Ischemic stroke (IS) is a globally life-threatening disease. Presently, few therapeutic medicines are available for treating IS, and rt-PA is the only drug approved by the US Food and Drug Administration (FDA) in the US. In fact, many agents showing excellent neuroprotection but no blood flow-improving activity in animals have not achieved ideal clinical efficacy, while thrombolytic drugs only improving blood flow without neuroprotection have limited their wider application. To address these challenges and meet the huge unmet clinical need, we have designed and identified a novel compound AAPB with dual effects of neuroprotection and cerebral blood flow improvement. AAPB significantly reduced cerebral infarction and neural function deficit in tMCAO rats, pMCAO rats, and IS rhesus monkeys, as well as displayed exceptional safety profiles and excellent pharmacokinetic properties in rats and dogs. AAPB has now entered phase I of clinical trials fighting IS in China.

Objective:To investigate the expressions of cystathionine-β-synthase(CBS)and cystathionine-γ-lyase(CSE)and their effects on the malignant biological behaviours of breast cancer cells,and to elucidate their mechanisms.Methods:The breast cancer tissue and paracancerous normal tissue from 15 cases of patients were selected,and RT-qPCR and Western blotting methods were used to detect the mRNA and protein expression levels of CBS and CSE in breast cancer tissue,paracancerous normal tissue,MCF-7 cells,and MDA-MB-231 cells.The MCF-7 cells were divided into siNC group(transfected with siNC)and siCBS group(transfected with siCBS),and the MDA-MB-231 cells were divided into ovNC group(transfected with CSE over-expression empty plasmid)and ovCSE group(transfected with CSE over-expression plasmid).CCK8 assay was used to detect the proliferation activities of breast cancer cells in various groups,Transwell assay was used to detect the numbers of migration and invasion cells in various groups,and Western blotting method was used to detect the protein expression levels of E-cadherin,N-cadherin and Vimentin proteins in the breast cancer cells in various groups.Results:Compared with paracancerous normal tissue,the expression levels of CBS and CSE mRNA and proteins in breast cancer tissue were increased(P＜0.05 or P＜0.01).Compared with MDA-MB-231 cells,the CBS mRNA expression level in the MCF-7 cells was increased(P＜0.05);compared with MCF-7 cells,the expression level of CSE protein in the MDA-MB-231 cells was decreased(P＜0.05).Compared with siNC group,the proliferation activity,the numbers of migration and invasion cells,the expression levels of N-cadherin and Vimentin proteins in the MCF-7 cells in siCBS group were significantly decreased(P＜0.05),and the expression level of E-cadherin protein was increased(P＜0.05).Compared with ovNC group,the proliferation activity,the numbers of migratoin and invasion cells,and the expression levels of N-cadherin and Vimentin proteins in the MDA-MB-231 cells in ovCSE group were increased(P＜0.05),while the expression level of E-cadherin protein was significantly decreased(P＜0.05).Conclusion:The expressions of CBS and CSE are upregulated in breast cancer tissue,and high levels of CBS and CSE promote proliferation,migration,invasion and epithelial-mesenchymal transition(EMT)of breast cancer cells.

Objective:To investigate the risk factors for esophageal varices in patients with liver cirrhosis,to establish a predictive model,and to provide reasonable guidance for the prevention of early esophageal varices in patients with liver cirrhosis.Methods:A retrospective analysis was performed for 1 113 patients with liver cirrhosis who attended the hospitals in Chongqing,China from Decem-ber 2006 to May 2021.Recursive feature elimination(RFE)and four machine learning methods were used for the screening of features,and five machine learning predictive models were established by logistic regression,random forest,support vector machine(SVM),de-cision tree,and eXtreme Gradient Boosting(XGBoost).The receiver operating characteristic(ROC)curve was used to evaluate the per-formance of each model,and the model with the best performance was used to investigate the risk factors for esophageal varices in pa-tients with liver cirrhosis.SHAP plots were used to explain the impact of each risk factor on patients.Results:The XGBoost model showed the best performance in predicting the risk of esophageal varices in patients with liver cirrhosis,with an area under the ROC curve of 0.872(95%CI=0.813-0.918).SHAP plots showed that platelet count,diameter of the portal vein,cholinesterase,albumin,ala-nine aminotransferase,hemoglobin,prothrombin ratio,prothrombin time,and serum total protein were risk factors for esophageal vari-ces in patients with liver cirrhosis.Conclusion:This study shows that the XGBoost predictive model has a relatively high predictive value,and the risk factors obtained by this model have a certain guiding significance for the clinical prevention and treatment of early esophageal varices in patients with liver cirrhosis.

Objective To investigate the effects of secukinumab combined with E'xian Huaban decoction on traditional Chinese medicine symptom scores and nailfold microcirculation morphology in patients with plaque psoriasis.Methods A total of 120 patients with plaque psoriasis were selected and randomly divided into monotherapy group(n=60)and combination therapy group(n=60).The monotherapy group received secukinumab treatment,while the combination therapy group was treated with secukinumab plus E'xian Huaban Decoction.Clinical therapeutic efficacy,traditional Chinese medicine symptom scores(including skin lesions,pruritus,rough skin,scales and irritabili-ty),relevant scale[Psoriasisarea and Severity Index(PASI),Dermatology Life Quality Index(DLQI)and Visual Analogue Scale(VAS)]scores,inflammatory factors[interleukin-17(IL-17),interleukin-23(IL-23)and vascular endothelial growth factor(VEGF)]levels and nailfold microcircu-lation morphology(loop tube morphology,blood flow state and loop periphery state)were observed in both groups.Results The overall clinical efficacy rate in the combination therapy group was 95.00％,which was significantly higher than 83.33％ in the monotherapy group(P＜0.05).After treatment,traditional Chinese medicine symptom scores(skin lesions,pruritus,rough skin,scales and irritability),inflammatory factors(IL-17,IL-23 and VEGF)levels,scale(PASI,DLQI and VAS)scores as well as loop tube morphology scores,blood flow state scores and loop periphery state scores were signifi-cantly lower compared to pre-treatment values,and these parameters were significantly lower in the combination therapy group than the monotherapy group(P＜0.05).Conclusion Secukinumab combined with E'xian Huaban Decoction can significantly improve clinical symptoms and signs,and enhancing the clinical therapeutic effect.

Objective To investigate CT features of Chlamydia psittaci(C.psittaci)pneumonia patients.Methods Ten patients with C.psittaci pneumonia were collected retrospectively based on macro gene second-generation sequencing(mNGS).The radiological manifestations of the disease were analyzed.Results Seven patients(70%)had contact history with birds(poultry)or their feces.Chest CT on the day of admission was mainly mass patchy consolidation,all of which were located in single lung,involving 8 cases(80%)with one lobe and 2 cases(20%)with two lobes.All of them were accompanied by air bronchogram,9 cases(90%)with ground glass shadow and 8 cases(80%)with interstitial changes.One case(10%)showed a reversed halo sign,and 1 case(10%)showed fan-shaped consolidation.Nine cases(90%)showed progress with increased fusion or new lesions within nine days.Conclusion CT findings of C.psittaci pneumonia have certain characteristics,and combining with history of contacting birds(poultry)can suggest diagnosis.

Objective To isolate the Japanese encephalitis virus carried by Culex tritaeniorhynchus in Dongchuan District of Yunnan Province and analyze its molecular characteristics, so as to provide insights into the prevention and control of Japanese encephalitis in Yunnan Province. Methods Mosquito specimens were collected using mosquito-trapping lamps from pig farms in Batang Village and Xiaoxin Village, Dongchuan District, Kunming City, Yunnan Province in July 2016, and the mosquito species was identified according to the mosquito morphology. Then, 60 to 100 mosquitoes of each species served as a group and were ground. Baby hamster kidney-21 (BHK-21) cells and Aedes albopictus clone C6/36 cells were used for virus isolation, and positive isolates were identified using flavivirus primers. The positive isolates were amplified using reverse transcription polymerase chain reaction (RT-PCR) assay with 15 pairs of specific primers covering the full length of the genotype I Japanese encephalitis virus, and DNA sequence assembly was performed using the software SeqMan in the DNASTAR package. The obtained sequences were aligned with the complete sequences of 38 Japanese encephalitis virus downloaded from the GenBank with the software MegAlign, and the nucleotide and amino acid homology analyses of the obtained sequences were performed. The difference in amino acid sites was analyzed with the software GeneDoc, and phylogenetic trees were created based on the sequences of the coding region and E protein of the isolated Japanese encephalitis virus with the software Mega X. In addition, the secondary and tertiary structures of the E protein of the Japanese encephalitis virus were predicted using the online tool SOPMA and the software Swiss-Model. Results A total of 5 820 mosquitoes were collected and 3 843 Cx. tritaeniorhynchus (66.03%) were identified according to the mosquito morphology. A positive virus isolate, termed YNDC55-33, was isolated from Cx. tritaeniorhynchoides following batches of virus isolation from mosquito specimens, and cytopathic effect was observed following inoculation into BHK-21 and C6/36 cells. The YNDC55-33 virus isolate was successfully amplified with the flavivirus primes, and a long sequence containing 300 nucleotides was obtained. Following sequence alignment using the BLAST tool, the sequence of the YNDC55-33 virus isolate had high homology with that of the genotype I Japanese encephalitis virus. A long sequence with 10 845 nucleotides in length, which encoded 3 432 amino acids, was obtained by splicing the full sequence of the YNDC55-33 virus isolate. Phylogenetic analysis based on the whole-genome sequence and E gene sequence of the YNDC55-33 virus isolate showed that the new YNDC55-33 virus isolate was most closely related to the genotype I Guizhou isolate (GenBank accession number: HM366552), with nucleotide homology of 98.5% and amino acid homology of 99.4%, and the YNDC55-33 virus isolate shared 97.96% ± 0.33% nucleotide homology and 99.35% ± 0.08% amino acid homology with other genotype I Japanese encephalitis virus isolates, and < 90% nucleotide homology and < 98% amino acid homology with other genotypes of Japanese encephalitis virus. The YNDC55-33 virus isolate and the live attenuated virus vaccine candidate SA14-14-2 isolate differed at 16 amino acid sites on E gene, and 7 out of 8 key amino acid sites related to neurovirulence. The secondary and tertiary structures of the E protein of the YNDC55-33 virus isolate were predicted to be characterized by random coils. Conclusions A genotype I Japanese encephalitis virus was isolated from Cx. tritaeniorhynchus in Dongchuan District, Kunming City. This virus isolate and the live attenuated virus vaccine candidate SA14-14-2 isolate does not differ at antigenic epitopes-related key amino acid sites, and the major protein structure of the virus isolate is random coils. This study adds new data for the epidemiological distribution of Japanese encephalitis virus in Yunnan Province, which may provide insights into the prevention and control of Japanese encephalitis in the province.

International registration of herbal drugs is a necessary prerequisite for the internationalization of Chinese materia medica. North America and European Union occupy an important position in the world herbal drugs market, and their drug administration and quality supervision requirements are relatively complete and progressiveness. By summarizing the definition of herbal drugs in North America and European Union, combing and interpreting the relevant laws, regulations and policy documents, this article constructed the registration path of herbal drugs, and discussed the current status of market registration of herbal drugs in North America and European Union based on the examples of successful marketing of herbal drugs under current application and approval in overseas markets. This article believed that in the future, an internationally matched TCM quality standard evidence system should be built, clinical trials of TCM products in line with international standards should be carried out, standards that are the same or higher than international mainstream GMP should be developed, the registration path of TCM compounds should be explored, and professionals to establish an international registration application team should be recruited to provide theoretical and practical support for China's overseas registration of Chinese TCM products, promote TCM products to enter the world mainstream market, and achieve high-quality development of TCM internationalization.

Summarizing the nursing experience of a child with HHV-6B encephalitis after umbilical cord blood transplantation and CAR-T therapy. The child was 4 years old and was diagnosed with acute T lymphocytic leukemia on May 28, 2021. Nursing points: meticulously observe symptoms for early diagnosis and treatment; develop a specialized management plan, implement individualized care; enhance medication management to improve the quality of care; establish a shared decision-making communication model to prevent hospital-acquired infections; provide patient-centered care for lumbar puncture; assess the needs of the child and family, alleviate negative emotions; improve pre-discharge preparation, emphasize continuity of care. With proactive treatment and careful nursing, the child′s condition improved, and they were discharged. Follow-up for six months showed the child in a sustained remission state with no adverse sequelae, and normal life resumed.

Objective To explore the role and efficacy of VEGF and HGF gene adenovirus vector in promoting angiogenesis in ischemic tissue.Methods 84 Kunming mice were randomly divided into sham group,control group,VEGF group,HGF group and VEGF+HGF group,and the left lower limb ischemia model was established.The blood supply of ischemic tissue was observed by rheometer,and the expression levels of VEGF and HGF in each group were detected by Western Blot and ELISA.Immunohistochemical staining was used to detect angiogenesis(CD31,SMA)in ischemic tissues.Safety was assessed by side effects during treatment in mice.Results After the successful modeling,the blood flow velocity of the left lower limb in each group decreased significantly.On the 7th day after operation,the blood flow of the left lower limb in each group was significantly better than that on the 0th day after operation(P<0.05),and the blood flow of the left lower limb in Ad-VEGF-HGF group was significantly better than that in other groups(P<0.05).On the 28th day after operation,the blood flow of the left lower limb in Ad-VEGF-HGF group gradually stabilized,the blood flow in Ad-VEGF-HGF group was significantly better than that in other groups,and both VEGF group and HGF group were significantly better than the control group(P<0.05).On the 7th,14th,and 28th days following surgery,HGF and VEGF protein levels in the Ad-HGF,Ad-VEGF,and Ad-VEGF-HGF groups were substantially greater than those in the control group(P<0.05).The expression level in the Ad-VEGF-HGF group peaked on the 14th day(all P<0.001)and subsequently declined to preoperative levels on the 28th day after operation.Conclusion Ad-VEGF-HGF gene injection can effectively boost VEGF and HGF protein expression and rapidly reach the relative peak level,encour-aging angiogenesis after lower limb ischemia,increasing blood flow,and improving lower limb circulation.

AIM: To study the protective effect of fenofibrate on diabetic retinal neurodegeneration and observe its effect on miR-26a-5p and its target gene PTEN in the retinal of diabetic mice.METHODS: Diabetic mice models were established and they were gavaged by fenofibrate. H& E staining and transmission electron microscopy were used to observe the impairments of retinal neurons. Real-time PCR was used to examine the expression of miR-26a-5p, and Western blotting was employed to measure the expression of phosphatase and tensin homologue(PTEN)in the retina of diabetic mice. The expression level of nuclear factor-κB(NF-κB), interleukin-1β(IL-1β)and the morphology of neural tissues were observed.RESULTS: When compared with the diabetic mice, fenofibrate significantly attenuated the damage to retinal ganglion cells and the atrophy of retinal nerve fiber layer. While the level of miR-26a-5p was increased and the levels of PTEN and inflammatory mediators were significantly decreased in the retina of fenofibrate treated diabetic mice, with significant statistical significance(P<0.05).CONCLUSIONS: Fenofibrate protects against diabetic retinal neurodegeneration by upregulating miR-26a-5p and inhibiting PTEN, attenuating the inflammatory response and alleviating retinal cell injury.