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.

Mining and analysis for adverse drug event signals of liver failure in underage population based on the FAERS database / 中国药房

OBJECTIVE To conduct data mining on drugs causing liver failure in underage populations based on the FDA Adverse Event Reporting System （FAERS） database， so as to provide reference for clinical use of related drugs. METHODS The data on reported adverse drug event （ADE） of liver failure in this population （under 18 years old） from the first quarter of 2013 to the third quarter of 2022 were retrieved from the FAERS database for mining and analysis； they were divided into infants（≤1 year old）， young children（＞1-＜6 years old）， children（6-＜12 years old） and adolescents（12-＜18 years old） according to the age. The reporting odds ratio （ROR）， proportional reporting ratio and Bayesian confidence propagation neural network of the proportional imbalance method were used to screen ADE signals. RESULTS A total of 1 051 ADE reports of liver failure were collected from the underage population involving 60 drugs. The highest incidence was found in adolescents （410 cases， 39.01%）， followed by young children （297 cases， 28.26%）. The instructions of 14 drugs did not mention hepatobiliary system injury and liver failure risk， including 31 cases of levetiracetam （2.95%），18 cases of metronidazole （1.71%）， 16 cases of each of topiramate and methylprednisolone （1.52% each）， 12 cases of dexamethasone （1.14%）， 11 cases of tisagenlecleucel （1.05%）， 10 cases of each of ferrous sulfate， metformin and busulfan （0.95% each）， 9 cases of propofol （0.86%）， 8 cases of onasemnogene abeparvovec （0.76%）， 5 cases of each of diphenhydramine and omeprazole （0.48% each）， 4 cases of sebeliesterase α （0.38%）， totaling 165 cases， accounting for 15.70% of the total reported cases. Metformin was contrary to the known liver safety， and E-mail：libingchemical@163.com metronidazole and levetiracetam were new risk signals， which caused more serious clinical outcomes. CONCLUSIONS Fourteen new pharmacovigilance signals which cause liver failure in the underage population are found in this study； the liver function of patients should be closely monitored when using these drugs. Among those drugs， metformin neither undergoes liver metabolism nor has been reported in the relevant literature， and the liver-related ADE caused by metformin deserves further attention. The clinical outcomes caused by metronidazole and levetiracetam are relatively serious and need to be given sufficient attention.

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.

Prevalence of maturity-onset diabetes of the young in phenotypic type 2 diabetes in young adults: a nationwide, multi-center, cross-sectional survey in China / 中华医学杂志(英文版)

BACKGROUND@#Maturity-onset diabetes of the young (MODY) is the most common monogenic diabetes. The aim of this study was to assess the prevalence of MODY in phenotypic type 2 diabetes (T2DM) among Chinese young adults.@*METHODS@#From April 2015 to October 2017, this cross-sectional study involved 2429 consecutive patients from 46 hospitals in China, newly diagnosed between 15 years and 45 years, with T2DM phenotype and negative for standardized glutamic acid decarboxylase antibody at the core laboratory. Sequencing using a custom monogenic diabetes gene panel was performed, and variants of 14 MODY genes were interpreted as per current guidelines.@*RESULTS@#The survey determined 18 patients having genetic variants causing MODY (6 HNF1A , 5 GCK , 3 HNF4A , 2 INS , 1 PDX1 , and 1 PAX4 ). The prevalence of MODY was 0.74% (95% confidence interval [CI]: 0.40-1.08%). The clinical characteristics of MODY patients were not specific, 72.2% (13/18) of them were diagnosed after 35 years, 47.1% (8/17) had metabolic syndrome, and only 38.9% (7/18) had a family history of diabetes. No significant difference in manifestations except for hemoglobin A1c levels was found between MODY and non-MODY patients.@*CONCLUSION@#The prevalence of MODY in young adults with phenotypic T2DM was 0.74%, among which HNF1A -, GCK -, and HNF4A -MODY were the most common subtypes. Clinical features played a limited role in the recognition of MODY.

Hypoglycemic effect of electroacupuncture at "Tianshu" (ST 25) combined with metformin on rats with type 2 diabetes mellitus based on AMPK / 中国针灸

OBJECTIVE@#To observe the hypoglycemic effect of electroacupuncture (EA) at "Tianshu" (ST 25) combined with metformin on rats with type 2 diabetes mellitus (T2DM) as well as its effect on expression of adenosine monophosphate activated protein kinase (AMPK) in liver and pancreas.@*METHODS@#Thirty-six male SD rats were randomly divided into a blank group (6 rats) and a model establishing group (30 rats). The rats in the model establishing group were fed with high-fat diet and treated with intraperitoneal injection of low-dose streptozotocin (STZ) to establish T2DM model. The rats with successful model establishment were randomly divided into a model group, a control group, a metformin group, an EA group and a combination group, 6 rats in each group. The rats in the EA group were treated with EA at "Tianshu" (ST 25), dense-disperse wave, 2 Hz/15 Hz in frequency and 2 mA in current intensity, 20 min each time. The rats in the metformin group were treated with intragastric administration of metformin (190 mg/kg) dissolved in 0.9% sodium chloride solution (2 mL/kg). The rats in the combination group were treated with EA at "Tianshu" (ST 25) and intragastric administration of metformin. The rats in the control group were treated with intragastric administration of 0.9% sodium chloride solution with the same dose. All the treatments were given once a day for 5 weeks. After the intervention, the body mass and random blood glucose were detected; the serum insulin level was detected by ELISA; the expression of AMPK and phosphorylated adenosine monophosphate activated protein kinase (p-AMPK) in liver and pancreas was detected by Western blot method; the expression of protein gene product 9.5 (PGP9.5) was detected by immunofluorescence.@*RESULTS@#①Compared with the blank group, the body mass in the model group was decreased (P<0.05); compared with the model group, the body mass in the EA group and the combination group was decreased (P<0.05); the body mass in the EA group and the combination group was lower than the metformin group (P<0.05). Compared with the blank group, the random blood glucose in the model group was increased (P<0.01); compared with the model group, the random blood glucose in the metformin group, the EA group and the combination group was decreased (P<0.01). The random blood glucose in the combination group was lower than the metformin group and the EA group (P<0.05). ②Compared with the blank group, the insulin level in the model group was decreased (P<0.05); compared with the model group, the insulin level in the metformin group, the EA group and the combination group was all increased (P<0.05). The insulin level in the combination group was higher than the metformin group and the EA group (P<0.05). ③Compared with the blank group, the protein expression of AMPK and p-AMPK in liver tissue was decreased (P<0.05), and the protein expression of AMPK and p-AMPK in pancreatic tissue was increased (P<0.05) in the model group. Compared with the model group, the protein expression of AMPK and p-AMPK in liver tissue in the metformin group, the EA group and the combination group was increased (P<0.05, P<0.01); the protein expression of AMPK in pancreatic tissue in the metformin group was increased (P<0.05); the protein expression of AMPK in pancreatic tissue in the EA group and the combination group was decreased (P<0.05); the protein expression of p-AMPK in pancreatic tissue in the metformin group, the EA group and the combination group was decreased (P<0.05). The protein expression of AMPK and p-AMPK in liver tissue in the combination group was higher than that in the metformin group and the EA group (P<0.05); the protein expression of AMPK in pancreatic tissue in the EA group and the combination group was less than that in the metformin group (P<0.05), and the expression of p-AMPK protein in pancreatic tissue in the combination group was less than that in the metformin group and the EA group (P<0.05). ④Compared with the blank group, the expression of PGP9.5 in pancreatic tissue in the model group was increased (P<0.01); compared with the model group, the expression of PGP9.5 in pancreatic tissue in the metformin group, the EA group and the combination group was decreased (P<0.05, P<0.01). The expression of PGP9.5 in pancreatic tissue in the EA group was lower than the metformin group and the combination group (P<0.05).@*CONCLUSION@#Electroacupuncture at "Tianshu" (ST 25) could promote the effect of metformin on activating AMPK in liver tissue of T2DM rats, improve the negative effect of metformin on AMPK in pancreatic tissue, and enhance the hypoglycemic effect of metformin. The mechanism may be related to the inhibition of pancreatic intrinsic nervous system.

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.

Growth and intelligence development among a cohort of low birth weight infants / 中国学校卫生

Objective@#To explore growth and intelligence development of low birth weight infants (LBWI) at 24 and 36 months of age, so as to provide reference for early monitoring and intervention of the development of LBWI.@*Methods@#A total of 100 LBWI born and managed in Hefei Maternal and Child Health Care Institution were selected from 2012 October 1 to 2015 December 30, and 99 normal birth weight infants (NBWI) under child health management in the same sitinstitution were selected as controls. According a prospective cohort study method, and based on the establishment of a cohort and monitoring of childhood growth and development, a unified method was used to longitudinally follow up and observe the physical fitness of two groups of infants at the determined time points. The development of LBWI and NBWI at 24 and 36 months of age was surveyed using the Gesell Development Scale.@*Results@#Weight, length and head circumference of LBWI children at the age of 15-36 months were significantly lower than those of NBWI children ( P <0.05). In addition, 117 children (43.98%) completed the full assessment of intelligent development scale, including 62 LBWI and 55 NBWI. The scores of Gesell in NBWI group was higher than that in LBWI group at 24 and 36 months of age, including adaptability, gross motor, fine metor skills, language and personal social functions ( t =-4.17, -3.82, -3.21 , -3.03, -2.61; -4.23, -3.16, -3.07, -3.13, -3.99, P <0.05). Multivariate linear regression analysis found that birth weight was positively correlated with adaptability, gross motor, fine motor skills, language functions at 24 and 36 months of age and personal social function at 36 months of age ( β =0.004, 0.010; 0.003, 0.008; 0.003, 0.007; 0.004, 0.009; 0.011, P ＜0.05).@*Conclusion@#The growth and development of LBWI children are significantly delayed compared to NBWI children. The scores of LBWI children are lower than those of NBWI children in all functional areas. Weight is the main factor affecting children s intellectual development. Early monitoring and intervention of low birth weight infants should be carried out to avoid or mitigate adverse consequences.

The relationship between compassion fatigue and workplace psychological violence, alexithymia, and empathy among clinical nurses / 中国职业医学

Objective: To study the relationship between compassion fatigue and workplace psychological violence, alexithymia, and empathy in clinical nurses. Methods: A total of 1 159 clinical nurses from 10 cities in Henan and Fujian Provinces were enrolled using the method of grabbing random balls. Questionnaires including Workplace Psychologically Violent Behaviors Instrument, the Toronto Alexithymia Scale, Jefferson Scale of Empathy Health Professionals, Professional Quality of Life Scale were used to investigate the status of workplace psychological violence, alexithymia, empathy, and compassion fatigue in participants. Bootstrap analysis was used to analyze the relationship between workplace psychological violence, alexithymia, empathy, and compassion fatigue scores. Results: The average score for workplace psychological violence among clinical nurses was (26.2±6.5), with 405 nurses (34.9%) having experienced workplace psychological violence. The scores for alexithymia, empathy and compassion fatigue were (58.3±12.3), (104.3±18.6) and (48.5±6.7) respectively. Mild compassion fatigue was detected in 34.9% of participants, while moderate to severe compassion fatigue accounted for 48.8%. Bootstrap test result showed that workplace psychological violence had a positive impact on compassion fatigue ［standardized effect value (β)=0.40, 95% confidence interval(CI)： 0.35-0.44］. Workplace psychological violence had separate mediating effects through alexithymia (β=0.15, 95%CI： 0.10-0.19), empathy (β=0.16, 95%CI： 0.10-0.21) , and a chain mediating effect through alexithymia and empathy on compassion fatigue (β=0.06, 95%CI： 0.03-0.09). Conclusion: Compassion fatigue symptoms are relatively common among clinical nurses. Experiencing workplace psychological violence directly affects compassion fatigue and can indirectly affect it through the mediating effects of alexithymia and empathy.

Practice of Huzhou in promoting the reform of countywide medical and health governance system / 中华医院管理杂志

The construction of a countywide community for medical and health services is designed to upgrade the service capacity of primary medical and health institutions, to promote resource sharing and collaborative services, and promote the hierarchical medical system. Huzhou of Zhejiang province has launched its initiative in building a countywide community for medical services since 2018. The authors summarized its main practices in promoting the integration of the management system and optimizing operating mechanism of countywide medical and health institutions, promoting the reform of the county medical and health governance system, as well as the achievements and shortcomings, with a view to providing reference for promoting the high-quality development of the countywide medical and health service system.

Analysis of accreditation results and development strategies of tertiary hospitals in Jiangsu province from 2018 to 2020 / 中华医院管理杂志

As an important measure starting for hospital management, hospital accreditation can effectively guide hospitals to improve their comprehensive service capabilities and management level. The accreditation results of 38 tertiary general hospitals in Jiangsu province from 2018 to 2020 showed that there were weaknesses existing in the development of hospitals, including the radiosity and influence of tertiary hospitals, patient service mode, construction of medical technology capabilities and disciplines, medical quality and safety, nursing quality management and specialized nursing, and information construction. The author suggested that hospitals should return to functional positioning, improve the service quality, strengthen construction of hospital disciplines and technical projects, consolidate the foundation of quality and safety management, improve the level of information technology construction, for references for promoting the high-quality sustainable development of tertiary general hospitals.

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.