ObjectiveTo analyze the adverse reactions associated with the clinical use of Banxia （Rhizoma Pinelliae）- Wutou （Aconitum） in the same formula， with the aim of providing a reference for the safety of their clinical application. MethodsLiterature on the clinical application of antagonistic herbs "Banxia-Wutou" used in the same formula， published from January 1st， 2014， to June 30th， 2023， was retrieved from databases including CNKI， VIP， Wanfang， SinoMed， PubMed， Cochrane Library， and Embase. A database was established， and information related to adverse reactions was extracted， including descriptions， classifications， specific manifestations， management and outcomes， patients' primary diseases （western medicine diseases and traditional Chinese medicine diagnoses and syndromes）， and medication information （dosage， ratio， administration routes， and dosage forms）. ResultsA total of 79 researches simultaneously used antagonistic herbs Banxia-Wutou in the same formula and reported associated advers reactions. Gastrointestinal adverse reactions were the most common， with 8 studies reporting management of adverse reactions and 3 studies reporting improvement with no intervention. Among the 11 researches， the adverse reaction relieved to extant， while other 69 researches didn't report the managment of adverse reaction and its prognosis. For the primary disease in western medicine system， chronic bronchitis and chronic obstructive pulmonary disease （COPD） were most common， while gastric pain was the most common symptom in traditional Chinese medicine with spleen and kidney deficiency and spleen stomach cold deficiency being the most frequent syndromes. The most common Banxia dosage was 10 g， while for the Wutou， Fuzi （Radix Aconiti Lateralis Praeparata） was predominant with the highest dose at 15 g. The most frequent herbal combination was Banxia-fuzi， with a 1∶1 ratio. The main administration route was oral， and the primary dosage form was decoction. ConclusionGastrointestinal adverse reactions are the most common in the clinical use of Banxia-Wutou antagonistic herb combinations. Research on the safety of "Banxia-Wutou" combinations should focus on respiratory system diseases and spleen-stomach related conditions.

Objective To analyze the correlation between serum cystatin C (Cys-C) and bone turnover markers in elderly patients with type 2 diabetes mellitus (T2DM) and osteoporosis. Methods A retrospective analysis was conducted on the data of 320 elderly patients with T2DM admitted to Huai'an First People's Hospital from August 2021 to June 2024. Patients were divided into the osteoporosis group and the non-osteoporosis group according to whether they had osteoporosis. General information, bone turnover markers, and serum Cys-C levels were collected from all patients. The data were compared between the two groups to analyze the influencing factors of osteoporosis in elderly patients with T2DM and the correlation between serum Cys-C and bone turnover markers. Results The levels of total cholesterol and LDL-C in the osteoporosis group were higher than those in the non-osteoporosis group, and the bone mineral density was lower than that in the non-osteoporosis group (P<0.05). The levels of TPINP, β-CTX, and Cys-C in the osteoporosis group were higher than those in the non-osteoporosis group, and 25-OH-D3 level was lower than that in the non-osteoporosis group (P<0.05). Serum Cys-C was positively correlated with TPINP and β-CTX, and negatively correlated with 25-OH-D₃ (P<0.05). Multivariate logistic regression analysis found that total cholesterol, LDL-C, TPINP, β-CTX, 25-OH-D₃, and Cys-C were factors influencing osteoporosis in elderly patients with T2DM (P<0.05). Conclusion Serum Cys-C levels in elderly patients with T2DM and osteoporosis are elevated. There is a significant correlation between Cys-C level and bone turnover markers.

Currently,the ethical review model for organ donation and transplantation in domestic hospitals is generally characterized by suddenness,unpredictability,tight time,difficulty in convening meetings and training committee members,as well as generally low quality and efficiency of ethical review,which cannot meet clinical needs and cause the waste of some scarce resources.The team of the Clinical Application Center of Human Organ Transplantation and the Ethics Committee of the First People's Hospital of Kunming combine more than 10 years of review practice experience,as well as continuously explore and optimize the ethical review process and operating procedures for organ donation and transplantation.The special application has been approved and jointly developed with Soochow University and the Medical Ethics Committee of Fujian Province to build a full-process information software system management platform for organ ethical review of donation and transplantation,giving the full play the advantages of the review information system in improving work efficiency and review quality,facilitating full-process information management,and conducting online training and learning for committee members,with a view to providing a specialized practical model for addressing the difficulties and challenges related to ethical review of human organ donation and transplantation.

Viral infection can induce endoplasmic reticulum stress(ERS)and unfolded protein re-sponse(UPR)in host cells,resulting in perturbation of endoplasmic reticulum homeostasis.To e-lucidate the action mechanism of isochlorogenic acid A(IAA)in regulating peste des petits rumi-nant virus(PPRV)-induced ERS and UPR,MTT assay,indirect immunofluorescence assay and Western blot were used to evaluate the anti-PPRV activity of IAA,and the effects of IAA on PPRV-induced ERS and PERK signaling pathway were studied by Western blot and quantitative real-time PCR.The results showed that the PPRV replication and virus-induced cytopathic in LDG-2 cells were significantly inhibited,and the survival rate of virus-infected cells was significantly in-creased due to IAA treatment.Compared with the virus control group,the expression levels of GRP78 and p-eIF2α,the ratios of p-PERK/PERK and p-eIF2α/eIF2α in IAA treated PPRV-infec-ted cells were significantly decreased.The expression level of GADD153 significantly decreased at 24,36 h,and significantly increased at 48,60 h.Furthermore,treatment with ERS inhibitor 4-PBA could significantly suppress the expression levels of GRP78,PPRV-N protein and GADD153 in PPRV-infected cells,and the ratios of p-eIF2α/eIF2α and p-PERK/PERK in PPRV-infected cells were also significantly decreased caused by treatment with IAA or 4-PBA and IAA combination.These findings implicated that the PPRV-induced ERS could be alleviated by inhibiting activation of the PERK-eIF2α-GADD1 53 signaling pathway,which led to restriction of PPRV replication in host cells.

Viral infection can induce endoplasmic reticulum stress(ERS)and unfolded protein reac-tion(UPR)in host cells.This study aims to further explore the effects of ERS induced by pest des petits ruminants virus(PPRV)infection on UPR signaling pathway,virus replication and apopto-sis of host cells.MTT assay,indirect immunofluorescence assay(IFA)and Western blot were used to observe the proliferation of PPRV in goat kidney cells(LDG-2).Western blot and real-time flu-orescence quantitative PCR(qRT-PCR)were used to observe the effects of PPRV infection on the expression levels of GRP78,PERK and its downstream signal molecules,apoptosis-related proteins Bcl-2 and Bax.The result indicated that the cell survival rate was significantly declined with evident cytopathic effect at 36 h post-infection,and the expression level of PPRV-N protein tended to be elevated,and was significantly higher than that of cell control at 30 h post-infection.Meanwhile,the expression levels of GRP78,p-eIF2α and GADD153,the ratio of p-PERK/PERK and p-eIF2α/eIF2α were significantly increased.Moreover,the expression levels of PPRV-N protein,GRP78,p-eIF2α and GADD1 53,the ratio of p-eIF2α/eIF2α and p-PERK/PERK were significantly decreased in PPRV-infected cells due to 4-PBA treatment.The expression level of apoptosis-related Bcl-2 was down-regulated,Bax was up-regulated,and the ratio of Bcl-2/Bax was significantly decreased.Therefore,the activation of PERK/eIF2α/GADD153 signaling pathway could be induced by PPRV infection resulting in alleviating of virus-induced ERS,which is beneficial to viral replication.Bloc-king PPRV-induced ERS could inhibit the activation of PERK signaling pathway and virus replica-tion.PPRV infection and prolonged ERS can induce apoptosis of LDG-2 cells.

MTT assay,indirect immunofluorescence assay(IFA)and real-time fluorescence quanti-tative PCR(qRT-PCR)were used to observe the proliferation of PPRV in goat kidney cells(LDG-2).Western blot and qRT-PCR were used to evaluate the effects of PPRV infection on the expres-sion levels of TLR2,MyD88,NF-κB signaling pathway-related factors and their downstream in-flammatory factors.The results indicated that the significantly decreased cell survival rate and ob-vious cytopathic effect were observed at 36 h post PPRV infection,and the mRNA expression level of PPRV-N gene was significantly up-regulated.At the same time,the expression levels of TLR2,MyD88,p-p65 and p-IκBα,the ratio of p-p65/p65 and p-IκBα/IκBα and the mRNA expression levels of downstream inflammatory factors TNFα,IL-1β,IL-4 and IL-10 were significantly increased.Mo-reover,the expression levels of PPRV-N mRNA,TLR2,MyD88,p-p65 and p-IκBα,the ratio of p-p65/p65 and p-IκBα/IκBα and the mRNA expression levels of downstream inflammatory factors IL-1β and IL-4 in PPRV-infected cells were significantly decreased in the presence of the inhibitor C29 of TLR2.These findings implied that the TLR2/MyD88/NF-κBα signaling pathway can be activated by PPRV infection,which is beneficial to the replication and spread of the virus.Blocking down the activation of TLR2 can inhibit MyD88/NF-κB signaling pathway and viral replication in PPRV-infected cells.

The ethics committee of organ transplantation technology and clinical application in a hospital has encountered some difficulties and typical cases in its review work and practice for many years. Sometimes, it is difficult to make a decision in these dilemmas. Based on the previous experience of the hospital in the ethical review of organ donation and transplantation, combined with two typical cases, this paper discussed and analyzed two review points of whether the voluntary unpaid donation and the principle of informed consent were met, and whether the risk-benefit ratio was reasonable, and put forward relevant ethical and legal countermeasure for further research by institutional ethics committees and other parties, in order to provide reference for discussing the practical problems and ethical confusion of ethical review of organ donation and transplantation.

ObjectiveTo observe the effects of Sargassum and Glycyrrhizae Radix et Rhizoma incompatible pair with the Haizao Yuhutang （HYT） on oxidative stress in the liver of goiter rats under the condition of 2 times the dose limit of the Pharmacopoeia of the People's Republic of China 2020. MethodA total of 128 male Wistar rats were randomly divided into a blank group， a model group， a euthyrox group （20 μg·kg^-1）， a HYT group （12.06 g·kg^-1）， a HYT without Sargassum （HYT-H） group （9.90 g·kg^-1）， a HYT without Glycyrrhizae Radix et Rhizoma （HYT-G） group （10.26 g·kg^-1）， a HYT without Sargassum and Glycyrrhizae Radix et Rhizoma （HYT-HG） group （8.10 g·kg^-1）， and a Sargassum and Glycyrrhizae Radix et Rhizoma （HG） group （3.96 g·kg^-1）. The blank group was given deionized water by gavage， and the others were given propylthiouracil （PTU） to replicate the goiter pathological model. Euthyrox was taken as a positive control drug， and the rest of the Chinese medicine groups were given the corresponding decoction by gavage， the material was collected 12 hours after the last dose. The serum levels of aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， alkaline phosphatase （ALP）， and the contents of superoxide dismutase （SOD）， glutathione peroxidase （GSH-Px）， malondialdehyde （MDA）， reactive oxygen species （ROS） in liver tissue were detected in each group. The pathological changes in the liver were observed via hematoxylin-eosin （HE） staining. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was utilized to detect the mRNA expressions of Kelch-like Ech-associated protein 1 （Keap1）， nuclear factor E₂-related factor 2 （Nrf2）， heme oxygenase-1 （HO-1）， p53 and Caspase-3 in liver tissues. Western blot was adopted to detect the protein expressions of Nrf2 and HO-1 in liver tissues in oxidative stress-related signaling pathways. ResultCompared with control group， the model group showed significantly increased serum ALT level and contents of MDA and ROS in liver tissues （P<0.05， P<0.01）， significantly reduced activities of SOD and GSH-Px in the liver （P<0.01）， significantly increased mRNA expression of Keap1 （P<0.01）， and significantly decreased mRNA and protein expressions of Nrf2 and HO-1 （P<0.05， P<0.01）. Compared with the model group， the HYT group manifested significantly reduced serum levels of AST， ALT， and ALP （P<0.05， P<0.01）， significantly reduced contents of MDA and ROS in liver tissue （P<0.01）， significantly increased the activities of SOD and GSH-Px （P<0.01）， significantly decreased mRNA expressions of Keap1， p53， and Caspase-3 （P<0.01）， and significantly increased mRNA and protein expressions of Nrf2 and HO-1 （P<0.05， P<0.01）. ConclusionUnder the condition of 2 times the dose limit of the Pharmacopoeia of the People's Republic of China 2020， Sargassum and Glycyrrhizae Radix et Rhizoma incompatible pair with the HYT on oxidative stress in the liver of goiter rats had different effects. The HYT that contains Sargassum and Glycyrrhizae Radix et Rhizoma has a protective effect on the liver of goiter rats， and the effect is better than that of the HG group， the euthyrox group， and the incomplete groups. Its mechanism may be related to activating the Nrf2/HO-1 signaling pathway to alleviate liver oxidative stress and inhibiting the p53/Caspase-3 signaling pathway to reduce hepatocyte apoptosis.

Background: Peste des petits ruminants (PPR) is a contagious and fatal disease of sheep and goats. PPR virus (PPRV) infection induces endoplasmic reticulum (ER) stress-mediated unfolded protein response (UPR). The activation of UPR signaling pathways and their impact on apoptosis and virus replication remains controversial. Objectives: To investigate the role of PPRV-induced ER stress and the IRE1-XBP1 and IRE1-JNK pathways and their impact on apoptosis and virus replication. Methods: The cell viability and virus replication were assessed by 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay, immunofluorescence assay, and Western blot. The expression of ER stress biomarker GRP78, IRE1, and its downstream molecules, PPRV-N protein, and apoptosis-related proteins was detected by Western blot and quantitative reverse transcription-polymerase chain reaction, respectively. 4-Phenylbutyric acid (4-PBA) and STF-083010 were respectively used to inhibit ER stress and IRE1 signaling pathway. Results: The expression of GRP78, IRE1α, p-IRE1α, XBP1s, JNK, p-JNK, caspase-3, caspase-9, Bax and PPRV-N were significantly up-regulated in PPRV-infected cells, the expression of Bcl-2 was significantly down-regulated. Due to 4-PBA treatment, the expression of GRP78, p-IRE1α, XBP1s, p-JNK, caspase-3, caspase-9, Bax, and PPRV-N were significantly downregulated, the expression of Bcl-2 was significantly up-regulated. Moreover, in PPRV-infected cells, the expression of p-IRE1α, p-JNK, Bax, and PPRV-N was significantly decreased, and the expression of Bcl-2 was increased in the presence of STF-083010. Conclusions PPRV infection induces ER stress and IRE1 activation, resulting in apoptosis and enhancement of virus replication through IRE1-XBP1s and IRE1-JNK pathways.

Animals ; SARS-CoV-2 ; Antibodies, Neutralizing ; Macaca mulatta ; COVID-19/prevention & control* ; Antibodies, Viral ; Vaccines