Efficacy analysis of blinatumomab in treatment of relapsed/refractory B-cell acute lymphoblastic leukemia / 白血病·淋巴瘤

Objective:To explore the efficacy and safety of blinatumomab in treatment of relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL).Methods:The data of 8 patients with relapsed/refractory B-ALL treated with blinatumomab in Shanghai Zhaxin Traditional Chinese and Western Medicine Hospital from September 2020 to December 2021 were retrospectively analyzed, and their clinical characteristics, overall survival, lymphocyte subsets, cytokines, tandem transplantation and adverse reactions were analyzed.Results:The median follow-up time of 8 patients was 143 d (range: 41-534 d). Five of the 8 patients were alive; among them, 4 of 6 patients assessed to be in minimal residual disease (MRD)-negative complete remission (CR) and 1 of 2 patients assessed to be in non-remission at the time of belintuzumab discontinuation were alive. The median duration of treatment with belintuzumab was 28 d (10-56 d), and it was 23 d (10-56 d) for patients with MRD-positive at baseline and 28 d (25-31 d) for the 4 non-remission patients. Six patients achieved MRD-negative CR after treatment, of which 4 were assessed as MRD-positive at baseline and 2 were assessed as non-remission at baseline. All 4 patients with MRD-positive CR achieved MRD-negative CR after treatment with belintuzumab, including 1 patient with Philadelphia chromosome-positive (Ph +) ALL bridged to autologous hematopoietic stem cell transplantation, and 1 patient with Ph + ALL and 1 patient with Ph - ALL received sequential allogeneic hematopoietic stem cell transplantation and had persistent MRD-negative CR. Two of the 4 non-remission patients achieved MRD-negative CR after treatment with belintuzumab, including 1 patient with Ph + ALL bridged to autologous hematopoietic stem cell transplantation, and 1 patient with Ph - ALL received sequential allogeneic hematopoietic stem cell transplantation, and the 2 patients had persistent MRD-negative CR. Leukocyte counts and neutrophils decreased in both MRD-positive CR and non-remission patients after receiving belintumomab. The proportion and absolute number of CD3 + T and CD3 + CD8 + T lymphocytes in patients with MRD-positive CR were higher than those in patients without remission, and both decreased after drug administration. Median interleukin-6 (46.23, 1.42 pg/ml), interleukin-8 (17.85, 2.10 pg/ml), interleukin-10 (7.43, 1.49 pg/ml) and interferon-γ (11.82, 0.39 pg/ml) levels were elevated in MRD-positive CR and non-remission patients at week 3 of treatment. Grade 1 cytokine release syndrome occurred in 1 case with clinical manifestations of fever, which improved after drug suspension. Three cases developed infections, 2 of which were pulmonary and 1 of which was upper respiratory tract infection. No immune effector cell-associated neurotoxic syndrome was observed. Conclusions:Belintumomab is effective for MRD clearance in relapsed/refractory B-ALL with manageable adverse reactions, providing an effective therapeutic option for bridging hematopoietic stem cell transplantation to prolong the survival of patients.

Genomics of next generation sequencing in pediatric B-acute lymphoblastic leukemia and its impact on minimal residual disease / 中华儿科杂志

Objective: To describe the gene mutation profile of newly diagnosed pediatric B-acute lymphoblastic leukemia (B-ALL) and analyze its effect on minimal residual disease (MRD). Methods: A total of 506 newly diagnosed B-ALL children treated in Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences from September 2018 to July 2021 were enrolled in this retrospective cohort study. The enrolled children were divided into MRD ≥1.00% group and <1.00% group according to MRD results on the 19th day since chemotherapy, and MRD ≥0.01% group and <0.01% group according to MRD results on the 46th day. Clinical characteristics and gene mutations of two groups were compared. Comparisons between groups were performed with chi-square test or Fisher's exact test. Independent risk factors of MRD results on the 19th day and the 46th day were analyzed by Logistic regression model. Results: Among all 506 patients, there were 318 males and 188 females. On the 19th day, there were 114 patients in the MRD ≥1.00% group and 392 patients in the MRD <1.00% group. On the 46th day, there were 76 patients in the MRD ≥0.01% group and 430 patients in the MRD <0.01% group. A total of 187 gene mutations were detected in 487 (96.2%) of 506 children. The most common gene mutations were signal transduction-related KRAS gene mutations in 111 cases (22.8%) and NRAS gene mutations in 99 cases (20.3%). Multivariate analysis showed that PTPN11 (OR=1.92, 95%CI 1.00-3.63), KMT2A (OR=3.51, 95%CI 1.07-11.50) gene mutations and TEL-AML1 (OR=0.48, 95%CI 0.27-0.87), BCR-ABL1 (OR=0.27, 95%CI 0.08-0.92) fusion genes and age >10 years (OR=1.91, 95%CI 1.12-3.24) were independent influencing factors for MRD ≥1.00% on the 19th day. BCORL1 (OR=2.96, 95%CI 1.18-7.44), JAK2 (OR=2.99, 95%CI 1.07-8.42) and JAK3 (OR=4.83, 95%CI 1.50-15.60) gene mutations and TEL-AML1 (OR=0.43, 95%CI 0.21-0.87) fusion gene were independent influencing factors for MRD ≥0.01% on the 46th day. Conclusions: Children with B-ALL are prone to genetic mutations, with abnormalities in the RAS signaling pathway being the most common. Signal transduction related PTPN11, JAK2 and JAK3 gene mutations, epigenetic related KMT2A gene mutation and transcription factor related BCORL1 gene mutation are independent risk factors for MRD.

A new elemane-type sesquiterpenoid glycoside from Curcuma phaeocaulis / 药学学报

To study the chemical constituents and their biological activities in the rhizomes of Curcuma phaeocaulis, silica gel column chromatography, reverse medium pressure liquid chromatography, preparative thin layer chromatography, and semi-preparative high performance liquid chromatography were used for isolation and purification and modern spectroscopic methods were used to determine the structure of the isolated compound. Moreover, the effect of the compound on the proliferation of HUVECs was determined by the MTT assay. A new elemane-type sesquiterpenoid glycoside was isolated from the n-butanol soluble fraction of 95% ethanolic extract of the rhizomes of Curcuma phaeocaulis. Its structure was identified as (1Z)-2-hydroxy-curzerenone 2-O-β-D-glucoside. It showed no inhibitory effect on the proliferation of HUVECs.

Properties of new exotic traditional Chinese medicinal Vernonia amygdalina leaves:a literature research / 中国中药杂志

The leaves of Vernonia amygdalina Delile of the family Asteraceae(also known as "bitter leaf"), rich in biological activities, are used as both medicine and food for a long time in West tropical Africa. They have been introduced into Southeast Asia and Fujian and Guangdong provinces of China in recent years. However, little is known about the properties of the plant in traditional Chinese medicine(TCM), which limits its combination with other Chinese medicinal herbs. In this study, 473 articles on V. amygdalina leaves were selected from PubMed, Web of Science, CNKI, Wanfang Data and VIP to summarize their components, pharmacological effects and clinical research. V. amygdalina leaves presented anti-microbial, hypoglycemic, anti-hypertensive, lipid-lowering, anti-tumor, anti-inflammatory, antioxidant, and other pharmacological effects. On the basis of the theory of TCM properties, the leaves were inferred to be cold in property and bitter and sweet in flavor, acting on spleen, liver, stomach and large intestine and with the functions of clearing heat, drying dampness, purging fire, removing toxin, killing insects and preventing attack of malaria. They can be used to treat dampness-heat diarrhea, interior heat and diabetes, malaria, insect accumulation and eczema(5-10 g dry leaves by decoction per day and an appropriate amount of crushed fresh leaves applying to the affected area for external use). Due to the lack of TCM properties, V. amygdalina leaves are rarely used medicinally in China. The determination of medicinal properties of the leaves is conducive to the introduction of new exotic medicinal herbs and the development of new TCM resources, which facilitated further clinical application and research and development of Chinese medicinal herbs.

Endometrioid adenocarcinoma of the rectovaginal septum: A case report / 中南大学学报(医学版)

Primary endometrioid adenocarcinoma of the rectovaginal septum is rare. Its pathogenesis is not clear and there is no standard treatment. One patient with endometrioid adenocarcinoma of the rectovaginal septum arising from deep infiltrative endometriosis was admitted to Qingdao Municipal Hospital. The patient presented with incessant menstruation and abdominal distension. She had bilateral ovarian endometriotic cystectomy 6 years ago. Imaging findings suggested a pelvic mass which might invade the rectovaginal septum. Pathological results of primary surgery confirmed endometrioid carcinoma of the pelvic mass arising from the rectovaginal septum. Then she had a comprehensive staged surgery. Postoperative chemotherapy was given 6 times. No recurrence or metastasis was found during the 2-year follow-up. The possibility of deep infiltrating endometriosis and its malignant transformation should be considered in the differential diagnosis of a new extragonadal pelvic lesion in a patient with a history of endometriosis, which would avoid misdiagnosis and missed diagnosis.

Enhanced recovery after surgery in transurethral surgery for benign prostatic hyperplasia / 亚洲男科学杂志(英文版)

Enhanced recovery after surgery (ERAS) measures have not been systematically applied in transurethral surgery for benign prostatic hyperplasia (BPH). This study was performed on patients with BPH who required surgical intervention. From July 2019 to June 2020, the ERAS program was applied to 248 patients, and the conventional program was applied to 238 patients. After 1 year of follow-up, the differences between the ERAS group and the conventional group were evaluated. The ERAS group had a shorter time of urinary catheterization compared with the conventional group (mean ± standard deviation [s.d.]: 1.0 ± 0.4 days vs 2.7 ± 0.8 days, P < 0.01), and the pain (mean ± s.d.) was significantly reduced through postoperative hospitalization days (PODs) 0-2 (POD 0: 1.7 ± 0.8 vs 2.4 ± 1.0, P < 0.01; POD 1: 1.6 ± 0.9 vs 3.5 ± 1.3, P < 0.01; POD 2: 1.2 ± 0.7 vs 3.0 ± 1.3, P < 0.01). No statistically significant difference was found in the rate of postoperative complications, such as postoperative bleeding (P = 0.79), urinary retention (P = 0.40), fever (P = 0.55), and readmission (P = 0.71). The hospitalization cost of the ERAS group was similar to that of the conventional group (mean ± s.d.: 16 927.8 ± 5808.1 Chinese Yuan [CNY] vs 17 044.1 ± 5830.7 CNY, P =0.85). The International Prostate Symptom Scores (IPSS) and quality of life (QoL) scores in the two groups were also similar when compared at 1 month, 3 months, 6 months, and 12 months after discharge. The ERAS program we conducted was safe, repeatable, and efficient. In conclusion, patients undergoing the ERAS program experienced less postoperative stress than those undergoing the conventional program.

Anti-fatigue effect of Lubian on kidney Yin deficiency and kidney Yang deficiency mice and mechanism based on PI3K-Akt pathway / 中国中药杂志

This study aimed to investigate the anti-fatigue effect and mechanism of Lubian(Cervi Penis et Testis) on kidney Yin deficiency and kidney Yang deficiency mice. After one week of adaptive feeding, 88 healthy male Kunming mice were randomly divided into a blank group, a kidney Yin deficiency model group, a kidney Yin deficiency-Panacis Quinquefolii Radix(PQR) group, kidney Yin deficiency-Lubian treatment groups, a kidney Yang deficiency model group, a kidney Yang deficiency-Ginseng Radix et Rhizoma(GR) group, and kidney Yang deficiency-Lubian treatment groups, with eight mice in each group. The kidney Yin deficiency model and kidney Yang deficiency model were prepared by daily regular oral administration of dexamethasone acetate and hydrocortisone, respectively, and meanwhile, corresponding drugs were provided. The mice in the blank group received blank reagent. The treatment lasted 14 days. The exhaustive swimming time was measured 30 min after drug administration on the 14th day. On the 15th day, blood was collected from eyeballs and the serum was separated to determine the content of lactic acid(LD), blood urea nitrogen(BUN), lactate dehydrogenase(LDH), cyclic adenosine monophosphate(cAMP), and cyclic guanosine monophosphate(cGMP). The liver was dissected to determine the content of liver glycogen and the protein expression of phosphoinositide 3-kinase(PI3K) and protein kinase B(Akt). Compared with the kidney Yang deficiency model group, the kidney Yang deficiency-Lubian treatment groups showed increased body weight(P<0.05), relieved symptoms of Yang deficiency, decreased cGMP content(P<0.01), increased cAMP/cGMP(P<0.01), prolonged exhausted swimming time(P<0.01), reduced LD(P<0.01), elevated BUN content(P<0.01), increased liver glycogen content(P<0.01), and increased protein expression of PI3K and Akt in the liver(P<0.05). Compared with the kidney Yin deficiency model group, the kidney Yin deficiency-Lubian treatment groups showed increased body weight(P<0.01), relieved symptoms of Yin deficiency, increased content of cGMP(P<0.01), decreased cAMP/cGMP(P<0.01), prolonged exhausted swimming time(P<0.01), decreased LD(P<0.01), decreased BUN content(P<0.01), increased liver glycogen content(P<0.01), and increased protein expression of PI3K(P<0.05) and Akt in the liver(P<0.05). To sum up, Lubian can regulate Yin deficiency and Yang deficiency and increase glycogen synthesis by affecting the PI3K-Akt pathway, thereby exerting an anti-fatigue role.

Mechanism of Key Ingredient of Astragalus membranaceus on Lung Adenocarcinoma via PI3K/AKT Signaling Clarified by Utilizing Network Pharmacology Approach and Experimental Validation / 中国结合医学杂志

OBJECTIVE@#To investigate the mechanism of the effect of Astragalus membranaceus (A. membranaceus) on lung adenocarcinoma at the molecular level to elucidate the specific targets according to the network pharmacology approach.@*METHODS@#The active components of A. membranaceus and their potential targets were collected from the Traditional Chinese Medicine Systems Pharmacology Database. Lung adenocarcinoma-associated genes were acquired based on GeneCards, Online Mendelian Inheritance in Man (OMIM), PharmGKB, and Therapeutic Targets databases. The PI3K/AKT signaling pathway-related genes were obtained using Reactome portal. Networks of "ingredient-target" and "ingredient-target-pathway-disease" were constructed using the Cytoscape3.6.0 software. The relationships among targets were analyzed according protein-protein interaction (PPI) network. Finally, molecular docking was applied to construct the binding conformation between active ingredients and core targets. Cell counting kit 8 (CCK8) and Western blot assays were performed to determine the mechanism of the key ingredient of A. membranaceus.@*RESULTS@#A total of 20 active components and their 329 targets, and 7,501 lung adenocarcinoma-related genes and 130 PI3K/AKT signaling pathway-related genes were obtained. According to Venn diagram and PPI network analysis, 2 mainly active ingredients, including kaempferol and quercetin, and 6 core targets, including TP53, MAPK1, EGF, AKT1, ERBB2, and EGFR, were identified. The two important active ingredients of A. membranaceus, kaempferol and quercetin, exert the therapeutic effect in lung adenocarcinoma partly by acting on the 6 core targets (TP53, MAPK1, EGF, AKT1, ERBB2, and EGFR) of PI3K/AKT signaling pathway. Expressions of potential targets in lung adenocarcinoma and normal samples were analyzed by using UALCAN portal and found that ERBB2 was overexpressed in lung adenocarcinoma tissues and upregulation of it correlated with clinicopathological characteristics. Finally, quercetin repressed viabilities of lung adenocarcinoma cells by targeting ERBB2 on PI3K/AKT signaling confirmed by CCK8 and Western blot.@*CONCLUSION@#Our finding unraveled that an active ingredient of A. membranaceus, quercetin, significantly inhibited the lung adenocarcinoma cells proliferation by repressing ERBB2 level and inactivating the PI3K/AKT signaling pathway.

Genetic analysis of a case of B-acute lymphoblastic leukaemia with double Philadelphia chromosomes and double derivative chromosome 9s / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for a rare case of acute B-lymphocytic leukemia (B-ALL) with double Philadelphia chromosomes (Ph) and double derivative chromosome 9s [der(9)].@*METHODS@#A patient with double Ph and double der(9) B-ALL who presented at Shanghai Zhaxin Intergrated Traditional Chinese and Western Medicine Hospital in June 2020 was selected as the subject. Bone marrow morphology, flow cytometry, G-banding karyotyping, fluorescence in situ hybridization (FISH), genetic testing and chromosomal microarray analysis (CMA) were used to analyze bone marrow samples from the patient at various stages.@*RESULTS@#At initial diagnosis, the patient's bone marrow morphology and flow immunotyping have both supported the diagnosis of B-ALL. G-banded karyotyping of the patient indicated double Ph, in addition with hyperdiploid chromosomes involving translocations between chromosomes 9 and 22. BCR-ABL1 fusion gene was positive. Genetic testing at the time of recurrence revealed presence of a heterozyous c.944C>T variant in the kinase region of the ABL1 gene. FISH showed a signal for ABL1-BCR fusion on both chromosome 9s. CMA showed that the mosaicism homozygosity ratio of chromosome 9 was about 40%, and the mosaicism duplication ratio of chromosome 22 was about 43%.@*CONCLUSION@#Since both der(9) homologs were seen in 40% of cells, the possible mechanism for the double der(9) in this patient may be similar to that of double Ph, which might have resulted from non-disjunction during mitosis in the Ph chromosome-positive cell clone.

Prevalence of HCV Antibody and its Associated Factors: A Study from Sentinel Hospitals in China / 生物医学与环境科学（英文）

OBJECTIVE@#The prevalence and related factors of serum anti-HCV in different regions and hospitals have not been studied extensively in China. We used routine screening data to determine the prevalence of HCV antibody in hospital patients, evaluate the epidemic trend of hepatitis C and formulate screening strategies.@*METHODS@#Patient information and HCV antibody testing results were collected from January 2017 to December 2019 in 77 HCV sentinel hospitals in China. Univariate and multivariate logistic regression was used to determine the characteristics and associations.@*RESULTS@#HCV antibody prevalence rates were distinct among patients in different departments, with a range of 0.33%-6.93%. Patients who were admitted to the liver disease-related departments (a OR = 10.76; 95% CI, 10.27-11.28), Internal Medicine (a OR = 2.87; 95% CI, 2.75-3.00), and Department of Surgery (a OR = 1.95; 95% CI, 1.87-2.04), were more likely to be tested for HCV antibody positive. HCV antibody prevalence was associated with patients aged 45 years and older (a OR = 2.74; 95% CI, 2.69-2.80), testing in infetious disease hospitals (a OR = 2.33; 95% CI, 2.26-2.40) and secondary hospitals (a OR = 1.72; 95% CI, 1.69-1.75). Patients in sentinel hospitals of the Northeast (a OR = 12.75; 95% CI, 12.40-13.11), the Central (a OR = 1.65; 95% CI, 1.61-1.70), and the West (a OR = 1.78; 95% CI, 1.73-1.83) China had higher HCV prevalence than those who were in the Eastern coastal area.@*CONCLUSION@#Those who were over 45 years old and saw doctors for liver diseases, and invasive diagnosis and treatment should be referred to HCV antibody testing.

Exploring Synergistic Mechanism of Vinegar-processed Olibanum in Treatment of Ulcerative Colitis Based on Bile Acid-regulated "Gut-liver" Crosstalk / 中国实验方剂学杂志

ObjectiveTo investigate the synergistic mechanism of vinegar-processed Olibanum on ulcerative colitis（UC） via the bile acids regulating "gut-liver" crosstalk. MethodRats were randomly divided into normal group， model group， Olibanum group and vinegar-processed Olibanum group. UC model of rats was induced by intracolonic instillation of 2，4，6-trinitrobenzenesulfonic acid（TNBS）. Ultra high performance liquid chromatography-triple quadrupole-mass spectrometry（UPLC-QQQ-MS） was used to perform the qualitative analysis of 30 bile acids in the colon of rats. Real-time fluorescence quantitative polymerase chain reaction（Real-time PCR） and Western blot were used to detect changes in the expression of farnesoid X receptor（FXR）， fibroblast growth factor 15（FGF15） and FGF receptor 4（FGFR4） in "gut-liver" crosstalk at mRNA and protein levels. And with the help of HcoEpiC cell model intervened by conjugated bile acids， simulating the UC state， and according to the different modes of intervention， they were divided into the blank group， conjugated bile acid group， Olibanum group， vinegar-processed Olibanum group and 3-O-acetyl-9，11-dehydro-β-boswellic acid（ADHBA） group. The effect of Olibanum before and after processing with vinegar and the main differential component ADHBA on the mRNA expression of FXR and FGF19 were explored by Real-time PCR. ResultCompared with the normal group， the levels of conjugated bile acids in the model group increased significantly（P<0.01）， and the mRNA and protein expressions of "gut-liver" crosstalk factors FXR， FGF15 and FGFR4 decreased significantly（P<0.05， P<0.01）. Compared with the model group， the content of conjugated bile acids in the Olibanum group and vinegar-processed Olibanum group was significantly decreased（P<0.01）， the mRNA and protein expressions of FXR， FGF15 and FGFR4 were significantly elevated（P<0.05， P<0.01）， and vinegar-processed Olibanum exhibited superior effects than Olibanum. In cellular experiments， a significant decrease in mRNA expression of FXR and FGF19 was observed in the conjugated bile acid group when compared with the blank group（P<0.01）. Compared with the conjugated bile acid group， the mRNA expressions of FXR and FGF19 were significantly higher in the Olibanum， vinegar-processed Olibanum and ADHBA groups（P<0.05， P<0.01）， and the effect of vinegar-processed Olibanum was more favorable. ConclusionVinegar-processed Olibanum may enhance the ameliorating effect on UC by enhancing the down-regulation of conjugated bile acids in the colon and the up-regulation of FXR-FGF15/19-FGFR4 "gut-liver" crosstalk pathway， and ADHBA may be the main material basis for the synergy.

Association between anti-tissue transglutaminase antibody titers and duodenal histopathology among adults with celiac disease / 中华内科杂志

To evaluate the association between serum anti-tissue transglutaminase antibody (anti-tTG) titers and the severity of histological damage to the duodenal mucosa and to predict a possible anti-tTG cutoff value for diagnosing celiac disease (CD) and villous atrophy in the domestic population. Clinical and pathological data from 76 adult CD patients with positive anti-tTG titers and duodenal biopsy results who were treated at the People′s Hospital of Xinjiang Uygur Autonomous Region from July 2017 to January 2022 were retrospectively analyzed. The correlation between anti-tTG titers and the severity of duodenal mucosal damage was statistically assessed to predict the optimal anti-tTG titer cut-off value for diagnosing CD and villous atrophy. Of the 76 patients, 10 had underlying CD, and of the 66 patients with duodenal histopathology, four were Marsh Ⅰ, six were Marsh Ⅱ, and 56 were Marsh Ⅲa-c grade. In adults with CD, anti-tTG titers were shown to be associated with the severity of histological damage to the duodenal mucosa. When the anti-tTG level was ≥5 times the upper limit of normal (ULN), the sensitivity and specificity for diagnosing CD were 83.9% and 92.9%, respectively. When the anti-tTG titer was ≥8 times the ULN, the sensitivity and specificity for diagnosing villous atrophy were 67.9% and 90.0%, respectively. Anti-tTG levels had a strong predictive value for diagnosing CD in adults when titers exceeded 10 times the ULN. Thus, the anti-tTG cut-off value can be combined with clinical judgment to diagnose CD, limiting the use of invasive endoscopy.

Clinical and endoscopic characteristics of adult celiac disease / 中华内科杂志

Objective:The study aimed to analyze the clinical and endoscopic characteristics of adult celiac disease (CD) to provide a scientific basis for more effective CD diagnosis and treatment.Methods:In this cross-sectional study, the clinical and endoscopic data of 96 adult CD patients treated in the Department of Gastroenterology of the People′s Hospital of Xinjiang Uygur Autonomous Region from March 2016 to December 2021 were retrospectively collected and analyzed.Results:A total of 96 CD patients were diagnosed, including 33 men and 63 women. The average age was 47±14 years (range, 18-81 years). The disease occurred mainly in the age group of 31-60 years. The median course of the disease was 2.0 (0.2-40.0) years. There were 41 (42.7%) classical and 55 (57.3%) non-classical CD patients. All patients with classical CD showed chronic diarrhea, often accompanied by abdominal pain (46.3%, 19/41), abdominal distension (17.1%, 7/41), anemia (65.9%, 27/41), and chronic fatigue (48.8%, 20/41). The main manifestations of non-classical CD were chronic abdominal pain (58.2%, 32/55), abdominal distension (32.7%, 18/55), anemia (40.0%, 22/55), and osteopenia/osteoporosis (38.2%, 21/55). Compared with non-classical CD, anemia developed more frequently in classical CD, and the difference was statistically significant ( P = 0.012). The incidence of complications in CD patients was 36.5% (35/96), and the main complications were thyroid disease (19.8%, 19/96), connective tissue disease (6.2%, 6/96), and kidney disease (6.2%, 6/96). There was no significant difference between classical and non-classical CD ( P>0.05). The frequency of endoscopic manifestations in CD patients was 84.4% (81/96). Duodenal bulb endoscopy showed nodular changes (72.9%, 70/96), grooved changes (10.4%, 10/96), and focal villous atrophy (9.4%, 9/96). The main manifestations of descending endoscopy were the decrease, flattening, or disappearance of duodenal folds (43.8%, 42/96), scallop-like changes (38.5%, 37/96), and nodular changes (34.4%, 33/96). Conclusions:Adult CD patients are mostly female. CD occurred mainly in the age group of 31-60 years. The clinical manifestations were mainly those of non-classical CD. Some patients often had other autoimmune diseases. Patients with characteristic endoscopic manifestations should be warned about the possibility of developing CD. Clinicians should strengthen the understanding of CD and reduce the related rates of missed diagnosis.

The effectiveness of dialectical behavior therapy for mental disorders / 中华行为医学与脑科学杂志

Dialectical behavior therapy (DBT), as an important representative of the " third wave" of cognitive behavior therapy (CBT), has been paid more attention. Since the publication of the treatment manual in 1993, DBT has been widely spread in several treatment settings, including outpatient, community, and inpatient settings, and has been applied to the diagnosis and treatment of various mental disorders. In recent years, more and more studies have proved that DBT has a clear effect on a variety of mental disorders and psychological and behavioral problems, especially the clinical problems related to emotion regulation. This article summarizes and evaluates the effectiveness of DBT in the treatment of mental disorders and discusses the limitations of the current research and the future development direction.

Causes and prognosis analysis of hyperdynamic left ventricular ejection fraction in intensive care unit patients with sepsis / 中华危重病急救医学

Objective:To analyze the causes of hyperdynamic left ventricular ejection fraction (LVEF) in sepsis patients in the intensive care unit (ICU) and its impact on prognosis.Methods:A retrospective cohort study was conducted. The clinical data of 273 sepsis patients admitted to the department of critical care medicine of the Affiliated People's Hospital of Jiangsu University from January 2018 to October 2021 were collected including gender, age, severity score, comorbidities, source of infection, vital signs, transthoracic echocardiographic (TTE) parameters, fluid intake and output, vasoactive drug dose, therapeutic measures and prognostic indicators. The patients were divided into normal LVEF group (LVEF 0.55-0.70), low LVEF group (LVEF < 0.55) and hyperdynamic LVEF group (LVEF > 0.70) according to the TTE examination results within 7 days of ICU admission. The clinical indicators among the three groups were compared and analyzed, and multivariate Logistic regression analysis was used to screen risk factors for the development of hyperdynamic LVEF in patients with sepsis. Spearman correlation analysis was used to determine the correlation between the mortality of different types of LVEF and clinical variables.Results:Among 273 patients, 20 patients with severe valvular or cardiomyopathy at admission and those who did not completed cardiac ultrasound within 7 days of ICU admission were excluded. A total of 253 patients were finally enrolled, including 169 patients in the normal LVEF group, 40 patients in the low LVEF group, and 44 patients in the hyperdynamic LVEF group. There were statistically significant differences in age, sequential organ failure assessment (SOFA) score, central venous pressure (CVP), heart rate (HR), oxygenation index (PaO 2/FiO 2), blood lactate (Lac), urine output, vasoactive drug dose, ratio of hypertension, ischemic heart disease, chronic liver disease, cancer, invasive mechanical ventilation and renal replacement therapy (RRT), and incidence of septic shock among the different types of LVEF groups. TTE results analysis showed that the hyperdynamic LVEF group had higher stroke volume (SV) and cardiac index (CI) than those in the normal LVEF and low LVEF groups, lower systemic vascular resistance (SVR) than that in the normal LVEF and low LVEF groups, and an increased E/A ratio. The 90-day mortality in the hyperdynamic LVEF group was significantly higher than that in the normal LVEF and low LVEF groups [59.1% (26/44) vs. 24.9% (42/169), 32.5% (13/40), both P < 0.05]. Multivariate Logistic regression analysis showed that chronic liver disease [odds ratio ( OR) = 1.712, 95% confidence interval (95% CI) was 0.912-3.234, P < 0.001], cancer ( OR = 2.784, 95% CI was 1.296-6.151, P < 0.001), HR ( OR = 1.026, 95% CI was 1.014-1.038, P < 0.001), vasoactive drug dose ( OR = 1.133, 95% CI was 1.009-1.291, P < 0.001), and invasive mechanical ventilation ( OR = 2.141, 95% CI was 1.285-3.651, P < 0.001) were independent factors for hyperdynamic LVEF in ICU sepsis patients. Correlation analysis showed that the mortality of hyperdynamic LVEF, normal LVEF and low LVEF patients was positively correlated with vasoactive drug dose ( r value was 0.251, 0.361, 0.289, respectively, all P < 0.001). The mortality of the hyperdynamic LVEF patients was negatively correlated with SVR ( r = -0.545, P < 0.001). Conclusions:Chronic liver disease, cancer, HR, vasoactive drugs dose, and invasive mechanical ventilation are independent risk factors for hyperdynamic LVEF in patients with sepsis. Hyperdynamic LVEF is positively associated with mortality in sepsis patients, which may be due to the the decrease of SVR caused by septic vascular paralysis.

Autopsies and placental examinations of perinatal fetal deaths: a clinicopathological analysis of 105 cases / 中华病理学杂志

Objective: To summarize the clinicopathological factors related to perinatal fetal death and to evaluate importance of fetal autopsy and placental pathology. Methods: The clinicopathological data of 105 perinatal fetal deaths in Beijing Haidian Maternal and Child Health Hospital from November 2012 to December 2020 were retrospectively analyzed. Relevant literature was also reviewed. Results: The maternal age of the deceased fetuses ranged from 22 to 43 years with the average (31.35±4.04 years), and the gestational weeks were 28-40+6 weeks. Among them, 101 were singleton cases and 4 twin cases. 103 fetuses died in uterus and 2 died during delivery. Relevant factors analysis of the 105 perinatal fetal deaths showed that 86 cases (81.9%, 86/105) were related to umbilical cord/placental abnormality, 10 cases (9.5%, 10/105) uterine infection, 6 cases (5.7%, 6/105) fetal factors, 1 case was fetal maternal blood transfusion syndrome, 1 case twin blood transfusion syndrome, and 1 case died of complete uterine rupture. Among the 86 cases related to umbilical cord/placental abnormality, the diagnosis was most often based on the gross examination of placenta. The most common cause of death was umbilical cord torsion with thin root, followed by placental abruption, tight umbilical cord winding, vascular rupture and umbilical cord true knot. The morphology of placenta revealed mainly functional changes. Among the 10 cases related to intrauterine infections, the placenta generally showed lobular placental edema. The morphological characteristics of ascending infection were mainly acute chorioamnionitis, and the morphological characteristics of blood-borne infection were mainly acute or chronic villitis, as well as villous interstitial inflammation. Identification of viral inclusions suggested viral etiology, while the final diagnosis was relied on laboratory testing. Among the 6 cases related to fetal abnormality, the diagnostic value of placenta was limited and the diagnosis could be made with fetal autopsy. Conclusion: The causes of perinatal fetal death are complex, diverse, and often the synergistic result of multiple factors. Fetal autopsy and placental pathology are the key technical means to identify the cause of death and deserve more attention and utilization.

Singleton placentas with abnormal shape: a clinicopathological analysis of 130 cases / 中华病理学杂志

Objective: To investigate the pathological characteristics of singleton placenta with abnormal shape and its influence on the outcome of maternal-fetal pregnancy. Methods: The clinicopathological data of singleton placentas with abnormal shape from January 2014 to December 2020 in the Department of Pathology, Haidian Maternal and Children Health Hospital were analyzed retrospectively. Results: There were 130 singleton placentas with abnormal shape in this cohort, including 48 succenturiate placentas, 12 bilobed placentas, 50 marginate placentas, 13 circumvallate placentas, 3 annular placentas, 2 membranous placentas and 2 fenestrated placentas. Gestational age ranged from 29+5 to 40+4 weeks. There were 51 cases of premature rupture of membranes, 11 cases of placenta previa, 5 cases of placental abruption, 15 cases of placental adhesion/implantation and 27 cases of postpartum hemorrhage. There were 46 preterm fetuses,28 fetuses with fetal growth restriction, 22 fetuses with intrauterine distress, and 1 fetus with intrauterine death. Grossly, the placental lobules of succenturiate placentas had apparent size difference, while two lobules of bilobate placenta were more consistent. The chorionic plate size was smaller than the bottom plate of circumvallate placenta, the folded fetal membrane in the rim of placenta was thickened (termed marginate placenta if there was no thickening). The membranous placenta was characterized by a thin, large membrane-like shape. Annular placenta showed characteristic hollow cylinder, ring or horseshoe-shape. Fenestrated placenta was characterized by tissue defects near central area. Microscopically, functional/morphologic changes were the main manifestations of inadequate maternal-fetal perfusion, including villous infarction, distal villous dysplasia and excessive villous maturation. Conclusions: The abnormal shaped singleton placentas showed variable extent of inadequate maternal-fetal perfusion, which may lead to adverse pregnancy outcomes such as premature delivery, fetal growth restriction, intrauterine distress or fetal death.

Generation and phenotype of myeloid cell specific Clcn7-mutation osteopetrosis mouse model / 中华内分泌代谢杂志

Objective:To construct a myeloid cell specific Clcn7-G763R mutant mouse model and characterize its phenotype.Methods:A mouse conditional knocked in p. G763R mutation in Clcn7 gene was constructed and bred with LysM cre mice to obtain osteopetrosis mice with myeloid cell specific Clcn7-G763R mutation. The differences of bone mass in mice with different genotypes were analyzed using Micro CT and the changes of histology were observed with HE staining. Osteoclasts were cultured and the expression levels of osteoclasts differentiation and maturation-related genes were detected by real-time PCR. The functions of osteoclasts were examined through bone resorption assay.Results:The body weight of homozygous mutant mice at 4 weeks old was reduced compared with the wild type mice [(12.000±1.666)g vs(15.630±2.314)g, P=0.021], with shorter femur length [(1.160±0.096)cm vs (1.300±0.082)cm, P=0.037]. Micro CT showed that bone mineral density of homozygous mutant mice was remarkably increased at 4 weeks old [(0.753±0.002)g/cm 3vs(0.143±0.034)g/cm 3, P=0.003], while bone mineral density of heterozygous mutant mice increased significantly at 8 weeks old [(0.236±0.021)g/cm 3vs(0.180±0.020)g/cm 3, P=0.030]. HE staining revealed increased trabecula bone volume in the mutant mice, especially in homozygous mutant mice with narrow bone marrow cavity and wider hypertrophic zone of chondrocytes. There was no significant difference in the number of osteoclasts between wild type mice and heterozygous mice in vitro( P=0.358), while total area of osteoclasts increased in heterozygous mutant mice [(3.590×10 6±0.911×10 6)μm 2vs(1.352×10 6±0.260×10 6)μm 2, P=0.043]. Impaired function of resorption was unveiled by bone resorption assay. There were no significant differences in the expressions of osteoclast differentiation and maturity-related genes including NFATc1, c-fos, Ctsk, and Acp5 between the two groups. Conclusion:A myeloid cell specific Clcn7-G763R mutation mice with impaired osteoclasts and increased bone mass is successfully constructed.

Dexmedetomidine attenuates neuroinflammation by inhibiting NF-κB nuclear translocation in rats with traumatic brain injury / 中华急诊医学杂志

Objective:To explore the mechanism of dexmedetomidine (DEX) regulating microglial (MG) polarization and neuroinflammation after traumatic brain injury (TBI) in rats.Methods:Forty-two adult male SD rats were randomly (random number) divided into the sham group, TBI group, TBI+DEX group (further divided into 1 d, 3 d and 7 d subgroups), TBI+NF-κB inhibitor (pyrrolidine dithiocarbamate, PDTC) group and TBI+DEX+PDTC group, with 6 animals in each group. The rat TBI model was established according to the modified Feeney free fall method. PDTC was intraperitoneally injected 1 h after modeling with a dose of 100 mg/kg, and DEX was intraperitoneally injected 2 h after modeling with a dose of 100 μg/kg. Modified neurological severity score (mNSS) was used to evaluate rat neurological function, ELISA was used to detect serum inflammatory factors, and rats’ damaged cortex was collected to detect the phenotype markers of MG and protein expressions of MyD88 and NF-κB p65, and immunofluorescence staining was used to observe the expression and nuclear entry of NF-κB p65 in MG in injured cortex. One-way and two-way ANOVA were used to compare the measurement data among multiple groups.Results:Compared with the sham group, the mNSS score was significantly higher in the TBI group, and DEX treatment significantly decreased the mNSS score of TBI rats ( P<0.05). ELISA and Western blot results showed that in the TBI group, the tumor necrosis factor-α (TNF-α), interleukin (IL)-1β in serum and M1 phenotype marker (TNF-α, IL-1β) in brain were increased, the expression of anti-inflammatory factor IL-10 in serum and M2 phenotype markers (arginase-1 and IL-10) in brain were decreased ( P<0.05), and DEX downregulated the expression of TNF-α, IL-1β in serum and M1 phenotype markers in brain, while upregulated the level of L-10 in serum and the M2 phenotype marker in brain ( P<0.05). In addition, the expression of MyD88 and the nuclear translocation of NF-κB p65 were inhibited in the DEX group, and this effect could be enhanced by PDTC. Conclusions:DEX modulates MG activation in TBI rats by inhibiting NF-κB nuclear translocation and reduces neuroinflammation.

Effect of 5 methods of critical illness score in the prognosis evaluation of sepsis-associated encephalopathy / 中华急诊医学杂志

Objective:To explore the effect of pediatric critical illness score (PCIS), pediatric risk of mortality Ⅲ score (PRISM Ⅲ), pediatric logistic organ dysfunction 2 (PELOD-2), pediatric sequential organ failure assessment (p-SOFA) score and Glasglow coma scale (GCS) in the prognosis evaluation of septic-associated encephalopathy (SAE).Methods:The data of children with SAE admitted to the Pediatric Intensive Care Unit (PICU), Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences from January 2010 to December 2020 were retrospectively analyzed. They were divided into the survival and death groups according to the clinical outcome on the 28th day after admission. The efficiency of PCIS, PRISM Ⅲ, PELOD-2, p-SOFA and GCS scores for predicting death were evaluated by the area under the ROC curve (AUC). The Hosmer-Lemeshow goodness-of-fit test assessed the calibration of each scoring system.Results:Up to 28 d after admission, 72 of 82 children with SAE survived and 10 died, with a mortality rate of 12.20%. Compared with the survival group, the death group had significantly lower GCS [7 (3, 12) vs. 12 (8, 14)] and PCIS scores [76 (64, 82) vs. 82 (78, 88)], and significantly higher PRISM Ⅲ [14 (12, 17) vs. 7 (3, 12)], PELOD-2 [8 (5, 13) vs. 4 (2, 7)] and p-SOFA scores [11 (5, 12) vs. 6 (3, 9)] ( P<0.05). The AUCs of PCIS, PRISM Ⅲ, PELOD-2, p-SOFA and GCS scores for predicting SAE prognosis were 0.773 ( P=0.012, AUC>0.7), 0.832 ( P=0.02, AUC>0.7), 0.767 ( P=0.014, AUC>0.7), 0.688 ( P=0.084, AUC<0.7), and 0.692 ( P=0.077,AUC<0.7), respectively. Hosmer-Lemeshow goodness-of-fit test showed that PCIS ( χ2=5.329, P=0.722) predicted the mortality and the actual mortality in the best fitting effect, while PRISM Ⅲ ( χ2=12.877, P=0.177), PELOD-2 ( χ2=8.487, P=0.205), p-SOFA ( χ2=9.048, P=0.338) and GCS ( χ2=3.780, P=0.848) had poor fitting effect. Conclusions:The PCIS, PRISM Ⅲ and PELOD-2 scores have good predictive ability assessing the prognosis of children with SAE, while the PCIS score can more accurately evaluate the fitting effect of SAE prognosis prediction.