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.

Objective To determine the content and distribution characteristics of the artificial radionuclide ¹³⁷Cs and the natural radionuclides ²¹⁰Pb, ²²⁶Ra, ²²⁸Ra, and ⁴⁰K in wild edible fungi, and calculate the committed effective dose due to ¹³⁷Cs and ²¹⁰Pb in wild edible fungi. Methods Thirty samples of wild edible fungi were collected and their caps and stems were separated. A total of 60 samples were measured for ¹³⁷Cs, ²¹⁰Pb, ²²⁶Ra, ²²⁸Ra, and ⁴⁰K using a BE5030 wide-energy, low-background, high-purity germanium γ spectrometer. The paired analysis of the four radionuclides ²²⁶Ra, ²¹⁰Pb, ¹³⁷Cs, and ⁴⁰K was performed using SPSS 11.5. Results Among the 60 samples, the detection rates and dry weight specific activity ranges of ¹³⁷Cs, ²¹⁰Pb, ²²⁶Ra, ²²⁸Ra, and ⁴⁰K were 97% and 0.62-384 Bq/kg, 73% and 6.4-159 Bq/kg, 52% and 0.7-28.8 Bq/kg, 5% and 0.43-2.18 Bq/kg and 100% and （77.4-264) × 10 Bq/kg, respectively. Conclusion Based on the analysis of the 60 samples, the detection rate of radionuclides is in the order of ⁴⁰K, ¹³⁷Cs, ²¹⁰Pb, ²²⁶Ra, and ²²⁸Ra. In terms of the specific activity, the distribution of ⁴⁰K and ²²⁶Ra in wild edible fungi in the same region is basically uniform, while the content of ²¹⁰Pb and ¹³⁷Cs fluctuates in different samples. Although ¹³⁷Cs and ²¹⁰Pb can be detected in most of the wild edible fungi, the annual committed effective dose due to ingestion of wild edible fungi is negligible.

Objective To explore the effects of Shaoyao Gancao granule on hair growth,behavior,and the hypothalamic pituitary adrenal(HPA)axis in mice with alopecia areata(AA).Methods Forty-two C3H/HeJ mice were randomly divided into control,model,Shaoyao Gancao granule high-,middle-,low-dose,corticotropin-releasing hormone receptor 1(CRHR1)antagonist,and compound glycyrrhizin tablet(CGT)groups.Photography,dermoscopy,weight analysis,and behavioral measurement were performed.Corticotropin-releasing hormone(CRH),adrenocorticotropic hormone(ACTH),cortisol,glucocorticoid receptor(GR),and brain-derived neurotrophic factor(BDNF)were also assessed.Results Compared with the model group,high-dose Shaoyao Gancao granules improve hair regeneration and weight gain(P＜0.05),increased the percentage of total exercise distance and central area exercise distance in an open field test(P＜0.05),reduced the immobility time in the forced swimming and tail suspension experiments(P＜0.05),reduced peripheral blood levels of CRH,ACTH,and cortisol(P＜0.05),and increased expression of GR and BDNF in the hippocampus(P＜0.05).Conclusions Shaoyao Gancao granule promotes hair growth and improves behavioral performance in mice with AA.These effects may be related to downregulating CRH,ACTH,and cortisol expression,upregulating GR and BDNF expression,and inhibiting excessive activation of the HPA axis.

Objective:To explore the effects of depressive symptoms on sleep quality in adolescents with depressive disorder, and the mediating roles of cognitive fusion and sleep belief.Methods:A sample of 210 adolescents with first episode depressive disorder aged 12-18 years were recruited to complete 17-item Hamilton depression scale (HAMD-17), Pittsburgh sleep quality index (PSQI), cognitive fusion questionnaire (CFQ), and dysfunctional beliefs and attitudes about sleep scale (DBAS-16) from November 2021 to July 2022. SPSS 26.0 software was used to perform descriptive analysis and correlation analysis. The mediating effect was tested by Bootstrap analysis using PROCESS V 3.4 Macro program.Results:The incidence of low sleep quality in adolescents with depressive disorder was 69.0%(145/210). HAMD-17 score was (22.4±7.9), PSQI score was (9.7±3.7), CFQ score was (51.6±7.8), DBAS-16 score was (43.5±8.4).PSQI was positively correlated with the scores of HAMD-17 and CFQ( r=0.613, 0.463, both P<0.001).HAMD-17 was positively correlated with CFQ score ( r=0.488, P<0.001).DBAS-16 was negatively correlated with scores of PSQI, HAMD-17 and CFQ( r=-0.326, -0.284, -0.354, all P<0.001). The direct effect of depression on sleep quality was 0.230(95% CI=0.169-0.293). The indirect effect of depression on sleep quality through two pathways, the separate mediating effect value of cognitive fusion was 0.041 (95% CI=0.011-0.074), and the chain mediating effect value of cognitive fusion and sleep beliefs was 0.008(95% CI=0.001-0.020). Conclusion:Depressive symptoms can directly affect sleep quality of depressive disorder adolescents and indirectly through cognitive fusion and sleep beliefs.

Objective To collect and sort out the literature on the clinical medication experience of traditional Chinese medicine(TCM)in the treatment of hepatic precancerous lesions,and to summarize the characteristics of the disease and the treatment ideas by analyzing the rules of its formula,in order to provide instructions for the treatment of precancerous lesions of hepatocellular carcinoma with TCM in terms of medication and experience addition and subtraction.Methods CNKI,VIP,WanFang Data,CBM,PubMed,Web of Science,EMBASE,Cochrane databases were systematically searched,the clinical research and personal experience literature of TCM in the treatment of hepatic precancerous lesions from the establishment of the databases to December 2023 was included,and the prescription information that met the inclusion criteria was extracted.Based on"Traditional Chinese Medicine data Miner(TCM Miner)",the medication database was established to analyze the frequency,properties and flavours of the drugs and meridian tropism.The cluster analysis were conducted by SPSS 25.0 statistical software,and the association rules were analyzed by using Apriori algorithm of SPSS Modeler 14.1,and the complex network analysis of high-frequency drugs was conducted by network module of SPSS Modeler.Results 34 researches including 34 formulas,110 drugs with 291 frequencies and 15 drug efficacy were included.Frequency analysis showed that the top eight types of frequently applied drugs were milkvetch root,largehead atractylodes rhizome,radix salviae miltiorrhhizae,hedyotis,carapax trionycis,zedorgy rhidoray,barbated skullcup herb,redix curcumae.The top three properties in the"four qi"were cold,warm and mild.The top three tastes of the"five flavors"were bitterness,sweetness and acridity.The top four in the frequency of meridian tropism were liver,spleen,kidney and lung.Apriori correlation analysis showed that the core drug pairs was"Hedyotis diffusa+Atractylodes".Complex network analysis showed that the core prescriptions were composed of Atractylodes,Radix Paeoniae Alba,Hedyotis diffusa,Poria cocos,Rhizoma Curcumae,Radix Curcumae Aromaticae,Trionycis Carapax,Radix Astragali,Sparganium stoloniferum,Salvia miltiorrhiza,Scutellaria barbata.Conclusion The TCM treatment of hepatic precancerous lesions should be based on tonifying spleen and nourishing liver,promoting blood circulation and detoxification,and combined with drugs that can promote qi-circulation,clear heat,remove blood-stasis,soften hard masses and resolve hard masses.

Objective To correct the counting loss of ³⁷Ar below the activity threshold during the measurement of the absolute activity of the inert radioactive gas ³⁷Ar using the proportional counter filled with gas. Methods Monte Carlo simulation with Geant4 was performed to establish a proportional counter model and output the energy deposition spectrum of ³⁷Ar, which were used to simulate and analyze the causes and correction of counting loss. Results The photon detection efficiency was only 38.7% at 60 kPa. The counting loss was mainly caused by the wall effect produced by the photons, which could be reduced by increasing the gas pressure and corrected by extrapolation. The influence of wall effect at 100 kPa was 4.4%, and the deviation between simulation and experiment was < 0.6%. Conclusion A factor could be calculated by Geant4 simulation for the correction of counting loss, thus achieving the accurate measurement of ³⁷Ar activity by proportional counter.

Tumor-associated macrophages (TAMs) play crucial roles in tumor progression and immune responses. However, mechanisms of driving TAMs to antitumor function remain unknown. Here, transcriptome profiling analysis of human oral cancer tissues indicated that regulator of G protein signaling 12 (RGS12) regulates pathologic processes and immune-related pathways. Mice with RGS12 knockout in macrophages displayed decreased M1 TAMs in oral cancer tissues, and extensive proliferation and invasion of oral cancer cells. RGS12 increased the M1 macrophages with features of increased ciliated cell number and cilia length. Mechanistically, RGS12 associates with and activates MYC binding protein 2 (MYCBP2) to degrade the cilia protein kinesin family member 2A (KIF2A) in TAMs. Our results demonstrate that RGS12 is an essential oral cancer biomarker and regulator for immunosuppressive TAMs activation.
Mice ; Humans ; Animals ; Tumor-Associated Macrophages/metabolism* ; Carcinoma, Squamous Cell ; Squamous Cell Carcinoma of Head and Neck ; Mouth Neoplasms ; GTP-Binding Proteins/metabolism* ; Head and Neck Neoplasms ; Ubiquitin-Protein Ligases/metabolism* ; Adaptor Proteins, Signal Transducing/metabolism* ; RGS Proteins/metabolism* ; Kinesins/metabolism* ; Repressor Proteins/metabolism*

Objective:To investigate the characteristics of obesity in adolescents with major depressive disorder (MDD) and its association with the depressed severity.Methods:A total of 278 adolescents with MDD were recruited according to the inclusion and exclusion criteria. Their demographic data were collected and 24-item Hamilton depression scale (HAMD-24) was used to evaluate their severity of depression. According to the body mass index (BMI) classification standard of adolescents in China, all subjects were classified into four groups(wasting group, normal BMI group, overweight group and obesity group). SPSS 26.0 statistical software was used for data analysis. The Kruskal-Wallis test and the Chi-square test were separately used for the comparison of the four groups.Spearman correlation was used to explore the relationship between BMI and HAMD-24 scores and severity.Results:Among 278 adolescents with MDD, the prevalence of body abnormality was 32.4% (90/278), among which wasting, overweight and obesity were 9.0% (25/278), 14.4% (40/278) and 9.0% (25/278) respectively. There were statistically differences in gender ( χ2=17.018, P<0.001), HAMD-24 scores ( H=9.427, P=0.024) and depressed severity( H=8.508, P=0.037) among the four groups. Multiple comparisons showed that there were only statistically differences between obesity group and normal BMI group, that was the prevalence of obesity in males was higher than that in females ( χ2=13.631, P<0.001), and the level in HAMD-24 scores ( Z=2.956, P=0.003) and depressed severity ( Z=2.832, P=0.005) was lower in obesity group than that in normal BMI group.Spearman correlation analysis showed that BMI was negatively correlated with HAMD-24 scores ( r=-0.162, P=0.007). Conclusion:There is gender difference in obesity rates among the adolescent patients with first-episode untreated MDD. And the obese patients are less depressed than those with normal BMI.

Objective:To evaluate the value of B-Raf proto-oncogene, serine/threonine kinase (BRAF) V600E mutation detection in the differentiating malignant from benign with Bethesda system for reporting thyroid cytopathology (BSRTC) categories Ⅰ and Ⅲ nodules. Methods:From January 2019 to December 2020, a total of 264 nodules from 263 patients (79 males, 184 females; median age 46 years) were retrospectively enrolled and all patients underwent BRAF V600E mutation detection, fine-needle aspiration cytology (FNAC) and thyroid nodulectomy in the Affiliated Drum Tower Hospital of Nanjing University Medical School. Thirteen nodules of 12 patients had repeat aspirate samples and 51 nodules were examined with multiple genes assay in formalin fixed paraffin embedded tissues. Taken the postoperative histopathological results as the gold standard, the diagnostic efficiency of BRAF V600E mutation was analyzed by comparing the results of multiple genes assay and BRAF V600E mutation detection of repeated puncture samples. Results:Of 264 nodules, 230 were malignant (papillary thyroid cancer (PTC)) and 34 were benign, with BSRTC categories Ⅰ (nondiagnostic) and Ⅲ (follicular lesion) nodules of 58 and 206. The sensitivities of BRAF V600E mutation detection in BSRTC categories Ⅰ and Ⅲ nodules were 77.1%(37/48) and 78.0%(142/182), the specificities were 9/10 and 91.7%(22/24), the positive predictive values were 97.4%(37/38) and 98.6%(142/144), the negative predictive values were 45.0%(9/20) and 35.5%(22/62), and the accuracy rates were 79.3%(46/58) and 79.6%(164/206). The diagnostic concordance of BRAF V600E mutation detection was 90.2%(46/51) in the preoperative and postoperative samples of 51 nodules with preoperative BRAF V600E wild type but postoperative pathology confirmed as PTC and was 11/13 in repeat puncture samples. Conclusion:BRAF V600E mutation detection is an effective diagnostic method for BSRTC categories Ⅰ and Ⅲ nodules.

Objective:To explore the clinical characteristics and risk factors of sarcopenia in elderly patients with chronic kidney disease (CKD) stage 3-4.Methods:It was a single-center, retrospective observational study. CKD stage 3-4 patients aged ≥60 years old from March 2019 to March 2022 in the Geriatrics Department of the First Affiliated Hospital of Zhengzhou University were enrolled in the study. General data of the patients were collected, and laboratory indicators, muscle strength, physical function and appendicular muscle mass index (ASMI) were measured. According to the diagnostic criteria of sarcopenia, the patients were divided into no sarcopenia CKD group and sarcopenia CKD group. Baseline data between these two groups were compared. Logistic regression analysis was used to analyze the related factors of sarcopenia in elderly CKD stage 3-4 patients.Results:A total of 162 CKD stage 3-4 patients were enrolled in this study, with 89 males (54.9%) and a median age of 75 (69, 82) years. Sarcopenia was diagnosed in 40 cases, and the prevalence was 24.7% (95% CI 18.1%-31.3%). Compared with no sarcopenia CKD group, age, proportion of dementia, cystatin C, urea nitrogen, C-reactive protein (CRP) and ratio of urine protein to creatinine were higher (all P<0.05), while body mass index (BMI), hemoglobin, carbon dioxide combining power, estimated glomerular filtration rate (eGFR), serum albumin and the proportion of regular exercise and using α-ketones were lower in sarcopenia CKD group (all P<0.05). Meanwhile, grip strength, walking speed, short physical performance battery score and ASMI were lower in sarcopenia CKD group (all P<0.05). Multivariable logistic regression analysis results showed that low eGFR ( OR=0.824, 95% CI 0.687-0.987, P=0.036), low BMI ( OR=0.463, 95% CI 0.304-0.704, P<0.001), low serum albumin ( OR=0.459, 95% CI 0.263-0.802, P=0.006) and high CRP ( OR=2.754, 95% CI 1.708-4.439, P<0.001) were the independent related factors of sarcopenia in elderly CKD patients. Conclusions:The prevalence of sarcopenia in elderly CKD stage 3-4 patients is high. Low eGFR, low BMI, low serum albumin and high CRP are the independent risk factors for sarcopenia in elderly CKD stage 3-4 patients.