ObjectiveTo investigate the effects of artemisinin （ART） on histopathological damage and salivary secretion in the submandibular gland （SMG） of mice with Sjögren's syndrome （SS） model，and on the expression of aquaporin 5 （AQP5） in SMG cells. MethodsThe NOD/Ltj mice were used as a model of SS and randomly divided into the SS model group，the ART group，and the hydroxychloroquine sulfate （HCQ） group，with six mice per group. Another 6 female BALB/c mice at the same week were selected as the control group. Mice in the ART group was fed with the ART solution daily in the dosage of 50 mg·kg^-1，and mice in the HCQ group was given with the HCQ solution （1 300 mg·kg^-1）. Mice in the SS model and control groups were given saline daily. The treatment lasted for 8 weeks. The 24-hour average water intake，salivary flow rate，SMG pathology scores of mice in each group were measured，as well as the expression levels of AQP5 protein and gene in the SMG tissues. ResultsCompared with the control group，the 24-hour average water intake of mice in the model group was significantly increased （P<0.01），and the saliva flow rate was significantly decreased （P<0.01）. Compared to the SS model group，the 24-hour average water intake of mice in the ART and HCQ groups was significantly reduced （P<0.01），and the salivary flow rate was significantly increased in the ART group（P<0.01），comparisons between groups showed that the ART was superior to the HCQ in reducing water intake and improving saliva flow rate in SS model mice （P<0.05）. The HE staining results showed that，compared with the normal group，the number of lymphocyte infiltration foci in SMG tissue in the model group increased，and the pathological score increased （P<0.01）. Compared to the SS model group，after the intervention of the ART and HCQ，the number of lymphocytic infiltration foci in the SMG tissue decreased，the area of the lymphocytic infiltration foci was reduced，and the pathology score of the SMG tissues was lowered in the ART group（P<0.01）. However，there was no difference in pathological scores between the ART and HCQ groups . The results of IHC，Western blot，and Real-time PCR showed that，compared with the normal group，the expression levels of AQP5 protein and gene in SMG tissue in the model group significantly decreased （P<0.05）. Comparing with the SS model group，the ART and HCQ groups could significantly up-regulated the expression levels of AQP5 protein and mRNA in the SMG tissue，and the treatment effect was better than that of HCQ. ConclusionART was able to ameliorate SMG structural damage and salivary secretion function in SS model mice，and its mechanism of action may be related to the up-regulation of AQP5 protein and gene expression levels in SMG cells.

BACKGROUND:Human periodontal stem cells have a certain inhibitory effect on the pro-inflammatory function of M1-type macrophages,and it is not clear whether icariin,which has anti-inflammatory and other pharmacological activities,can enhance the inhibitory effect of human periodontal stem cells on M1-type macrophages. OBJECTIVE:To investigate the effect of icariin on M1 macrophages after pretreatment of human periodontal stem cells. METHODS:Primary human periodontal stem cells were isolated,cultured and characterized.THP-1 was induced and M1-type macrophages were identified by immunofluorescence staining and PCR.Human periodontal stem cells were cultured with α-MEM complete medium containing concentrations of 10-7,10-6,10-5,and 10-4 mol/L icariin,and the cytotoxicity of Icariin on human periodontal stem cells was detected by the CCK-8 assay at 1,3,5,and 7 days,respectively.α-MEM complete medium,untreated α-MEM conditioned medium for human periodontal stem cells and α-MEM conditioned medium for human periodontal stem cells pretreated with icariin for 24 hours were conditioned with RPMI-1640 complete medium in a 1:1 ratio for M1-type macrophages in the control,untreated,and pretreated groups,and 24 hours later,the mRNA expression of inflammatory factors in M1 macrophages was detected by RT-PCR.The protein expression of inflammatory factors in M1 macrophages was detected by ELISA.The expression of surface markers and nuclear factor-κB pathway-related proteins in M1/M2 macrophages was detected by western blot assay. RESULTS AND CONCLUSION:(1)CCK-8 assay results showed that 10-7,10-6,10-5,10-4 mol/L icariin was not cytotoxic to the human periodontal stem cells,and from day 5 onwards,all the concentrations increased the cell viability,and promoted the cell proliferation.10-4 mol/L icariin was selected for follow-up experiment.(2)RT-PCR and ELISA results showed that compared with the control group,the untreated group and the pretreated group both decreased the expression and secretion of interleukin-1β,interleukin-6,and tumor necrosis factor-α of M1-type macrophages(P<0.05),and the pretreated group was lower than the untreated group(P<0.05).(3)Western blot assay results showed that compared with the untreated group,the expression of CD86 was significantly lower in the pretreated group(P<0.05);compared with the control group,the expression of CD206,a surface marker of M2-type macrophages,was elevated in both the untreated and pretreated groups(P<0.01),and it was significantly higher in the pretreated group than in the untreated group(P<0.01).In M1-type macrophages after 24 hours of conditioned culture,compared with the control group,the expression of nuclear factor-κB/P65 was decreased in the untreated group and the pretreated group(P<0.01),and the expression of p-IκBα was decreased only in the pretreated group(P<0.01);the expression of both nuclear factor-κB/P65 and p-IκBα was significantly reduced in the pretreated group compared with the untreated group(P<0.05),while the difference of IκBα in the three groups was not statistically significant.(4)These results indicated that icariin enhanced the inhibitory effect of human periodontal stem cells on M1-type macrophages,and this effect may be related to the inhibition of the nuclear factor-κB signaling pathway of macrophages.

ObjectiveTo explore effect of Xianlian Jiedu prescription on the recurrence of colorectal cancer （CRC） and investigate the related mechanisms. MethodsA postoperative recurrence model was established in 25 Balb/c mice by injecting CT26 cells subcutaneously into the armpit， followed by surgical removal of 99% of the subcutaneous tumor. The mice were randomly divided into model group， low-dose Xianlian Jiedu prescription （XLJDP-L） group （6.45 g·kg^-1·d^-1）， medium-dose Xianlian Jiedu prescription （XLJDP-M） group （12.9 g·kg^-1·d^-1）， high-dose Xianlian Jiedu prescription （XLJDP-H） group （25.8 g·kg^-1·d^-1）， and 5-fluorouracil （5-FU） group （1×10^-3 g·kg^-1·d^-1）. The mice were euthanized after 14 days of continuous intervention， and recurrent tumor tissue was harvested. Hematoxylin and eosin （HE） staining was used to observe pathological and morphological changes in the recurrent tumor tissue. Immunohistochemistry （IHC） was employed to assess the expression of proliferating cell nuclear antigen （Ki67）， vascular endothelial growth factor （VEGF）， and platelet-endothelial cell adhesion molecule （CD31） in recurrent tumor tissue. The Western blot was used to detect the protein expression levels of angiopoietin-2 （ANG-2）， VEGF， phosphorylated-protein kinase B （p-Akt）， protein kinase B （Akt）， phosphorylated-phosphatidylinositol 3-kinase （p-PI3K）， and phosphatidylinositol 3-kinase （PI3K） in recurrent tumor tissue. ResultsBefore treatment， there were no statistical differences in tumor volume， tumor weight， and body mass among the XLJDP-L， XLJDP-M， and XLJDP-H groups and the 5-FU group compared to the model group， indicating model stability. After treatment， compared with those in the model group， the tumor volume and tumor weight in the XLJDP-L， XLJDP-M， and XLJDP-H groups and the 5-FU group were significantly reduced （P<0.01）， showing dose dependency. Meanwhile， there were no significant differences in body weight among the XLJDP-L， XLJDP-M， and XLJDP-H groups and the 5-FU group compared to the model group. HE staining showed that compared with that in the model group， tumor tissue in the XLJDP-L， XLJDP-M， and XLJDP-H groups and the 5-FU group had loosely arranged cells， increased intercellular spaces， small and shriveled nuclei， light staining， fewer mitotic figures and atypical nuclei， and increased necrotic areas. IHC showed that compared with those of the model group， the positive rates of Ki67， VEGF， and CD31 in the recurrent tumor tissue of the XLJDP-L， XLJDP-M， and XLJDP-H groups and the 5-FU group were significantly reduced （P<0.01） in a dose-dependent manner. Western blot results showed that compared with those of the model group， the protein expression levels of ANG-2 and VEGF in the recurrent tumor tissue of the XLJDP-L， XLJDP-M， and XLJDP-H groups and the 5-FU group were significantly downregulated （P<0.05， P<0.01）， and the p-Akt/Akt and p-PI3K/PI3K ratios were significantly decreased in a dose-dependent manner （P<0.05， P<0.01）. ConclusionXianlian Jiedu prescription significantly inhibits the recurrence of CRC in mice after subcutaneous tumor surgery. The mechanism may involve regulating the PI3K/Akt pathway and downregulating key angiogenic proteins such as ANG-2， VEGF， and CD31.

Pyroptosis is the programmed death of cells accompanied by an inflammatory response and is widely involved in the development of a variety of diseases, such as infectious diseases, cardiovascular diseases, and neurodegeneration. It has been shown that cellular scorching is involved in the pathogenesis of pulmonary arterial hypertension ( PAH) in cardiovascular diseases. Patients with PAH have perivascular inflammatory infiltrates in lungs, pulmonary vasculopathy exists in an extremely inflam-matory microenvironment, and pro-inflammatory factors in cellular scorching drive pulmonary vascular remodelling in PAH patients. This article reviews the role of cellular scorch in the pathogenesis of PAH and the related research on drugs for the treatment of PAH, with the aim of providing new ideas for clinical treatment of PAH.

Objective To comprehensively excavate and analyze the research status,research hotspots and future trends of the literature related to the field of acupoint catgut embedding therapy for pain treatment in the CNKI database.Methods We searched the CNKI database from its establishment to June 2022,and scientifically analyzed the authors,keywords,and institutions of the included literature of acupoint catgut embedding therapy for pain treatment through specific algorithms of Citespace to generate a visual knowledge map.Results A total of 319 documents were included for statistical analysis,the number of publications in the field of acupoint catgut embedding therapy for the treatment of pain was generally on the rise,the number of publications by various authors was on the low side,and there was a lack of co-operation between the research teams,with the main institutions being the Guang'anmen Hospital,Chinese Academy of Chinese Medical Sciences,Affiliated Hospital of Youjiang Medical Universities of Nationalities and the Guangzhou University of Chinese Medicine,forming a 10-keyword clustering,and the hotspots of diseases under study were mainly mixed haemorrhoids,postoperative pain,low back and leg pain and dysmenorrhoea,etc..The main interventions were pure acupoint catgut embedding therapy and the combination of acupoint catgut embedding therapy and other acupuncture therapies,and the main research method was clinical research.Conclusion Acupoint catgut embedding therapy for the treatment of pain has a good development prospect,the future needs to deepen the clinical research,strengthen the mechanism research,pay attention to the joint use of acupoint catgut embedding therapy and other traditional Chinese medicine methods,and pay attention to the research of different thread materials.

Objective To compare the value of the 2018 Chinese guideline prognostic score with that of the 2019 European Society of Cardiology(ESC)in the predicting efficiency for acute pulmonary embolism(APE)in 30-day all-cause mortality.Methods The data of the hospitalized patients with confirmed APE from January 2015 to December 2019 were retrospectively collected.According to death within 30 days,the patients were divided into a death group and a survival group.Subgroup analysis was performed according to gender,oxygen saturation and infection.The SPSS software was used to establish the receiver operating characteristic curve(ROC)for the two scores and calculated the area under the curve(AUC).The Delong's test was applied to compare the AUC differences.The net reclassification index(NRI)and integrated discrimination improvement(IDI)were calculated using the R software packages of survival,survIDINRI,and PredictABEL.Results 626 APE patients were enrolled,and 30-day death was predicted in those patients using two scores.In terms of overall discrimination,the 2018 Chinese guideline prognostic score was better than the 2019 ESC guideline prognostic score,with an AUC of 0.782 and 0.749,respectively;but there were no statistical differences between the two AUC(P＞0.05).In terms of prediction accuracy,the NRI of the 2019 ESC guideline prognostic score was 44.4%(95%CI:0.091～0.753),higher than that of the 2018 Chinese guidelines prognostic score,which increased by 58.6%(95%CI:0.161～0.917)in the correct reclassification to death group,while decreased by 14.2%(95%CI:-0.249～0.08)in the correct reclassification to survival group.IDI increased by 3.38%(P＜0.05).Subgroup analysis showed the prognostic scores of the 2018 Chinese guidelines and the 2019 ESC guidelines prognostic scores had predictive ability for patients with different gender and different oxygen saturation(P＜0.05),and the prognostic scores for co-infected population(AUC:0.749,0.772)(P＞0.05),non-coinfected population(AUC:0.652,0.833).Conclusions Both the 2018 Chinese guideline prognostic score and the 2019 ESC guideline prognostic score can predict 30-day mortality in APE patients,and have a better predictive ability for the co-infected population.However,the predictive accuracy of the former is higher than that of the latter in the survival group,and the score is more rapid and convenient for clinical application,while the latter has improved the prediction ability in the death group.

This article presents a case of acute ST-segment elevation myocardial infarction (STEMI) in a pregnant woman caused by coronary artery dissection. The 41-year-old patient had undergone cardiac valve surgery at the age of 1 and had no risk factors such as hypertension, diabetes, smoking, alcohol use, or a family history of coronary artery disease. At 31 +1 weeks of gestation, she experienced sudden chest pain for 4 hours and was emergently referred to Peking University First Hospital on June 1, 2021. Electrocardiogram revealed ST-segment elevation in leads I, aVL, and V 2 to V 6. Biochemical assays showed elevated levels of high-sensitivity cardiac troponin I and creatine kinase-MB. Echocardiography indicated segmental ventricular wall motion abnormalities (apical) and reduced left ventricular function, confirming the diagnosis of acute anterior wall STEMI. The patient promptly underwent emergency coronary angiography and percutaneous coronary intervention and confirmed coronary artery dissection. Postoperative care included antiplatelet, anticoagulation, and supportive treatment. At 34 +3 weeks of gestation, with the condition of acute anterior wall STEMI being relatively stable, a cesarean section was successfully performed. Regular cardiology follow-ups were scheduled postpartum, and cardiac function was normal in two years after discharge.

Objective To explore the effects of modulating the Hippo-YAP/TAZ pathway using Huashi Runzao Prescription(HRP)on the apoptosis and salivary secretion function of submandibular gland cells in a naive non-obese diabetic(NOD/Ltj)mouse model of Sj?gren's syndrome(SS).Methods Eight-week-old female BALB/c mice were selected as the blank group.Eight-week-old female NOD/Ltj were randomly divided into the model,HRP-L,HRP-M,HRP-H,and hydroxychloroquine sulphate(HCQ)groups.After eight weeks of drug administration,the water consumption and salivary flow rate of each group were recorded.The histopathological damage of the submandibular gland in each group was determined using hematoxylin and eosin staining,the apoptosis rate of the submandibular gland was determined using TUNEL staining,and AQP5,Bax,Bcl-2,beclin-1,YAP,p-YAP,and TAZ expressions in submandibular gland tissues were determined using immunohistochemistry and Western blotting.Results Compared with the blank group,the Hippo-YAP/TAZ pathway was inhibited in the submandibular gland tissues of the model group,lymphocyte infiltration increased,water consumption increased,salivary flow rate decreased,AQP5 expression decreased,and submandibular gland cells apoptosis rate increased(P<0.05).Compared with all other administered groups,in the HRP-M group,the Hippo-YAZ/TAZ pathway was significantly activated,lymphocyte infiltration in submandibular gland tissues was reduced,water consumption was reduced,the salivary flow rate and AQP5 expression were increased,and the apoptosis rate of submandibular gland cells was reduced(P<0.05).Conclusion HRP reduced the pathological damage and apoptosis of submandibular gland cells in SS model mice.It improved the overall secretory function of submandibular gland tissues,which may be related to Hippo pathway activation and downregulating YAP/TAZ expression.

Objective To explore the effects of modulating the Hippo-YAP/TAZ pathway using Huashi Runzao Prescription(HRP)on the apoptosis and salivary secretion function of submandibular gland cells in a naive non-obese diabetic(NOD/Ltj)mouse model of Sj?gren's syndrome(SS).Methods Eight-week-old female BALB/c mice were selected as the blank group.Eight-week-old female NOD/Ltj were randomly divided into the model,HRP-L,HRP-M,HRP-H,and hydroxychloroquine sulphate(HCQ)groups.After eight weeks of drug administration,the water consumption and salivary flow rate of each group were recorded.The histopathological damage of the submandibular gland in each group was determined using hematoxylin and eosin staining,the apoptosis rate of the submandibular gland was determined using TUNEL staining,and AQP5,Bax,Bcl-2,beclin-1,YAP,p-YAP,and TAZ expressions in submandibular gland tissues were determined using immunohistochemistry and Western blotting.Results Compared with the blank group,the Hippo-YAP/TAZ pathway was inhibited in the submandibular gland tissues of the model group,lymphocyte infiltration increased,water consumption increased,salivary flow rate decreased,AQP5 expression decreased,and submandibular gland cells apoptosis rate increased(P<0.05).Compared with all other administered groups,in the HRP-M group,the Hippo-YAZ/TAZ pathway was significantly activated,lymphocyte infiltration in submandibular gland tissues was reduced,water consumption was reduced,the salivary flow rate and AQP5 expression were increased,and the apoptosis rate of submandibular gland cells was reduced(P<0.05).Conclusion HRP reduced the pathological damage and apoptosis of submandibular gland cells in SS model mice.It improved the overall secretory function of submandibular gland tissues,which may be related to Hippo pathway activation and downregulating YAP/TAZ expression.

Objective To investigate changes in the urinary metabolite profiles of children exposed to polycyclic aromatic hydrocarbons(PAHs)during critical brain development and explore their potential link with the intestinal microbiota. Methods Liquid chromatography-tandem mass spectrometry was used to determine ten hydroxyl metabolites of PAHs(OH-PAHs)in 36-month-old children.Subsequently,37 children were categorized into low-and high-exposure groups based on the sum of the ten OH-PAHs.Ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry was used to identify non-targeted metabolites in the urine samples.Furthermore,fecal flora abundance was assessed by 16S rRNA gene sequencing using Illumina MiSeq. Results The concentrations of 21 metabolites were significantly higher in the high exposure group than in the low exposure group(variable importance for projection>1,P<0.05).Most of these metabolites were positively correlated with the hydroxyl metabolites of naphthalene,fluorine,and phenanthrene(r=0.336-0.531).The identified differential metabolites primarily belonged to pathways associated with inflammation or proinflammatory states,including amino acid,lipid,and nucleotide metabolism.Additionally,these distinct metabolites were significantly associated with specific intestinal flora abundances(r=0.34-0.55),which were mainly involved in neurodevelopment. Conclusion Higher PAH exposure in young children affected metabolic homeostasis,particularly that of certain gut microbiota-derived metabolites.Further investigation is needed to explore the potential influence of PAHs on the gut microbiota and their possible association with neurodevelopmental outcomes.