ObjectiveTo investigate the effect of Danggui Shaoyaosan on the expression of Toll-like receptor 4/nuclear factor-kappa B p65/NOD-like receptor protein 3 （TLR4/NF-κB p65/NLRP3） signaling pathway in the renal tissues of db/db mice with spontaneous diabetes， and to explore the potential mechanism by which Danggui Shaoyaosan alleviates inflammation in diabetic kidney disease （DKD）. MethodsThirty db/db mice were divided into five groups： A model group， Danggui Shaoyaosan low- （16.77 g·kg^-1·d^-1）， medium- （33.54 g·kg^-1·d^-1）， and high-dose （67.08 g·kg^-1·d^-1） intervention groups， as well as an irbesartan group （0.025 g·kg^-1·d^-1） by the random number table method， with 6 mice in each group. Additionally， 6 db/m mice were assigned to the normal group. After 8 weeks of intervention， the following parameters were determined by corresponding methods： body weight， fasting blood glucose （FBG）， 24-hour urinary protein （24 h-UTP）， and serum creatinine （SCr） levels， renal histopathological analysis by hematoxylin-eosin （HE） staining， Masson staining， and periodic acid-Schiff （PAS） staining， the protein and mRNA expression levels of TLR4， NF-κB p65， NLRP3， tumor necrosis factor-alpha （TNF-α）， interleukin-1β （IL-1β）， interleukin-6 （IL-6）， interleukin-10 （IL-10）， and interleukin-18 （IL-18） by Western blot and Real-time quantitative polymerase chain reaction （Real-time PCR）， as well as TLR4， NF-κB p65， and NLRP3 protein expression in renal tissues by immunohistochemistry （IHC）. ResultsCompared with the normal group， the model group exhibited increased body weight， FBG， 24 h-UTP， and SCr levels （P<0.05）； disordered renal structure， thickened basement membrane， and interstitial inflammatory cell infiltration， elevated TLR4， NF-κB p65， NLRP3， TNF-α， IL-1β， IL-6， and IL-18 expression； as well as decreased IL-10 expression （P<0.05）. Compared with the model group， these pathological changes and biochemical abnormalities were reversed in the medicine intervention groups to varying degrees （P<0.05）. ConclusionDanggui Shaoyaosan may delay DKD progression by alleviating renal inflammatory response and reducing urinary protein excretion via modulating the TLR4/NF-κB p65/NLRP3 signaling pathway.

Traditional development of small protein scaffolds has relied on display technologies and mutation-based engineering, which limit sequence and functional diversity, thereby constraining their therapeutic and application potential. Protein design tools have significantly advanced the creation of novel protein sequences, structures, and functions. However, further improvements in design strategies are still needed to more efficiently optimize the functional performance of protein-based drugs and enhance their druggability. Here, we extended an evolution-based design protocol to create a novel minibinder, BindHer, against the human epidermal growth factor receptor 2 (HER2). It not only exhibits super stability and binding selectivity but also demonstrates remarkable properties in tissue specificity. Radiolabeling experiments with ^99mTc, ⁶⁸Ga, and ¹⁸F revealed that BindHer efficiently targets tumors in HER2-positive breast cancer mouse models, with minimal nonspecific liver absorption, outperforming scaffolds designed through traditional engineering. These findings highlight a new rational approach to automated protein design, offering significant potential for large-scale applications in therapeutic mini-protein development.

BACKGROUND: World Health Organization recommends that influenza vaccines should benefit as much of the population as possible, especially where resources are limited. Corona virus disease 2019 (COVID-19) has become one of the greatest threats to health systems worldwide. The present study aimed to extend the evidence of the association between influenza vaccination and COVID-19 to promote the former. METHODS: In this systematic review, four electronic databases, including the Cochrane Library, PubMed, Embase, and Web of Science, were searched for related studies published up to May 2022. All odds ratios (ORs) with 95% confidence intervals (CIs) were pooled by meta-analysis. RESULTS: A total of 36 studies, encompassing 55,996,841 subjects, were included in this study. The meta-analysis for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection provided an OR of 0.80 (95% CI: 0.73-0.87). The statistically significant estimates for clinical outcomes were 0.83 (95% CI: 0.72-0.96) for intensive care unit admission, 0.69 (95% CI: 0.57-0.84) for ventilator support, and 0.69 (95% CI: 0.52-0.93) for fatal infection, while no effect seen in hospitalization with an OR of 0.87 (95% CI: 0.68-1.10). CONCLUSION: Influenza vaccination helps limit SARS-CoV-2 infection and severe outcomes, but further studies are needed. REGISTRATION PROSPERO, CRD42022333747.
Humans ; COVID-19/epidemiology* ; SARS-CoV-2 ; Influenza, Human ; Intensive Care Units ; Vaccination

BACKGROUND:Gastric cancer stem cels involved in the neoadjuvant chemotherapy and conventional treatment are closely associated with relapse of gastric cancer. However, this conclusion has not yet been confirmed.
OBJECTIVE:To investigate the effects of gastric cancer stem cels in tumor invasion and metastasis and its effect on angiogenesis ability.
METHODS:We prepared nude mouse models of gastric cancer to isolate and culture gastric cancer stem cels. Harvested gastric cancer stem cels were detected in cel scratch test, ring test, inhibition rate test, cel migration test and tumorigenicity test.
RESULTS AND CONCLUSION:After 7 days of culture, the cels exhibited adherent growth but a lack of regularity that most cels were in a tadpole shape. In the cel scratch test, the scratch width was significantly different at 0 and 24 hours (P < 0.05). Under an inverted microscope, the cels were found to form a ring in the ring test. The 50% inhibiting concentration of gastric cancer stem cels induced by oxaliplatin was significantly lower than that induced by 5-fluorouracil (P < 0.05). The number of cels passing through the basilar membrane was significantly increased after cel migration (P < 0.05). After implantation of gastric cancer stem cels, the gastric tissue quality was significantly higher than that in normal nude mice of gastric cancer (P < 0.05). These findings indicate that gastric cancer stem cels responsible for tumor invasion and migration have stronger angiogenesis ability.

Objective o evaluate the association between IL-28B ( rs12979860 ) polymorphism andantiviraltherapeutic effectbydetecting the genotype of interleukin-28B( IL-28 B) in patients with hepatitis C ( HCV ) .Methods Of total 1153 HCV patients, 303 diagnosed with CHC had been treated with pegylated interferon plus ribavirin for 24-48 weeks.IL-28B ( rs12979860 ) was genotyped by two-color fluorescent TaqMan assay.Results Among 1153 patients, CC, CT and TT genotype frequencies of IL-28B rs12979860 are 83.26%, 16.22%and 0.52%respectively.The results of HCV genotypingof 580 in 1153 cases, the frequencies of 1b, 2a and their non-1b/2a type are 63.45%, 35.00%and 1.55%respectively;In 303 CHC patients with clear medical history, the proportion of SVR was71.98% in patients with CC genotype and 16.90%in those with either the CT or TT genotypes.Logistic regression model was adopted to analyze the association of rs12979860 with SVR while adjusting for age, gender, viral load and HCV GT factors.Populations carrying combined genotype ( CT +TT) are making it harder to get SVR compared with those with CC genotype (OR, 95%CI:11.10,5.35-23.04;P<0.000 1).The percentages of SVR in HVC patients with 1b and 2a genotypeare 48.02% and 81.19% respectively.there is a statistically significant difference between these subgroups (χ2 =30.639,P<0.000 1).Conclusion IL-28B rs12979860 genotype is closely related to SVR in CHCpatients.Patients with CC genotype have a higher virus sustained response rate than those carrying CT or TT genotype.The SNP , rs12979860, might be applied as a predictor of clinical antiviral efficacy in the furture.

Objective To observe the protein expressions of PI3Kp110, pAkt, pGSK3β of phosphatidylinositol 3-kinase (PI3K) and protein kinase B (Akt) signaling pathway in the whole blood of patients with Kashin-Beck disease and analyze the status of PI3K/Akt signaling pathway. Methods Patients with Kashin-Beck disease ( KBD group ) were from six counties ( Xunyi , Linyou , Yongshou , Qianyang , Changwu and Long County) of Shannxi Province in Kashin-Beck disease areas , and the healthy controls (control group) were matched by age and sex. Venous blood was collected from patients and healthy controls. Trizol method was applied to extract the whole blood protein; protein expression levels of PI3K/Akt signaling pathway in whole blood were detected by Western blotting; the gray values were observed and recorded by the sodium dodecyl sulfate polyacrylamide gel electrophoresis(SDS-PAGE) and GDS-8000 gel imaging analysis system. Differences between the two groups were assessed by Student’s t-test. Results Compared age and sex between KBD group and control group, differences were not statistically significant(t=0.701, P>0.05;χ2=0.400, P>0.05). The protein expression levels of PI3Kp110, pAkt and p-GSK3β in KBD group were higher than that in control group(156.1 ± 92.1 vs. 79.5 ± 21.5, 113.7 ± 15.2 vs. 43.3 ± 10.7 and 105.9 ± 17.5 vs. 37.3 ± 12.0, respectively) and the differences were statistically significant (t=2.563, 6.567, 7.916; all P < 0.05 or < 0.01). Conclusion The PI3Kp110, pAkt and p-GSK3β expressions of signaling pathway proteins in the whole blood of patiens with Kashin-Beck disease are up-regulated significantly and the status of PI3K/Akt signaling pathway is activated.

Objective To examine whether microinjectlon of morphine into the rat thaiamle nucleus submedlus (Sin) could depress the bee venom (BV)-induced nociceptive behaviours. Methods In inflammatory pain model induced by BV subcutaneous injection into rat unilateral hind paw, the inhibitory effects of morphine microinjection into thalamic nucleus suhmedius (Sin) on the spontaneous nociecptlve behavior, heat hyperalgesia and tactile ailodynia, and the influence of naioxone on the morphine effects were observed in the rat. Results A single dose of morphine (5.0 μg, 0. 5μL) applied into the Sm ipsilaterni to the BV injected paw significantly depressed the spontaneous paw flinching response. Morphine also significantly increased the heat paw withdrawal iateneies in the bilateral hind paw and the tactile paw withdrawal threshold in the ipsilnteral hind paw 2 hours after BV injection. All these depressive effects could be effectively antagonized by pre-treatment with the opiuld receptor antagonist naloxone (1.0μg, 0. 5μL) in the Sm 5rain prior to morphine administration. Naloxone alone injected to the Sm had no effect on the BV-induecd nociceptive behavior. Conclusion These results suggest that Sm is involved in opioid receptor-mediated antt-nociception in the rat with the BV-induced inflammatory pain. Together with results from previous studies, it is likely that this effect is produced by activation of the Sm-ventrolateral orbital cortex-periaqueductal gray pathway, leading to activation of the brainstem descending inhibitory system and depression of the nodceptive inputs at the spinal cord level.