A domestically produced self-expanding transcatheter aortic valve controllable bending delivery system(VitaFlow? Ⅲcontrollable bending retrievable delivery system)was first used to perform transcatheter aortic valve replacement(TAVR)in a symptomatic severe aortic valve stenosis patient with severe heart failure and high risk of surgery in China on September 22,2023.The patient successfully completed TAVR under general anesthesia,with good valve position and function after the operation.Before discharge and at one month of follow-up,the patient's symptoms and degree of heart failure were significantly improved.The follow-up results of this case showed that the VitaFlow? Ⅲ controllable bending retrievable delivery system for TAVR is safe and feasible,and future prospective,multicenter clinical trials are expected to evaluate its efficacy.

Objective:To investigate the effect of modified percutaneous closure in the treatment of ventricular septal rupture.Methods:This study is a retrospective cohort study. Forty-four patients with ventricular septal rupture who underwent percutaneous closure at the Fuwai Central China Cardiovascular Hospital from December 2017 to October 2023 were included. According to the closure method, patients were divided into the modified group (11 cases) and the traditional group (33 cases). Surgical success was defined as successful placement of the occluder. The operation time, X-ray intake, sheath bending rate, incidence of ventricular fibrillation and pericardial tamponade, and postoperative residual shunt were compared between the two groups.Results:The age of the patients was (75.0±5.7) years, with 20 (45%) males. There were 3 cases of operation failure in the traditional group, while all patients in the modified group were successfully occluded. The procedure time in the modified group was shorter than that in the traditional group (40 (35, 45) min vs. 60 (50, 65)min, P<0.001); X-ray dose intake was lower ((442.43±73.26)mGy vs. (784.45±247.78)mGy, P<0.001). There was no occurrence of sheath bending in the modified group, while the incidence of sheath bending in the traditional surgery group was 46% (15/33), and the difference was statistically significant ( P=0.017). Intraoperative ventricular fibrillation and pericardial tamponade occurred in 7 cases (21%) and 2 cases (6%) in the traditional group respectively, while none occurred in the modified group, but the differences between the groups were not statistically significant (both P>0.05). There was no significant difference in residual shunt between the two groups (3.6 (2.5, 4.3) mm vs. 4.0 (3.5, 4.5) mm, P=0.506). Conclusion:The procedure of modified ventricular septal rupture closure is more simplified, with a lower incidence ofventricular fibrillation and pericardial tamponade.

Objective To explore the therapeutic effect of lymphatic venous anastomosis based on MRI lymphangiography classifi-cation on lower limb lymphedema,and to analyze the factors affecting the therapeutic effect of lymphatic venous anastomosis.Methods A total of 378 patients with secondary lymphedema of lower limbs were selected.All of them underwent MRI lymphangiography.The differ-ence of circumference diameter and complication rate of the lower limbs of different types of patients before and after lymphatic venous anastomosis were compared.After 6 months of follow-up,the therapeutic effect was evaluated according to the International Lymphology Society classification standards for lymphedema.The risk factors affecting the therapeutic effect of lymphatic venous anastomosis was ana-lyzed,and a prediction model was established to analyze the value of this model in evaluating the clinical efficacy of lymphatic venous anastomosis.Results There was no significant difference in treatment efficiency and postoperative complication rate among different types of patients(P＞0.05).The difference of circumference diameter of the lower limbs of type 3,type 4,type 5 and type 6 before and after treatment was greater than that of type 1,type 2 and type 7(P＜0.05).Age,concomitant infection and lymph node venous fistula were the factors affecting the clinical efficacy of lymphatic venous anastomosis(P＜0.05).The risk prediction model for the clinical efficacy of lymphatic venous anastomo-sis was developed through logistic regression analysis:P=1/[1+e(0.531Xage+0.722Xconcomitant infection+0.807Xlymph node venous fistula-1.249)].The Hosmer-Leme-show test indicated that the fitted model matched the standard curve with x2=2.190,P=0.975.The area under the curve(AUC)of the prediction model for the clinical efficacy of lymphatic venous anastomosis was 0.985,with a standard error(S.E)value of 0.009 and a 95％confidence interval(CI)of 0.967 to 1.000.Conclusion Lymphatic venous anastomosis based on MRI lymphangiography classifi-cation has better clinical efficacy and fewer complications in the treatment of lower limb lymphedema,and the prediction model based on the risk factors analysis has a high predictive value for the clinical efficacy of lymphatic venous anastomosis.

Neck dissection(ND)is one of the main treatment methods for oral and maxillofacial malignancies.Although ND type is in con-stant improvement,but intraoperative peal-pull-push injury of the accessory nerve,muscle,muscle membrane,fascia and ligament induced shoulder syndrome(SS)is still a common postoperative complication,combined with the influence of radiochemotherapy,not only can cause pain,stiffness,numbness,limited dysfunction of shoulder neck and arm,but also may have serious impact on patient's life quality and phys-ical and mental health.At present,there is still a lack of a systematic evaluation and rehabilitation management program for postoperative SS of oral and maxillofacial malignant tumors.Based on the previous clinical practice and the current available evidence,refer to the relevant lit-erature at home and abroad,the experts in the field of maxillofacial tumor surgery and rehabilitation were invited to discuss,modify and reach a consenusus on the etiology,assessment diagnosis,differential diagnosis,rehabilitation strategy and prevention of SS,in order to provide clinical reference.

Objective:To analyze the clinical phenotype and genetic etiology of a child with Multiple congenital anomalies-hypotonia-seizures syndrome 1 (MCAHS1).Methods:Clinical data of a 2-year-old boy who had presented at the Affiliated Hospital of Qingdao University in March 2023 for "intermittent limb twitching for 2 years" was collected. Peripheral blood samples were collected from the child and his parents for whole-exome sequencing (WES). Candidate variants were verified by Sanger sequencing and bioinformatic analysis based on the guidelines from the American College of Medical Genetics and Genomics (ACMG).Results:The child had manifested with distinctive facial features, limb deformities, hypotonia, motor and intellectual delays, and epileptic seizures. WES revealed that he has harbored compound heterozygous variants of the PIGN gene, namely c. 963G>A (p.Q321=) and c. 994A>T (p.I332F), which were inherited from his phenotypically normal mother and father, respectively. Based on the ACMG guidelines, the c. 963G>A was classified as a pathogenic variant (PVS1+ PM2_Supporting+ PM3), whilst the c. 994A>T was classified as a variant of uncertain significance (PM2_Supporting+ PP3). Conclusion:Above discovery has expanded the mutational spectrum of the PIGN gene variants associated with MCAHS1, which may facilitate delineation of its genotype-phenotype correlation.

AIM:To explore the effect and mechanism of action of the aqueous extract of Fritillaria ussuriensis(FU-AE)against nonalcoholic fatty liver disease(NAFLD).METHODS:The association between Fritillaria ussuriensis Maxir.(FU)and NAFLD was analyzed by network pharmacology.A mouse model of NAFLD was induced in mice by high fat diet(HFD)+10%fructose drinking water,and three doses of Fritillaria ussuriensis aqueous extract were given to the mice for intervention.Colorimetric assay was used for detection of aspartate aminotransferase(AST),alanine aminotrans-ferase(ALT),triglyceride(TG),total cholesterol(TC),high-density lipoprotein cholesterol(HDL-C),and low-density lipoprotein cholesterol(LDL-C)levels in the serum of experimental mice.Hematoxylin and eosin staining was used to as-sess the pathological and histological changes in the liver of mice and to clarify the anti-NAFLD effect of aqueous extracts of Fritillaria ussuriensis.Liver tissue proteins were extracted,and expression of proteins related to the AMP-activated pro-tein kinase(AMPK)/acetyl-CoA carboxylase(ACC)pathway was detected by Western blot to clarify the mechanism of an-ti-NAFLD action of Fritillaria ussuriensis.The microbial composition of cecum contents was explored using 16S rRNA se-quencing to reveal the modulatory effect of the aqueous extract of Fritillaria ussuriensis on the structure of intestinal flora in mice with nonalcoholic fatty liver disease.RESULTS:Aqueous extract of Fritillaria ussuriensis(high dose)ameliorated exogenous adipocyte infiltration in the liver of mice with NAFLD(P<0.05).AST,ALT,TG,TC and LDL-C levels were significantly decreased(P<0.05)and HDL-C levels were significantly increased(P<0.05)in the high-dose group.Aque-ous extract of Fritillaria ussuriensis(high dose)significantly increased expression of phosphorylated AMPKα,AMPKα,and phosphorylated ACC in the livers of the model mice(P<0.05),significantly reduced expression of ACC(P<0.05),and significantly increased the relative abundance of the potentially beneficial bacteria Faecalibaculum rodentium,Lacto-bacillus johnsonii,Akkermansia muciniphila(P<0.05).CONCLUSION:Aqueous extract of Fritillaria ussuriensis may ameliorate NAFLD in mice by activating the AMPK/ACC pathway and modulating the structure of intestinal flora.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective:To investigate whether cavitation induced by ultrasound stimulated perfluorobutane microbubbles can enhance the therapeutic effect of colchicine and reduce its side effects on acute gouty arthritis (AGA) in rats.Methods:The AGA rat model was established by injection of monosodium urate (MSU) crystals. The rats were randomly divided into 6 groups (A: blank control group, B: model control group, C: cavitation group, D: standard concentration drug group, E: low concentration drug cavitation group, F: standard concentration drug cavitation group) according to whether they were given different doses of colchicine. The area under the curve (AUC) of contrast-enhanced ultrasound (CEUS) was calculated at 7 h and 8 h after MSU injection to compare the effect of cavitation on ankle blood perfusion. The symptoms of AGA were evaluated according to the degree of ankle swelling and gait score at 24 h. The infiltration of neutrophils was detected by HE staining, and the inflammatory response was analyzed by detecting the level of interleukin-1β (IL-1β) in plasma. Vascular dilatation was analyzed by detecting the concentration of endothelial nitric oxide synthase (eNOS). The degree of adverse reactions in each group was analyzed by gastrointestinal reaction score.Results:The CEUS blood perfusion and AUC values of the three groups with cavitation (groups C, E and F) were significantly higher than those of the non-cavitation groups (groups A, B and D) (all P<0.05). Compared with group D, there were no significant differences in the degree of ankle swelling, gait score, and plasma IL-1β level in group E (all P>0.05), but the plasma eNOS concentration was higher and the incidence of gastrointestinal reactions was significantly lower in group E (all P<0.05). Compared with group D, the degree of ankle swelling and gait score in group F were decreased, and HE staining showed that the degree of synovial infiltration of neutrophils in the ankle joints of AGA rats in group F was lighter (all P<0.05), but there was no significant difference in plasma IL-1β level and the incidence of gastrointestinal reactions between group D and group F (all P>0.05). Conclusions:The cavitation of perfluorobutane microspheres stimulated by ultrasound can enhance the blood perfusion of the ankle joint of AGA rats, enhance the therapeutic effect of local colchicine, and help to reduce the dosage of colchicine and its side effects.

To effectively play the guiding role of pathogenic diagnosis in the rational use of antibiotics, hospitals at all levels urgently need to establish an effective control system for clinical microbial specimen submission. In response to the common problems in medical institutions in China, such as the low rate of microbiological specimen submission before antibiotic treatment, unreasonable structure of microbiological specimens, and the majority of morning sputum and urine specimens collected for pathogen testing, the Second Affiliated Hospital of Zhejiang University School of Medicine has constructed a management system for clinical microbiological specimen submission using artificial intelligence technology. It used a built-in intelligent rule engine to implement full process control over the sampling and submission of microbiological specimens by doctors when prescribing antibiotics, urge doctors to implement the requirement of collecting samples before using antibiotics for treatment, and recommend priority the collection of sterile specimens. In addition, the hospital transformed the laboratory and testing process with the goal of receiving microbial samples 24 hours without interruption and inoculating in real-time. The informatization management system began to be applied throughout the hospital in December 2015. The average rate of microbial sample submission before the first therapeutic use of antibiotics from June 2016 to 2023 was 79.2%, an increase of 90.2 percentage points from 41.7% in June 2014 ( χ2=467.781, P<0.01). The structure of microbial specimens continued to be optimized, and the proportion of sterile specimens in all submitted specimens increased from 47.2% in 2014 to 49.9% in 2023 ( χ2=139.119, P<0.01). The proportion of morning sputum and morning urine specimens decreased from 65.2% and 60.6% in 2014 to 11.1% and 16.9% in 2023, respectively ( χ2 values were 19 787.434 and 4 346.664, respectively, P<0.01), providing a more reliable basis for pathogenic diagnosis in clinical practice and providing reference for improving the management of pathogenic specimen submission in medical institutions.

OBJECTIVE To explore whether diterpenoid 12-deoxyphorbol-13-palmitate （DP） from Euphorbia fischeriana can exert anti-leukemia effects through the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signal pathway， and to provide experimental evidence for developing it into a new anti-leukemia drug. METHODS Using LY294002 （PI3K specific inhibitor） as tool drug， the effects of 24 h DP treatment on the proliferation and apoptosis of human myeloid leukemia HL60 cells were detected by MTT method， Annexin Ⅴ-FITC/PI staining and AO-EB staining. ELISA method was used to detect lactic dehydrogenase （LDH） release and the activities of cysteinyl aspartate specific proteinase 3 （caspase-3） and caspase-9. The transcriptional level of caspase-3， caspase-9， forkhead box O3a （FoxO3a） and B cell lymphoma 2 interacting mediator of cell death （Bim） mRNA were detected by real-time quantitative polymerase chain reaction （qRT-PCR）. The protein expression of phosphorylated FoxO3a （p- FoxO3a） and phosphorylated Akt （p-Akt） were detected by Western blot method. The nuclear translocation of FoxO3a protein was detected by immunostaining combined with laser confocal microscopy. RESULTS 10 μmol/L DP and 10 μmol/L DP+LY294002 could inhibit the proliferation and induce the apoptosis of HL60 cells （P＜0.01）. After treatment of 5， 10， 20 μmol/L DP， HL60 cells showed typical morphological characteristics of apoptosis； DP could significantly increase the levels of LDH release and the activities of caspase-3 and caspase-9 （P＜0.05 or P＜0.01）， in dose-dependent manner. After treatment of 10 μmol/L DP and 10 μmol/L DP+LY294002， the transcriptional levels of caspase-3， caspase-9 and Bim mRNA were increased significantly （P＜0.05 or P＜0.01）， and transcriptional level of FoxO3a mRNA and protein expressions of p-FoxO3a and p-Akt were decreased significantly （P＜0.05 or P＜0.01）. Nuclear translocation changes were observed in FoxO3a protein in 10 μmol/L DP+LY294002 group， and the change was more significant than that of LY294002 group. CONCLUSIONS DP can inhibit the proliferation and induce the apoptosis of HL60 cells via inhibiting PI3K/Akt signaling pathway.