Formulation and technology of oxymatrine-astragaloside IV coloaded liposomes based on quality by design / 药学学报

To optimize the formulation and technology of oxymatrine-astragaloside IV coloaded liposomes (Om-As-Lip) based on quality by design (QbD) principles, and further to verify the feasibility of its amplification process, Om-As-Lip was prepared by ethanol injection combined with pH gradient method. The critical material attributions of Om-As-Lip were evaluated by dual-risk analysis tools and Plackett-Burman design (PBD). The formulation of Om-As-Lip was further optimized with the Box-Behnken design (BBD). The design space was also established based on the contour plots of BBD. In order to further investigate the amplification process of Om-As-Lip, the critical process parameters of high-pressure homogenization (HPH) were optimized by single-factor test, and the quality of the final product was also evaluated. The results of risk analysis and PBD confirmed that the astragaloside concentration, cholesterol concentration, and phospholipid ratio (HSPC∶SPC) were the ctitical material attributes. The model established by BBD had a good predictability, and the optimized mass ratio of As to phospholipids was 1∶40, cholesterol to phospholipids was 1∶10, HSPC to SPC was 51∶9. The design space of Om-As-Lip was as follows: the ratio of cholesterol to phospholipids was 1∶12-1∶5 and HSPC to SPC was 1∶7-17∶3. The optimized high-pressure homogenization pressure was 600 bar, temperature was 4 ℃, and cycle times was 6 times for HPH-Om-As-Lip. The quality of Om-As-Lip prepared based on the QbD concept can meet the expected CQAs, and the formulation and technology established can provide a reliable experimental basis for its future development and applications.

Population pharmacokinetics of mycophenolic acid in pediatric patients with primary IgA nephropathy / 中国药房

OBJECTIVE To develop a population pharmacokinetic （PPK） model for mycophenolate mofetil active metabolite mycophenolic acid （MPA） in children with primary IgA nephropathy， explore the factors affecting the pharmacokinetic parameters of MPA， and provide a basis for clinical individualized therapy. METHODS Retrospective collection was conducted on 636 concentrations and clinical data from 47 pediatric patients with primary IgA nephropathy. PPK analysis was carried out by using the nonlinear mixed-effects model； the covariates were tested with a stepwise method. Goodness-of-fit plots， Bootstrap and visual predictive check were employed to evaluate the final model. RESULTS The pharmacokinetics of MPA in children with IgA nephropathy in vivo conformed to the first-order absorption and elimination two-compartment model （objective function value of 3 276.31）. Covariate analysis suggested that body weight and albumin （ALB） levels were significant influencing factors on apparent clearance rate and apparent distribution volume. The typical values of PPK parameters of MPA in the final model were as follows： the central room had a distributed volume of 5.79 L， the clearance rate was 4.06 L/h， the volume of peripheral ventricular distribution was 430.93 L， the clearance rate between compartments was 15.40 L/h， the oral absorption rate constant was 1.29 h－1. After verification， most of the predicted corrected observed concentration points were within the 90% confidence interval of the predicted corrected simulated concentration， indicating that the MPA final model had good predictive performance. CONCLUSIONS The PPK model of MPA in children with primary IgA nephropathy is established in this study， identifying body weight and ALB levels are significant factors affecting MPA metabolism.

Bibliometrics study on the pathogenesis of primary open angle glaucoma / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To understand the publication status, research trends, and cutting-edge and hot topics in this field by conducting a bibliometrics analysis of relevant literatures on the pathogenesis of primary open angle glaucoma(POAG)in the past 30 a.METHODS:A total of 986 relevant literatures on the pathogenesis of POAG published on the core databases of China National Knowledge Infrastructure(CNKI)and Web of Science(WOS)from 1 September 1993 to 1 September 2023 were retrieved. CiteSpace(6.2.R.4)and VOSviewer(1.6.18)software were used to conduct knowledge graph analysis on the retrieved literature, including publication volume, author, research institution, country/region, and keywords.RESULTS:The United States(243 articles)has the highest number of publications, followed by China(121 articles). The foreign institution with the highest number of publications is Harvard University(37 articles), while domestic institutions such as Zhongshan Ophthalmic Center, Sun Yat-sen University, ophthalmology department of Xuanwu Hospital of Capital Medical University, and Peking University First Hospital tied for the highest number of publications. Louis R. Pasquale(21 articles)is the most prolific English author. Wang Ningli is the most active Chinese researcher in this field. Keywords include trabecular meshwork, intraocular pressure, aqueous humor, glucocorticoid, hemorheology, etc.CONCLUSION: The research on the pathogenesis of POAG is in a period of vigorous development. The United States has the largest number of publications in this field, and Harvard University is a leading institution in this field. The research focus in the field of POAG has shifted from the structural aspect to the genetic level, and gene research and traditional Chinese medicine treatment have broad application prospects in this field.

Influencing factors for the prognosis of patients with drug-induced liver injury and establishment of a nomogram model / 临床肝胆病杂志

ObjectiveTo investigate the influencing factors for the clinical outcome of patients with drug-induced liver injury （DILI）， and to establish a nomogram prediction model for validation. MethodsA retrospective analysis was performed for the general information and laboratory data of 188 patients with DILI who were admitted to Heilongjiang Provincial Hospital Affiliated to Harbin Institute of Technology from January 2017 to December 2022， and according to their clinical outcome， they were divided into good outcome group with 146 patients and poor outcome group with 42 patients. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups； the chi-square test was used for comparison of categorical data between two groups. Univariate and multivariate Logistic regression analyses were used to investigate the independent influencing factors for the clinical outcome of DILI patients. R Studio 4.1.2 software was used to establish a nomogram model， and calibration curve， receiver operating characteristic （ROC） curve， and decision curve analysis （DCA） were used to perform internal validation. ResultsThe univariate Logistic regression analysis showed that liver biopsy for the diagnosis of DILI， platelet count， cholinesterase， albumin， prothrombin time activity， IgM， and IgG were associated with adverse outcomes in patients with DILI. The multivariate Logistic regression analysis showed that liver biopsy for the diagnosis of DILI （odds ratio ［OR］=0.072， 95% confidence interval ［CI］： 0.022‍ ‍—‍ ‍0.213， P<0.001）， clinical classification （OR=0.463， 95%CI： 0.213‍ ‍—‍ ‍0.926， P=0.039）， alanine aminotransferase （OR=0.999， 95%CI： 0.998‍ ‍—‍ ‍1.000， P=0.025）， prothrombin time activity （OR=0.973， 95%CI： 0.952‍ ‍—‍ ‍0.993， P=0.011）， and IgM （OR=1.456， 95%CI： 1.082‍ ‍—‍ ‍2.021， P=0.015） were independent influencing factors for clinical outcome in patients with DILI. The nomogram prediction model was established， and after validation， the calibration curve was close to the reference curve. The area under the ROC curve was 0.829， and the DCA curve showed that the model had good net clinical benefit. ConclusionThe nomogram prediction model established in this study has good clinical calibration， discriminative ability， and application value in evaluating the clinical outcome of patients with DILI.

Hepatolenticular degeneration with depressive episodes of bipolar disorder： a case report / 四川精神卫生

This case reported a 17-year-old female patient who presented to the hospital with "poor mood and irritability for more than 5 months". The patient was diagnosed with hepatolenticular degeneration at the age of five. According to the International Classification of Diseases， tenth edition （ICD-10）， she was diagnosed with hepatolenticular and depressive episodes of bipolar disorder. The condition improved after administration of a combination of a mood stabilizer and an antidepressant. There are few reports of hepatolenticular degeneration combined with depressive episodes of bipolar disorder， and it is controversial whether the diagnosis should be considered a psychiatric disorder due to a physical illness or a co-morbidity. In addition， somatic conditions are often overlooked in the treatment of patients with psychiatric disorders. This case analyzed the diagnosis and medication by integrating the patient's psychiatric symptoms and somatic conditions， suggesting that psychiatrists should pay attention to both psychiatric symptoms and the patient's previous history of somatic diseases in their clinical work for rational diagnosis and treatment.

Histopathological evaluation of cirrhosis reversal / 中华肝脏病杂志

A normal liver can develop cirrhosis through long-term and repeated stimulation from various etiologies. Histological manifestations like the collapse of hepatic lobular structure (including microvascular structure) and the formation of pseudolobules can lead to portal hypertension and even decompensated cirrhosis. More and more evidence suggests that effective etiological treatment can not only delay but also reverse the progression of cirrhosis. The mechanism of cirrhosis reversal mainly includes the degradation of extracellular matrix, hepatocyte regeneration, and hepatic lobular remodeling. The "gold standard" for the evaluation of cirrhosis reversal at present is still a liver biopsy. Therefore, the histopathological evaluation of cirrhosis reversal is very important for determining the disease's prognosis, efficacy, and mechanism of exploration.

The influencing factors of functional somatic discomfort in clinical nurses / 中华劳动卫生职业病杂志

Objective: To investigate the functional somatic discomfort status, and to analyze the effect of job stress, hostile attribution bias and ego depletion on functional somatic discomfort in clinical nurses. Methods: In May 2019, 10 cities in Henan Province and Fujian Province were randomly selected as sampling cities. Using the stratified cluster sampling method, nurses of clinical nursing posts in 22 third class hospitals and 23 second class hospitals were selected as the research objects. The general information, job stress, hostile attribution bias, ego depletion and functional somatic discomfort of clinical nurses were investigated by self-designed general information questionnaire, Perceived Stress Scale, Social Information Processing-attribution Bias Questionnaire, Self-regulatory Fatigue Scale, Patient Health Questionnaire-15. 1200 clinical nurses included, and a total of 1159 valid questionnaires were collected, the effective rate of questionnaire collection was 96.6%. The t test was used to compare the difference of the functional somatic discomfort scores of clinical nurses with different demographic characteristicst. The influence of job stress, hostile attribution bias and ego depletion on functional somatic discomfort of clinical nurses were analyzed with Bootstrap. Results: The functional somatic discomfort score of clinical nurses was (8.95±4.38), of which 859 (74.12%) had functional somatic discomfort symptom. The functional somatic discomfort score of clinical nurses aged 36-50 years old was higher than that of 19-35 years old, the functional somatic discomfort score of clinical nurses with service age ≥5 years was higher than that of <5 years, the functional somatic discomfort score of non-permanent clinical nurses was higher than that of permanent clinical nurses, the functional somatic discomfort score of clinical nurses in tertiary hospitals was higher than that of secondary hospitals, the functional somatic discomfort score of clinical nurses in surgical departments were higher than those in non-surgical departments, and the differences were statistically significant (P<0.05). Job stress affected functional somatic discomfort through the single mediating role of hostile attribution bias, the single mediating role of ego depletion, and the chain mediating role of hostile attribution bias and ego depletion (β=0.17, 95%CI: 0.10-0.20; β=0.16, 95%CI: 0.10-0.20; β=0.07, 95%CI: 0.03-0.10; P<0.05) . Conclusion: The functional somatic discomfort symptoms of clinical nurses are significant and varied among different age, working age, employment form, hospital grade and department groups. They are affected by work stress directly and through the separate mediating effect of hostile attribution bias and ego depletion, and the chain mediating effect of hostile attribution bias and ego depletion.

A real-world study on the efficacy and safety analysis of paclitaxel liposome in advanced breast cancer / 中华肿瘤杂志

Objective: To explore the application and efficacy of paclitaxel liposome in the treatment of advanced breast cancer among Chinese population in the real world. Methods: The clinical characteristics of patients with advanced breast cancer who received paclitaxel liposome as salvage treatment from January 1, 2016 to August 31, 2019 in 11 hospitals were collected and retrospectively analyzed. The primary outcome was progression free survival (PFS), and the secondary outcome included objective response rate (ORR) and safety. The survival curve was drawn by Kaplan-Meier analysis and the Cox regression model were used for the multivariate analysis. Results: Among 647 patients with advanced breast cancer who received paclitaxel liposome, the first-line treatment accounted for 43.3% (280/647), the second-line treatment accounted for 27.7% (179/647), and the third-line and above treatment accounted for 29.1% (188/647). The median dose of first-line and second-line treatment was 260 mg per cycle, and 240 mg in third line and above treatment. The median period of paclitaxel liposome alone and combined chemotherapy or targeted therapy is 4 cycles and 6 cycles, respectively. In the whole group, 167 patients (25.8%) were treated with paclitaxel liposome combined with capecitabine±trastuzumab (TX±H), 123 patients (19.0%) were treated with paclitaxel liposome alone (T), and 119 patients (18.4%) were treated with paclitaxel liposome combined with platinum ± trastuzumab (TP±H), 108 patients (16.7%) were treated with paclitaxel liposome combined with trastuzumab ± pertuzumab (TH±P). The median PFS of first-line and second-line patients (5.5 and 5.5 months, respectively) were longer than that of patients treated with third line and above (4.9 months, P<0.05); The ORR of the first line, second line, third line and above patients were 46.7%, 36.8% and 28.2%, respectively. Multivariate analysis showed that event-free survival (EFS) and the number of treatment lines were independent prognostic factors for PFS. The common adverse events were myelosuppression, gastrointestinal reactions, hand foot syndrome and abnormal liver function. Conclusion: Paclitaxel liposomes is widely used and has promising efficacy in multi-subtype advanced breast cancer.

Clinical features and long-term prognosis of diabetic patients with low or intermediate complexity coronary artery disease post percutaneous coronary intervention / 中华心血管病杂志

Objective: To investigate the clinical features and long-term prognostic factors of diabetic patients with low or intermediate complexity coronary artery disease (CAD) post percutaneous coronary intervention (PCI). Methods: This was a prospective, single-centre observational study. Consecutive diabetic patients with SYNTAX score (SS)≤32 undergoing PCI between January and December 2013 in Fuwai hospital were included in this analysis. The patients were divided into two groups based on SS, namely SS≤22 group and SS 23-32 group. Multivariate Cox regression analysis was performed to identify independent factors related to poor 5-year prognosis. The primary outcomes were cardiac death and recurrent myocardial infarction, the secondary outcomes were all cause death and revascularization. Results: Of the 3 899 patients included in the study, 2 888 were men (74.1%); mean age was 59.4±9.8 years. There were 3 450 patients in the SS≤22 group and 449 patients in the SS 23-32 group. Compared with SS≤22 group, the incidence of revascularization was higher in SS 23-32 group (18.9% (85/449) vs. 15.2% (524/3450), log-rank P=0.019). There was no significant difference in all-cause death, cardiac death and recurrent myocardial infarction between the two groups (log-rank P>0.05). Multivariate Cox regression analysis showed that age (HR=1.05, 95%CI 1.02-1.08, P<0.001), chronic obstructive pulmonary disease (HR=3.12, 95%CI 1.37-7.07, P=0.007) and creatinine clearance rate (CCr)<60 ml/min (HR=3.67, 95%CI 2.05-6.58, P<0.001) were independent risk factors for 5-year cardiac death, while left ventricular ejection fraction (HR=0.94, 95%CI 0.91-0.96, P<0.001) was a protective factor. Previous PCI (HR=2.04, 95%CI 1.38-3.00, P<0.001), blood glucose level≥11.1 mmol/L on admission (HR=2.49, 95%CI 1.32-4.70, P=0.005) and CCr<60 ml/min (HR=1.85, 95%CI 1.14-2.99, P=0.012) were independent risk factors for 5-year recurrent myocardial infarction. The SS of 23-32 was independently associated with risk of revascularization (HR=1.54, 95%CI 1.09-2.16, P=0.014), after adjusting for residual SS. Residual SS was not a risk factor for 5-year prognosis. Conclusions: In diabetic patients with low-or intermediate complexity CAD, SS 23-32 is associated with increased risk of 5-year revascularization; the clinical characteristics of the patients are associated with the long-term mortality and recurrent myocardial infarction, but not related to revascularization.

Internal carotid artery pseudoaneurysm caused by parapharyngeal abscess: A case report / 北京大学学报(医学版)

Pseudoaneurysms of the neck are seldom, and those caused by neck infections especially parapharyngeal abscess are even rarer. However, it is life-threatening and may bring sudden death due to the obstruction of airway and the pseudoaneurysms rupture. We analyzed the clinical features, diagnosis and treatment of the disease through a case summary and literature review in order to guide clinical diagnosis and treatment of pseudoaneurysms. The patient, whom we presented was an 87-year-old male and admitted in emergency of our hospital with the chief complaint of neck swelling for 7 days and shortness of breath for 2 days. Cervical ultrasound examination showed that there was an liquid dark area next to the left common carotid artery which was approximately 8.0 cm × 5.0 cm, consideration of formation of left carotid artery pseudoaneurysm, and the liquid dark area which was visible on the right considered of pseudoaneurysm or infection. Angiography of neck showed a clustered high-density shadow around the bifurcation of the left carotid artery, with an overall range of approximately 65 mm × 52 mm × 72 mm, the pseudoaneurysms for sure, while on the right side of the lesion, mixed low density shadows with air could be seen, the parapharyngeal abscess for sure.Then he was diagnosed as the pseudoaneurysm of left internal carotid artery which was caused by parapharyngeal abscess. After tracheal intubation and anti-infection treatment, the patient died due to hemorrhagic shock of the ruptured of the pseudoaneurysm. Morever we performed literature search on PubMed, Wanfang database and CNKI with keywords of "neck pseudoaneurysm, neck infection, parapharyngeal abscess" and enrolled 10 cases. Then we summarized the clinical characteristics and treatment. We analyzed and summarized the 10 case reports, in which the number of male was 7. Among them, there were 4 pediatric, and 6 adults were enrolled overall. Most of the symptoms were neck swelling, and the diseased blood vessel was mainly the right internal carotid artery which accounted for half overall. All the patients underwent surgical intervention, and recovered well. So we draw the conclusion that the clinical incidence of cervical pseudoaneurysms is low and can be caused by a variety of factors, especially caused by infectious factors. When a patient has a progressive pulsating mass in the neck, the preliminary diagnosis should be made by ultrasound as soon as possible, and the aortic enhancement CT should be used to further confirm.For a patient with cervical pseudo-aneurysms caused by parapharyngeal infections, he should take operation timely combined with antibiotic treatment in time.

Analysis of HKαα Genotype and Hematological Characteristics in South Guangxi / 中国实验血液学杂志

OBJECTIVE@#To investigate the detection rate and hematologic phenotype of HKαα thalassemia in south Guangxi, in order to provide reference for the prevention and control of thalassemia and prenatal and postnatal care consultation in this region.@*METHODS@#Gene testing was performed on pre-marital medical examinations, pre-pregnancy eugenic health examinations, prenatal examinations and hospitalized thalassemia-positive persons in south of Guangxi, and the results were analyzed.@*RESULTS@#A total of 183 190 thalassemia patients were included in this study, the age was mainly concentrated in 26-35 years old (101 709 cases, accounting for 55.521%), and 40 HKαα mutations were detected, detection rate was 0.022%, including 5 cases in Nanning, 22 cases in Qinzhou, 2 cases in Fangchenggang, 11 cases in Beihai. A total of 29 ethnic groups were included in the survey, but HKαα gene was observed only in Han nationality (0.0380%) and Zhuang nationality (0.0068%). A total of 8 genotypes carrying HKαα mutations were detected in this study ( HKαα/--SEA, βN/ βN, HKαα/αα, β-28/ βN, HKαα/αα, β-50/ βN, HKαα/αα, βCD17/ βN, HKαα/αα, βCD27/28/β N, HKαα/αα, βCD41-42/ βN, HKαα/αα, βCD71-72/ βN, and HKαα/αα, βN/ βN). Except for most cases with HKαα/αα, βN/ βN genotypes with no significant changes in the hematological indexes, mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) of other genotypes were decreased, showing microcytic hypochromic performance, mild anemia or no anemia.@*CONCLUSION@#HKαα carrier is often misdiagnosed as -α3.7 carrier, which easily leads to missed diagnosis or misdiagnosis. Therefore, it is necessary to continuously improve the diagnostic level of laboratory testing personnels and genetic counselors to avoid unnecessary interventional puncture operations and birth of children with moderate and severe thalassemia.

Gene Mutation Types of Thalassemia in Chongzuo Childbearing-age Population of Guangxi Zhuang Autonomous Region of China / 中国实验血液学杂志

OBJECTIVE@#To investigate the gene mutation and genotype distribution of thalassemia in the population of childbearing age in Chongzuo area of Guangxi.@*METHODS@#Six α-thalassemia and 17 β-thalassemia gene mutations common in Chinese were detected by gap-polymerase chain reaction (gap-PCR) combined with agarose gel eletrophoresis and reserve dot bolt hybridization in 29 266 cases of child-bearing age suspected of thalassemia.@*RESULTS@#A total of 19 128 (65.36%) cases were identified with thalassemia. The detection rate of α-thalassemia, β-thalassemia and α-combining β-thalassemia was 45.25% (13 242/29 266), 15.47% (4 526/29 266) and 4.65% (1 360/29 266), respectively. A total carrying rate of 8 kinds of α-thalassemia gene mutations was 26.74% (15 649/58 532), including 12.51% for --SEA, followed by 5.70% for -α3.7, and 0.24% for --Thai. Among 32 α-thalassemia genotypes, the most common five were --SEA/αα, -α3.7/αα, αCSα/αα, -α4.2/αα and αWSα/αα, accounting for 47.27%, 18.31%, 8.56%, 8.52% and 7.91%, respectively, as well as 0.97% for --Thai/αα. A total carrying rate of 13 kinds of β-thalassemia gene mutations was 10.07% (5 897/58 532), including 3.63% for CD41-42, followed by 2.55% for CD17, and 0.003% for -50 (G>A). Among 17 β-thalassemia genotypes, the most common six were CD41-42/N, CD17/N, CD71-72/N, CD26/N, 28/N and IVSI-1/N, accounting for 36.15%, 25.81%, 9.43%, 8.18%, 8.09% and 7.75%. The homozygous genotype CD26/CD26 [hemoglobin (Hb): 121 g/L] and -28/-28 (Hb: 56 g/L) were respectively detected in one case, and double heterozygous genotype were detected in 5 cases, including 3 cases of CD41-42/CD26 (Hb: 41 g/L, 51 g/L, 63 g/L, respectively), 1 case of -28/IVSI-1 (Hb: 53 g/L), and 1 case of CD71-72/CD26 (Hb: 89 g/L), in which patients with moderate or severe anemia had a history of blood transfusion. Among 104 α-combining β-thalassemia genotypes, the most common were --SEA/αα, -α3.7/αα combining CD41-42/N and --SEA/αα combining CD17/N, accounting for 12.13%, 9.63% and 9.26%, respectively. In addition, 1 case of --SEA/-α3.7 combining -28/IVSI-1 (Hb: 83 g/L) and 1 case of -α3.7/αα combining CD41-42/ CD41-42 (Hb: 110 g/L) were detected without history of blood transfusion, while 1 case of αWSα/αα combining CD41-42/CD17 (Hb: 79 g/L) and 1 case of --SEA/αα combining CD17/-28 (Hb: 46 g/L) were detected with history.@*CONCLUSIONS@#The detection rate of thalassemia genes is high and the mutations are diverse in the population of childbearing age in Chongzuo area of Guangxi. The common deletion genotype is --SEA/αα in α-thalassemia and CD41-42/N in β-thalassemia, and deletion genotype --Thai is not rare. There is a certain incidence of intermediate and severe β-thalassemia, and most patients require transfusion therapy. The results are beneficial for genetic consultation and intervention of thalassemia.

A survey on disability status of patients with inflammatory bowel disease in China / 中华消化杂志

Objective:To investigate the disability status of patients with inflammatory bowel disease (IBD) in China and to identify the influencing factors of the inflammatory bowel disease disability index (IBD-DI).Methods:From October 1 to December 31, 2021, a total of 1 170 IBD patients were recruited from 7 IBD centers and WeChat public platforms in China. All the patients were surveyed by the IBD-DI questionnaire, which included demographic information, disease activity, medication history, treatment and surgical history. Demographic information included gender, age, income status, etc. Multiple linear regression was used to analyze the influencing factors of IBD-DI.Results:Among the 1 170 IBD patients, 746 patients (63.76%) were male and 424 patients (36.24%) were female; there were 871 cases (74.44%) of Crohn′s disease(CD), 277 cases (23.68%) of ulcerative colitis (UC) and 22 cases (1.88%) of inflammatory bowel disease undassified (IBDU). The age was 36.00 years old (29.00 years old, 45.00 years old), and the IBD-DI score was 9.00 (5.00, 15.00). The results of multiple linear regression analysis revealed that the disease activity ( β=0.65, t=22.33, P<0.001), current treatment with enteral nutrition ( β=0.09, t=3.06, P<0.001), and history of perianal surgery ( β=0.06, t=2.12, P=0.034) were influencing factors of IBD-DI in the CD patients. Disease activity ( β=0.65, t=14.37, P<0.001), household per capita annual income ( β=-0.16, t=-3.59, P<0.001), current usage of immunosuppressants ( β=0.12, t=2.66, P=0.008), current treatment with enteral nutrition ( β=0.12, t=2.57, P=0.011), and the duration of each exercise ( β=-0.12, t=-2.67, P=0.008) were influencing factors of IBD-DI in UC patients. Conclusions:Disability is common in Chinese IBD patients, and their IBD-DI were different. Disease activity is the most important factor affecting IBD-DI. The IBD-DI is higher in IBD patients receiving enteral nutrition treatment, CD patients with a history of perianal surgery and UC patients with current usage of immunosuppressants. However, household per capita annual income and the duration of each exercise are negatively correlated with IBD-DI in UC patients.

Phylogeny and virulence gene profile of Francisella salimarina / 中华微生物学和免疫学杂志

Objective:To study the molecular phylogeny and virulence gene profile of Francisella salimarina. Methods:Phylogenetic analysis of Francisella salimarina was performed based on the global genome data of related Francisella species on GenBank database. The consistency in phylogenetic analysis based on single marker genes (such as 16S rRNA gene, rpoB gene and mdh gene) and the core genome as compared. Virulence genes and antibiotic resistance genes were annotated using the virulence factor database (VFDB) and the Comprehensive Antibiotic Resistance Database (CARD), respectively. The virulence of Francisella salimarina was analyzed with a Galleria mellonella (greater wax moth) infection model using Francisella philomiragia ATCC 25015 T as reference strain. Results:The phylogenetic analysis revealed that Francisella salimarina was closely related to Francisella philomiragia. The phylogenetic tree based on mdh gene was highly similar to that based on the core genome. Francisella salimarina could be differentiated from other related species by 16S rRNA gene or mdh gene, with the latter being more accurate. Eight Francisella salimarina strains carried multiple virulence genes, mainly involved in secretion, adhesion, immune regulation, motility and stress survival. Moreover, beta-lactam resistance gene blaFPH was identified in all eight strains. Francisella salimarina showed high lethality in the Galleria mellonella infection model, which was similar to Francisella philomiragia ATCC 25015 T. Conclusions:Francisella salimarina was a rare pathogen with similar pathogenicity to Francisella philomiragia. The mdh gene could be used as a molecular target for rapid identification of Francisella salimarina.

Isolation and identification of Balneatrix alpica from patient′s blood and hot spring water / 中华微生物学和免疫学杂志

Objective:To identify and characterize two Balneatrix alpica strains isolated from a patient′s blood sample (strain X117) and the natural hot spring water in the patient′s residential district (strain GN-1), and to provide experimental evidence for the pathogenic diagnosis of clinical infection caused by this rare pathogen. Methods:Biochemical phenotypic identification, matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS), 16S rRNA gene sequencing, phylogenetic analysis, single-nucleotide polymorphism (SNP) analysis, and genome-wide analysis were performed to accurately determine the taxonomic status of the isolates X117 and GN-1 by using Balneatrix alpica DSM 16621 T as a reference. Microdilution broth method was used to test their antimicrobial susceptibility. The virulence genes carried by them were annotated and analyzed using the virulence factor database (VFDB). Results:Strains X117 and GN-1 formed light yellow or tan colonies with mottled surfaces on Columbia blood agar and chocolate agar plates after 4 d of culture. They were Gram-negative rods and positive for oxidase and indole tests, which were consistent with the characteristics of Balneatrix alpica DSM 16621 T. The phylogenetic analysis based on the 16S rRNA gene showed that the isolates X117 and GN-1 were both Balneatrix alpaca. The average nucleotide identity (ANI) values between the two isolates and Balneatrix alpica DSM 16621 T were 98.44% and 98.41%, respectively, and the digital DNA-DNA hybridization (dDDH) values were both 87.1%. The SNP distance between the two strains was 13, indicating that X117 and GN-1 might belong to the same clone. The antibiotic susceptibility testing showed that all of the three Balneatrix alpica strains were sensitive to the commonly used antibiotics against Gram-negative rods. The virulence genes carried by the three Balneatrix alpica strains were mainly involved in adhesion, invasion, flagella and biofilm formation. Conclusions:This study identified a case of bloodstream infection caused by Balneatrix alpica which was closely related to natural hot spring water. Natural hot spring water migh be an important source of clinical infections caused by this species.

Genetic typing, virulence genes and drug resistance analysis of Campylobacter fetus subsp. testudinum / 中华微生物学和免疫学杂志

Objective:To analyze the molecular epidemiological characteristics of Campylobacter fetus subsp. testudinum ( Cft). Methods:Fifteen strains of Cft collected in our laboratory from 2010 to 2022 were subjected to whole-genome sequencing. Their epidemiological characteristics were analyzed based on the global genome data of Cft on GenBank database. MLST-GrapeTree software was used to obtain the genetic structure of Cft strains. A phylogenetic tree was constructed using core-genome single nucleotide polymorphism (cgSNP) analysis, and the sequence clusters were identified using rhierBAPS. Virulence genes and drug resistance genes of Cft strains were annotated using CARD, ResFinder and VFDB database. Their susceptibility to antibiotics was tested using E-test method and the results were analyzed using the CLSI-M45 sensitivity standard for Campylobacter jejuni/ Campylobacter coli. Results:Based on average nucleotide identity (ANI) analysis, the genome data of 41 Cft strains including 24 isolated from human, 13 from animals and four of unknown sources were collected from GenBank database. Among the 24 human-derived strains, 20 were linked to Asian descent and only one was linked to Caucasian descent (spouse of Asian descent), showing statistically significant differences in human ethnicity. All of the 13 animal-derived strains were originated from reptilian sources, including six from turtles, four from snakes and three from lizards. MLST revealed that ST46 was the predominant ST in China, while ST15 was the major sequence type in the United States. Grapetree analysis also demonstrated that the genetic diversity in China was greater than that in the United States. The phylogenetic tree constructed based on cgSNP and BAPS identified six distinct sequence clusters. The Chinese isolates were scattered in diverse sequence clusters and closely related to animal-derived strains, while the American isolates mainly belonged to ST15. The genes encoding virulence factors such as flagella, glycosylation systems and adhesins were carried by all of the 41 Cft strains (100.00%). The invasion-related virulence genes, such as the genes encoding the IV type secretion system ( virB4, virB9, virD4) and the resistance-related tetO efflux pump gene were specifically identified in the emerging ST74 clones. In vitro drug susceptibility testing of 15 Chinese isolates revealed 46.67% of the Cft strains were resistant to ciprofloxacin and 100.00% were sensitive to erythromycin. Conclusions:The global sequence clusters of Cft isolates showed a great genetic diversity. Most of the people with Cft infection had basic immune diseases and might have eaten or had contact with reptiles. Notably, the Chinese domestic infection of ST46 and the emerging ST74 should arouse our more attention.

Identification and characterization of one Spiroplasma species isolated from blood culture of a rare case of sepsis / 中华微生物学和免疫学杂志

Objective:To identify and characterize one Spiroplasma strain (designated as DGKH1) isolated from the blood of a patient with sepsis. Methods:The traditional bacterial culture, staining, morphological observation, physiological and biochemical identification, 16S rRNA gene sequencing, phylogenetic analysis, genome sequencing, and the genome-related index analysis were performed to accurately determine the taxonomic status of the strain DGKH1. Antibiotic susceptibility testing was performed using a specific kit for culturing and testing Ureaplasma urealyticum/ Metamycoplasma hominis. Results:The strain DGKH1 could weakly grow on Columbia blood agar, chocolate agar, and Haemophilus chocolate 2 agar. However, it did not grow in liquid culture medium containing tetracycline (4 μg/ml), doxycycline (1 μg/ml), minocycline (1 μg/ml), josamycin (2 μg/ml), roxithromycin (1 μg/ml), clarithromycin (1 μg/ml), or telithromycin (1 μg/ml). DGKH1 resembling Metamycoplasma hominis formed "fried egg-like colonies" on Mycoplasma solid culture medium. DGKH1 could not be stained by Gram staining. When observed under transmission electron microscopy (TEM) using phosphate buffer as the matrix, the bacteria were spiral-shaped. Results of 16S rRNA gene sequence alignment showed that DGKH1 was highly similar (99.85%) to Spiroplasma eriocheiris CCTCC M 207170 T. However, the urea decomposition test was positive, which was different from all of the known Spiroplasma species. The phylogenetic analysis based on whole genome showed that DGKH1 was clustered in a small branch along with Spiroplasma eriocheiris CCTCC M 207170 T. However, the average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) values between the two strains were 94.14% and 56.00%, respectively, both below the threshold for prokaryotic species identification. Conclusions:DGKH1 represented a potential new species of genus Spiroplasma, closely related to Spiroplasma eriocheiris. Some microbiological characteristics of DGKH1 were similar to Mycoplasmas. However, the natural host and epidemiological data of DGKH1 need to be further studied.

Role of Nrf2/HO-1 signaling pathway in edaravone-induced attenuation of long-term cognitive impairment caused by long-time sedation with propofol in neonatal rats / 中华麻醉学杂志

Objective:To evaluate the role of nuclear factor E2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway in edaravone-induced attenuation of long-term cognitive impairment caused by long-time sedation with propofol in the neonatal rats.Methods:Eighty SPF healthy newborn Sprague-Dawley rats of both sexes, aged 7 days, weighing 15-20 g, were divided into 4 groups ( n=20 each) using a random number table method: control group (group C), propofol group (group P), edaravone+ propofol group (group EP) and Nrf2 inhibitor ML385+ edaravone+ propofol group (group MEP). Propofol 75 mg/kg was intraperitoneally injected once a day for 7 consecutive days in P group, EP group and MEP group, respectively, while the equal volume of medium/long chain fat emulsion injection was intraperitoneally injected in C group. Edaravone 3 mg/kg was intraperitoneally injected at 30 min before each propofol injection in EP and MEP groups, and ML385 15 mg/kg was intraperitoneally injected simultaneously in group MEP. The spontaneous activity was evaluated by the open field test on day 29 after birth, and the cognitive function was assessed by Morris water maze test on days 30-34 after birth. The rats were sacrificed after the end of water maze test, and brains were removed and hippocampal tissues were obtained for determination of reactive oxygen species (ROS) levels (by flow cytometry), superoxide dismutase (SOD) and malondialdehyde (MDA) levels (by enzyme-linked immunosorbent assay) and expression of Nrf2 and HO-1 (by Western blot) and for microscopic examination of the pathological changes in the hippocampal CA1 area (using HE staining). Results:There was no significant difference in the speed, distance and time of stay at the center of the open field among the four groups ( P>0.05). Compared with C group, the escape latency was significantly prolonged, the number of crossing the original platform quadrant was reduced, the levels of MDA and ROS were increased, the activity of SOD was decreased, the expression of Nrf2 and HO-1 was down-regulated ( P<0.05), and the pathological injury was observed in the hippocampal CA1 region in group P. Compared with P group, the escape latency was significantly shortened, the number of crossing the original platform quadrant was increased, the levels of MDA and ROS in the hippocampus were decreased, the activity of SOD was increased, the expression of Nrf2 and HO-1 was up-regulated ( P<0.05), and the pathological injury in the hippocampal CA1 region was significantly alleviated in EP group. Compared with EP group, the escape latency was significantly prolonged, the number of crossing the original platform quadrant was reduced, the levels of MDA and ROS were increased, the activity of SOD was decreased, the expression of Nrf2 and HO-1 was down-regulated ( P<0.05), and the pathological injury was aggravated in the hippocampal CA1 region in MEP group. Conclusions:The mechanism by which edaravone attenuates long-term cognitive impairment caused by long-time sedation with propofol is related to activation of Nrf2/HO-1 signaling pathway and inhibition of oxidative stress in the neonatal rats.

Role of TLR4/NF-κB signaling pathway in long-term cognitive impairment induced by multiple exposures to sevoflurane anesthesia in neonatal rats / 中华麻醉学杂志

Objective:To evaluate the role of Toll-like receptor 4 (TLR4)/nuclear transcription factor κB (NF-κB) signaling pathway in long-term cognitive impairment induced by multiple exposures to sevoflurane anesthesia in neonatal rats.Methods:Seventy-five SPF healthy newborn Sprague-Dawley rats of either sex, aged 6 days, weighing 12-20 g, were divided into 3 groups ( n=25 each) using a random number table method: control group (group C), multiple exposures to sevoflurane anesthesia group (group S) and TLR4 inhibitor plus multiple exposures to sevoflurane anesthesia group (group I+ S). The rats in group S and group I inhaled 3% sevoflurane for 2 h at 6, 7 and 8 days after birth. TLR4 inhibitor TAK-242 10 mg/kg was intraperitoneally injected before each exposure to sevoflurane in group I, and the equal volume of normal saline was given instead in the other two groups. The spontaneous activity was evaluated by open field test on day 29 after birth, and the cognitive function was assessed by Morris water maze test on days 30-34 after birth. After the behavioral test, the blood samples from the abdominal aorta were collected, and then the rats were sacrificed under deep anesthesia to isolate the hippocampal tissues for measurement of the levels of S100β and neuron-specific enolase (NSE) in serum and hippocampal interleukin-1β (IL-1β), IL-6 and tumor necrosis factor α (TNF-α) (by enzyme-linked immunosorbent assay), expression of TLR4, NF-κB p65 and phosphorylated NF-κB p65 (p-NF-κB p65) (by Western blot) and for microscopic examination of the pathological changes of hippocampal CA1 region after HE staining. Results:Compared with group C, the escape latency was significantly prolonged, the number of crossing the original platform was reduced, the TLR4 expression was up-regulated, the ratio of p-NF-κB p65/NF-κB p65 was increased, the levels of serum S100β protein and NSE and hippocampal IL-1β, IL-6 and TNF-α were increased ( P<0.05), and the pathological changes in the hippocampal CA1 region were aggravated in group S. Compared with group S, the escape latency was significantly shortened, the number of crossing the original platform was increased, TLR4 expression was down-regulated, the ratio of p-NF-κB p65/NF-κB p65 was decreased, the levels of S100β and NSE in serum and hippocampal IL-1β, IL-6 and TNF-α were decreased ( P<0.05), and the pathological changes in hippocampal CA1 area were significantly attenuated in group P. Conclusions:The mechanism by which multiple exposures to sevoflurane anesthesia induces long-term cognitive impairment is related to activation of TLR4/NF-κB signaling pathway and increase in hippocampal inflammatory responses in neonatal rats.

Primary anastomosing hemangioma of the left kidney: a case report / 中华泌尿外科杂志

Anastomosing hemangioma is a newly reported variant subtype of capillary hemangioma, and its biological behavior is mostly benign. We reported a case of anastomosing hemangioma originating from the kidney. After nephrectomy, the patient was followed up for 13 months, and no recurrence or distant metastasis was observed.