ObjectiveTo explore the pharmacological mechanism involved in the treatment of allergic cough （AC） by Xiaoer Huatan Zhike granules （XEHT） based on proteomics and network pharmacology. MethodsAfter sensitization by intraperitoneal injection of 1 mL suspension containing 2 mg ovalbumin （OVA） and 100 mg aluminum hydroxide， a guinea pig model of allergic cough was constructed by nebulization with 1% OVA. The modeled guinea pigs were randomized into the model， low-， medium- and high-dose （1， 5， 20 g·kg^-1， respectively） XEHT， and sodium montelukast （1 mg·kg^-1） groups （n=6）， and another 6 guinea pigs were selected as the blank group. The guinea pigs in drug administration groups were administrated with the corresponding drugs by gavage， and those in the blank and model groups received the same volume of normal saline by gavage， 1 time·d^-1. After 10 consecutive days of drug administration， the guinea pigs were stimulated by 1% OVA nebulization， and the coughs were observed. The pathological changes in the lung tissue were observed by hematoxylin-eosin staining. The enzyme-linked immunosorbent assay was performed to measure the levels of C-reactive protein （CRP）， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， superoxide dismutase （SOD）， and malondialdehyde （MDA） in the bronchoalveolar lavage fluid （BALF） and immunoglobulin G （IgG） and immunoglobulin A （IgA） in the serum. Immunohistochemistry （IHC） was employed to observe the expression of IL-6 and TNF-α in the lung tissue. Transmission electron microscopy was employed observe the alveolar type Ⅱ epithelial cell ultrastructure. Real-time PCR was employed to determine the mRNA levels of IL-6， interleukin-1β （IL-1β）， and TNF-α in the lung tissue. Label-free proteomics was used to detect the differential proteins among groups. Network pharmacology was used to predict the targets of XEHT in treating AC. The Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis was performed to search for the same pathways from the results of proteomics and network pharmacology. ResultsCompared with the blank group， the model group showed increased coughs （P<0.01）， elevated levels of CRP， TNF-α， IL-6， and MDA and lowered level of SOD in the BALF （P<0.05， P<0.01）， elevated levels of IgA and IgG in the serum （P<0.05， P<0.01）， congestion of the lung tissue and infiltration of inflammatory cells， increased expression of IL-6 and TNF-α （P<0.01）， large areas of low electron density edema in type Ⅱ epithelial cells， obvious swelling and vacuolization of the organelles， karyopyknosis or sparse and dissolved chromatin， and up-regulated mRNA levels of IL-6， IL-1β， and TNF-α （P<0.01）. Compared with the model group， the drug administration groups showed reduced coughs （P<0.01）， lowered levels of CRP， TNF-α， IL-6， and MDA and elevated level of SOD in the BALF （P<0.05， P<0.01）， alleviated lung tissue congestion， inflammatory cell infiltration， and type Ⅱ epithelial cell injury， and decreased expression of IL-6 and TNF-α （P<0.01）. In addition， the medium-dose XEHT group and the montelukast sodium group showcased lowered serum levels of IgA and IgG （P<0.05， P<0.01）. The medium- and high-dose XEHT groups and the montelukast sodium showed down-regulated mRNA levels of IL-6， IL-1β， and TNF-α and the low-dose XEHT group showed down-regulated mRNA levels of IL-6 and TNF-α （P<0.05， P<0.01）. Phospholipase D， mammalian target of rapamycin （mTOR）， and epidermal growth factor receptor family of receptor tyrosine kinase （ErbB） signaling pathways were the common pathways predicted by both proteomics and network pharmacology. ConclusionProteomics combined with network pharmacology reveal that XEHT can ameliorate AC by regulating the phospholipase D， mTOR， and ErbB signaling pathways.

ObjectiveTo explore the possible mechanism of Osteoking （OK） on postmenopausal osteoporosis （PMOP）. MethodForty adult female mice were randomly divided into a sham operation （Sham） group， osteoporosis model （OVX） group， estradiol intervention （E₂） group， and OK group， with 10 mice in each group. The modeling was completed by conventional back double incision ovariectomy， and the corresponding drugs were given one week later. After 12 weeks， the body mass and uterine index of mice were measured， and the pathological changes of bone tissue and the number of osteoclasts （OCs） were determined by hematoxylin-eosin （HE） and tartrate-resistant acid phosphatase （TRAP） staining， respectively. Bone mineral density （BMD）， trabecular number （Tb.N）， trabecular separation （Tb.Sp）， and bone volume fraction （BV/TV） were measured by microcomputed tomography （Micro-CT）. The maximum load of the femur was detected by a three-point bending test. The contents of tumor necrosis factor-α （TNF-α） and bone resorption marker C-terminal telopeptide of type Ⅰ collagen （CTX-1） were measured by enzyme linked immunosorbent assay （ELISA）. The protein expression levels of nuclear factor-kappa B p65 （NF-κB p65）， phosphorylated nuclear factor-kappa B p65 （p-NF-κB p65）， nuclear factor kappa B inhibitor alpha （IκBα）， phosphorylated nuclear factor kappa B alpha （p-IκBα）， nuclear factor of activated T cells 1 （NFATc1）， and proto-oncogene （c-Fos） were detected by Western blot. The mRNA expressions of OCs-related specific genes matrix metalloproteinase-9 （MMP-9）， NFATc1， TRAP， cathepsin K （CTSK）， and c-Fos were detected by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. ResultCompared with the Sham group， the uterine index decreased significantly in the OVX group， and the body mass （BMI） increased significantly. The structure of bone trabeculae was completely damaged， and the number of OCs increased. BMD， Tb.N， BV/TV， and maximum load decreased， while Tb.Sp was up-regulated. The levels of TNF-α and CTX-1 in serum were up-regulated. The protein expressions of c-Fos， p-NF-κB p65/NF-κB p65， NFATc1， and p-IκBα/IκBα were increased. The mRNA expressions of NFATc1， c-Fos， CTSK， TRAP， and MMP-9 were up-regulated （P<0.05， P<0.01）. Compared with the OVX group， the body mass of the OK and E₂ groups decreased， and the uterine index increased. The bone trabeculae increased， and the number of OCs decreased. BMD， Tb.N， BV/TV， and maximum load increased， while Tb.Sp decreased. The levels of TNF-α and CTX-1 in serum were decreased. The protein expressions of c-Fos， p-NF-κB p65/NF-κB p65， NFATc1， and p-IκBα/IκBα were decreased， and the mRNA expressions of NFATc1， c-Fos， CTSK， TRAP， and MMP-9 were decreased （P<0.05， P<0.01）. ConclusionOK can inhibit the NF-κB/NFATc1 signaling pathway and reduce bone mass loss by reducing the level of inflammatory injury factors in PMOP mice， which is one of the mechanisms for treating PMOP.

Objective To investigate the content of thorium (Th) in surface water in Sichuan Province, China, and to evaluate Th-associated health risk via water intake for residents. Methods Twenty-three monitoring sections were set in main surface water bodies in Sichuan Province. From 2016 to 2021, the Th radioactivity level in the water bodies was measured during dry and normal-water seasons. The health risk of residents was evaluated by calculating radioactive Th intake from the surface water bodies combined with the use of a health risk assessment model. Results The Th radioactivity level of the surface water bodies in Sichuan Province was 0.02-0.67 μ./L. There was no significant difference in the Th radioactivity level of different years or different surface water bodies (P > 0.05). A significant difference was observed in the Th radioactivity level of different water seasons (P < 0.05). The total mean annual committed effective doses of Th in all age groups caused by drinking water and water immersion ranged from 3.14 × 10⁻⁸ to 8.75 × 10⁻⁷ Sv, all lower than the World Health Organization (WHO)-recommended reference level of 0.1 mSv. The overall carcinogenic risks for residents in all age groups ranged from 3.93 × 10⁻¹⁰ to 1.09 × 10⁻⁸, all below the most rigorous control limits issued by WHO and International Commission on Radiological Protection. Conclusion The Th-associated health risk via direct water intake and water immersion in main surface water bodies of Sichuan Province is at an acceptable level. Th in main surface water bodies of Sichuan Province is safe for all age groups.

Although the tumor suppressor P53 is known to regulate a broad network of signaling pathways, it is still unclear how certain drugs influence these P53 signaling networks. Here, we used a comprehensive single-cell multiomics view of the effects of ginsenosides on cancer cells. Transcriptome and proteome profiling revealed that the antitumor activity of ginsenosides is closely associated with P53 protein. A miRNA-proteome interaction network revealed that P53 controlled the transcription of at least 38 proteins, and proteome-metabolome profiling analysis revealed that P53 regulated proteins involved in nucleotide metabolism, amino acid metabolism and "Warburg effect". The results of integrative multiomics analysis revealed P53 protein as a potential key target that influences the anti-tumor activity of ginsenosides. Furthermore, by applying affinity mass spectrometry (MS) screening and surface plasmon resonance fragment library screening, we confirmed that 20()-protopanaxatriol directly targeted adjacent regions of the P53 DNA-binding pocket and promoted the stability of P53-DNA interactions, which further induced a series of omics changes.

Objective To assess the value of serum amyloid A(SAA)in patients with acute exacerbation of chronic pulmonary diseases. Methods Seventy AECOPD patients were randomly chosen. The AECOPD patients were divided into bacterial infection induced group and non-bacterial infection induced group by sputum bacteria culture. Thirty five SCOPD patients were chosen as control group. General data was collected. Lung function ,chest X ray,blood routine,CRP,SAA,IL6 and PCT were deteced and compared in the 3 groups. The diagnostic value of SAA to distinguish bacterial infection induced AECOPD was estimated. Results SAA of both AECOPD sub-groups were significantly higher than that of healthy controls. SAA in infection group is higher that that in exacerba-tion group. In terms of ROC curve,AUC was 0.8682 for SAA to distinguish merging bacterial infection,and the cut-off value was 72.10 mg/L with sensitivity of 94.29% and specificity of 65.71%. Conclusion SAA increases in AECOPD patients,and more obviously in AECOPD patients with bacterial infection. SAA may be used as a reliable biomarker not only to distinguish AECOPD patients from SCOPD patients ,but also distinguish merging bacterial infection during AECOPD.

Objective To evaluate the feasibility of combining the sedation performed by propofol targeted concentration in-fusion with epidural anesthesia in patients undergoing total pelvic floor reconstruction.Methods A total of 80 eligible patients were recruited and were assigned randomly into the study group(n=40)and the control group(n=40).All patients in both groups were administered epidural anesthesia with the puncture and catheter placing in the space between the 2nd-3rd lumbar vertebras.After the epidural anesthesia,patients in the study group were administered propofol by targeted concentration infusion (TCI)system. The plasma concentration of propofol was modulated to obtain the BIS maintaining between 65-80,and the OAA/S maintaining at 3 scores.The propofol was continuously infused until closing the incision.Values of HR,MAP at different time points in the opera-tion were recorded,and the plasma concentrations of propofol,the incidences of adverse events were recorded.Results The HR and MAP of patients in the study group decreased at T1 (given the anesthetic),T2 (the beginning of the operation),T3 (the beginning of the operation),compared with those at T0 (before the anesthetic)and T4 (30 min after the operation)(P <0.05).The HR and MAP of patients in the control group elevated at T2 ,T3 ,compared with those at T0 and T4 (P <0.05).The HR of study group at T1 ,T2 , T3 and the MAP at T2 were lower than those in control group.In study group,two asphyxia patients were founded.The incidence of shivering in the study group was lower than that in control group (P =0.014).No statistical difference was found in the incidences of other adverse event between this two groups (P >0.05).BIS of study group was (73.3 ±4.8)-(76.1 ±3.4),and the plasma concentrations of propofol was(1.32 ± 0.29 )μg/mL - (1.52 ± 0.26 )μg/mL.Conclusion The combination of propofol sedation performed by TCI and epidural anesthesia could be safely and effectively used in patients undergoing total pelvic floor reconstruc-tion.

Objective To explore the impact of laparoscopic surgery and that of open surgery on the coagulation function and incidence of deep venous thrombosis(DVT) in lower limbs in patients undergoing hysterectomy .Methods From April 2014 to A‐pril 2015 ,110 eligible patients were recruited .There was 57 patients received laparoscopic surgery ,and 53 patients received open surgery for hysterectomy .All patients underwent surgery under the general anesthesia .The APTT ,PT ,FIB ,and D‐dimer was de‐tected at 5 time points:before surgery ,surgery completion ,24 h after surgery ,48 h after surgery ,and 72 h after surgery .All patients were scheduled to ultrasound exam in lower limbs to detect the DVT at 24 ,48 and 72 h after surgery .Results Both groups showed decreased PT at surgery completion as compared with other time points (P<0 .05) ,decreased APTT at surgery completion and 24 h after surgery as compared with other time points(P<0 .05) ,and increased FIB at surgery completion and 24 h after surgery as compared with other time points(P<0 .05) .No significant difference was found in APTT ,PT ,and FIB at each time points between two groups(P>0 .05) .Both groups showed increased D‐dimer after surgery compared with that before surgery ;the laparoscopic group showed higher D‐dimer at 24 h after surgery ,and lower D‐dimer at 48 h after surgery than open group(P<0 .05) .The inci‐dence of DVT in laparoscopic group and open group was 14 .04(8/57) and 5 .66% (3/53) ,respectively ,with no significant difference between two groups(P>0 .05) .Conclusion Both the laparoscopic surgery and open surgery will activate the coagulation system , and lead to DVT ;as compared with open surgery ,the laparoscopic surgery could not reduce the incidence of DVT in lower limbs in patients undergoing hysterectomy .

Objective To explore the mechanism of melanoma differentiation associated gene-7(mda-7) in combination with adriamycin(ADM) killing the HCC HepG2 cells and reversing their multidrug resistance (MDR). Methods The experiment was conducted in three groups including the combined group, ADM group and mda-7 group. MTT assay and FCM were used to determine the differences among the 3 groups and clarify the reversing effect of combined treatment on multidrug resistance of the tumor cells. Expression levels of MDR-1, STAT-3, BCL-2, BAXmRNA were determined with real-time PCR. Western blotting was performed to observe the changes of proteins gp-l70, stat3,P-stat3, PKB, bcl-2,bax in all 3 groups. Result After transfection with 100VP/cell Ad. mda-7,the growth suppression rate of HepG2 treated by ADM (1.5 mg/L) rose from 17.46% to 79. 5%.According to the changes, killed HepG2 cells were increased by a factor of 4.55. times. MDR-1 mRNA was decreased from (16.49 ± 0. 11) to (5.48±0.05) and STAT-3 mRNA increased from (13.17±0. 08) to (21. 57±0. 11)(P＜0.05). Western blotting also showed that P-170 and PKB was decreased and the phosphorylation-stat-3 increased after the combined treatment. Conclusion Ad.mda-7 can reverse the multidrug resistance HepG2 cells. It inhibits the expression of MDR-1 mRNA,then arrests PKB protein and the signaling pathway of active stat-3 to induce apoptosis of HCC cells.

Objective To study the value of microwave coagulation therapy for liver malignant tumors.Methods Under local anesthesia,19 cases with hepatic malignant tumors treated with microwave knife under CT-guided.Results There were totally 23 tumors in 19 cases,13 tumors with≤3.5 cm in diameters were destroyed absolutely after the first treatmet,10 tumors among them were followed-up for 6-12 months and no recurred.10 tumors with＞3.5 cm in diameters treated at multiple points or angle,3～6 months later,CT showed that the tumors were destroyed completely in 6 and mostly in 4,by the hot condensate treatment secondly,3 tumors of 4 were destroyed completely 3 months later.There were no obvious complications.Conclusion The therapeutic effect under CT-guided microwave coagulation therapy for liver tumor which are ≤3.5 cm in diameter of the tumors is very reliable,the tumors＞3.5 cm in diameter can be destroyed mostly or completely by microwave treatment.

Objective To compare the efficacy of transrectal ultrasonography(TRUS)and spiral computed tomography(SCT)in preoperative staging of rectal carcinoma contrasted with the postoperative pathologic findings.Methods Both TRUS and SCT were performed prior to surgery in 92 patients with rectal carcinoma.After radical operation,the preoperative findings were compared with the histological findings,and the the efficacy of TRUS and SCT in staging the rectal carcinoma were evaluated.Results The accuracy of TRUS for T stage and N stage was 87.0% and 64.1% respectively,while the accuracy of SCT was 68.5% and 66.3%.Conclusions TRUS is superior to SCT for the judgment of tumor infiltration depth,TRUS may become the first choice in preoperative staging of rectal carcinoma.But neither is able to provide satisfaction assessment for lymph node metastases.When both methods are used together,it would be better.