats all decreased （P＜0.05）； CEUS shows that the TTP， AT and AUC of renal TIC curve in drug treatment groups all decreased （P＜0.01）， and the DPI in PG， HSCG， LUCG and HUCG rats increased （P＜0.01）. ConclusionsCGLZ has the effect of treating NS， and the small dose is the best. CEUS combined with CDFI can be used to evaluate the renal morphology and hemodynamic changes of NS model rats before and after drug treatment， which is helpful to guide clinical application.