Objective:To investigate the efficacy of Xingnaojing injection combined with Angong Niuhuang pill in the treatment of cerebral hemorrhage and their effects on neuronal injury. Methods:A prospective study was conducted on 117 patients with cerebral hemorrhage admitted to Department of Neurosurgery, Shaoxing Second Hospital, from January 2023 to August 2024. The patients were randomly divided into a control group and an observation group using a random number table method. The control group ( n = 59) was treated with Xingnaojing injection, while the observation group ( n = 58) was treated with Angong Niuhuang pill and Xingnaojing injection for 1 month. Clinical efficacy, neuronal cytokines (S-100B protein, neuron-specific enolase, and brain-derived neurotrophic factor), oxidative stress indicators (superoxide dismutase, malondialdehyde, and glutathione peroxidase), inflammatory factor levels (interleukin-1β, C-reactive protein, and interleukin-6), and adverse reactions (itching, chest tightness, gastrointestinal discomfort, rash, and increased heart rate) were compared between the two groups. Results:The total response rate in the observation group was significantly higher than that in the control group [94.83% (55/58) vs. 81.36% (48/59), Z = 2.27, P = 0.023]. After treatment, the levels of S-100B and neuron-specific enolase in the observation group were (0.43 ± 0.16) μg/L and (6.79 ± 1.28) μg/L, respectively, which were significantly lower than those in the control group [(0.62 ± 0.15) μg/L, (8.37 ± 1.15) μg/L, t = -6.62, -7.02, both P < 0.001]. Additionally, the level of brain-derived neurotrophic factor in the observation group was significantly higher than that in the control group [(63.58 ± 4.05) ng/L vs. (57.13 ± 4.39) ng/L, t = 8.26, P < 0.001]. After treatment, the levels of superoxide dismutase and glutathione peroxidase in the observation group were significantly higher than those in the control group ( t = 6.39, 6.94, both P < 0.001). The level of malondialdehyde in the observation group was significantly lower than that in the control group ( t = -5.95, P < 0.001). The levels of interleukin-1β, C-reactive protein and interleukin-6 in the observation group were significantly lower than those in the control group group ( t = -6.64, -8.29, -7.06, all P < 0.05). There was no significant difference in incidence of adverse reactions between the observation and control groups [13.79% (8/58) vs. 22.03% (13/59), χ2 = 1.35, P > 0.05]. Conclusions:The combination of Xingnaojing injection and Angong Niuhuang pill shows good efficacy in the treatment of cerebral hemorrhage, as it can reduce neuronal damage, oxidative stress reactions, and inflammatory responses. This combined treatment is worthy of clinical application.

LHFPL5 gene is involved in the electromechanical conduction of cochlear hair cells and plays an important role in maintaining hearing and balance functions.This review aims to investigate the mechanism of LHF-PL5 gene and its related proteins in the pathogenesis of hearing loss.We analyzed the hearing loss caused by LHF-PL5 gene mutation,and discussed the characteristics of hearing loss population.The molecular etiology of deafness caused by LHFPL5 gene was discussed through the conclusion and summary of the study results,which provided a basis for whether LHFPL5 gene screening was necessary for deaf people in China,and provided theoretical guidance for subsequent basic research and clinical diagnosis and treatment.

Objective To investigate the relationship between CT lung volume parameters(CT-LVP)and pulmonary function grade in patients with idiopathic pulmonary fibrosis(IPF)and its prediction of acute exacerbation.Methods A total of 204 patients with IPF were selected and divided into mild group(67 cases),moderate group(72 cases)and severe group(65 cases)according to the semi-quantitative scoring method of high-resolution computed tomography(HRCT).The correlation between CT-LVP and pul-monary function parameters(PFP)were analyzed.The predictive value of CT-LVP for acute exacerbation in severe IPF was ana-lyzed.Results The whole lung volume(WLV),normal lung volume(NLV)and normal lung volume percentage(NLV%)in severe group were lower than those in mild and moderate groups,whereas interstitial lung disease volume(ILDV)and interstitial lung disease volume percentage(ILDV%)were higher than those in mild and moderate groups,with statistical significance(P<0.05).WLV,NLV,ILDV,NLV%,ILDV%showed strong correlations with forced expiratory volume in 1 second percentage(FEV1%),forced expiratory volume in 1 second to forced vital capacity ratio(FEV1/FVC),diffusing capacity of the lung for carbon monoxide percent-age(DLCO%),and residual volume to total lung capacity ratio(RV/TLC).Receiver operating characteristic(ROC)curve analysis showed that the combination of WLV,NLV,ILDV,NLV%and ILDV%had higher accuracy in predicting acute exacerbation,area under the curve(AUC)>0.75(P<0.05).Conclusion CT-LVP is closely related to PFP,and the accuracy of CT-LVP combination in predicting acute exacerbation is high,which provides a theoretical basis for preventing acute exacerbation of IPF.

Objective To investigate the relationship between CT lung volume parameters(CT-LVP)and pulmonary function grade in patients with idiopathic pulmonary fibrosis(IPF)and its prediction of acute exacerbation.Methods A total of 204 patients with IPF were selected and divided into mild group(67 cases),moderate group(72 cases)and severe group(65 cases)according to the semi-quantitative scoring method of high-resolution computed tomography(HRCT).The correlation between CT-LVP and pul-monary function parameters(PFP)were analyzed.The predictive value of CT-LVP for acute exacerbation in severe IPF was ana-lyzed.Results The whole lung volume(WLV),normal lung volume(NLV)and normal lung volume percentage(NLV%)in severe group were lower than those in mild and moderate groups,whereas interstitial lung disease volume(ILDV)and interstitial lung disease volume percentage(ILDV%)were higher than those in mild and moderate groups,with statistical significance(P<0.05).WLV,NLV,ILDV,NLV%,ILDV%showed strong correlations with forced expiratory volume in 1 second percentage(FEV1%),forced expiratory volume in 1 second to forced vital capacity ratio(FEV1/FVC),diffusing capacity of the lung for carbon monoxide percent-age(DLCO%),and residual volume to total lung capacity ratio(RV/TLC).Receiver operating characteristic(ROC)curve analysis showed that the combination of WLV,NLV,ILDV,NLV%and ILDV%had higher accuracy in predicting acute exacerbation,area under the curve(AUC)>0.75(P<0.05).Conclusion CT-LVP is closely related to PFP,and the accuracy of CT-LVP combination in predicting acute exacerbation is high,which provides a theoretical basis for preventing acute exacerbation of IPF.

LHFPL5 gene is involved in the electromechanical conduction of cochlear hair cells and plays an important role in maintaining hearing and balance functions.This review aims to investigate the mechanism of LHF-PL5 gene and its related proteins in the pathogenesis of hearing loss.We analyzed the hearing loss caused by LHF-PL5 gene mutation,and discussed the characteristics of hearing loss population.The molecular etiology of deafness caused by LHFPL5 gene was discussed through the conclusion and summary of the study results,which provided a basis for whether LHFPL5 gene screening was necessary for deaf people in China,and provided theoretical guidance for subsequent basic research and clinical diagnosis and treatment.

OBJECTIVE To provide practical basis and policy recommendations for improving the pharmacovigilance （PV） system construction in medical institutions across China. METHODS A questionnaire survey was conducted using a mixed sampling strategy of “online random sampling+offline supplementary sampling” to distribute questionnaires among pharmaceutical professionals in tertiary medical institutions nationwide. The questionnaire covered aspects such as the construction of PV systems， job position settings， information system support， operational practices， and multi-stakeholder collaboration. The data were analyzed using descriptive methods and SPSS 20.0 statistical software. RESULTS A total of 70 valid questionnaires were collected from 66 medical institutions， primarily Class A tertiary hospitals. The survey found that 90.00% had designated PV personnel and 74.29% routinely conducted PV activities. However， there were notable disparities in resource allocation and information system capacity， with less than 50% of the institutions conducting post-marketing drug re-evaluation. PV activities were primarily focused on the collection and reporting of adverse drug reactions， with limited capabilities in signal detection and risk assessment. CONCLUSIONS Among the surveyed tertiary hospitals， PV systems have begun to take shape. However， challenges persist in terms of system establishment， resource allocation， risk assessment， and inter-organizational coordination. Policy efforts should focus on strengthening regulatory frameworks， improving information sharing mechanisms， enhancing professional training， and strengthening collaboration between hospitals and market authorization holders to ensure the effective implementation of PV in medical institutions.

Objective:To investigate the efficacy of Xingnaojing injection combined with Angong Niuhuang pill in the treatment of cerebral hemorrhage and their effects on neuronal injury. Methods:A prospective study was conducted on 117 patients with cerebral hemorrhage admitted to Department of Neurosurgery, Shaoxing Second Hospital, from January 2023 to August 2024. The patients were randomly divided into a control group and an observation group using a random number table method. The control group ( n = 59) was treated with Xingnaojing injection, while the observation group ( n = 58) was treated with Angong Niuhuang pill and Xingnaojing injection for 1 month. Clinical efficacy, neuronal cytokines (S-100B protein, neuron-specific enolase, and brain-derived neurotrophic factor), oxidative stress indicators (superoxide dismutase, malondialdehyde, and glutathione peroxidase), inflammatory factor levels (interleukin-1β, C-reactive protein, and interleukin-6), and adverse reactions (itching, chest tightness, gastrointestinal discomfort, rash, and increased heart rate) were compared between the two groups. Results:The total response rate in the observation group was significantly higher than that in the control group [94.83% (55/58) vs. 81.36% (48/59), Z = 2.27, P = 0.023]. After treatment, the levels of S-100B and neuron-specific enolase in the observation group were (0.43 ± 0.16) μg/L and (6.79 ± 1.28) μg/L, respectively, which were significantly lower than those in the control group [(0.62 ± 0.15) μg/L, (8.37 ± 1.15) μg/L, t = -6.62, -7.02, both P < 0.001]. Additionally, the level of brain-derived neurotrophic factor in the observation group was significantly higher than that in the control group [(63.58 ± 4.05) ng/L vs. (57.13 ± 4.39) ng/L, t = 8.26, P < 0.001]. After treatment, the levels of superoxide dismutase and glutathione peroxidase in the observation group were significantly higher than those in the control group ( t = 6.39, 6.94, both P < 0.001). The level of malondialdehyde in the observation group was significantly lower than that in the control group ( t = -5.95, P < 0.001). The levels of interleukin-1β, C-reactive protein and interleukin-6 in the observation group were significantly lower than those in the control group group ( t = -6.64, -8.29, -7.06, all P < 0.05). There was no significant difference in incidence of adverse reactions between the observation and control groups [13.79% (8/58) vs. 22.03% (13/59), χ2 = 1.35, P > 0.05]. Conclusions:The combination of Xingnaojing injection and Angong Niuhuang pill shows good efficacy in the treatment of cerebral hemorrhage, as it can reduce neuronal damage, oxidative stress reactions, and inflammatory responses. This combined treatment is worthy of clinical application.

Recent clinical studies have shown that mutation of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) gene in cancer cells may be associated with immunosuppressive tumor microenvironment (TME) and poor response to immune checkpoint blockade (ICB) therapy. Therefore, efficiently restoring PTEN gene expression in cancer cells is critical to improving the responding rate to ICB therapy. Here, we screened an adeno-associated virus (AAV) capsid for efficient PTEN gene delivery into B16F10 tumor cells. We demonstrated that intratumorally injected AAV6-PTEN successfully restored the tumor cell PTEN gene expression and effectively inhibited tumor progression by inducing tumor cell immunogenic cell death (ICD) and increasing immune cell infiltration. Moreover, we developed an anti-PD-1 loaded phospholipid-based phase separation gel (PPSG), which formed an in situ depot and sustainably release anti-PD-1 drugs within 42 days in vivo. In order to effectively inhibit the recurrence of melanoma, we further applied a triple therapy based on AAV6-PTEN, PPSG^@anti-PD-1 and CpG, and showed that this triple therapy strategy enhanced the synergistic antitumor immune effect and also induced robust immune memory, which completely rejected tumor recurrence. We anticipate that this triple therapy could be used as a new tumor combination therapy with stronger immune activation capacity and tumor inhibition efficacy.

Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) functions as a key regulator in inflammation and cell death and is involved in mediating a variety of inflammatory or degenerative diseases. A number of allosteric RIPK1 inhibitors (RIPK1i) have been developed, and some of them have already advanced into clinical evaluation. Recently, selective RIPK1i that interact with both the allosteric pocket and the ATP-binding site of RIPK1 have started to emerge. Here, we report the rational development of a new series of type-II RIPK1i based on the rediscovery of a reported but mechanistically atypical RIPK3i. We also describe the structure-guided lead optimization of a potent, selective, and orally bioavailable RIPK1i, 62, which exhibits extraordinary efficacies in mouse models of acute or chronic inflammatory diseases. Collectively, 62 provides a useful tool for evaluating RIPK1 in animal disease models and a promising lead for further drug development.

Due to the insufficient long-term protection and significant efficacy reduction to new variants of current COVID-19 vaccines, the epidemic prevention and control are still challenging. Here, we employ a capsid and antigen structure engineering (CASE) strategy to manufacture an adeno-associated viral serotype 6-based vaccine (S663V-RBD), which expresses trimeric receptor binding domain (RBD) of spike protein fused with a biological adjuvant RS09. Impressively, the engineered S663V-RBD could rapidly induce a satisfactory RBD-specific IgG titer within 2 weeks and maintain the titer for more than 4 months. Compared to the licensed BBIBP-CorV (Sinopharm, China), a single-dose S663V-RBD induced more endurable and robust immune responses in mice and elicited superior neutralizing antibodies against three typical SARS-CoV-2 pseudoviruses including wild type, C.37 (Lambda) and B.1.617.2 (Delta). More interestingly, the intramuscular injection of S663V-RBD could overcome pre-existing immunity against the capsid. Given its effectiveness, the CASE-based S663V-RBD may provide a new solution for the current and next pandemic.