This study aims to investigate the effect of salvianolic acid B (Sal B), the active ingredient of Salvia miltiorrhiza, on H9C2 cardiomyocytes injured by oxygen and glucose deprivation/reperfusion (OGD/R) through regulating mitochondrial fission and fusion. The process of myocardial ischemia-reperfusion injury was simulated by establishing OGD/R model. The cell proliferation and cytotoxicity detection kit (cell counting kit-8, CCK-8) was used to detect cell viability; the kit method was used to detect intracellular reactive oxygen species (ROS), total glutathione (t-GSH), nitric oxide (NO) content, protein expression levels of mitochondrial fission and fusion, apoptosis-related detection by Western blot. Mitochondrial permeability transition pore (MPTP) detection kit and Hoechst 33342 fluorescence was used to observe the opening level of MPTP, and molecular docking technology was used to determine the molecular target of Sal B. The results showed that relative to control group, OGD/R injury reduced cell viability, increased the content of ROS, decreased the content of t-GSH and NO. Furthermore, OGD/R injury increased the protein expression levels of dynamin-related protein 1 (Drp1), mitofusions 2 (Mfn2), Bcl-2 associated X protein (Bax) and cysteinyl aspartate specific proteinase 3 (caspase 3), and decreased the protein expression levels of Mfn1, increased MPTP opening level. Compared with the OGD/R group, it was observed that Sal B had a protective effect at concentrations ranging from 6.25 to 100 μmol·L^-1. Sal B decreased the content of ROS, increased the content of t-GSH and NO, and Western blot showed that Sal B decreased the protein expression levels of Drp1, Mfn2, Bax and caspase 3, increased the protein expression level of Mfn1, and decreased the opening level of MPTP. In summary, Sal B may inhibit the opening of MPTP, reduce cell apoptosis and reduce OGD/R damage in H9C2 cells by regulating the balance of oxidation and anti-oxidation, mitochondrial fission and fusion, thereby providing a scientific basis for the use of Sal B in the treatment of myocardial ischemia reperfusion injury.

ObjectiveThe bioinformatics method was used to screen ferroptosis differential genes （FRGs） closely related to ulcerative colitis （UC）， and animal experiments were conducted to verify whether the mechanism of Xiezhuo Jiedu recipe in treating UC is related to the regulation of ferroptosis. MethodThe differentially expressed genes （DEGs） of colonic mucosa tissue of UC patients were obtained from the GEO database， and the intersection of the genes with ferroptosis genes was used to obtain FRGs. The core FRGs were obtained by cluster analysis， minimum absolute contraction and selection operator （LASSO） regression， and receiver operating characteristic curve （ROC） curve analysis. In animal experiments， the UC mouse model was prepared by making the mouse freely drink 2.5% dextran sodium sulfate （DSS）. Xiezhuo Jiedu recipe and mesalazine were given by gavage for seven days， and the inflammatory infiltration of colonic mucosa was observed by hematoxylin-eosin （HE） staining. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression levels of E3 ubiquitin ligase （FBXW7）， zinc finger protein （ZFP36）， solute carrier family 7 member 11 （SLC7A11）， and Toll-like receptor 4 （TLR4） in colon tissue. The protein expression levels of FBXW7， ZFP36， SLC7A11， and TLR4 in colon tissue were detected by Western blot. ResultDataset GSE87466 was screened from the GEO database， and its intersections with the ferroptosis gene were analyzed to obtain 21 FRGs. After cluster analysis， LASSO regression， and ROC analysis， core FRGs （FBXW7， ZFP36， SLC7A11， and TLR4） were obtained. Immunoinfiltration analysis showed significant differences in the expression of initial B cells， M1 macrophages， plasma cells， and M2 macrophages in the colonic mucosa tissue of UC mice， and there was a significant correlation between core FRGs and these immune cells. Further animal experiments showed that the colonic mucosa tissue of mice in the model group was disorganized and infiltrated by a large number of inflammatory cells. The inflammation of the colonic mucosa tissue of mice in each group was relieved to varying degrees after treatment with Xiezhuo Jiedu recipe and mesalazine， while the colonic mucosa tissue of mice in the high-dose group of Xiezhuo Jiedu recipe showed almost no inflammatory changes. Compared with the normal group， the protein and mRNA expressions of FBXW7， ZFP36， SLC7A11， and TLR4 in the model group were significantly increased， and the expression of core FRGs in colonic mucosa tissue of mice in all groups was significantly down-regulated after treatment with Xiezhuo Jiedu recipe and mesalazine. ConclusionFBXW7， ZFP36， SLC7A11， and TLR4 are ferroptosis genes closely related to the pathogenesis of UC， and Xiezhuo Jiedu recipe can significantly alleviate colonic mucosa inflammation in mice by down-regulating core ferroptosis genes.

Influenza virus causes serious threat to human life and health. Due to the inherent high variability of influenza virus, clinically resistant mutant strains of currently approved anti-influenza virus drugs have emerged. Therefore, it is urgent to develop antiviral drugs with new targets or mechanisms of action. RNA-dependent RNA polymerase is directly responsible for viral RNA transcription and replication, and plays key roles in the viral life cycle, which is considered an important target of anti-influenza drug design. From the point of view of medicinal chemistry, this review summarizes current advances in diverse small-molecule inhibitors targeting influenza virus RNA-dependent RNA polymerase, hoping to provide valuable reference for development of novel antiviral drugs.

ObjectiveIt was reported that the transthyretin (TTR) has a neuroprotective effect on Alzheimer’s disease (AD), which is manifested by the ability of TTR to inhibit the pathological aggregation of amyloid beta protein (Aβ). In this work, we investigated the mechanism of the interactions between TTR and Aβ at the molecular level to reveal the neuroprotective effect of TTR on AD. MethodsProtein-protein docking was used to explore the models of interaction between different structural forms of TTR and Aβ, and molecular dynamics simulation was further applied to investigate the dynamic process of the interaction between the two. ResultsBoth TTR tetramer and monomer can interact with Aβ monomer, and the thyroxine-binding channel of TTR tetramer is the main binding site of Aβ monomer. In addition, the EF helix and EF loop of TTR tetramer were also able to bind Aβ monomer. When the TTR tetramer dissociates, the hydrophobic site of the internal TTR monomer is exposed, which has a strong affinity for Aβ monomer. For the interaction between Aβ aggregates and TTR, a higher degree of aggregation can be formed between TTR monomer and Aβ aggregates due to the β-sheet-rich property of TTR monomer and Aβ aggregates, which may therefore reduce the cytotoxicity of Aβ aggregates. ConclusionBoth TTR tetramer and monomer can inhibit Aβ aggregation by “sequestering” Aβ monomer, while TTR monomer can reduce the cytotoxicity of Aβ aggregates by forming large co-aggregation with Aβ aggregates. This work can provide an important theoretical basis for the design and discovery of anti-AD drugs based on the neuroprotective effects of TTR.

ObjectiveTo investigate the effect of mucin 1 (MUC1) on the proliferation and apoptosis of nasopharyngeal carcinoma (NPC) and its regulatory mechanism. MethodsThe 60 NPC and paired para-cancer normal tissues were collected from October 2020 to July 2021 in Quanzhou First Hospital. The expression of MUC1 was measured by real-time quantitative PCR (qPCR) in the patients with PNC. The 5-8F and HNE1 cells were transfected with siRNA control (si-control) or siRNA targeting MUC1 (si-MUC1). Cell proliferation was analyzed by cell counting kit-8 and colony formation assay, and apoptosis was analyzed by flow cytometry analysis in the 5-8F and HNE1 cells. The qPCR and ELISA were executed to analyze the levels of TNF-α and IL-6. Western blot was performed to measure the expression of MUC1, NF-кB and apoptosis-related proteins (Bax and Bcl-2). ResultsThe expression of MUC1 was up-regulated in the NPC tissues, and NPC patients with the high MUC1 expression were inclined to EBV infection, growth and metastasis of NPC. Loss of MUC1 restrained malignant features, including the proliferation and apoptosis, downregulated the expression of p-IкB、p-P65 and Bcl-2 and upregulated the expression of Bax in the NPC cells. ConclusionDownregulation of MUC1 restrained biological characteristics of malignancy, including cell proliferation and apoptosis, by inactivating NF-κB signaling pathway in NPC.

Eighteen compounds were isolated from the methanol extract of the fruits of Litsea cubeba by silica gel, ODS, Sephadex LH-20 column chromatography, semi-preparative RP-HPLC, chiral HPLC and recrystallization. Their structures were elucidated by spectroscopic analyses and by comparison with reported spectroscopic data and physicochemical properties, and the absolute configurations of the enantiomers were established by experimental and calculated electronic circular dichroism spectra. These compounds were identified as (+)-(R)-4-hydroxypiperitenone (1a), (-)-(S)-4-hydroxypiperitenone (1b), (3S,4S,6R)-3,6-dihydroxy-1-menthene (2), (4S,5R)-4-hydroxy-5-isopropyl-2-methylcyclohex-2-en-1-one (3), (R)-6-hydroxy-3-(2-hydroxypropan-2-yl)-6-methylcyclohex-2-enone (4), (4S,6R)-4-hydroxy-6-isopropyl-3-methylcyclohex-2-enone (5), (1R,3S,4R)-3-hydroxy isopulegol (6), subamone (7), (6S)-3,7-dimethyl-7-hydroxy-2(Z)-octen-6-olide (8), (6S)-6,7-dihydroxy-3,7-dimethyloct-2(Z)-enoate (9), holostylactone (10), sesamin (11), dimethylmatairesinol (12), p-hydroxybenzoylcarbinol (13), syringaldehyde (14), p-hydroxybenzaldehyde (15), 4-hydroxy-3-methoxybenzaldehyde (16), 5,4ʹ-dihydroxy-7-methoxyflavone (17). Among them, compounds 1a and 1b were a pair of new monoterpenoid enantiomers, 8 and 9 were new natural products, 2-7, 10, 11 and 17 were isolated from Litsea genus for the first time. The in vitro anti-inflammatory effects of compounds 1-17 were evaluated using lipopolysaccharide-stimulated RAW264.7 cells, the results showed that compound 14 exhibited significant anti-inflammatory activity with NO inhibitory rate of 66.27% at a concentration of 40 μmol·L^-1.

In the progression of end-stage liver disease,the incidence of sleep disorders in patients with liver cirrhosis is high.Currently,western medicine treatment has obvious liver and kidney damage and adverse reactions after discontinuation,which affects the therapeutic effect.Cirrhosis and sleep disorders can be separately attributed to the category of"abdominal mass"and"insomnia"in traditional Chinese medicine.The"abdominal mass"is caused by the disorder of liver and spleen qi movement,as well as the obstruction of phlegm-dampness and blood stasis.In the development of"abdominal mass",the liver failed in ensuring free movement of qi,the spleen failed in transportation and transformation,liver yin and liver blood became insufficiency and the imbalance of yin and yang in the zang-fu organs became imbalanced,and then the ethereal soul depart from the housing,which leads to"insomnia"as an outward manifestation.Professor ZHOU Xiao-Zhou focuses on the concept of qi and blood,and points out that the pathogenesis of sleep disorder in cirrhosis is characterized by liver stagnation and spleen deficiency.He proposed that the treatment principle is to regulate the liver and spleen simultaneously,as well as to nourish the heart and calm the mind.Professor ZHOU has developed Ganyinghua Anshen Formula for treating sleep disorders in cirrhosis,which is derived from the modification of Xiangsha Liujunzi Decoction,and is composed of 14 Chinese medicines of vinegar-prepared Cyperi Rhizoma,Amomi Fructus,Coicis Semen,Dioscoreae Rhizoma,bran-fried Atractylodis Macrocephalae Rhizoma,Galli Gigerii Endothelium Corneum,Gardeniae Fructus,Codonopsis Radix,Salviae Miltiorrhizae Radix et Rhizoma,Citri Reticulatae Pericarpium,Sclerotium Poriae Pararadicis,Longan Arillus,Albiziae Cortex,and Glycyrrhizae Radix et Rhizoma Praeparata cum Melle.The formula has achieved remarkable clinical effect.The clinical experience of Professor ZHOU Xiao-Zhou for treating sleep disorders in cirrhosis through regulating the liver and spleen simultaneously will provide a reference for its clinical treatment with traditional Chinese medicine.

Objective To investigate the short-term efficacy and safety of chemotherapy induced by nimotuzumab(NTZ)combined with TP regimen and sequential concurrent chemoradiotherapy in patients with epidermal growth factor receptor positive(EGFR-positive)locally advanced nasopharyngeal carcinoma.Methods A total of 48 patients with stage Ⅲ to Ⅳ A nasopharyngeal carcinoma in Guizhou Provincial People's Hospital from January 2020 to December 2022 were prospectively enrolled,and were randomized into two groups:NTP(NTZ+docetaxel/albumin-paclitaxel+cisplatin)group and TP(Docetaxel/albumin-paclitaxel+cisplatin)group(24 cases per group)by random number table method.After 2 or 3 cycles of induction chemotherapy in NTP group,NTZ was sequentially used in combination with cisplatin for concurrent chemoradiotherapy.Immunohistochemistry was used to detect the EGFR expression level,exploring EGFR expression intensity and the therapeutic effect of NTZ in NTP group patients.Meanwhile,short-term efficacy,withdrawal rate and toxic side effects were compared between the two groups after induction chemotherapy.Results In NTP group,the positive expression rate of EGFR was 100％,and EGFR expression intensity significantly correlated with the efficacy of NTZ-combined induction therapy(P<0.05).After induction chemotherapy,the objective response rate(ORR)of cervical lymph nodes in NTP group was significantly higher than that in TP group(75％vs.45.8％,P=0.039).The primary lesion ORR and overall(primary lesion and cervical lymph node)ORR showed no significant difference between the two groups(P>0.05).Comparison of adverse reactions between the two groups during induction therapy:leukopenia and gastrointestinal reaction in NTP group were lower than those in TP group(P<0.05),but rash was higher than those in TP group(P<0.05).There was no significant difference in liver function,hemoglobin and thrombocytopenia between two groups(P>0.05).Conclusions EGFR expression intensity varies in nasopharyngeal carcinoma tissues,with higher levels indicating greater clinical benefit of combined induction therapy with NTZ.NTZ combined with TP induction regimen demonstrates good short-term efficacy and safety for cervical lymph nodes in patients with locally advanced nasopharyngeal carcinoma.

Objective To investigate the risk factors for bronchopulmonary dysplasia(BPD)in twin preterm infants with a gestational age of<34 weeks,and to provide a basis for early identification of BPD in twin preterm infants in clinical practice.Methods A retrospective analysis was performed for the twin preterm infants with a gestational age of<34 weeks who were admitted to 22 hospitals nationwide from January 2018 to December 2020.According to their conditions,they were divided into group A(both twins had BPD),group B(only one twin had BPD),and group C(neither twin had BPD).The risk factors for BPD in twin preterm infants were analyzed.Further analysis was conducted on group B to investigate the postnatal risk factors for BPD within twins.Results A total of 904 pairs of twins with a gestational age of<34 weeks were included in this study.The multivariate logistic regression analysis showed that compared with group C,birth weight discordance of>25%between the twins was an independent risk factor for BPD in one of the twins(OR=3.370,95%CI:1.500-7.568,P<0.05),and high gestational age at birth was a protective factor against BPD(P<0.05).The conditional logistic regression analysis of group B showed that small-for-gestational-age(SGA)birth was an independent risk factor for BPD in individual twins(OR=5.017,95%CI:1.040-24.190,P<0.05).Conclusions The development of BPD in twin preterm infants is associated with gestational age,birth weight discordance between the twins,and SGA birth.

Objective To explore feasibility of 3D metal printing technology combined with virtual design proximal clavicle anatomical plate.Methods A 52-year-old male healthy volunteer was retrospectively selected to design proximal clavicle anatomical plate system by using Mimics15.01,NX12.0 and other software.STL data were input into 3D printer to print 1∶1 clavicle model and proximal clavicle anatomical plate.The fit of the plate was tested in vitro and the accuracy of screw position was evaluated by imaging.Printing time of model,nail path design and fabrication time of the anatomical plate at proximal clavicle were recorded.Results The 3D metal printing proximal clavicle anatomical plate fitted well to clavicle model,orienta-tion of proximal clavicle locking screw was accurate,and X-ray and CT scan showed the screw position was good.Printing time of model,the time of nail path design,and the time of making anatomical plate of proximal clavicle were 120,15 and 300 min respectively.Conclusion The proximal clavicular anatomical plate system based on 3D metal printing technology could achieve good lamination of proximal clavicular fracture plate and precise screw placement,providing a new and accurate surgical method for the treatment of the proximal clavicular fracture.