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 summarize the clinical and genetic characteristics of children with β-ketothiolase deficiency (BKTD).Methods:The clinical characteristics, biochemical, markers detected by tandem mass spectrometry (MS/MS) and gas chromatography-mass spectrometry (GC/MS), as well as the variants in ACAT1 gene among 5 children with BKTD in Children′s Hospital of Chongqing Medical University between October 2018 and December 2022 were retrospectively analyzed.Results:The onset age of the disease in 5 patients (4 males and 1 female) ranged from 9.7 to 28.0 months. During the acute phase, severe metabolic acidosis was observed with a pH of 6.9-7.1, as well as hypoglycaemia (2.3-3.4 mmol/L) and positive urinary ketone bodies (+-++++). Blood levels of methylcrotonyl carnitine, methylmalonyl carnitine and malonyl carnitine were 0.03-0.42, 0.34-1.43 and 0.83-3.53 μmol/L respectively and were significantly elevated. Urinary 2-methyl-3-hydroxybutyric acid was 22-202 and 3-hydroxybutyric acid was 4-6 066, both were higher than the normal levels. Methylcrotonylglycine was mild elevated (0-29). The metabolites detected by MS/MS and GC/MS were significantly reduced after treatment. Analysis of ACAT1 gene mutation was performed in 5 children. Most variants were missense (8/9). Four previously unreported variants were identified: c.678G>T (p.Trp226Cys), c.302A>G (p.Gln101Arg), c.627_629dupTGA (p.Asn209_Glu210insAsp) and c.316C>T (p.Gln106Ter), the first 2 variants were predicted to be damaging by SIFT, PolyPhen-2 and Mutation Taster software. c.316C>T (p.Gln106Ter) is a nonsense variant.Conclusions:β-ketothiolase deficiency is relatively rare, lacks specific clinical manifestations, however severe metabolic acidosis, hypoglycemia, and ketosis during the acute onset were consistent findings. Missense mutations in the ACAT1 gene are common genetic causes of β-ketothiolase deficiency.

Objective To investigate the risk factors for multiple organ dysfunction syndrome(MODS)in elderly patients with severe stroke.Methods A total of 112 elderly severe stroke pa-tients admitted to our hospital from January 2020 to December 2022 were recruited prospectively,and then according to the results of sequential organ failure assessment(SOFA)within 14 d after admission,they were divided into MODS group(n=38)and non-MODS group(n=74).Based on their clinical outcomes,they were also assigned into survival group(n=-33)and death group(n=79).General clinical data,acute physiology,chronic health evaluationⅡ(APACHEⅡ)score,Glas-gow coma scale(GCS)score,and head computed tomography parameters were collected.Logistic regression analysis was used to analyze the risk factors of MODS.Results The MODS group had significantly larger proportions of stroke/hemorrhage,chronic obstructive pulmonary disease,cor-onary heart disease and smoking,higher NIHSS and APACHE Ⅱ scores,elevated ratios of multi-vessel disease,urinary tract infection,venous thrombosis,hemorrhage,epilepsy and myocardial in-farction,more patients using acute mechanical ventilation and osmotic therapy,and increased hos-pital mortality,but lower GCS score when compared with the non-MODS group(P＜0.05,P＜0.01).Binary logistic regression analysis showed that NIHSS score,APACHE Ⅱ score,and mul-tivessel disease were independent risk factors for MODS(OR=1.124,95％CI:1.121-1.163,P=0.015;OR=1.265,95％CI:1.296-1.426,P=0.001;OR=2.532,95％CI:1.126-5.013,P=0.026).The MODS score and APACHE Ⅱ score were significantly higher in the death group than the survival group(P＜0.05).Conclusion Elderly severe stroke patients are prone to MODS during the acute period.

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.

Objective:To compare drug-coated balloon (DCB) and standard angioplasty balloon (SAB) in the treatment of postoperative in-stent restenosis (ISR) in patients with arteriosclerosis obliterans (ASO) of the lower extremity.Methods:From Jan 2017 to Dec 2018, 43 ISR patients after percutaneous transluminal angioplasty for ASO of the lower extremity at our hospital were enrolled.Patients were divided into 2 groups with 18 patients treated by DCB and 25 by SAB. The patients were followed up for 6~12 months.Results:There was no significant difference in the incidence of complications between DCB group and SAB group ( P>0.05).Compared with that in SAB group, the plasma level of ET-1 in DCB group was lower while NO was higher at 6, 24 h and 2 weeks after surgery ( P<0.05), there was no significant difference in P-selectin ( P>0.05). The ABI values in both groups increased, and that in DCB group were higher than SAB group at 6 and 12 months after surgery ( P<0.05). The lumen loss in DCB group at 6 and 12 months after surgery was significantly lower ( P<0.05). At 6 and 12 months, the primary patency of target lesions in the DCB group was 100.00% and 88.89%, which was higher than the 72.00% and 52.00% in the SAB group ( P<0.05); the CD-TLR rate in the DCB group was 11.11%, which was lower than 48.00% in the SAB group ( P<0.05). Conclusion:DCB comes with lower postoperative ISR in ASO patients of the lower extremity.

Objective:To explore the predictive value of stroke-related early tracheotomy score (SET) for tracheotomy in neurocritical patients.Methods:A retrospective analysis of the clinical data of neurocritical patients admitted to the department of intensive care unit (ICU) of the Xindu District People's Hospital of Chengdu from January 1st to December 31st, 2019. Patients were divided into tracheostomy group and non-tracheostomy group according to whether they underwent tracheotomy during hospitalization; according to SET score, patients were divided into groups with SET score < 10 points and SET score ≥ 10 points. The differences in gender, age, acute physiology and chronic health evaluation Ⅱ (APACHEⅡ), Glasgow coma score (GCS), SET score, the length of ICU stay and mechanical ventilation time were compared between the two groups. The receiver operator characteristic curve (ROC curve) was used to analyze the predictive value of SET score for the length of ICU stay > 10 days, mechanical ventilation time > 5 days, and tracheotomy treatment, and the predictive value of APACHEⅡ score for tracheotomy treatment.Results:Among 66 patients, 35 cases underwent a tracheotomy, 31 cases did not; SET score < 10 points in 19 cases, while SET score ≥ 10 points in 47 cases. Compared with the non-tracheostomy group, there were more male patients in the tracheostomy group (cases: 27 vs. 13), the GCS score was lower (7.00±2.41 vs. 11.52±2.00), the APACHEⅡ score and the SET score were higher (22.43±4.45 vs. 19.58±5.86, 16.11±3.67 vs. 8.61±4.27), and the length of ICU stay and mechanical ventilation time was longer [days: 27.54±18.82 vs. 7.45±5.30, 13 (9, 19) vs. 0 (0, 2)], and all differences were statistically significant (all P < 0.05). Compared with SET score < 10 points group, the proportion of traumatic brain injury and tracheotomy in the SET score ≥ 10 points group was higher (44.68% vs. 15.79%, 70.21% vs. 5.26%), the GCS score was lower (8.00±2.87 vs. 11.89±1.97), APACHEⅡ score was higher (22.30±4.80 vs. 18.11±5.49), and the length of ICU stay and mechanical ventilation time was longer [days: 22.38±18.74 vs. 7.53±4.60, 9 (4, 16) vs. 0 (0, 2)], and the differences were statistically significant (all P < 0.05). ROC curve analysis showed that the area under the curve (AUC) of SET score predicting the length of ICU stay > 10 days of neurocritical patients was 0.877, and the 95% confidence interval (95% CI) was 0.790-0.964 ( P = 0.000), and its cut-off value was 13.50, the sensitivity was 80.0%, and the specificity was 87.1%. The SET score predicts the AUC for mechanical ventilation time > 5 days was 0.915, the 95% CI was 0.851-0.979 ( P = 0.000), the cut-off value was 13.50, the sensitivity was 78.4%, and the specificity was 89.7%. SET score predicts the AUC of tracheotomy treatment was 0.919, 95% CI was 0.853-0.985 ( P = 0.000), its cut-off value was 13.50, the sensitivity was 82.9%, and the specificity was 90.3%, which was significantly better than that of APACHEⅡ score in predicting the value of tracheotomy (AUC was 0.647, 95% CI was 0.512-0.783, P = 0.040, its cut-off value was 17.50, the sensitivity was 91.4%, and the specificity was 41.9%). Conclusion:SET score has a good predictive value for the length of ICU stay, mechanical ventilation time and tracheotomy in neurocritical patients.

Objective:To explore the effect of dual antiplatelet combined with calf serum deproteinized injection in the treatment of mild ischemic stroke after intravenous thrombolysis.Methods:From October 2017 to December 2018, 82 patients with mild ischemic stroke who were diagnosed in the People's Hospital of Ruian were selected.The patients were divided into control group (41 cases) and observation group (41 cases) according to random number table method.The control group was treated with aspirin after intravenous thrombolysis.On this basis, the observation group was treated with dual antiplatelet combined with calf serum deproteinized injection.The course of treatment was 3 months in both two groups.The total effective rate, the changes of hemorheological indicators, the improvement of neurological deficit, the ability of daily living and the ability of returning to society were compared between the two groups before and after treatment.The complications and prognosis were recorded.Results:The total effective rate of the observation group was 95.12% (39/41), which was higher than 78.05% (32/41) of the control group (χ 2=5.145, P<0.05). After treatment, the National Institutes of Health Stroke Score Scale (NIHSS) score, Modified Rankin Score (mRS), Barthel index (BI) score of the observation group were (0.34±0.18)points, (92.15±6.73)points, (0.87±0.36)points, respectively, which of the control group were (0.92±0.35)points, (76.05±4.86)points, (1.64±0.52)points, respectively, there were statistically significant differences between the two groups ( t=8.592, 11.308, 7.099, all P<0.05). The whole blood viscosity, plasma viscosity and platelet aggregation rate of the observation group were (4.13±0.36)mPa/s, (1.39±0.31)mPa/s, (32.35±2.61)%, respectively, which were lower than those of the control group [(8.65±0.72)mPa/s, (1.62±0.47)mPa/s, (39.07±3.25)%] ( t=32.740, 2.382, 9.400, all P<0.05). There were no cases of cerebral hemorrhage and death in the two groups, and there was no statistically significant difference in recurrence rate between the two groups (χ 2=2.565, P>0.05). Conclusion:After intravenous thrombolytic therapy for patients with mild ischemic stroke, dual antiplatelet therapy combined with calf serum deproteinized injection can improve the neurological function, life ability and hemorheological indicators of patients, with good prognosis, it is safe and effective.

OBJECTIVE: To investigate the effect of Chinese medicine Wubi Shanyao pills on sexual function of kidney-yang-deficiency mice induced by hydrocortisone. METHODS: Male Kunming mice were injected with hydrocortisone for 10 days to prepare the kidney-yang-deficiency model, and administrated with Wubi Shanyao pills (0.91, 1.82, 2.73 g/kg) for 9 weeks. The general behaviors of mice (autonomous activity, grasping power) were observed; sexual behaviors (capture, straddle, ejaculation frequency and incubation period) of mice were detected by mating experiment. The serum levels of cortisol, adrenocorticotropic hormone (ACTH), luteinizing hormone (LH), follicle stimulating hormone (FSH), estradiol (E RESULTS: Wubi Shanyao pills increased the number of independent activities, grasping power, capture frequency of model mice and shortened the capture latency (all CONCLUSIONS Wubi Shanyao pills can improve the sexual function of mice with kidney-yang-deficiency induced by hydrocortisone, which may be related to regulating the hypothalamus-pituitary-adrenal axis (HPA axis), promoting the proliferation of testicular cells, and inhibiting cell apoptosis.
Animals ; Follicle Stimulating Hormone/blood* ; Hydrocortisone ; Hypothalamo-Hypophyseal System ; Kidney/drug effects* ; Kidney Diseases/drug therapy* ; Male ; Mice ; Pituitary-Adrenal System/drug effects* ; Random Allocation ; Sexual Behavior, Animal/drug effects* ; Yang Deficiency/drug therapy*

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