ObjectiveTo explore the effects of Renshentang on atherosclerosis （AS） in mice based on the role of transient receptor potential vanilloid1 （TRPV1） in regulating cholesterol metabolism in foam cells. MethodsNine SPF-grade 8-week-old C57BL/6J mice were set as a normal group， and 60 ApoE^-/- mice were randomized into model， positive drug （simvastatin， 0.02 g·kg^-1·d^-1）， and low-， medium-， and high-dose （1.77， 3.54， 7.08 g·kg^-1·d^-1， respectively） Renshentang groups （n=12） according to body weight. The normal group was fed with a normal diet， and the other groups were fed with a high-fat diet and given corresponding drugs by oral gavage for the modeling of AS. The mice were administrated with corresponding drugs once a day for 12 weeks. After the last administration and fasting for 12 h， the aorta was collected. Plaque conditions， pathological changes， levels of total cholesterol （TC）， triglcerides （TG）， low-density lipoprotein-cholesterol （LDL-C）， and high-density lipoprotein-cholesterol （HDL-C）， and the expression of TRPV1， liver X receptor （LXR）， inducible degrader of the low-density lipoprotein receptor （IDOL）， and low-density lipoprotein receptor （LDLR） in the aortic tissue were observed and detected by gross oil red O staining， HE staining， Western blot， immunohistochemistry， and real-time PCR. ResultsCompared with the normal group， the model group presented obvious plaque deposition in the aorta， raised levels of TC， TG， and LDL-C in the serum （P<0.01）， up-regulated expression level of LDLR in the aorta （P<0.01）， lowered level of HDL-C in the serum， and down-regulated expression levels of TRPV1， LXR， and IDOL in the aorta （P<0.05， P<0.01）. Compared with the model group， the positive drug and Renshentang at different doses alleviated AS， elevated the levels of HDL-C， TRPV1， LXR， and IDOL （P<0.05， P<0.01）， while lowering the levels of TC， TG， LDL-C， and LDLR （P<0.05， P<0.01）. ConclusionRenshentang has a lipid-lowering effect on AS mice. It can effectively reduce lipid deposition， lipid levels， and plaque area of AS mice by activating TRPV1 expression and regulating the LXR/IDOL/LDLR pathway.

ObjectiveTo explore the effects of Renshentang on atherosclerosis （AS） in mice based on the role of transient receptor potential vanilloid1 （TRPV1） in regulating cholesterol metabolism in foam cells. MethodsNine SPF-grade 8-week-old C57BL/6J mice were set as a normal group， and 60 ApoE^-/- mice were randomized into model， positive drug （simvastatin， 0.02 g·kg^-1·d^-1）， and low-， medium-， and high-dose （1.77， 3.54， 7.08 g·kg^-1·d^-1， respectively） Renshentang groups （n=12） according to body weight. The normal group was fed with a normal diet， and the other groups were fed with a high-fat diet and given corresponding drugs by oral gavage for the modeling of AS. The mice were administrated with corresponding drugs once a day for 12 weeks. After the last administration and fasting for 12 h， the aorta was collected. Plaque conditions， pathological changes， levels of total cholesterol （TC）， triglcerides （TG）， low-density lipoprotein-cholesterol （LDL-C）， and high-density lipoprotein-cholesterol （HDL-C）， and the expression of TRPV1， liver X receptor （LXR）， inducible degrader of the low-density lipoprotein receptor （IDOL）， and low-density lipoprotein receptor （LDLR） in the aortic tissue were observed and detected by gross oil red O staining， HE staining， Western blot， immunohistochemistry， and real-time PCR. ResultsCompared with the normal group， the model group presented obvious plaque deposition in the aorta， raised levels of TC， TG， and LDL-C in the serum （P<0.01）， up-regulated expression level of LDLR in the aorta （P<0.01）， lowered level of HDL-C in the serum， and down-regulated expression levels of TRPV1， LXR， and IDOL in the aorta （P<0.05， P<0.01）. Compared with the model group， the positive drug and Renshentang at different doses alleviated AS， elevated the levels of HDL-C， TRPV1， LXR， and IDOL （P<0.05， P<0.01）， while lowering the levels of TC， TG， LDL-C， and LDLR （P<0.05， P<0.01）. ConclusionRenshentang has a lipid-lowering effect on AS mice. It can effectively reduce lipid deposition， lipid levels， and plaque area of AS mice by activating TRPV1 expression and regulating the LXR/IDOL/LDLR pathway.

Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T _NANC), time to symptom improvement (T _SI), and time of hospital stay (T _HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T _NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.

OBJECTIVE: To investigate the mechanism of human embryonic stem cell-derived mesenchymal stem cells (hESC-MSC) in alleviating brain injury after resuscitation in swine with cardiac arrest (CA). METHODS: Twenty-nine healthy male large white swine were randomly divided into Sham group (n = 9), cardiopulmonary resuscitation (CPR) group (n = 10) and hESC-MSC group (n = 10). The Sham group only completed animal preparation. In CPR group and hESC-MSC group, the swine model of CA-CPR was established by inducing ventricular fibrillation for 10 minutes with electrical stimulation and CPR for 6 minutes. At 5 minutes after successful resuscitation, hESC-MSC 2.5×10⁶/kg was injected via intravenous micropump within 1 hour in hESC-MSC group. Venous blood samples were collected before resuscitation and at 4, 8, 24, 48 and 72 hours of resuscitation. The levels of neuron specific enolase (NSE) and S100B protein (S100B) were detected by enzyme linked immunosorbent assay (ELISA). At 24, 48 and 72 hours of resuscitation, neurological deficit score (NDS) and cerebral performance category (CPC) were used to evaluate the neurological function of the animals. Three animals from each group were randomly selected and euthanized at 24, 48, and 72 hours of resuscitation, and the hippocampus tissues were quickly obtained. Immunofluorescence staining was used to detect the distribution of hESC-MSC in hippocampus. Immunohistochemical staining was used to detect the activation of astrocytes and microglia and the survival of neurons in the hippocampus. The degree of apoptosis was detected by TdT-mediated dUTP nick end labeling (TUNEL). RESULTS: The serum NSE and S100B levels of brain injury markers in CPR group and hESC-MSC group were significantly higher than those in Sham group at 24 hours of resuscitation, and then gradually increased. The levels of NSE and S100B in serum at each time of resuscitation in hESC-MSC group were significantly lower than those in CPR group [NSE (μg/L): 20.69±3.62 vs. 28.95±3.48 at 4 hours, 27.04±5.56 vs. 48.59±9.22 at 72 hours; S100B (μg/L): 2.29±0.39 vs. 3.60±0.73 at 4 hours, 2.38±0.15 vs. 3.92±0.50 at 72 hours, all P < 0.05]. In terms of neurological function, compared with the Sham group, the NDS score and CPC score in the CPR group and hESC-MSC group increased significantly at 24 hours of resuscitation, and then gradually decreased. The NDS and CPC scores of hESC-MSC group were significantly lower than those of CPR group at 24 hours of resuscitation (NDS: 111.67±20.21 vs. 170.00±21.79, CPC: 2.33±0.29 vs. 3.00±0.00, both P < 0.05). The expression of hESC-MSC positive markers CD73, CD90 and CD105 in the hippocampus of hESC-MSC group at 24, 48 and 72 hours of resuscitation was observed under fluorescence microscope, indicating that hESC-MSC could homing to the damaged hippocampus. In addition, compared with Sham group, the proportion of astrocytes, microglia and apoptotic index in hippocampus of CPR group were significantly increased, and the proportion of neurons was significantly decreased at 24, 48 and 72 hours of resuscitation. Compared with CPR group, the proportion of astrocytes, microglia and apoptotic index in hippocampus of hESC-MSC group decreased and the proportion of neurons increased significantly at 24 hours of resuscitation [proportion of astrocytes: (14.33±1.00)% vs. (30.78±2.69)%, proportion of microglia: (12.00±0.88)% vs. (27.89±5.68)%, apoptotic index: (12.89±3.86)% vs. (52.33±7.77)%, proportion of neurons: (39.44±3.72)% vs. (28.33±1.53)%, all P < 0.05]. CONCLUSIONS Application of hESC-MSC at the early stage of resuscitation can reduce the brain injury and neurological dysfunction after resuscitation in swine with CA. The mechanism may be related to the inhibition of immune cell activation, reduction of cell apoptosis and promotion of neuronal survival.
Animals ; Heart Arrest/therapy* ; Cardiopulmonary Resuscitation ; Swine ; Humans ; Male ; Human Embryonic Stem Cells/cytology* ; Mesenchymal Stem Cell Transplantation ; Mesenchymal Stem Cells/cytology* ; Phosphopyruvate Hydratase/blood* ; Brain Injuries/therapy* ; S100 Calcium Binding Protein beta Subunit ; Apoptosis ; Disease Models, Animal

ObjectiveTo explore the effect and mechanism of Zhishi Xiebai Guizhitang on the progression of atherosclerosis （AS） mice based on the regulation of cholesterol metabolism in foam cells by transient receptor potential channel ankyrin 1 （TRPA1）. MethodThe AS model was established on apolipoprotein E knockout （ApoE^-/-） mice with a high-fat diet. The mice were randomly divided into low-dose， middle-dose， and high-dose groups of Zhishi Xiebai Guizhitang （2.97， 5.94， 11.88 g·kg^-1） and simvastatin group （0.002 g·kg^-1）， and the drug was administered along with a high-fat diet. C57BL/6J mice were fed an ordinary diet as a normal group. After the above process， the aorta and serum of mice were taken. The pathological changes of the aortic root were observed by hematoxylin-eosin （HE） staining. The lipid plaques in the aorta were observed by gross oil redness. Serum levels of total cholesterol （TC）， triglyceride （TG）， low density lipoprotein cholesterol （LDL-C）， and high density lipoprotein cholesterol （HDL-C） were detected， and the levels of interleukin-1β （IL-1β） and interleukin-18 （IL-18） were detected by enzyme-linked immunosorbent assay （ELISA）. Western blot and immunohistochemical method were used to analyze the expression of TRPA1， ATP-binding cassette transporter A1 （ABCA1）， ATP-binding cassette transporter G1 （ABCG1）， and mannose receptor （CD206）. ResultFrom the perspective of drug efficacy， compared with the normal group， pathological changes such as plaque， a large number of foam cells， and cholesterol crystals appeared in the aorta of the model group， and the serum levels of TC， LDL-C， IL-1β， and IL-18 were significantly increased （P<0.01）. The HDL-C level was significantly decreased （P<0.01）， and the CD206 level in aortic tissue was significantly decreased （P<0.01）. Compared with the model group， the lipid deposition in the aorta was alleviated in all drug administration groups. In addition， except for the high-dose group of Zhishi Xiebai Guizhitang， all drug administration groups could significantly decrease the levels of TC and LDL-C （P<0.01）. In terms of inflammation， except for the middle-dose group of Zhishi Xiebai Guizhitang， the levels of IL-1β and IL-18 were significantly decreased in all drug administration groups （P<0.05）. Moreover， Zhishi Xiebai Guizhitang could also up-regulate the levels of CD206， and the difference was significant in the middle-dose and high-dose groups （P<0.05）. From the perspective of mechanism， the expression levels of TRPA1， ABCA1， and ABCG1 in the aorta in the model group were lower than those in the normal group （P<0.05）. Compared with the model group， all drug administration groups significantly increased the expression of TRPA1 in the aorta （P<0.05）， and the expressions of ABCA1 and ABCG1 were increased. The differences in the middle-dose and high-dose groups and the simvastatin group were significant （P<0.05）， which was basically consistent with the trend of immunohistochemical results. ConclusionZhishi Xiebai Guizhitang can effectively reduce blood lipid and inflammation levels and inhibit the formation of aortic plaque. The mechanism may be explained as follows： the expressions of ABCA1 and ABCG1 downstream are increased through TRPA1， which promotes cholesterol outflow in foam cells， thereby regulating cholesterol metabolism， intervening in inflammation level to a certain extent， and finally treating AS.

Objective:To discuss the effect of human umbilical cord mesenchymal stem cells culture supernatant(hUCMSCs-Sup)on the proliferation,apoptosis,and endometrium receptivity of the human endometrial stromal cells(hEndoSCs)treated with mifepristone(Ms),and to clarify the possible mechanism.Methods:The hEndoSCs were cultured in vitro and divided into control group and 40,60,80,and 100 μmol·L-1 Ms groups.The survival rates of the cells in various groups were detected by MTT assay.The hEndoSCs were divided into control group,40 μmol·L-1 Ms group,and 60 μmol·L-1 Ms group.The apoptotic rates of the cells in various groups were detected by flow cytometry;the expression levels of apoptosis-related protein B-cell lymphoma-2(Bcl-2)and Bcl-2-associated X protein(Bax)proteins in the cells in various groups were detected by Western blotting method,and the ratio of Bcl-2/Bax was calculated.After treated with hUCMSCs-Sup,the hEndoSCs were divided into control group,Ms group,Ms+hUCMSCs-Sup group,and Ms+hUCMSCs-Sup+3-methyladenine(3-MA)group.The survival rates of the cells in various groups were detected by MTT assay;the apoptotic rates of the cells in various groups were detected by flow cytometry;the expression levels of microtubule-associated protein 1 light chain 3B-Ⅱ(LC3B-Ⅱ)and microtubule-associated protein 1 light chain 3B-I(LC3B-Ⅰ)proteins in the cells in various groups were detected by Western blotting method,and the ratio of LC3B-Ⅱ/LC3B-Ⅰwas calculated;the expression levels of endometrium receptivity marker molecules mRNA in the cells in various groups were detected by real-time fluorescence quantitative PCR(RT-qPCR)method.Results:Compared with control group,the survival rates of the cells in 40,60,80,and 100 μmol·L-1 Ms groups were significantly decreased(P<0.05)in a time-dependent and dose-dependent manner.Compared with control group,the apoptotic rates of the cells in 40 and 60 μmol·L-1 Ms groups were significantly increased(P<0.05),and the ratios of Bcl-2/Bax were significantly decreased(P<0.05).After treated with hUCMSCs-Sup,compared with control group,the survival rate of the cells and ratio of LC3B-Ⅱ/LC3B-Ⅰ in the cells in Ms group were significantly decreased(P<0.05),the apoptotic rate was significantly increased(P<0.05),and the expression levels of homeobox A10(HOXA10),leukemia inhibitory factor(LIF),and integrin subunit beta 3(ITGB3)mRNA in the cells were significantly decreased(P<0.05);compared with Ms group,the survival rate of the cells and ratio of LC3B-Ⅱ/LC3B-Ⅰin the cells in Ms+hUCMSCs-Sup group were significantly increased(P<0.05),the apoptotic rate was significantly decreased(P<0.05),and the expression levels of HOXA10,LIF,and ITGB3 mRNA in the cells were significantly increased(P<0.05);compared with Ms+hUCMSCs-Sup group,the survival rate of the cells and ratio of LC3B-Ⅱ/LC3B-Ⅰ in the cells in Ms+hUCMSCs-Sup+3-MA group were significantly decreased(P<0.05).Conclusion:hUCMSCs-Sup can increase the survival rate and decrease the apoptotic rate of the hEndoSCs after treated with Ms,and increase the endometrium receptivity,and its mechanism may be associated with the activation of autophagy of the hEndoSCs by hUCMSCs-Sup.

ObjectiveTo investigate the mechanism and effect of Qingfei Paidu decoction on transient receptor potential vanilloid-1/Transient receptor potential ankyrin1 （TRPV1/TRPA1） based on heat-sensitive channel and inflammatory response. MethodAccording to body weight， 80 8-week-old C57BL/6 mice were randomly divided into the normal group， model group， dexamethasone group （5 mg·kg^-1）， and low-dose， medium-dose， and high-dose groups of Qingfei Paidu decoction （14.865， 29.73， 59.46 g·kg^-1）， with 12 mice in each group. In addition to the normal group， the other groups were administered 20 μL （1×10^-3 g·kg^-1） to each mouse by airway infusion to establish the acute lung injury （ALI） model. In the administration group， the drug was given 1 h after modeling and again after an interval of 24 h. The lung tissue was taken 36 h after modeling. Double lung wet/dry weight ratio（W/D）， hematoxylin-eosin （HE） staining， enzyme-linked immunosorbent assay （ELISA）， and Western blot were used to observe and detect the pathological changes of lung tissue， expression levels of inflammatory cytokine tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6）， and expressions of TRPV1 and TRPA1 proteins in heat-sensitive channel， nuclear factor kappa-B （NF-κB）， inhibitor of NF-κB （IκBα） in inflammatory pathway， and phosphorylated proteins. The phosphorylated protein/total protein ratio was calculated. ResultCompared with that in the normal group， the lung tissue of mice in the model group was seriously damaged， and pulmonary capillary permeability increased. Alveolar capillary congestion and dilation destroyed the complete structure of the alveolar， and the alveolar wall thickened. A large number of inflammatory cells and red blood cells were infiltrated， and pulmonary edema was significantly aggravated. The expressions of TNF-α， IL-6， TRPV1， TRPA1， phosphorylated NF-κB p65/NF-κB p65， and phosphorylated IκBα/IκBα were significantly increased （P<0.01）， and the whole lung W/D was significantly increased （P<0.01）. Compared with the model group， the dexamethasone group and low-dose， medium-dose， and high-dose groups of Qingfei Paidu decoction could significantly improve pulmonary edema. TNF-α， IL-6， TRPV1， TRPA1， lung tissue NF-κB p65， and IκBα phosphorylated protein/total protein ratio decreased significantly （P<0.05， P<0.01）. The whole lung W/D also decreased significantly （P<0.05， P<0.01）. ConclusionQingfei Paidu decoction has anti-inflammatory and protective effects on LPS-ALI mice， which can effectively reduce inflammation， induce diuresis， and alleviate edema. Its mechanism may be related to the regulation of the expression of TRPA1 and TRPV1 and the inhibition of the activation of the NF-κB pathway.

Osteoporosis （OP） is a common bone disease affecting the quality of life and causing huge medical burden to the patients and society. The occurrence of OP is mainly caused by excessive bone resorption and insufficient bone formation， which are directly influenced by external calcium ion balance. Calcium imbalance can impair bone integrity， reduce the calcium supply to the bone， and lower the calcium content in the bone， thus triggering OP. Drugs are the main anti-OP therapy in modern medicine， which， however， may cause adverse reactions and drug dependence. Chinese medicines have good clinical effects and high safety in treating OP， being suitable for long-term use. Recent studies have shown that Chinese medicines can alleviate estrogen deficiency， regulate bone cell and calcium metabolism， which is crucial for the formation and development of OP. The transient receptor potential cation channel superfamily V members 5 and 6 （TRPV5 and TRPV6， respectively） affect bone homeostasis by mediating the transmembrane calcium ion transport in the intestine （TRPV6） and kidney （TRPV5）. Therefore， TRPV5/6 is one of the key targets to understand the anti-OP mechanisms of the effective parts of Chinese medicines， which is worthy of further study. This paper summarizes the research results about the anti-OP effects of Chinese medicines in the last two decades， especially the mechanism of regulating calcium metabolism， aiming to provide new ideas for the basic research， clinical application， and drug development of OP treatment.

Objective:To investigate the value of peripheral blood neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and serum lactate dehydrogenase (LDH) levels for predicting the occurrence of radiation pneumonia (RP) in small cell lung cancer.Methods:A total of 84 patients with small cell lung cancer who received image-guided radiotherapy in Xuzhou Cancer Hospital between September 2019 and September 2022 were retrospectively analyzed. They were divided into an RP group ( n = 25) and a non-RP group ( n = 59) according to whether RP occurred. Peripheral blood NLR and PLR and serum LDH levels were compared between the two groups before and after radiotherapy. The receiver operating characteristic curve (ROC curve) was used to analyze the value of peripheral blood NLR, PLR, and serum LDH levels for the diagnosis of RP in small cell lung cancer. Results:Before radiotherapy, there were no significant differences in peripheral blood NLR and PLR between the two groups (both P > 0.05). After radiotherapy, peripheral blood NLR and PLR in the RP group were (3.39 ± 0.81) and (129.06 ± 24.90), respectively, which were significantly higher than those in the non-RP group [(2.54 ± 0.71), (104.76 ± 26.26), t = 3.61, 3.83, both P < 0.05]. The NLR (2.86 ± 0.30) and PLR (110.07 ± 10.05) were the lowest in patients with grade 2 RP and they were highest in patients with grade 4 RP [(4.49 ± 0.63), (168.88 ± 14.11)]. The grade of RP was positively correlated with peripheral blood NLR and PLR. The sensitivity of peripheral blood NLR in the diagnosis of RP was 88.0%, the specificity was 66.1%, and the area under the curve (AUC) was 0.791. The sensitivity of PLR in the diagnosis of RP was 48.0%, the specificity was 94.9%, and the AUC was 0.735. The sensitivity of NLR combined with PLR in the diagnosis of RP was 92.0%, the specificity was 59.3%, and the AUC was 0.801. There was no significant difference in serum LDH levels between the two groups before and after radiotherapy (both P > 0.05). Logistic regression analysis showed that NLR and PLR were risk factors for RP in patients with small cell lung cancer ( OR = 2.309, 1.037; 95% CI: 1.061-5.024, 1.004-1.071). Conclusion:In patients with small cell lung cancer who develop RP, peripheral blood NLR, and PLR are markedly elevated compared with those in patients who do not develop RP, and combined detection of peripheral blood NLR and PLR has a high value for early diagnosis of RP in patients with small cell lung cancer.

Objective:To evaluate the effect of transcutaneous auricular vagus nerve stimulation (taVNS) on tourniquet-induced hypertension (TIH) in the patients undergoing anterior cruciate ligament reconstruction.Methods:Seventy-four patients of either sex, aged 18-60 yr, of American Society of Anesthesiologists Physical Status classification I or II, with body mass index of 18-30 kg/m 2, undergoing elective anterior cruciate ligament reconstruction under general anesthesia combined with preoperative femoral nerve block, were divided into 2 groups ( n=37 each) using a random number table method: sham stimulation group (group SS) and group taVNS. Group SS received stimulation on the ear lobe and the tail of the helix of the left ear. Group taVNS received stimulation on the cymba concha and the earlobe of the left ear. Both groups received stimulation from 1 h before induction of anesthesia until the end of the procedure (frequency of 30 Hz, pulse width of 300 μs, and amplitude of the strongest current that could be tolerated by the patient in the absence of pain). The tourniquet inflation pressure was 280 mmHg, with an inflation time of 60-90 min. Systolic blood pressure, diastolic blood pressure and heart rate were recorded before tourniquet inflation to assess the development of intraoperative TIH. The consumption of intraoperative propofol, remifentanil, nitroglycerin, esmolol, norepinephrine and atropine was recorded, and the occurrence of postoperative nausea and vomiting, skin itching and headache and dizziness was also recorded. Results:Compared with group SS, the incidence of TIH and the number of patients used nitroglycerin were significantly reduced ( P<0.05), and no significant changes were found in the other parameters in group taVNS ( P>0.05). Conclusions:taVNS can decrease the occurrence of TIH in the patients undergoing anterior cruciate ligament reconstruction.