Objective:To explore the effect of venetoclax-based therapy on relapsed/refractory multiple myeloma (MM) patients harboring t(11;14).Methods:The data of a relapsed/refractory MM patient harboring t(11;14) treated with venetoclax-based regimen admitted to Shanghai Changzheng Hospital in June 2019 was retrospectively analyzed and the literatures were reviewed.Results:The relapsed/refractory MM patient harboring t(11;14) had progression of disease after 3 lines of therapies, and then was treated with the selective bcl-2 inhibitor venetoclax combined with daratumumab and dexamethasone. As a result, the patient achieved partial remission and better hemogram recovery. The Eastern Cooperative Oncology Group (ECOG) score of physical status decreased from 3 to 1, and the quality of life was improved significantly.Conclusions:The relapsed/refractory MM patients harboring t(11;14) could benefit from venetoclax-based therapy. In the future, the safety, sensitivity and other performances of venetoclax in the treatment of MM should be further explored.

Objective To investigate the genetic evolution of VP1 gene of pathogenic coxsackievirus A16 (CV-A16) strain isolated from clinical hand,foot,and mouth disease (HFMD) patients.Methods A total of 160 HFMD cases with CV-A16-positive results were collected from hospitals in Kunming during January 2015 to June 2017.Fecal samples were collected.Real-time polymerase chain reaction (PCR) was used to detect the CV-A16 virus nucleic acid.The VP1 genes of CV-A16-positive samples were amplified by reverse transcription-PCR.The amplified positive products were sequenced and aligned.The homologies were identified and their subgenotypes were determined.The phylogenetic tree was constructed and homology modeling was conducted.Results All the 160 CV-A16 isolates were B2 subtypes.The genetic distance between detected strains of CV-A16 and the strains in Fujian,Beijing,Nanjing was 0.76.The genetic distance to the strains in Malaysia was 0.78,and to the strains in Australia was 1.86.Homologous modeling revealed that the amino acid sequence of the VP1 gene of the strain had a G227R mutation.Conclusions There is no major genetic variation in the CV-A16 strains during 3 years.CV-A16 isolates are close to those of epidemic strains in Beijing,Fujian and Malaysia,but are far fram the strains from Australia.

Objective:To explore the application and effect of autologous cartilage in rhinoplasty for patients with traumatic hernia and nasal dysfunction.Methods:From January 2017 to April 2019,30 patients with nasal trauma admitted to Department of Otorhinolaryngology Head and Neck Surgery, Daping Hospital, Army Medical University were treated for 6 days to 14 years. All patients were accompanied by different degrees of nasal deformity and nasal ventilatory disorders. They were classified into three categories: light, medium and heavy. All of them were open at the same time. Rhinoplasty and nasal septum deviation correction. For mild to moderate nasal deformity and nasal ventilatory disorders, ear cartilage was used to modify the tip of the nose and strengthen the nasal septal cartilage support to modify the deformity of the nasal back. For severe nasal deformity and nasal ventilatory disorders, we engraved the costal cartilage into a "Y" shaped monolithic stent or flank costal cartilage to form a 2+1 or 4+1 stent, and the costal cartilage stent and the septal cartilage tail end were sutured. Reshape the nasal septum frame support and the nasal column to avoid collapse of the nose.Results:Three patients had a septal hematoma after operation and recovered normally after cleansing. All patients were followed up for 2 months to 2 years, and no complications such as nasal septum perforation and nasal bridge collapse occurred. The postoperative cure rate was 60.0% (18/30). All patients had a grade I nasal drop after surgery, and the effective rate was 100% (30/30). The patient′s preoperative measurement deviation was (6.85±2.43) mm, the postoperative measurement deviation was (2.4±1.58) mm, the preoperative nasal appearance VAS score was (1.93±1.31), and the postoperative nasal appearance VAS score was (6.60±1.16), the difference in facial appearance deviation and VAS score before and after surgery was statistically significant ( P<0.05). All patients had improved nasal ventilation after operation. The preoperative nasal ventilation VAS score was (1.97±1.07), the postoperative nasal ventilation VAS score was (6.53±1.04), and the difference between preoperative and postoperative nasal ventilation VAS scores was statistically significant ( P<0.05). Conclusions:Autologous cartilage is effective in rhinoplasty in patients with traumatic nasal contraction and nasal dysfunction. One stage open rhinoplasty and nasal septum deviation surgery are performed to shorten the treatment time and improve the nasal appearance and nasal ventilation function. The patients got satisfaction.

Objective To explore the relationship between basic motor skills and social interaction ability in school-age children with moderate autism,and the mediating role of executive function and the realization path.Methods A cross-sectional design was used to investigate 117 school-age children with autism from Sep.to Dec.2020.The level of basic motor skills was assessed by the test of gross motor development(TGMD),the impairment of executive function was assessed by the behavior rating inventory of executive function(BRIEF),and the social disorder was assessed by the social responsive scale-second edition(SRS-2).Pearson correlation analysis was used to explore the interrelationship,and structural equation modeling was applied to explore the path relationship.Results There was a significant negative correlation between the level of basic motor skills and SRS-2 scores(r=-0.312,P＜0.001).There were significant negative correlations between the level of basic motor skills and the BRIEF scores of inhibition(r=-0.336,P＜0.001),switching(r=-0.325,P＜0.001),affective control(r=-0.338,P＜0.001),task initiation(r=-0.240,P=0.009),working memory(r=-0.278,P=0.002),and planning(r=-0.224,P=0.015).The SRS-2 score was positively correlated with the BRIEF scores of inhibition(r=0.378,P＜0.001),switching(r=0.299,P=0.001),affective control(r=0.417,P＜0.001),task initiation(r=0.246,P=0.007),working memory(r=0.409,P＜0.001),and monitoring(r=0.258,P=0.005).Executive function played a complete intermediary role between basic motor skills and social interaction ability(B=-1.912,95％confidence interval:-3.116 to-1.069).Conclusion In school-age children with moderate autism,executive function and social interaction ability change positively with the level of basic motor skills.Basic motor skills can affect social interaction ability through the mediating role of executive function,and inhibition and affective control are important pathways to achieve this.

Objective:To summarize the evidence on preventing and managing feeding intolerance (FI) in ICU patients with enteral nutrition, providing a basis for clinical practice.Methods:Clinical practice guidelines, systematic reviews, evidence summaries, expert consensus, and randomized controlled trials related to the prevention and management of FI in ICU patients with enteral nutrition were systematically searched in Chinese and English databases, guideline websites, and professional association websites. The search period was from January 1, 2013, to March 29, 2023. Two researchers conducted quality evaluation, evidence extraction, and summarization of the included literature.Results:A total of 25 articles were included, including five clinical practice guidelines, three evidence summaries, 11 systematic reviews, one expert consensus, and five randomized controlled trials. Thirty-seven pieces of evidence were summarized from four aspects risk assessment, preventive measures, intervention measures, and evaluation.Conclusions:This study summarizes the best evidence for FI prevention and management in ICU patients with enteral nutrition. It is recommended that medical and nursing staff apply evidence based on clinical situations and patient preferences.

Objective: To investigate the effects of sinomenine on brain edema and the expression of aquaporin 4 (AQP-4) and aquaporin 5 (AQP-5) in rats with acute brain injury. Methods: According to random number table method, rats were divided into sham operation group, model group, low-dose sinomenine group, high-dose sinomenine group, 20 in each group. In addition to the sham operation group, the rat brain injury model was established by Feeney free falling impact method. Rats in low and high dose of sinomenine group were given sinomenine 30, 60 mg/kg by intraperitoneal injection, and the sham operation group and model group were injected intraperitoneally with the same volume of normal saline, once per day for 7 days. Histopathological changes in each group were observed by HE staining and electron microscope. Western blot and RT-PCR were used to detect AQP-4 and AQP-5 protein and gene expression in brain tissue. Results: The pathological results showed that the nerve cells in the model group were loosely arranged, disordered in hierarchy, some cells appear to have degenerated. The degeneration and necrosis of nerve cells in the low and high dose sinomenine group were less than those in the model group. Compared to the model group, the expression of AQP-4 (0.74 ± 0.13, 0.49 ± 0.11 vs. 1.30 ± 0.21), AQP-5 (0.98 ± 0.07, 0.45 ± 0.10 vs. 1.47 ± 0.18) in the low dose and high dose sinomenine group significantly decreased (P<0.05). The expression of AQP-4 (1.48 ± 0.18, 1.26 ± 0.12 vs. 2.04 ± 0.14), AQP-5 (1.31 ± 0.17, 1.20 ± 0.11 vs. 1.87 ± 0.15) mRNA in the low dose and high dose sinomenine group significantly decreased (P<0.05). Conclusions Sinomenine could alleviate cerebral injury by lowering the expression of AQP-4 and AQP-5.

Primary biliary cholangitis (PBC) is a cholestatic autoimmune liver disease characterized by a high incidence rate in middle-aged and elderly women, lymphocyte infiltration in small bile ducts, and cholestasis. Main clinical manifestations include fatigue and pruritus caused by cholestasis. Ursodeoxycholic acid and obeticholic acid are currently approved therapeutic drugs for PBC and exert a therapeutic effect by regulating bile acid metabolism and specifically and effectively improving cholestasis. This article introduces the physiological and pathological changes of bile acids in disease states and summarizes the possible ways in which bile acid metabolism is involved in the pathogenesis of diseases and the current treatment methods for bile acid metabolism. It is pointed out that the changes of bile acid metabolism in PBC are mainly associated with anion exchanger 2 deficiency, innate genetic variation and acquired adaptive changes of bile acid metabolism transporters and nuclear receptors, and changes in the structure of intestinal flora.

Objective:To summarize the clinical characteristics and prognosis of 51 patients with Waldenstr?m’s macroglobulinemia (WM) and evaluate the efficacy and adverse reactions of ibrutinib in the treatment of WM.Methods:We carried out a single-center retrospective study, including 51 patients with WM of our single center from November 2008 to October 2019.Results:The median age at diagnosis was 65 years with a male-to-female ratio of 2.64∶1. There were 9 (18%) , 21 (41%) , and 21 (41%) ISSWM stage low-, intermediate- and high-risk patients identified, respectively. A total of 27 (73%) patients harbored MYD88 L265P mutation. The median follow-up time was 38.6 (0.3-120.0) months, the median progression free survival was 46.4 months, and the median overall survival was not reached. The overall remission and major remission rates of patients who received ibrutinib were 87% and 80%, respectively. The median time to achieve at least partial remission of patients treated with ibrutinib was 8 weeks, which was earlier than those treated with other drugs ( P<0.05) . Conclusion:WM is often seen in elderly men. MYD88 L265P had a high frequency in WM. The findings of our study validate the efficacy of ibrutinib monotherapy. Even in patients with advanced age and at high risk of ISSWM, the overall remission rate and major remission rate are high. Ibrutinib is a safe and effective therapy because of its rapid onset and rare serious adverse reactions.

ObjectiveTo investigate the effects of Aconiti Coreani Radix and Typhonii Rhizoma on the urinary metabolites of gerbils with stroke by non-targeted metabolomics technique， and then to clarify the mechanism of the two， as well as their similarities and differences. MethodTwenty-four gerbils were randomly divided into control group（CG）， model group（MG）， Aconiti Coreani Radix group（RA） and Typhonii Rhizoma group（RT）. Except for the CG， ischemic stroke model was constructed using right unilateral ligation of gerbil carotid artery in the remaining groups. Except for the CG and MG， rats in the other groups received whole powder suspension（0.586 mg·g^-1） was administered for 14 days. The neurological deficit in each group was scored by Longa scoring on days 0， 3， 7 and 14. After the end of administration， the serum， brain tissue and urine of gerbils in each group were collected， and the rate of cerebral infarction was detected by 2，3，5-triphenyltetrazolium chloride（TTC）， and the levels of interleukin（IL）-6， tumor necrosis factor（TNF）-α， malondialdehyde（MDA）， superoxide dismutase（SOD）， glutathione（GSH）， and nitric oxide（NO） in serum and brain tissue were determined by enzyme-linked immunosorbent assay（ELISA）. The urine metabolomics of gerbils in each group was studied by ultra performance liquid chromatography-quadrupole-electrostatic field orbitrap high resolution mass spectrometry（UPLC-Q-Orbitrap-MS）， and the data were processed by multivariate statistical analysis， and differential metabolites were screened based on value of variable importance in the projection（VIP） of the first principal component>1 and t-test P<0.05. Metabolic pathway analysis of the screened differential metabolites was performed using Kyoto Encyclopedia of Genes and Genomes（KEGG） database and Metaboanalyst 5.0. ResultCompared with the CG， the neurological deficit score was significantly increased in the MG（P<0.05）， compared with the MG， the neurological deficit scores in the RA and RT were significantly reduced after 7 d and 14 d（P<0.05）. Compared with the CG， the rate of cerebral infarction was significantly increased in the MG（P<0.05）， compared with the MG， the rates of cerebral infarction in the RA and RT were significantly reduced（P<0.05）. Compared with the CG， the levels of IL-6， TNF-α， and MDA in the serum and brain tissue of gerbils from the MG were significantly increased（P<0.05）， and the levels of SOD， GSH and NO were significantly reduced（P<0.05）. Compared with the MG， Aconiti Coreani Radix and Typhonii Rhizoma could down-regulate the levels of IL-6， TNF-α and MDA， and up-regulated the levels of SOD， GSH and NO. A total of 112 endogenous differential metabolites were screened by urine metabolomics， of which 16 and 26 metabolites were called back by Aconiti Coreani Radix and Typhonii Rhizoma， and could be used as potential biomarkers for both treatments in stroke gerbils， respectively. The results of the pathway analysis showed that both Aconiti Coreani Radix and Typhonii Rhizoma had regulatory effects on arginine and proline metabolism， pyrimidine metabolism， and aminoacyl-tRNA biosynthesis. In addition， Aconiti Coreani Radix could also regulate riboflavin metabolism， Typhonii Rhizoma could also regulate purine metabolism， glycine， serine and threonine metabolism， arachidonic acid metabolism， biosynthesis of pantothenate and coenzyme A， and β-alanine metabolism. ConclusionBoth Aconiti Coreani Radix and Typhonii Rhizoma have better therapeutic effects on stroke， with Aconiti Coreani Radix having stronger effects. From the metabolomics results， the main metabolic pathways regulated by Aconiti Coreani Radix involve amino acid metabolism， oxidative stress and so on， while Typhonii Rhizoma mainly involve amino acid metabolism， lipid metabolism， energy metabolism， etc.