Research progress of IDO1-mediated tryptophan metabolism in sepsis / 药学学报

Sepsis is a condition characterized by organ dysfunction resulting from the systemic inflammatory response triggered by an infection. Excessive inflammation and immunosuppression are intertwined, and severe cases may even develop into multiple organ failure. Studies have shown that indoleamine 2,3-dioxygenase 1-mediated tryptophan metabolism is involved in the occurrence and development of sepsis, and elevated plasma kynurenine levels and Kyn/Trp ratios are early indicators of sepsis development. In this paper, we provide a comprehensive summary of the role of IDO1 in the acute inflammatory phase of sepsis, late immunosuppression, and organ damage. This includes its regulation of inflammatory state, immune cell function, blood pressure, and other aspects. Additionally, we analyze preclinical studies on targeted IDO1 drugs. An in-depth understanding and study of IDO may help to understand the pathogenesis and clinical significance of sepsis and multiple organ damage from a new perspective and provide new research ideas for exploring its prevention and treatment methods.

Multimodal magnetic resonance imaging of subjective tinnitus related mood disorder / 中华行为医学与脑科学杂志

Subjective tinnitus refers to the subjective sound perception of patients in the absence of an external sound stimulus.Tinnitus patients are often accompanied by emotional disorders, such as depression and anxiety, which seriously affect the quality of life of patients.Therefore, understanding the mechanism underlying the occurrence of tinnitus emotional disorders can help relieve the pain of tinnitus.Tinnitus was considered a simple ear disease in the early stages, but with the progress of neuroimaging technology and the development of animal models, increasing attention has been given to the changes in the neural structure and function of tinnitus patients.As a powerful technique for in vivo investigation of neural activity in the brain, multimodal magnetic resonance has been widely used in the study of subjective tinnitus.By observing the changes of brain structure in subjective tinnitus patients, the neural mechanism of the occurrence and development of tinnitus has been explored.This article reviewed recent multimodal magnetic resonance imaging studies on the neuroimaging mechanisms of tinnitus with mood disorders, compared the differences in neural activity between subjective tinnitus patients and healthy people, and found that the limbic system, default mode network and other neural network abnormalities were closely related to the mood disorders of tinnitus.The application and development of multimodal magnetic resonance techniques in subjective tinnitus were also discussed to elucidate the neural mechanism of subjective tinnitus accompanied by mood disorders with the help of multimodal magnetic resonance techniques.

Changes in functional connectivity in patients with acute mild traumatic brain injury based on a triple-network model: a resting state functional MRI study / 中华行为医学与脑科学杂志

Objective:To investigate the resting state functional connectivity changes of the " triple network model" composed of salient network (SN), executive control network (ECN) and default mode network (DMN) in patients with acute mild traumatic brain injury (mTBI).Methods:From August 2020 to December 2021, forty-five acute mTBI patients (mTBI group) and 40 healthy controls (HC group) with matched sex, age, and education were included.The Montreal cognitive assessment (MoCA) scale was used to evaluate the cognitive status of all subjects.The resting state network (RNS) was established based on independent component analysis (ICA), and the SN, ECN and DMN were extracted, then functional network connectivity (FNC) was analyzed.Subsequently, the correlation between functional connectivity abnormalities and the performance of cognitive impairment was analyzed.SPSS 19.0 was used for statistical analysis and double sample t test was used for comparison between the tow groups. Results:Compared with HC group, mTBI group had enhanced functional connectivity between SN(L-insula) (MNI: x, y, z=-36, 15, 0, t=3.693)and ECN (left superior parietal gyrus, L-SPG) (MNI: x, y, z=-33, -69, 54, t=3.333)(FDR adjust, P<0.05), and decreased functional connectivity between DMN(left superior frontal gyrus, L-SFG) (MNI: x, y, z=-30, 30, 42, t=-4.063)and DMN(L-angular gyrus)(MNI: x, y, z=-21, -66, 33, t=-4.101)(FDR adjust, P<0.05). For FNC analysis, functional network connectivity in SN(IC26)-DMN(IC8) was enhanced in the acute mTBI group and decreased between SN(IC26)-DMN(IC12) and ECN(IC3)-DMN(IC12). The changes of left superior parietal gyrus functional connection were negatively correlated with MoCA score ( r=-0.627, P<0.01), and SN (IC26) -DMN(IC12) connection was positively correlated with MoCA score ( r=0.411, P=0.005). Conclusions:In patients with acute mTBI, the resting functional connectivity changes within and between the networks of the " triple network model" composed of SN, ECN and DMN, and is related to the decline of cognitive function.This will help to better understand the neuropathological mechanism of acute mTBI and post-traumatic cognitive impairment, and may become an effective imaging marker for identifying and predicting cognitive impairment after mTBI.

Novel wine in an old bottle:Preventive and therapeutic potentials of andrographolide in atherosclerotic cardiovascular diseases / 药物分析学报

Atherosclerotic cardiovascular disease(ASCVD)frequently results in sudden death and poses a serious threat to public health worldwide.The drugs approved for the prevention and treatment of ASCVD are usually used in combination but are inefficient owing to their side effects and single therapeutic targets.Therefore,the use of natural products in developing drugs for the prevention and treatment of ASCVD has received great scholarly attention.Andrographolide(AG)is a diterpenoid lactone compound extracted from Andrographis paniculata.In addition to its use in conditions such as sore throat,AG can be used to prevent and treat ASCVD.It is different from drugs that are commonly used in the prevention and treatment of ASCVD and can not only treat obesity,diabetes,hyperlipidaemia and ASCVD but also inhibit the pathological process of atherosclerosis(AS)including lipid accumulation,inflammation,oxidative stress and cellular abnormalities by regulating various targets and pathways.However,the pharmaco-logical mechanisms of AG underlying the prevention and treatment of ASCVD have not been corrobo-rated,which may hinder its clinical development and application.Therefore,this review summarizes the physiological and pathological mechanisms underlying the development of ASCVD and the in vivo and in vitro pharmacological effects of AG on the relative risk factors of AS and ASCVD.The findings support the use of the old pharmacological compound('old bottle')as a novel drug('novel wine')for the pre-vention and treatment of ASCVD.Additionally,this review summarizes studies on the availability as well as pharmaceutical and pharmacokinetic properties of AG,aiming to provide more information regarding the clinical application and further research and development of AG.

An Investigation of the Effects of B7-H4 Gene rs10754339 and miR-125a Gene rs12976445 on Cancer Susceptibility / 生物医学与环境科学（英文）

OBJECTIVE@#To investigate the effects of the B7-H4 gene rs10754339 and miR-125a gene rs12976445 on cancer susceptibility through a case-control study and meta-analysis.@*METHODS@#A total of 1,490 cancer patients (lung/gastric/liver/: 550/460/480) and 800 controls were recruited in this case-control study. The meta-analysis was performed by pooling the data from previous related studies and the present study.@*RESULTS@#The results of this study showed that in the Hubei Han Chinese population, the rs10754339 gene was significantly associated with the risk of lung and gastric cancer but not liver cancer, and the rs12976445 gene was significantly associated with the risk of lung cancer but not liver or gastric cancer. The meta-analysis results indicated that rs10754339 and rs12976445 contributed to cancer susceptibility in the Chinese population and also revealed a significant association between rs10754339 and breast cancer risk, as well as between rs12976445 and lung cancer risk.@*CONCLUSION@#The B7-H4 gene rs10754339 and miR-125a gene rs12976445 may be the potential genetic markers for cancer susceptibility in the Chinese population, which should be validated in future studies with larger sample sizes in other ethnic populations.

Clinical and etiological characteristics of infectious vulvovaginitis in children in Zhejiang province from 2009 to 2019 / 中华儿科杂志

Objective: To explore the clinical characteristics, common pathogens in children with vulvovaginitis. Methods: This was a retrospective cases study. A total of 3 268 children with vulvovaginitis were enrolled, who visited the Department of Pediatric and Adolescent Gynecology, Children's Hospital, Zhejiang University School of Medicine from January 2009 to December 2019. Patients were divided into 3 groups according to the age of <7, 7-<10 and 10-18 years. Patients were also divided in to 4 groups according to the season of first visit. The pathogen distribution characteristics of infective vulvovaginitis were compared between the groups. Their clinical data were collected and then analyzed by χ2 test. Results: The were 3 268 girls aged (6.2±2.5) years. There were 1 728 cases (52.9%) aged <7 years, 875 cases (26.8%) aged 7-<10 years, and 665 cases (20.3%) aged 10-18 years. Of these cases, 2 253 cases (68.9%) were bacterial vulvovaginitis, 715 cases (21.9%) were fungal vulvovaginitis and 300 cases (9.2%) were vulvovaginitis infected with other pathogens. Bacterial culture of vaginal secretions was performed in 2 287 cases, and 2 287 strains (70.0%) of pathogens were detected, of which the top 5 pathogens were Streptococcus pyogenes (745 strains, 32.6%), Haemophilus influenzae (717 strains, 31.4%), Escherichia coli (292 strains, 12.8%), Staphylococcus aureus (222 strains, 9.7%) and Klebsiella pneumoniae (67 strains, 2.9%). Regarding different age groups, H.influenzae was the most common in children under 7 years of age (40.3%, 509/1 263), S.pyogenes (41.9%, 356/849) was predominantly in children aged 7 to 10 years, and E.coli was predominant in children aged 10 to 18 years (26.3%, 46/175). Susceptibility results showed that S.pyogenes was susceptible to penicillin G (610/610, 100.0%), ceftriaxone (525/525, 100.0%), and vancomycin (610/610, 100.0%); the resistance rates to erythromycin and clindamycin were 91.9% (501/545)and 90.7% (495/546), respectively. For H.influenzae, 32.5% (161/496) produced β-elactamase, and all strains were sensitive to meropenem (489/489, 100.0%) and levofloxacin (388/388, 100.0%), while 40.5% (202/499) were resistant to ampicillin. Among E.coli, all strains were sensitive to imipenem(100%, 175/175). The resistance rates of E.coli to levofloxacin and ceftriaxone were 29.1% (43/148) and 35.1% (59/168), respectively. A total of 48 strains of methicillin-resistant Staphylococcus aureus (MRSA) were isolated with a proportion of 28.3% (45/159) in 3 268 patients. The results of drug susceptibility test showed that all MRSA strains were sensitive to linezolid 100.0% (40/40), vancomycin (45/45, 100.0%), and tigecycline (36/36, 100.0%); the resistance rates of MRSA to penicillin G, erythromycin and clindamycin were 100% (45/45), 95.6% (43/45) and 88.9% (40/45), respectively. All methicillin-sensitive Staphylococcus aureus (MSSA) strains were sensitive to oxacillin (114/114, 100.0%), linezolid (94/94, 100.0%), vancomycin (114/114, 100.0%), and tigecycline (84/84, 100.0%); it's resistance rates to penicillin G, erythromycin and clindamycin were 78.1% (89/114), 59.7% (68/114) and 46.5% (53/114), respectively. The drug resistance rate of MSSA to penicillin G, erythromycin and clindamycin were lower than those of MRSA (χ²=11.71,19.74,23.95, respectively, all P<0.001). Conclusions: The age of consultation for pediatric infectious vulvovaginitis is mainly around 6 years. The most common pathogens are S.pyogenes, H.influenzae and Escherichia coli. Third generation cephalosporins can be used as the first choice of empirical anti-infection drugs. However, the results of drug susceptibility should be considered for targeted treatment.

Research progress on the development of human neutrophil elastase inhibitors / 药学学报

Human neutrophil elastase (hNE) is a serine proteolytic enzyme mainly distributed in neutrophils. When the balance between anti-hNE protein and hNE is broken, excessive release of hNE can cause the occurrence of various diseases. Therefore, inhibition of hNE is a promising therapeutic strategy. In this paper, the structure, action mechanism, physiological function of hNE and the development of hNE inhibitors were briefly summarized, in order to provide information for the related research.

Mechanism of Banxia Baizhu Tianma decoction to prevent the development of prehypertension and excessive phlegm-dampness syndrome in rats based on metabonomics technology / 药学学报

The alterations of serum biological endogenous chemicals in rats with phlegm dampness accumulation syndrome of prehypertension (PHT) were interfered by Banxia Baizhu Tianma decoction (BBT), and the metabolic regulatory pathway of BBT was clarified using serum metabonomics analysis. To replicate the rat model of prehypertension phlegm dampness syndrome, blood pressure, behavioral markers, and serum biochemical markers of rats were collected. BBT's effectiveness in controlling blood pressure and blood lipids was assessed, and changes in endogenous small molecules in rat serum were determined using UPLC-Q-Orbitrap MS metabolic analysis. The results showed that BBT could regulate 9 metabolites, including arachidonic acid, cholic acid, glycodeoxycholic acid, N-adenosyltyrosine, arginine, lysophosphatidylethanolamine (20:0/0:00), lysophospholipid (P-18:0), lysophospholipid (18:0), lysophospholipid (22:5(7Z,10Z,13Z,16Z,19Z)). MetaboAnalyst was used to analyze the metabolic pathway. There were 7 metabolic pathways closely related to the change of blood pressure in rats, among which arachidonic acid metabolic pathway was the most critical. The metabolism difference foreign body in the model rats tends to return to the normal level, which provides a research basis for the mechanism of BBT from the perspective of metabonomics. This study was approved by the Experimental Animal Welfare Ethics Review Committee of Shandong University of Traditional Chinese Medicine (approval number: SDUTCM20211103001).

Relationships of Low Serum Levels of Interleukin-10 With Poststroke Anxiety and Cognitive Impairment in Patients With Clinical Acute Stroke

Background@#and Purpose The relationships among interleukin (IL)-10 levels, anxiety, and cognitive status after stroke remain controversial. We aimed to determine the associations of serum IL-10 levels with poststroke anxiety (PSA) and poststroke cognitive impairment (PSCI). @*Methods@#We recruited 350 patients with stroke, of whom only 151 completed a 1-month follow-up assessment. The Mini Mental State Examination (MMSE) and Hamilton Anxiety Scale (HAMA) were used to assess the cognitive status and anxiety, respectively. Serum IL-10 levels were measured within 24 hours of admission. @*Results@#IL-10 levels were significantly lower in the PSA group than in the non-PSA group, and they were negatively associated with HAMA scores (r=-0.371, p<0.001). After adjusting for all potential confounders, IL-10 levels remained an independent predictor of PSA (odds ratio=0.471, 95% confidence interval=0.237–0.936, p=0.032). IL-10 levels were strongly correlated with behavior during interviews, psychic anxiety, and somatic anxiety. Patients without PSCI had higher IL-10 levels were higher in non-PSCI patients than in PSCI patients, and they were positively associated with MMSE scores in the bivariate correlation analysis (r=0.169, p=0.038), and also with memory capacity, naming ability, and copying capacity.However, IL-10 did not predict PSCI in the univariable or multivariable logistic regression. @*Conclusions@#Low IL-10 levels were associated with increased risks of PSA and PSCI at a 1-month follow-up after stroke. Serum IL-10 levels may therefore be helpful in predicting PSA.

CHD1 deletion stabilizes HIF1α to promote angiogenesis and glycolysis in prostate cancer / 亚洲男科学杂志(英文版)

Chromodomain-helicase-DNA-binding protein 1 (CHD1) deletion is among the most common mutations in prostate cancer (PCa), but its role remains unclear. In this study, RNA sequencing was conducted in PCa cells after clustered regularly interspaced palindromic repeat (CRISPR)/CRISPR-associated protein 9 (Cas9)-based CHD1 knockout. Gene set enrichment analysis (GSEA) indicated upregulation of hypoxia-related pathways. A subsequent study confirmed that CHD1 deletion significantly upregulated hypoxia-inducible factor 1α (HIF1α) expression. Mechanistic investigation revealed that CHD1 deletion upregulated HIF1α by transcriptionally downregulating prolyl hydroxylase domain protein 2 (PHD2), a prolyl hydroxylase catalyzing the hydroxylation of HIF1α and thus promoting its degradation by the E3 ligase von Hippel-Lindau tumor suppressor (VHL). Functional analysis showed that CHD1 deletion promoted angiogenesis and glycolysis, possibly through HIF1α target genes. Taken together, these findings indicate that CHD1 deletion enhances HIF1α expression through PHD2 downregulation and therefore promotes angiogenesis and metabolic reprogramming in PCa.

Impact of different types of heart failure on long-term renal prognosis in patients with renal insufficiency and heart failure / 中华肝脏病杂志

Objective: To investigate the effects of different types of heart failure on long-term renal prognosis in patients with renal insufficiency and heart failure. Methods: The patients with renal insufficiency [baseline estimated glomerular filtration rate < 60 ml·min-1·(1.73 m2)-1] and heart failure followed-up for more than 2 years and hospitalized in Beijing Anzhen Hospital, Capital Medical University from January 1, 2018 to June 30, 2019 were enrolled in this retrospective cohort study. The patients were divided into three groups based on the baseline left ventricular ejection fraction (LVEF): heart failure with reduced ejection fraction (HFrEF, LVEF < 40%) group, heart failure with mildly reduced ejection fraction (HFmrEF, 40% ≤ LVEF < 50%) group, and heart failure with preserved ejection fraction (HFpEF, LVEF ≥ 50%) group. Clinical data were collected and endpoint events (adverse renal outcome: the composite outcome of all-cause death or worsening renal function) were recorded through the electronic medical record system. Kaplan-Meier survival curve was used to analyze the incidence of endpoint events of different heart failure subgroups. Cox regression model was performed to analyze the risk factors of endpoint events. Results: A total of 228 patients with renal insufficiency complicated with heart failure were included, with age of (68.14±14.21) years old and 138 males (60.5%). There were 85 patients (37.3%) in the HFrEF group, 40 patients (17.5%) in the HFmrEF group, and 103 patients (45.2%) in the HFpEF group. There were statistically significant differences in age, proportion of age > 65 years old, sex distribution, systolic blood pressure, pulmonary artery pressure, serum sodium, serum calcium, hemoglobin, serum cholesterol, low-density lipoprotein cholesterol, serum uric acid, troponin I, hypersensitive C-reactive protein, LVEF, ventricular septal thickness, left ventricular end-diastolic diameter, B-type natriuretic peptide, estimated glomerular filtration rate, and proportions of using beta blockers, using spirolactone, myocardial infarction, hypertension, cardiomyopathy and atrial fibrillation (all P < 0.05). During the median follow-up of 36.0 (28.0, 46.0) months, 73 patients (32.0%) had adverse renal outcomes. The total incidences of adverse renal outcomes were 32.9% (28/85) in the HFrEF group, 35.0% (14/40) in the HFmrEF group, and 30.1% (31/103) in the HFpEF group. Kaplan-Meier survival curve showed that there was no significant difference in the incidence of endpoint events among the three groups (log-rank test χ2=0.17, P=0.680). Multivariate Cox regression analysis showed that HFpEF (HFrEF as reference, HR=2.430, 95% CI 1.055-5.596, P=0.037) was an independent influencing factor of endpoint events. Conclusions: The long-term renal prognosis of patients with renal insufficiency and heart failure is poor. Compared with HFrEF, HFpEF is an independent risk factor of poor long-term renal prognosis in renal insufficiency patients with heart failure.

Thoughts of treatment of tumor diseases based on toxic pathogen theory / 中国中药杂志

The toxic pathogen theory, an important part of the theories of traditional Chinese medicine(TCM), began in the Qin and Han dynasties, formed in the Jin, Sui, Tang, and Song dynasties, developed rapidly in the Ming and Qing dynasties, and conti-nued to develop in contemporary times based on the achievements of its predecessors. The continuous exploration, practice, and inheri-tance of many medical practitioners over the generations have facilitated the enrichment of its connotation. The toxic pathogen is violent, fierce, dangerous, prolonged, rapid in transmission, easy to hurt the internal organs, hidden, and latent, with many changes, and it is closely related to the development of tumor diseases. TCM has a history of thousands of years in the prevention and treatment of tumor diseases. It is gradually realized that the etiology of tumor is mainly attributed to the deficiency of healthy Qi and excess of to-xic pathogen, and the struggle between healthy Qi and toxic pathogen runs through the whole course of tumor, with the deficiency of healthy Qi as the prerequisite and the invasion of toxic pathogen as the root of the occurrence. The toxic pathogen has a strong carcinogenic effect and is involved in the whole process of tumor development, which is closely related to the malignant behaviors of tumors, including proliferation, invasion, and metastasis. This study discussed the historical origin and modern interpretation of the toxic pathogen theory in the prevention and treatment of tumors, with aims of sorting out the theoretical system based on the toxic pathogen theory in the treatment of tumor diseases, and illustrating the importance of the toxic pathogen theory in the treatment of tumors in the context of modern research on pharmacological mechanisms and the development and marketing of relevant anti-tumor Chinese medicinal preparations.

Gene mutation profiles and clinicopathological features of patients with non-small cell lung cancer harboring KRAS G12C mutation: a single-center retrospective study / 中华病理学杂志

Objective: To accurately screen non-small cell lung cancer (NSCLC) patients with KRAS G12C mutation and to evaluate their clinicopathological features, prognostic factors and current treatment status. Methods: A total of 19 410 NSCLC cases diagnosed at the Department of Pathology of Shanghai Chest Hospital, Shanghai, China from January 2018 to September 2021 were retrospectively reviewed, and the cases with KRAS gene mutation detected by next-generation sequencing were included. The clinicopathological and genetic mutation data of these cases were collected and analyzed. Results: A total of 1 633 (8.4%) NSCLC patients carried a KRAS gene mutation, among whom G12C was the most frequent (468 cases, 28.7%) mutant subtype. The mutation was more commonly found in males (414/468, 88.5%), patients with a history of smoking (308/468, 65.8%), and patients with a pathological type of invasive adenocarcinoma (231/468, 49.4%). The most common co-mutated genes in KRAS G12C mutant NSCLC were TP53 (52.4%, 245/468), STK11 (18.6%, 87/468) and ATM (13.2%, 62/468). The proportion of PD-L1 expression (≥1%) in KRAS G12C mutant NSCLC was significantly higher than that in patients without G12C mutation [64.3% (90/140) vs. 56.1% (193/344), P=0.014]. Immune checkpoint inhibitors (ICIs) treatment significantly prolonged progression-free survival (PFS) in NSCLC patients (10.0 months vs. 5.0 months, P=0.011). However, combination of chemotherapy and ICIs with anti-angiogenesis inhibitors or multi-target inhibitors did not significantly improve PFS in patients with KRAS G12C mutant NSCLC (P>0.05). Patients with KRAS G12C mutation NSCLC treated with ICIs and KRAS G12C patients with TP53 mutation had significantly longer median PFS than those with STK11 mutation (9.0 months vs. 4.3 months, P=0.012). Conclusions: Patients with KRAS G12C mutant NSCLC have relatively higher levels of PD-L1 expression and can benefit from ICIs treatment. The feasibility of chemotherapy, ICIs therapy and their combination needs further investigation.

Research Progress in the Efficacy and Safety of ALK Inhibitors in the Treatment of NSCLC Brain Metastasis / 中国肺癌杂志

Lung cancer is one of the most lethal malignancies in the world, with non-small cell lung cancer (NSCLC) accounting for approximately 80%-85% of all pathological types. Approximately 30%-55% of NSCLC patients develop brain metastases. It has been reported that 5%-6% of patients with brain metastases harbor anaplastic lymphoma kinase (ALK) fusion. ALK-positive NSCLC patients have shown significant therapeutic benefits after treatment with ALK inhibitors. Over the past decade, ALK inhibitors have rapidly evolved and now exist in three generations: first-generation drugs such as Crizotinib; second-generation drugs including Alectinib, Brigatinib, Ceritinib, and Ensartinib; and third-generation drugs like Lorlatinib. These drugs have exhibited varying efficacy in treating brain metastases in ALK-positive NSCLC patients. However, the numerous options available for ALK inhibition present a challenge for clinical decision-making. Therefore, this review aims to provide clinical guidance by summarizing the efficacy and safety of ALK inhibitors in treating NSCLC brain metastases.
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Analysis of recurrent factors and therapeutic effect after laparoscopic inguinal hernia repair / 中华外科杂志

Objective: To analyze the recurrence factors and reoperation effect of laparoscopic inguinal hernia repair. Methods: A total of 41 patients with recurrence after laparoscopic repair of the inguinal hernia admitted to the Department of Hernia and Abdominal Wall Surgery, Beijing Chaoyang Hospital Affiliated to Capital Medical University from January 2017 to December 2021 were retrospectively analyzed. All patients were males, aging (62±7) years (range: 51 to 75 years). The recurrence intervals were 3 days to 7 years postoperatively. The surgical methods, causes of recurrence, and treatment outcomes of the patients were analyzed. Fisher exact probability method is used to compare the rates. Results: Among all cases, the primary surgical procedures included transabdominal preperitoneal herniorrhaphy (TAPP) in 31 cases and total extraperitoneal herniorrhaphy in 10 cases. The reoperative procedures included the TAPP of 11 cases and the Lichtenstein procedure of 30 cases. The factors of recurrent cases in all patients could be divided into 4 categories, including insufficient mesh coverage in 23 cases, mesh curling in 9 cases, mesh contractuture in 7 cases, and improper mesh fixation in 2 cases. Recurrence, infection, chronic pain, foreign body sensation didn't occur in the followed period of(M(IQR)) 18(24) months(range: 12 to 50 months). There was no statistical difference in the incidence of postoperative seroma between the TAPP and Lichtenstein procedure (3/11 vs. 20.0% (6/30), P=0.68). Conclusions: Postoperative recurrence of laparoscopic inguinal hernia is mostly caused by the lack of mesh coverage. Due to the emphasis on standardized surgical operation, a good outcome could be achieved through reoperation by the TAPP or Lichtenstein procedure.

Predictive value of serum lactate dehydrogenase on prognosis of patients with paraquat poisoning / 中华劳动卫生职业病杂志

Objective: To investigate the predictive value of serum lactate dehydrogenase (LDH) in the prognosis of patients with paraquat (PQ) poisoning, and to provide evidence for early prognosis assessment. Methods: In February 2022, 50 patients with PQ poisoning who completed serum LDH detection admitted to the Department of Emergency Medicine, the First Affiliated Hospital of Wenzhou Medical University from January 2012 to December 2021 were selected as the observation group, and 50 healthy physical examination personnel were randomly selected as the control group. Patients with PQ poisoning were divided into survival group and death group according to the prognosis, and the differences of blood routine routine, liver and kidney function and other indicators in the first admission between the two groups were compared. Multivariate logisitic regression model was established, ROC curve was drawn, and the influencing factors of prognosis of patients with PQ poisoning were analyzed. Results: Compared with the control group, the white blood cell count (WBC), total bilirubin (TBil), alanine aminotransferase (ALT), aspartate aminotransferase (AST), LDH, glucose (GLU) and creatinine (Cr) in observation group were significantly increased, while albumin (ALB) and total cholesterol (TC) were significantly decreased (P<0.05). Univariate analysis showed that WBC, elevated LDH (>247 U/L), TBil, ALT, AST and Cr were significantly different between PQ poisoning survival group and death group (P<0.05). Multivariate logisitic regression analysis showed that elevated serum LDH was an independent risk factor for the prognosis of PQ poisoning patients (OR=9.95, 95%CI: 1.34-73.82, P=0.025). The area under the ROC curve of LDH was 0.811 (95%CI: 0.692-0.930). When the cut-off value was 340 U/L, the sensitivity was 0.889 and the specificity was 0.719. Log-rank test showed that there was a statistically significant difference in survival rate between the normal LDH group and the elevated LDH group (P=0.001) . Conclusion: Serum LDH has a good predictive value in evaluating the prognosis of patients with PQ poisoning. Elevated LDH is a risk factor for poor prognosis of patients with PQ poisoning.

Risk factors for poorly controlled and recurrence-prone ingrown toenails treated with nail braces: A retrospective observational study of 238 cases

Background: Nail braces are reportedly effective for treating both acute inflamed and chronic dystrophic type ingrown toenails. Aims: In this study, risk factors for poorly controlled and recurrence-prone ingrown toenails treated with nail braces were identified. Methods: We performed a retrospective study on patients with ingrown toenails between June 1, 2015, and May 31, 2018. The last follow-up date was January 31, 2019. Multivariate logistic regression was performed to evaluate the possible factors associated with poorly controlled status (ongoing paronychia during treatment) and recurrence. Results: There were 120 (244 sides) and 118 patients (167 sides) with chronic dystrophic and acute inflamed type ingrown toenails, respectively. The mean treatment duration and follow-up period were 161.2 ± 98.3 days and 432.7 ± 320.9 days, respectively. Poor control and recurrence were seen in 7.3% (17/232) and 12.2% (27/221) of the patients, respectively. In the multivariate analysis, acute inflamed ingrown toenails, previous nail avulsion, proximal nail fold hypertrophy and more than one affected side remained significantly associated with poorly controlled ingrown toenails. Foot bone deformity was significantly associated with recurrence. Limitations: This study was a retrospective study so that confounding factors such as comorbidities, body mass index, accompanying nail changes and lifestyle could not be evaluated. Conclusion: Several risk factors related to poor control and recurrence were identified. Patients could therefore benefit from more suitable treatment plans with reasonable expectation.

Deubiquitinase JOSD2 Promotes the Survival and Metastasis of Hepatoma Cells / 中国生物化学与分子生物学报

Ubiquitination is a reversible post-translational modification that regulates protein stability and plays a function in numerous signaling pathways. Deubiquitinases play important roles in the regulation of the occurrence and development of different cancers. In this study, we analyzed the survival and prognosis of liver cancer patients according to the expression levels of 63 deubiquitinases. Results discovered that JOSD2 expression in tumor was significantly higher than that in the adjacent tissue (P<0. 0001) and was negatively associated with overall survival of patients (P < 0. 05). JOSD2 is a deubiquitinase from MJD sub-family. Other members of this sub-family were not correlated with liver cancer. The pathways related to cell proliferation were significantly enriched (FDR < 0. 05) in a differential gene function enrichment analysis of JOSD2 high-expressing samples in TCGA data. In hepatoma cell lines, we demonstrated that the overexpression of JOSD2 significantly enhances cell survival, migration and invasion. In conclusion, this study found that JOSD2 is highly expressed in liver cancer (P = 0. 041), and that patients with high-expressed JOSD2 have significantly shorter overall survival. Furthermore, overexpression of JOSD2 can promote the survival and metastasis of hepatoma cells (P < 0. 01), which suggests that JOSD2 might promote the survival and metastasis of hepatocellular carcinoma.

Effect of Angelica dahurica extract and imperatorin on gouty arthritis / 中国药理学通报

Aim To investigate the effects of Angelica dahurica extract and imperatorin on gouty arthritis induced by monosodium urate(MSU)crystal.Methods The model of gouty arthritis was established by injecting MSU crystals into the left ankle of rats.The degree of ankle swelling was measured at 0-24 h in rats.The histopathological changes of synovial tissues were observed.Meanwhile the mRNA and protein expression levels of Nod-like receptor protein 3(NLRP3), interleukin-1β(IL-1β), cysteinyl aspartate specific proteinase-1(caspase-1), interleukin-1 receptor type 1(IL-1R1), interleukin-6(IL-6), tumor necrosis factor-α(TNF-α)were detected by Western blot and RT-PCR in synovial tissues.Results Angelica dahurica extract and imperatorin significantly reduced MSU induced left ankle swelling in rats, and improved inflammatory infiltration in synovial tissues.The expression of NLRP3, IL-1β, caspase-1, IL-1R1, IL-6, TNF-α protein or mRNA in synovial tissues decreased significantly.Conclusion Angelica dahurica extract and its active component imperatorin could ameliorate gouty arthritis, which supplys basic data support for its clinical application.

Tanshinone IIa attenuates vascular calcification through inhibition of NF-κB and β-catenin signaling pathways / 生理学报

Tanshinone IIa is a key ingredient extracted from the traditional Chinese medicine Salvia miltiorrhiza (Danshen), and is widely used to treat various cardiovascular diseases. Vascular calcification is a common pathological change of cardiovascular tissues in patients with chronic kidney disease, diabetes, hypertension and atherosclerosis. However, whether Tanshinone IIa inhibits vascular calcification and the underlying mechanisms remain largely unknown. This study aims to investigate whether Tanshinone IIa can inhibit vascular calcification using high phosphate-induced vascular smooth muscle cell and aortic ring calcification model, and high dose vitamin D3 (vD3)-induced mouse models of vascular calcification. Alizarin red staining and calcium quantitative assay showed that Tanshinone IIa significantly inhibited high phosphate-induced vascular smooth muscle cell and aortic ring calcification. qPCR and Western blot showed that Tanshinone IIa attenuated the osteogenic transition of vascular smooth muscle cells. In addition, Tanshinone IIa also significantly inhibited high dose vD3-induced mouse aortic calcification and aortic osteogenic transition. Mechanistically, Tanshinone IIa inhibited the activation of NF-κB and β-catenin signaling in normal vascular smooth muscle cells. Similar to Tanshinone IIa, inhibition of NF-κB and β-catenin signaling using the chemical inhibitors SC75741 and LF3 attenuated high phosphate-induced vascular smooth muscle cell calcification. These results suggest that Tanshinone IIa attenuates vascular calcification at least in part through inhibition of NF-κB and β-catenin signaling, and Tanshinone IIa may be a potential drug for the treatment of vascular calcification.