ObjectiveThis study aimed to establish a monocrotaline （MCT）-induced pulmonary arterial hypertension （PAH） rat model to systematically evaluate the protective effect of Xiao Qinglongtang （XQLT） on right cardiac function in model rats and further elucidate the underlying regulatory mechanism. MethodsSixty male SD rats were randomly assigned to the normal group， model group， XQLT low-， medium-， and high-dose groups （XQLT-L/M/H）， and the beraprost sodium tablet group （BST）. Except for the normal group， rats in all other groups were given a single subcutaneous injection of MCT （60 mg·kg^-1） to induce PAH. Three weeks after injection， rats in the XQLT-L/M/H groups were administered XQLT intragastrically at 3.07， 6.14， 12.28 g·kg^-1·d^-1， respectively. Rats in the BST group received beraprost sodium at 12.6 μg·kg^-1·d^-1， and rats in the model group received an equal volume of saline. All treatments lasted for 3 weeks. Right ventricular systolic pressure （RVSP） was measured by right ventricular catheterization. Cardiac function was assessed by echocardiography. The right ventricle was weighed to calculate the right ventricular hypertrophy index （RVHI）. Hematoxylin-eosin （HE） staining， Masson staining， and transmission electron microscopy were used to observe myocardial morphology. Serum metabolomic changes were analyzed using ultra-performance liquid chromatography-tandem mass spectrometry （UPLC-MS/MS）. Data-independent acquisition （DIA） proteomics was used to detect differentially expressed （DE） proteins in the right ventricle， and Western blot was used to measure the expression of uncoupling protein 3 （UCP3）， phosphatidylinositol 3-kinase catalytic subunit p110α （PIK3CA）， L1 cell adhesion molecule （L1CAM）， and quinone oxidoreductase （CRYZ）. UPLC-MS/MS was used to analyze the chemical components of XQLT. ResultsCompared with the normal group， the model group showed significantly increased RVSP and RVHI （P<0.05）， along with pathological changes in myocardial morphology. Compared with the model group， all XQLT-treated groups exhibited reductions in RVSP and RVHI as well as significant improvements in cardiac function and myocardial morphology. Among the XQLT groups， XQLT-M showed the most pronounced effects （P<0.05）， comparable to the BST group. Serum metabolomics revealed 105 differential metabolites in the XQLT groups versus the model group ［variable importance in projection （VIP） >1， P<0.05］， including 58 upregulated and 47 downregulated metabolites. KEGG enrichment analysis indicated that XQLT intervention downregulated phenylalanine metabolism （P<0.01） and upregulated unsaturated fatty acid biosynthesis （P<0.05）. Proteomics analysis showed that 982 DE proteins were identified in the MCT groups versus the normal group， including 455 upregulated and 527 downregulated proteins （|fold change （FC）| >1.3， P<0.05）. Compared with the model group， 237 DE proteins were identified in the XQLT groups， including 124 upregulated and 113 downregulated proteins （|FC| >1.3， P<0.05）， with 57 overlapping DE proteins. KEGG enrichment suggested that XQLT mainly modulated pathways related to mineral absorption， ribosomal biogenesis， peroxisomes， glycolysis/gluconeogenesis， spliceosomes， and thyroid hormone signaling. Western blot analysis showed that， compared with the model group， XQLT increased the expression of UCP3， PIK3CA， and L1CAM， while decreasing the expression of CRYZ （P<0.05）. ConclusionXQLT exerts a protective effect on right heart function in MCT-induced PAH rats， and its mechanism is associated with maintaining myocardial homeostasis and alleviating right ventricular remodeling.

ObjectiveTo investigate whether intestinal deficiency of lanosterol synthase （LSS）， a key enzyme in cholesterol synthesis， influences the progression of metabolic dysfunction-associated steatotic liver disease （MASLD） by regulating intestinal cholesterol absorption and immune response. MethodsLSS heterozygous knockout （LSS^+/-） mice and wild-type （WT） controls were generated using CRISPR/Cas9 technology and fed either a high-fat diet （HFD） or regular chow （CHOW）. The model was validated by genotyping. Hepatic steatosis was assessed by HE and oil red O staining. Immunohistochemistry was used to detect the localization and expression of NPC1L1 and CD36 proteins in the intestine. Western blot analysis was performed to measure JNK phosphorylation and TLR4 protein levels in intestinal tissues. Real-time quantitative polymerase chain reaction （qPCR） was employed to examine the mRNA expression of TLR4 and IL-6. ResultsLSS^+/- mice were successfully validated by genotyping and reduced intestinal LSS protein expression. HE and oil red O staining of liver sections showed that， compared with WT mice fed a CHOW diet， WT mice fed a HFD exhibited a marked increase in hepatic lipid vacuoles. In contrast， compared with HFD-fed WT mice， HFD-fed LSS^+/- mice displayed significantly attenuated hepatic lipid deposition and reduced serum ALT levels （P<0.05）. Immunohistochemical analysis revealed that， compared with WT mice， the expression of the cholesterol absorption protein NPC1L1 in the intestinal villi of LSS^+/- mice was downregulated under both CHOW and HFD conditions （P_HFD<0.001）. Conversely， the expression of the fatty acid transporter CD36 was upregulated in the intestines of LSS^+/- mice （P_CHOW<0.05， P_HFD<0.01）. Western blot analysis demonstrated that， compared with WT mice， TLR4 protein expression in the intestines of LSS^+/- mice significantly increased under both CHOW and HFD conditions （both P<0.05）. JNK phosphorylation level was significantly elevated in LSS^+/- mice under CHOW condition （both P<0.05）. Under HFD condition， total JNK protein expression increased， but its phosphorylation level showed no significant change. qPCR analysis showed that， compared with WT mice， the mRNA levels of TLR4 （P_CHOW<0.01， P_HFD<0.000 1） and IL-6 （P_CHOW<0.001， P_HFD<0.01） were significantly upregulated in the intestines of LSS^+/-mice. ConclusionLSS deficiency counteracts hepatic lipid deposition by orchestrating a synergistic reprogramming involving restricted intestinal cholesterol absorption， enhanced fatty acid utilization， and activation of immune pathways， suggesting intestinal LSS as a potential therapeutic target of MASLD.

BACKGROUND:In recent years,numerous studies have shown that autophagy and mitophagy play an important role in the regulation of bone metabolism.Under non-physiological conditions,mitophagy breaks the balance of bone metabolism and triggers metabolism disorders,which affect osteoblasts,osteoclasts,osteocytes,chondrocytes,bone marrow mesenchymal stem cells,etc. OBJECTIVE:To summarize the mechanism of mitophagy in regulating bone metabolic diseases and its application in clinical treatment. METHODS:PubMed,Web of Science,CNKI,WanFang and VIP databases were searched by computer using the keywords of"mitophagy,bone metabolism,osteoblasts,osteoclasts,osteocytes,chondrocytes,bone marrow mesenchymal stem cells"in English and Chinese.The search time was from 2008 to 2023.According to the inclusion criteria,90 articles were finally included for review and analysis. RESULTS AND CONCLUSION:Mitophagy promotes the generation of osteoblasts through SIRT1,PINK1/Parkin,FOXO3 and PI3K signaling pathways,while inhibiting osteoclast function through PINK1/Parkin and SIRT1 signaling pathways.Mitophagy leads to bone loss by increasing calcium phosphate particles and tissue protein kinase K in bone tissue.Mitophagy improves the function of chondrocytes through PINK1/Parkin,PI3K/AKT/mTOR and AMPK signaling pathways.Modulation of mitophagy shows great potential in the treatment of bone diseases,but there are still some issues to be further explored,such as different stages of drug-activated mitophagy,and the regulatory mechanisms of different signaling pathways.

AIM: To explore the efficacy of 0.05% cyclosporine A combined with olopatadine eye drops in treating allergic conjunctivitis-related dry eye disease.METHODS: A total of 63 patients(63 eyes)with allergic conjunctivitis-related dry eye disease in the People's Hospital of Guangxi Zhuang Autonomous Region from August 2022 to April 2023 were enrolled and randomly divided into control group(n=33)and observation group(n=30). The patients of the control group were administrated with 0.1% olopatadine eye drops and 0.3% sodium hyaluronate eye drops, while the observation group was administrated with 0.1% olopatadine eye drops and 0.05% cyclosporine A eye drops. The ocular surface disease index(OSDI), total ocular symptom score(TOSS), conjunctival congestion score, conjunctival papillae and follicle score, Schirmer I test(SⅠt), tear meniscus height(TMH), meibomian gland secretion ability and property score, meibomian gland loss area score, corneal fluorescein staining(CFS), tear film break-up time(BUT), noninvasive first tear film break-up time(NIBUTf), noninvasive average tear film break-up time(NIBUTav)before and after treatment and the drug safety during the treatment period of both groups of patients were evaluated.RESULTS: After treatment, OSDI, TOSS, conjunctival congestion score, conjunctival papillae and follicle score, SⅠt, TMH, meibomian gland secretion ability score and property score, CFS, BUT, NIBUTf, and NIBUTav of the observation group showed improvements compared with those before treatment(all P<0.017). Among these, OSDI, TOSS, conjunctival congestion score, conjunctival papillae and follicle score, BUT, NIBUTf, and NIBUTav demonstrated significant improvement compared with the control group(all P<0.05). There was no statistically significant difference in meibomian gland loss area score between the two groups before and after treatment(P>0.05). During the treatment period, there were no local or systemic adverse reactions.CONCLUSION: The combined use of 0.05% cyclosporine A and olopatadine eye drops can significantly improve ocular discomfort symptoms of patients with dry eye disease associated with allergic conjunctivitis, such as red eyes, itchy eyes and foreign body sensation, promote tear film stability and have high safety.

Tibetan sheep,the main domestic animal raised in the Qinghai-Tibet Plateau region,are a source of human plague transmission.In the Qinghai-Tibet Plateau region,Tibetan sheep are considered valuable breeding resources,because of their large body size and high adaptability to high-altitude environments.In recent years,many pastoral areas,particularly those with marmot plague sources,have improved the structure of sheep breeds through pure breeding of Tibetan sheep or hybridization with Tibetan sheep to improve breed quality.The scale of breeding of Tibetan sheep or hybrid sheep is increasing,and their participation in the spread of plague poses a severe challenge to plague prevention and control.This article provides a comprehensive review of the current status of Tibetan sheep plague and related research progress,to provide a theoretical basis for further exploration and research on plague infection and transmission in Tibetan sheep and hybrid sheep.The findings will be critical for conducting risk assessment of Ti-betan sheep plague in marmot plague source areas,enhancing monitoring and early warning capabilities,formulating and implement-ing risk control measures,and strictly preventing the occurrence and spread of human plague.

AIM:A strain was isolated and identified as the H3N8 subtype of the avian influenza virus from a sick chicken at a farm in Yangjiang,Guangdong Province,named A/chicken/Yangjiang/552/2023(abbreviated as YJ/552).The aim of this research is to determine its genetic evolution,biological properties and pathogenicity in hamsters.This study may provide a theoretical strategy for preventing and treating the H3N8 subtype avian influenza virus-induced epidemic.METHODS:A strain of H3N8 avian influenza virus from chickens was characterised by phylogenetic analy-sis,antigenic diversity,receptor-binding specificity,neuraminidase activity,replication,and transmission in hamsters and a systematic pathological analysis was conducted.RESULTS:This novel avian influenza virus was generated through complex recombination of Eurasian avian H3 genes,North American avian N8 genes and six internal genes of H9N2 sub-type AIV.The cleavage site of the outer protein,HA,was PEKQTR↓GLF,which is characteristic of the low pathogenic avian influenza virus.The HA gene of YJ/552 exhibited the highest nucleotide homology with A/China/ZMD-22-2/2022(H3N8)at 99.09%,while the NA gene showed the highest homology with A/chicken/Dongguan/879/2022(H3N8)at 99.01%.This strain preferentially binds to avian-type receptors and could bind to human-type receptors.This virus could effectively replicate in the trachea and lungs of inoculated and contact hamsters.CONCLUSION:YJ/552 is a recombi-nant H3N8 avian influenza virus replicated in the upper respiratory system and transmitted in hamsters.This study pro-vides data support for the early warning and prevention of H3 subtype avian influenza viruses.

Autism spectrum disorder(ASD) is a neurodevelopmental disorder, and social impairment was one of the core symptoms of ASD, which can seriously affects the social life of patients.The pathogenesis of social impairment in ASD is unclear and it may involves many brain abnormalities.The related theories and hypotheses are numerous and there is no unified conclusion. Studies have shown that the cerebellum has extensive connections with brain networks and is involved in the regulation of social cognition, but its role in ASD has not been fully emphasized.The structural and functional abnormalities of the cerebellar-cortex (CC) loop in ASD patients can lead to language communication disorders, empathy disorders, difficulties in interpreting social cues, abnormal social reward processing and emotional regulation disorders, which are closely related to ASD social impairment. Noninvasive brain stimulation of the superficial cerebellum can improve the abnormal CC circuit in ASD patients, and the cerebellum can be considered as a target for the treatment of social disorders in ASD in the future.Based on the clinical and basic researches on social impairment in ASD in recent years, this article reviews the relevant manifestations of disorders which cerebellar and CC circuit involved, aiming to promote the development of related research in the future.

In order to promote the construction of a multi-point trigger intelligent surveillance and early warning system of the plague in China, the development process, application practice, advantages, and limitations of the plague surveillance and early warning system in China and its role in plague prevention and control are reviewed and analyzed. It is suggested to include multiple departments, carry out a multi-channel monitoring mechanism for plague from different perspectives, further improve the plague surveillance and early warning system, and enhance surveillance and early warning capability.

Objective To explore the value of MRI radiomics based on the frontal and temporal lobes combined with multiple machine learning algorithms in the diagnosis of mild cognitive impairment(MCI).Methods Patients who underwent cranial MR examination were retrospectively selected.According to the inclusion and exclusion criteria,a total of 173 subjects were finally included and randomly divided into training set and test set in a ratio of 7∶3.After delineating the regions of interest(ROI)of the frontal and temporal lobes on T2-fluid attenuated inversion recovery(FLAIR)images,radiomics features were extracted based on the Pyradiomics data package.Features were screened through inter-and intraclass correlation coefficient(ICC),independent samples t-test,and the LightGBM algorithm.Diagnostic models were constructed using support vector machine(SVM),random forest(RF),decision tree(DT),K-nearest neighbor(KNN),gradient boosting decision tree(GBDT),and extreme gradient boosting(XGBoost)combined with 10-fold cross-validation respectively.The training set was further divided into 9 training data sets and 1 validation data set through 10-fold cross-validation,and the hyperparameters were optimized through iterative cycles.The diagnostic efficacy of the model was evaluated by receiver operating characteristic(ROC)curve and area under the curve(AUC),and the DeLong test was applied to compare the differences between different models.Results The AUC of the radiomics models constructed by SVM,DT,RF,KNN,GBDT,XGBoost in the training set were 0.951,0.992,0.998,0.957,1.000,and 1.000 respectively,in the validation set were 0.890,0.843,0.934,0.878,0.930,and 0.945 respectively,and in the test set were 0.902,0.711,0.899,0.849,0.889,and 0.882 respectively.Conclusion MRI radiomics based on the frontal and temporal lobes combined with multiple machine learning algorithms can diagnose MCI,and the model constructed based on SVM shows the highest diagnostic value.

Tibetan sheep,the main domestic animal raised in the Qinghai-Tibet Plateau region,are a source of human plague transmission.In the Qinghai-Tibet Plateau region,Tibetan sheep are considered valuable breeding resources,because of their large body size and high adaptability to high-altitude environments.In recent years,many pastoral areas,particularly those with marmot plague sources,have improved the structure of sheep breeds through pure breeding of Tibetan sheep or hybridization with Tibetan sheep to improve breed quality.The scale of breeding of Tibetan sheep or hybrid sheep is increasing,and their participation in the spread of plague poses a severe challenge to plague prevention and control.This article provides a comprehensive review of the current status of Tibetan sheep plague and related research progress,to provide a theoretical basis for further exploration and research on plague infection and transmission in Tibetan sheep and hybrid sheep.The findings will be critical for conducting risk assessment of Ti-betan sheep plague in marmot plague source areas,enhancing monitoring and early warning capabilities,formulating and implement-ing risk control measures,and strictly preventing the occurrence and spread of human plague.