BACKGROUND:Wogonin is a flavonoid extracted from the root of Scutellaria baicalensis.Previous studies have shown that baicalein has protective effects against cerebral ischemia-reperfusion injury,and can also reduce blood sugar and complications in diabetic mice,but its role and mechanism in diabetic cerebral infarction remain unclear. OBJECTIVE:To explore the effect of wogonin on nerve injury in rats with diabetic cerebral infarction and its mechanism. METHODS:Sprague-Dawley rats were randomly divided into six groups:control group,model group,low-dose wogonin group,medium-dose wogonin group,high-dose wogonin group,and high-dose wogonin+Ras homolog gene family member A(RhoA)activator group.Except for the control group,the other rats were established with diabetes and cerebral ischemia models using intraperitoneal injection of streptozotocin and middle cerebral artery occlusion.Low,medium-and high-dose wogonin groups were intragastrically given 10,20,40 mg/kg wogonin,respectively;high-dose wogonin+RhoA activator group was intragastrically given 40 mg/kg wogonin and intraperitoneally injected 10 mg/kg lysophosphatidic acid;control group and model group were given the same amount of normal saline once a day for 7 consecutive days.Rats in each group were evaluated for neurological deficits and their blood glucose levels were measured after the last dose.TTC staining was applied to detect the volume of cerebral infarction.Hematoxylin-eosin staining was applied to observe pathological changes in brain tissue.ELISA kit was applied to detect tumor necrosis factor-α,interleukin-6,malondialdehyde,and superoxide dismutase levels in brain tissue.Western blot was applied to detect the protein expression of RhoA and Rho-associated protein kinase(ROCK)2 in brain tissue. RESULTS AND CONCLUSION:Compared with the control group,the neuronal structure of rats in the model group was severely damaged,with cell necrosis and degeneration,the neurological deficit score,blood glucose level,and infarct volume were significantly elevated(P<0.05),the levels of tumor necrosis factor-α,interleukin-6,and malondialdehyde,and the protein expression of RhoA and ROCK2 in brain tissue were significantly increased(P<0.05),and the superoxide dismutase level was decreased(P<0.05).Compared with the model group,the low-,medium-,and high-dose wogonin groups showed improved neuronal damage,reduced cell degeneration and necrosis,a significant reduction in neurological deficit score,blood glucose level,infarct volume,and the levels of tumor necrosis factor-α,interleukin-6,and malondialdehyde,and the protein expression of RhoA and ROCK2 in brain tissue,and an increase in the superoxide dismutase level(P<0.05).Compared with the high-dose wogonin group,the high-dose wogonin+RhoA activator group significantly weakened the improvement in the above indexes of rats with diabetic cerebral infarction(P<0.05).To conclude,wogonin can improve the blood glucose level in rats with diabetic cerebral infarction,reduce cerebral infarction and nerve injury,and its mechanism may be related to the inhibition of RhoA/ROCK signaling pathway.

Objective The prevalence of drug-resistant Mycobacterium tuberculosis (Mtb) strains is exacerbating the global burden of tuberculosis (TB), highlighting the urgent need for new treatment strategies for TB. Methods The recombinant adenovirus vaccine expressing cyclic di-adenosine monophosphate (c-di-AMP) phosphodiesterase B (CnpB) (rAd-CnpB), was administered to normal mice via mucosal immunization, either alone or in combination with drug therapy, to treat Mtb respiratory infections in mice.Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of antibodies in serum and bronchoalveolar lavage fluid (BALF). Real-time quantitative PCR was performed to assess the transcription levels of cytokines interferon γ(IFN-γ) and interleukin 10(IL-10) in mouse lungs. Flow cytometry was used to determine the proportions of CD4⁺ and CD8⁺ T cell subsets in the lungs and spleens. ELISA was employed to measure the levels of cytokines IFN-γ, IL-2, IL-10, inflammatory factors IL-6, and tumor necrosis factor α (TNF-α) secreted by spleen cells following antigen stimulation. The bacteria loads in the lungs and spleens of Mtb-infected mice were enumerated by plate counting methods. Resluts Intranasal immunization with rAd-CnpB induced high titers of IgG in mouse serum and the production of IgG and IgA in BALF, along with alterations in T lymphocyte subsets in the lungs and spleens. Administration of rAd-CnpB, either alone or in combination with drugs, to Mtb-infected mice significantly increased serum IgG levels as well as IgA and IgG levels in BALF. rAd-CnpB immunization promoted the secretion of CnpB-specific cytokines and inflammatory factors by splenocytes in Mtb-infected mice. However, rAd-CnpB immunotherapy, either alone or combined with drugs, did not significantly affect the bacterial loads in the lungs and spleens of mice with Mtb respiratory infections. Conclusion Mucosal immunization with rAd-CnpB induced significant mucosal, humoral and cellular immune responses in mice, and significantly enhanced CnpB-specific cellular immune responses in Mtb-infected mice.
Animals ; Adenoviridae/immunology* ; Mycobacterium tuberculosis/genetics* ; Mice ; Female ; Phosphoric Diester Hydrolases/genetics* ; Tuberculosis Vaccines/administration & dosage* ; Tuberculosis/prevention & control* ; Mice, Inbred BALB C ; Cytokines ; Lung/microbiology* ; Immunization ; Bronchoalveolar Lavage Fluid/immunology* ; Immunity, Mucosal

Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T _NANC), time to symptom improvement (T _SI), and time of hospital stay (T _HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T _NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.

Objective To explore the effect of sorafenib on HeLa cell proliferation by inducing cell apoptosis and autophagy and its impact on drug resistance.Methods The drug-resistant cell strains were constructed through in-termittent induction method,with concentrations of 0,2.5,5.0,7.5,10.0,15.0,20.0 μmol/L.HeLa cells were incubated with increasing concentrations of sorafenib with each concentration for 1 week.The drug-resistant cell strains with stable passages were collected.MTT assay was used to detect the effect of sorafenib on cell prolifer-ation.Cell cycle distribution was analyzed by flow cytometry.The change in the expression of drug-resistant and ap-optotic genes in the parents and drug-resistant cell strains under different drug concentrations was examined by semi-quantitative PCR.The changes of apoptotic related marker proteins LC3-Ⅰ and LC3-Ⅱ were detected by Westernblot.Results Stable drug-resistant strains were successfully obtained;Drug-treated cells were more blocked in the G1 phase.In drug-resistant cells,the expression of apoptosis suppressor gene Bcl-2 was significantly decreased and the apoptotic gene Bax as well as the drug-resistant genes were all significantly increased(P＜0.05).The LC3-Ⅱ/LC3-Ⅰ ratio of drug-resistant cells was significantly higher than that of parent cells(P＜0.05).Conclusions Sorafenib may block the cell cycle,suppress malignant cell proliferation and promote autophage.On one hand,autophagy participates in the development of cell drug resistance and promotes cell survival.On the other hand,drug-induced autophagy may activate some of apoptotic signaling pathway in drug-resistant cells and promote the reversal of cell drug resistance.

With bio-materials being widely applied in clinical practice, acellular dermal matrix (ADM), one of the most competitive techniques in tissue engineering, has been developed rapidly in recent years, gaining popularity for its advantages in clinical application. What’s more, micronized acellular dermal matrix (mADM) has received an increasing amount of attention for its unique morphological characteristics, particularly in the field of cosmetic injection. Compared with other techniques, mADM has the advantages of great safety and sustainability, with less minimal invasion. However, further practical validation is still needed to determine the most suitable media for mADM injection as well as the most appropriate ratio of media to mADM transplantation. This paper reviews the relevant research findings.

With bio-materials being widely applied in clinical practice, acellular dermal matrix (ADM), one of the most competitive techniques in tissue engineering, has been developed rapidly in recent years, gaining popularity for its advantages in clinical application. What’s more, micronized acellular dermal matrix (mADM) has received an increasing amount of attention for its unique morphological characteristics, particularly in the field of cosmetic injection. Compared with other techniques, mADM has the advantages of great safety and sustainability, with less minimal invasion. However, further practical validation is still needed to determine the most suitable media for mADM injection as well as the most appropriate ratio of media to mADM transplantation. This paper reviews the relevant research findings.

Objective To compare the safety and comfort of patients with or without postoperative gastric tube placement after esophageal cancer surgery, and analyze the cost and nursing time of gastric tube placement. Methods The patients with esophageal cancer undergoing minimally invasive surgery in West China Hospital of Sichuan University in 2021 were enrolled. The patients were divided into a gastric tube indwelling group and a non gastric tube indwelling group according to whether the gastric tube was indwelled after the operation. The safety and comfort indicators of the two groups were compared. Results A total of 130 patients were enrolled. There were 66 patients in the gastric tube indwelling group, including 53 males and 13 females, aged 61.80±9.05 years and 64 patients in the non gastric tube indwelling group, including 55 males and 9 females, aged 64.47±8.00 years. Six patients in the non gastric tube indwelling group needed to place gastric tube 1 to 3 days after the operation due to their condition. There was no statistical difference in the incidence of postoperative complications between the two groups (P>0.05). The subjective comfort of patients in the gastric tube indwelling group was significantly lower than that in the non gastric tube indwelling group (P<0.001), and the incidence of foreign body sensation in the throat of patients in the gastric tube indwelling group was higher than that in the non gastric tube indwelling group (P<0.001). The average nursing time in the gastric tube indwelling group was about 59.58 minutes, and the average cost of gastric tube materials and nursing was 378.24 yuan per patient. Conclusion No gastric tube used after operation for appropriate esophageal cancer patients will not increase the incidence of postoperative complications (pulmonary infection, anastomotic leakage, chylothorax), but can increase the comfort of patients, save cost and reduce nursing workload, which is safe, feasible and economical.

Objective:To observe the effect of combining robot-assisted gait training (RAGT) with task-oriented training (TOT) on the walking ability of children with dyskinetic cerebral palsy (DCP).Methods:Sixty DCP children were randomly divided into a conventional intervention group, an RAGT group, and a combined intervention group, each of 20. All of the children received conventional rehabilitation therapy, while the RAGT and combined intervention groups were additionally provided with RAGT, and RAGT combined with TOT, respectively. Before the experiment and after 12 and 24 weeks of treatment, the subjects′ walking ability was evaluated using the 10-metre walk test (10MWT), and the D energy zone (standing position) and the E energy zone (walking, running and jumping) of the Gross Motor Function Measurement-88 (GMFM-88) instrument.Results:After 12 and 24 weeks of treatment, the average 10MWT speed and D and E energy zone scores of all three groups had improved significantly. After 24 weeks the combined group′s averages on all three measures were significantly better than those of the other two groups.Conclusion:RAGT combined with TOT and conventional rehabilitation training significantly improves the walking ability of DCP children.

As a noval class of nucleic acid drugs,messenger ribonucleic acid(mRNA)has great application potential in vaccines,immunotherapy,regenerative medicine,gene editing and so on.In particular,coronavirus disease 2019(COVID-19)in 2020 has greatly accelerated the mRNA technology development globally.However,mRNA being negatively charged,face challenges in cell entry and is easy to be phagocytized by cells of the innate immune system or degraded by nucleases in vivo.The instability and low delivery efficiency hinder widespread application of mRNA-based therapy.Therefore,safe,effective and stable delivery was needed carriers to protect mRNA from degradation and break through the barrier of cell membrane in order to ensure it express in intracellular.This paper systematically reviews the latest research progress of mRNA delivery carriers and briefly describes lipid carriers,polymer carriers,peptide carriers and viral carriers.The future directions of mRNA delivery carriers research are prospected so as to provide reference for the development of new mRNA drug delivery carriers.

Objective:To explore the relationship between olfactory dysfunction and mild cognitive impairment (MCI) among elderly people in the community so as to provide a reference for screening and risk factor management of the MCI population.Methods:From March to June 2023, elderly individuals from Donghuashi and Fangzhuang communities in Beijing were selected as the study subjects by convenience sampling. Study subjects were surveyed using the General Information Questionnaire, Mini-Mental State Examination, Montreal Cognitive Assessment, Barthel Index, Sniffin' Sticks Test, 7-item Generalized Anxiety Disorder Scale, and 15-item Geriatric Depression Scale. Binary logistic regression was used to analyze the factors that influence MCI among elderly people in the community.Results:A total of 252 questionnaires were distributed and 243 valid questionnaires were collected, with an effective response rate of 96.4% (243/252). Among 243 elderly people in the community, 75 experienced MCI, with an incidence of 30.9% (75/243). Binary Logistic regression analysis showed that the probability of MCI in elderly people with olfactory dysfunctions was 1.979 times that in elderly people without olfactory dysfunctions and age, previous occupational type and frequency of mental activity were the influencing factors for the occurrence of MCI ( P<0.05) . Conclusions:The incidence of MCI is high among elderly people in the community, especially those with olfactory dysfunctions. Nursing staff should pay attention to the role of olfactory dysfunction in cognitive function screening and risk factor management.