α-thalassemia is a type of microcytic hypochromic anemia caused by variants of alpha-globin gene, and is one of the most common monogenic disorders in southern China. The population screening model based on hematologic phenotype has achieved great results in areas with high incidence of thalassemia. However, with the continuous decline of the cost of genetic testing and implementation of screening programs for thalassemia gene carriers, more variants in the alpha-globin gene have been discovered, which also brings great challenges to clinical genetic counseling. From the perspective of alpha-globin genetic analysis, this consensus has discussed the contents of pre- and post-test genetic counseling, with an aim to provide standardized guidance for clinicians.

Objective To study the core behavioral symptoms,biological indicators,and pathological changes of a mouse model of breast cancer complicated with depression induced using 4T1 breast cancer cell inoculation combined with chronic restraint stress(CRS).Methods BABL/c mice were randomly divided into Control,Stress,Tumor,and stress combined with tumor(S+T)groups.Mice in the tumor and S+T groups were inoculated under the front legs with breast cancer 4T1 cells.After tumor formation,mice in the stress and S+T groups were subjected to CRS for 21 days.The body weight and food intake of each group were monitored during modeling.After the experiment,the occurrence of depression-like behavior of mice in each group was evaluated by sucrose preference test,open field test,elevated plus-maze test,and forced swimming test.After the mice were decapitated,the weights and volumes of the tumors were measured.Concentrations of serum tumor markers,including carbohydrate antigen(CA199),carcinoembryonic antigen(CEA),and vascular endothelial growth factor(VEGF),and related neurotransmitters,including 5-hydroxytryptamine(5-HT),norepinephrine(NE),and corticosterone(CORT),were determined using ELISA.HE staining was used to observe histopathological changes to the hippocampus and tumor.Results In S+T group mice,body weight and food intake were significantly decreased,tumor weight and volume were significantly increased,serum tumor marker(CA199,CEA,VEGF)levels were significantly increased,enthusiasm and desire to explore a new environment were reduced,stress and despair behaviors were significantly increased,and levels of the serum neurotransmitters 5-HT and NE and levels of CORT were significantly increased.In addition,the cell arrangement in the tumor tissue was loose,the amount of intercellular substance decreased,the pathological nuclear classification phase was increased,the arrangement and morphology of neurons in the CA3 region of the hippocampus were disordered,and there were obvious nuclear vacuolation-like changes.Conclusions A mouse model of breast cancer complicated with depression induced by 4T1 breast cancer cell inoculation combined with CRS showed the typical dual symptoms and biological indicators of breast cancer and depression and can be used as a good reference model for experimental studies of breast cancer complicated with depression.

Objective To investigate the protective effect and mechanism of J147 on the injury of human neuroblastoma cells(SH-SY5Y)induced by high glucose(HG).Methods We established HG-induced SH-SY5Y cell injury model.Then SH-SY5Y cells were divided into blank control(Con)group HG group,HG+J147 0.5 μmol/L(HG+J147 0.5)group,HG+J147 1 μmol/L(HG+J147 1)group,HG+J147 2 μmol/L(HG+J147 2)group,HG+PI3K/AKT inhibitor LY294002(LY)10 μmol/L(HG+LY)group,HG+ERK1/2 inhibitor U0126(U0)5 μmol/L(HG+U0)group,HG+J147 2 μmol/L+LY 10 μmol/L(HG+J147 2+LY)group,HG+J147 2 μmol/L+U0 5 μmol/L(HG+J147 2+U0)group.Cell viability was detected by MTS cell proliferation and toxicity detection kit;LDH activity was tested by lactate dehydrogenase kit;morphological changes of SH-SY5Y cells were evaluated by microscope;cell apoptosis was detected by flow cytometry;and apoptosis-related proteins(Bcl-2,Bax)and signaling pathway-related proteins(p-AKT,AKT,p-ERK1/2,ERK1/2,p-CREB,CREB,BDNF)were detected by Western blot.Results Compared with Con group,the cell viability,Bcl-2/Bax ratio,p-AKT/AKT,p-ERK/ERK,p-CREB/CREB and BDNF protein expressions decreased(P<0.01),while LDH activity and apoptosis rate increased in HG group(P<0.01).Compared with HG group,the cell viability,Bcl-2/Bax ratio,p-AKT/AKT,p-ERK/ERK,p-CREB/CREB and BDNF protein expressions increased(P<0.01),while LDH activity and apoptosis rate decreased in HG+J147 2 group(P<0.01).Compared with HG+J147 2 group,the cell viability,Bcl-2/Bax ratio,p-AKT/AKT and BDNF protein expression decreased(P<0.05 or P<0.01),while LDH activity and apoptosis rate increased(P<0.05 or P<0.01),the expression of p-ERK/ERK protein in HG+J147 2+LY group decreased(P<0.05),and the expression of p-CREB/CREB protein in HG+J147 2+U0 group decreased in HG+J147 2+LY and HG+J147 2+U0 groups(P<0.05).Conclusions J147 can alleviate HG-induced SH-SY5Y cell damage,and the mechanism may be related to the activation of PI3K/AKT and ERK1/2 signaling and the reduction of apoptosis.

Objective:This was a retrospective study to analyze the risk factors for death in patients with acute myocardial infarction complicated with cardiogenic shock(AMICS) under mechanical circulatory support(MCS).Methods:This study included 234 patients with AMICS who were admitted to Anzhen Hospital in Beijing from January 2018 to January 2024.Among them, 79 cases died and 155 cases survived. 117 patients received MCS after percutaneous coronary intervention(PCI)(defined as delayed MCS treatment). Baseline and clinical data of patients in the death group and the survival group were compared to analyze the potential risk factors that may affect death.Results:Statistical analysis showed that higher white blood cell count( OR=1.017, P=0.003, 95% CI: 1.005-1.028), higher arterial lactate level( OR=2.021, P<0.001, 95% CI: 1.463-2.794), three-vessel coronary artery disease( OR=3.179, P<0.001, 95% CI: 1.679-6.019), delayed MCS treatment( OR=4.691, P=0.001, 95% CI: 1.955-11.258), MCS assisted aortic balloon counterpulsation alone(IABP)( OR=4.140, P<0.001, 95% CI: 2.230-7.786)were independent risk factors for in-hospital mortality in AMICS patients under mechanical circulatory support. The arterial lactate level were shown to be predictive of death in patients with AMICS assisted by MCS, and an area under the receiving operating characteristic curve of 0.719, P<0.001, 95% CI: 0.667-0.770, the maximum Youden index was 0.395, and the cutoff value of 5.05 mmol/L. Conclusion:Higher number of white blood cells, high arterial lactate level(>5.05 mmol/L), three-vessel coronary artery disease, delayed MCS treatment, and McS-assisted aortic balloon counterpulsation alone were independent risk factors for mortality in patients with McS-assisted AMICS.

Objective To investigate the effect of intrarectal local anesthesia (IRLA) with heated oxybuprocaine gel on pain during transrectal ultrasound guided prostate biopsy (TRUSPB).Methods A total of 150 cases patients who underwent TRUSPB in Huzhou Central Hospital from January to June 2023 were prospectively taken into.The patients were randomly divided into group A (routine group),group B (oxybuprocaine gel for IRLA at room temperature) and group C (oxybuprocaine gel for IRLA at 40℃),with 50 cases in each group.Nurses who were unaware of the anesthesia type used visual analog scale (VAS) to score the pain level of patients at each stage (VAS Ⅰ:when the ultrasound probe was inserted into the rectum;VAS Ⅱ:during the biopsy;VAS Ⅲ:30 minutes after biopsy),and the incidence of complications after biopsy were compared.Results The VAS Ⅱ score of group C was lower than that of group A and group B,and the difference was statistically significant (P<0.05).There was no statistically significant difference (P>0.05) in the VAS Ⅰ,VAS Ⅲ scores,and incidence of complications after biopsy among the three groups.There was no allergic reaction to oxybuprocaine gel.Conclusion In TRUSPB,IRLA with heated oxybuprocaine gel can effectively control pain without increasing incidence of complications.

Objective In this paper,the harmful effects and mechanisms induced by traditional Chinese medicine were expounded by combining the mechanism of programmed cell death and inflammatory reaction.It is expected to provide data support and theoretical reference for the rational use of traditional Chinese medicine and toxicology research.Methods By systematically analyzing the correlation between cell death and inflammatory response,the molecular mechanisms of pyroptosis,programmed cell necrosis and ferroptosis at home and abroad were summarized,and the harmful outcomes induced by traditional Chinese medicine were further discussed.Results Different toxic traditional Chinese medicines and their active ingredients have different tolerances to biological organisms.Programmed cell death is an important molecular mechanism for the toxicity of traditional Chinese medicines.Its signaling pathways are complex and diverse and are often accompanied by inflammatory reactions.Both of them have a certain effect on the toxic effects of traditional Chinese medicine.Conclusion Traditional Chinese medicine can provide inflammatory mediators for inflammatory response pathways through cell death or change the physiological balance of cells,thereby inducing inflammatory cascade reactions and promoting harmful outcomes in various systems of the body under the dual effects of cell death and inflammatory response.

Objective:To summarize the clinical characteristics of primary retroperitoneal tumors (PRT).Methods:All PRT cases undergoing surgical resection during recent 10 years at our center were retrospectively analyzed.Results:Tumors in all 92 cases were of malignant in 64 cases, borderline in 10 and benign PRT in 18, among which liposarcoma and leiomyosarcoma were the most common types. The tumor size and Ki-67 was significantly higher in malignant compared to borderline or benign PRT. The multifocal rate was 50%, en-bloc resection rate was 72%, R 0 rate was 61%, and combined organ resection rate was 41% in malignant PRTs. Small intestine and the colon were the most frequently resected organs. During 9.3 years of follow-up period, the 1-, 3- and 5-year cumulative reoperation rate of malignant PRT was 10.6%, 44.7% and 62.9%, respectively, and the median re-operation period was 4.0 years. The 1-, 3- and 5-year cumulative survival rate was 90.1%, 73.0% and 64.2%, respectively, and the median survival period was 6.1 years. None of postoperative borderline or benign PRT recurred or needed re-operation or deceased. Conclusion:Most of PRTs were malignant, presenting themsehies as a challenge to surgery with unfaror prognosis.

Objective:To construct a preoperative rehabilitation program for gastric cancer patients, aiming to provide scientific and reasonable preoperative guidance for gastric cancer patients.Methods:On the basis of literature research and expert group meeting, the first draft of the preoperative rehabilitation program for gastric cancer patients was constructed. From October 2021 to January 2022, the Delphi method was used to conduct 2 rounds of expert letter inquiries to 16 experts in related fields from 11 hospitals in Jiangsu Province, and the entries were revised according to the experts′ inquiries.Results:In the two rounds of expert correspondence, the positive coefficients of experts were 88.89% and 100.00%, and the authority coefficients of experts were both 0.88. The coordination coefficients of the items in the two rounds of inquiry were 0.279 and 0.290, respectively. The final program consisted of 3 first-level entries, 11 second-level entries and 32 third-level entries.Conclusions:The scheme constructed in this study is scientific, reliable and applicable, and is worth being promoted further in clinical practice.

OBJECTIVE: To explore the genetic basis for a patient with Dilated cardiomyopathy. METHODS: A patient admitted to Beijing Anzhen Hospital Affiliated to Capital Medical University in April 2022 was selected as the study subject. Clinical data and family history of the patient was collected. Targeted exome sequencing was carried out. Candidate variant was verified by Sanger sequencing and bioinformatic analysis based on guidelines of the American College of Medical Genetics and Genomics (ACMG). RESULTS: DNA sequencing revealed that the patient has harbored a heterozygous c.5044dupG frameshift variant of the FLNC gene. Based on the ACMG guidelines, the variant was predicted to be likely pathogenic (PVS1+PM2_Supporting+PP4). CONCLUSION The heterozygous c.5044dupG variant of the FLNC gene probably underlay the pathogenesis in this patient, which has provided a basis for the genetic counseling for his family.
Humans ; Cardiomyopathy, Dilated/genetics* ; Genetic Testing ; Genetic Counseling ; Computational Biology ; Frameshift Mutation ; Mutation ; Filamins

Objective:To investigate the Chinese anesthesiologist′s proficiency, training experience and needs of flexible bronchoscope-guided awake flexible bronchoscopy intubation (AFBI) using a questionnaire method.Methods:The cluster sampling was used, and self-designed questionnaires that addressed 54 questions in 5 categories were distributed through WeChat and online platforms. The survey took one month, and the answers were automatically recorded by the WeChat server.Results:A total of 1 250 anesthesiologists participated in the survey in 30 provinces of China, 9 of them were not anesthesiologists, and 1 241 (99.28%) questionnaires were validated. In the valid questionnaires, 52.70% (654) of the anesthesiologists were from tertiary hospitals, and 74.78% (928) of the anesthesiologists were attending physicians or above, only 7.57% (94) of the anesthesiologists had sufficient confidence in AFBI. Twenty-five point two two percent (313) of the anesthesiologists preferred fiberoptic intubation as the first tool when dealing with the anticipated difficult airway. Forty-eight point one one percent (597) of the anesthesiologists had implemented AFBI. Among them, 80.74% (482) had experienced unsuccessful AFBI practices. Eight hundred and ninety-four anesthesiologists had received AFBI training, and the most common AFBI training strategy was theoretical lectures. In addition, the degree of satisfaction regarding the theoretical lectures quality, technical training, clinical practice relativity and non-technical skills training was 21.47% (192), 14.32% (128), 12.3% (110) and 17.90% (160), respectively. The degree of satisfaction with all the 4 training elements mentioned above was 7.27% (65).Conclusions:The awareness and practice of Chinese anesthesiologists in terms of clinical application of AFBI to treat difficult airways need to be strengthened at present, and the lack of high-quality AFBI training may be the key.