ObjectiveTo investigate the potential mechanism of action of the Qufeng Tongqiao Cough-relieving Decoction （祛风通窍止咳方， QTCD） in the treatment of upper airway cough syndrome （UACS）. MethodsTwenty-four guinea pigs were randomly divided into blank group， model group， traditional Chinese medicine （TCM） group， and inhibitor group， with six guinea pigs in each group. Except for the blank group， guinea pigs were sensitized with ovalbumin and aluminum hydroxide via intraperitoneal injection， followed by ovalbumin nasal drops combined with smoke exposure to establish the UACS model. After modeling， the TCM group was administered QTCD 0.9 g/（100 g·d） by gavage， the inhibitor group received the transient receptor potential vanilloid receptor 4 （TRPV4） inhibitor GSK2193874 1 mmol/L， 5 min by nebulisation， and the blank group and model group were given 2 ml/（100 g·d） normal saline by gavage once daily. After 7 days of treatment， a cough provocation test was performed using 0.4 mol/L citric acid. The levels of IgE in serum and inflammatory cytokines， including interleukin-6 （IL-6）， interleukin-8 （IL-8） in serum， bronchoalveolar lavage fluid （BALF）， and nasal lavage fluid （NLF） were detected by enzyme-linked immunosorbent assay （ELISA）. Histopathological changes in lung and nasal mucosal tissues were observed by hematoxylin-eosin （HE） staining. Immunohistochemistry was used to detect the protein levels of TRPV4， substance P （SP）， and calcitonin gene-related peptide （CGRP） in lung and nasal mucosal tissues. Real-time polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of TRPV4， SP， and CGRP in lung tissues. ResultsHE staining showed significant structural damage and infiltration of inflammatory cells in the lung and nasal mucosal tissues in the model group， while the TCM group and inhibitor group showed improved pathological changes. Compared with the blank group， the model group showed increased cough frequency， serum IgE level， and IL-6 and IL-8 levels in serum， BALF， and NLF. The protein levels of TRPV4， SP， and CGRP in lung and nasal mucosal tissues and their mRNA expression were elevated （P＜0.05 or P＜0.01）. Compared with the model group， the TCM group and inhibitor group showed reduced cough frequency， serum IgE level， and TRPV4 and SP mRNA expression in lung tissues. The TCM group showed reduced IL-6 and IL-8 levels in serum， BALF， and NLF， and reduced TRPV4 and CGRP protein levels in lung and nasal mucosal tissues. The inhibitor group showed reduced IL-6 and IL-8 levels in serum， BALF， and NLF， reduced IL-6 in BALF， reduced IL-8 in NLF， and decreased TRPV4， SP， and CGRP protein levels in lung tissues and SP and CGRP protein levels in nasal mucosal tissues （P＜0.05 or P＜0.01）. Compared with the TCM group， the inhibitor group had increased serum IgE， IL-6， and IL-8 levels， increased IL-6 level in BALF， and increased IL-8 levle in NLF， but decreased SP protein level in lung tissues and increased TRPV4 and SP mRNA expression in lung tissues （P＜0.01）. ConclusionQTCD effectively reduces cough frequency in the UACS guinea pig model. Its mechanism may involve inhibiting the activation of the TRPV4 pathway， improving airway neurogenic inflammation， alleviating inflammatory responses， and reducing cough hypersensitivity.

Objective To analyze the infection status of Mycoplasma pneumoniae(MP)in the First Affilia-ted Hospital of Shandong First Medical University(the hospital)from 2019 to 2023 and explore the related influencing factors.Methods Basic admission information,test results,and related diagnostic results of 16 465 MP positive patients admitted to the hospital were collected,and the distribution characteristics of the number and disease types of MP positive patients in the hospital were analyzed.Results The positive rate of MP from high to low in the 5 years was in the years of 2021,2019,2020,2022,2023(P＜0.05).The proportion of MP positive cases in outpatient department from high to low was in the years of 2023,2021,2022,2019 and 2020(P＜0.05).Incidence was higher in spring and winter.In 5 years,the positivity rate of MP in respiratory tract infection patients was slightly higher in males than in females,the proportions of males in 2020 and 2022 were higher than those in 2019 and 2021(P＜0.05),and the proportions of males in 2019,2020,and 2022 were higher than that in 2023(P＜0.05).The age groups of MP infected patients were mainly concentrated in ado-lescents and infants under 14 years old.The positive results of patients in the 5 years were mainly distributed in titers of 1∶40,1∶80,and＞1∶160.There was no statistically significant difference in the proportion of positive results with MP total antibody≥1∶160 detected(P＞0.05).The top 5 clinical diagnoses of MP in-fected patients in thed hospital were fever,acute bronchitis,bronchopneumonia,chronic bronchitis,and pneu-monia,and the difference in the proportion of diagnostic results was statistically significant(P＜0.05).Conclu-sion This study clarifies the infection status of MP in the hospital from 2019 to 2023,and analyzes the impact of factors such as season,gender,and age on MP infection,which is of great significance for the prevention and control of respiratory infectious diseases in the hospital.

Background and purpose:Rectal cancer occurs on the inner wall of the rectum,and metastasis-associated in colon cancer 1(MACC1)can promote drug resistance in colon cancer cells.This study aimed to investigate the effect of MACC1 on oxaliplatin resistance in rectal cancer and its mechanism.Methods:Biosignal analysis of MACC1 and TCF7 expressions in rectal cancer tissues and signaling pathways enriched for MACC1 were carried out.The expressions of MACC1 and TCF7 in rectal cancer cells and rectal cancer oxaliplatin-resistant cells were detected by real-time fluorescence quantitative polymerase chain reaction(RTFQ-PCR),cell viability was detected by cell counting kit-8(CCK-8),and cell proliferation was detected by cell colony formation assay.ECAR values,lactate production and glucose consumption were detected by Seahorse Biosciences XF96.Western blot was used to detect the expressions of glycolysis-related proteins.Dual luciferase reporter gene and ChIP were used to validate the regulatory relationship between MACC1 and TCF7.Normality test and homogeneity of variance analysis was performed on the data of each group by GraphPad Prism 8.0.If it conformed to normal distribution,one-way ANOVA or t-test would be used for inter group comparison,otherwise the comparison between groups would be conducted using Wilcoxon rank sum test.Using a two-sided test,P＜0.05 was considered statistically significant.Results:MACC1 and TCF7 expressions were upregulated in rectal cancer,and knockdown of MACC1 significantly inhibited the viability of rectal cancer drug-resistant cells and the IC50 values of different concentrations of oxaliplatin treatments,as well as reduced the proliferation ability of rectal cancer oxaliplatin-resistant cells.Overexpression of MACC1 was able to promote the proliferation and glycolytic capacity of rectal cancer cells.Further studies revealed that the transcription factor TCF7 existed in the upper reaches of MACC1.Besides,this study analyzed the data from Cancer Genome Atlas Program(TCGA),and the result showed that knockdown of TCF7 was able to attenuate the promotional effect of overexpression of MACC1 on the glycolytic capacity and oxaliplatin resistance of rectal cancer cells.Conclusion:This study demonstrated that the TCF7/MACC1 axis could promote aerobic glycolysis and thus oxaliplatin resistance in rectal cancer cells.The findings suggest that targeting the TCF7/MACC1 axis or inhibiting the aerobic glycolysis pathway may be a novel therapeutic approach to inhibit oxaliplatin resistance in rectal cancer.

Objective To investigate the effects of microRNA(miR)-432-5p on the proliferation,metasta-sis and radiosensitivity of gastric cancer cells and the targeted regulatory relationship with DEAD-box helicase 41(DDX41)in this process.Methods The expressions of miR-432-5p and DDX41 in different gastric cancer cells were detected by quantitative real-time PCR(qRT-PCR).HGC-27 cells were transfected and divided into NC group(not transfected with plasmid),miR-NC group(transfected with miR-432-5p mimics negative con-trol),miR-432-5p group(transfected with miR-432-5p mimics),miR-432-5p+pcDNA-NC group(transfection miR-432-5p and pcDNA-DDX41 negative control)and miR-432-5p+pcDNA-DDX41 group(transfection miR-432-5p mimics and pcDNA-DDX41).After 48 h,qRT-PCR was used to detect the expression of miR-432-5p and DDX41 in each group of cells,MTT assay was used to detect the proliferation activity of each group of cells,Transwell assay was used to detect the migration ability of each group of cells,colony formation assay and flow cytometry were used to detect the radiosensitivity of each group of cells.The dual luciferase reporter gene assay was used to verify the targeting relationship between miR-432-5p and DDX41.The tumor growth of nude mice was detected,and the expression of DDX41 protein in tumor tissues was detected by Western blot.Results Compared with normal cells,cancer of the stomach cells miR-432-5p levels were decreased(P<0.05),DDX41 mRNA levels were increased(P<0.05).Compared with NC group and miR-NC group,the cell survival rate and DDX41 mRNA level in miR-432-5p group were decreased,the number of migrating cells was decreased(P<0.05),the miR-432-5p level was increased,and the radiosensitivity was enhanced(P<0.05).Overexpression of DDX41 reversed the effects of miR-432-5p on proliferation,migration and radiosensitivity of gastric cancer cells(P<0.05).Compared with NC group and miR-NC group,the volume and weight of tumor tissue and the expression of DDX41 protein in miR-432-5p group were significantly decreased(P<0.05).Con-clusion miR-432-5p through targeted cut DDX41 to inhibit the proliferation and metastasis of gastric cancer cells,enhance cell radiation sensitivity.

Objective:To investigate the neuroprotective effect of histone deacetylase 3 (HDAC3) specific inhibitor RGFP966 on traumatic brain injury (TBI) and its mechanism in rats.Methods:Forty-eight SD rats were randomly divided into sham-operated group, TBI group, TBI+vehicle group and TBI+RGFP966 group ( n=12). Rats in the later 3 groups accepted hydraulic impact brain injury to establish TBI models; and then, RGFP966 (dissolved in 1% DMSO at a dose of 10 mg/kg) was injected intraperitoneally 30 min after modeling, twice a day for 3 d, in TBI+RGFP966 group; same amount of DMSO was injected into TBI+vehicle group at the same time. Three d after modeling, neurological function was tested by modified neurological severity score (mNSS), water content of brain tissues was detected by dry-wet weight method, proportion of injured neurons at the frontal cortical tissues on the affected side was detected by Nissl staining, expressions of HDAC3 and pyroptosis related proteins were detected by immunohistochemical staining and Western blotting, and serum content of inflammatory factors was detected by ELISA. Results:Three d after modeling, compared with the TBI+vehicle group, the TBI+RGFP966 group had significantly decreased mNSS scores (9.83±0.75 vs. 6.67±0.82), water content of the injured cerebral cortex (82.73%±0.36% vs. 80.92%±0.66%), proportion of damaged neurons (75.60%±7.44% vs. 55.87%±4.10%), and HDAC3 protein expression (0.67±0.09 vs. 0.51±0.07), and significantly increased acetylated H3 (Ace-H3) and acetylated H4 (Ace-H4) protein expressions (0.81±0.02 vs. 1.22±0.02; 0.74±0.01 vs. 1.07±0.02), and statistically decreased protein expressions of nuclear factor-κB (NF-κB, 1.20±0.05 vs. 0.94±0.04), NOD-like receptor thermal protein domain associated protein 3 (NLRP3, 0.72±0.02 vs. 0.40±0.03), Caspase-1 containing cysteine (Caspase-1), dermatin D N-terminal fragment (GSDMD-N, 0.71±0.03 vs. 0.52±0.01), significantly decreased NF-κB and NLRP3 immunohistochemical staining scores, and significantly decreased serum contents of tumor necrosis factor-α, interleukin(IL)-1β and IL-18 ( P<0.05). Conclusion:Early intervention with RGFP966 after TBI can reduce the pyroptosis and inflammatory reaction of nerve cells and play neuroprotective role, whose mechanism may be related to inhibited activation of NF-κB/NLRP3/GSDMD pathway.

Objective:To learn about the epidemic situation and trend of human brucellosis in Menyuan Hui Autonomous County (referred to as Menyuan County) of Qinghai Province, and to provide reference for formulating brucellosis prevention and control measures in Menyuan County.Methods:Data on human brucellosis in Menyuan County reported by the Infectious Disease Reporting Information Management System of China Disease Control and Prevention Information System from 2013 to 2020 were collected and analyzed by descriptive epidemiological analysis (three distribution).Results:A total of 186 cases of brucellosis were confirmed from 2013 to 2020, with an average annual incidence of 14.553/100 000. The annual incidence rate was increasing year by year(χ 2trend = 22.08, P = 0.002). The cases were distributed in 67 villages of 12 towns; cases were more common in the age group of 15-< 65 years old (96.24%, 179/186), and there were more men than women cases (sex ratio was 3.89∶1.00, 148/38). Conclusions:The incidence rate of brucellosis cases in Menyuan County is increasing year by year, and the scope of its impact is constantly expanding. A multi-sectoral joint prevention and control mechanism should be established to strengthen management, increase the prevention and control of brucellosis, and stop the spread of the epidemic to surrounding counties and cities.

Objective    To investigate the feasibility and effectiveness of using ultrasound to evaluate the internal mammary artery (IMA) and explore the related factors affecting the quality of IMA. Methods    From July 2020 to January 2021, for patients who underwent coronary artery bypass grafting at the Department of Cardiovascular Surgery, Fuwai Hospital, ultrasound was applied to measure bilateral IMA at the parasternal second intercostal space. There were 62 males and 18 females with an average age of 59.9±8.3 years. The clinical data of the patients were recorded and analyzed. Results    A total of 160 IMA were measured. The IMA was detected in 99.4% (159/160), and the one that was not measured was proved to be occluded by enhanced CT. A total of 157 (98.1%) IMA intima were smooth, 2 (1.3%) were found to have uneven intimal thickening and less smooth, and only 1 (0.6%) was occluded. The intravascular diameter, peak systolic flow rate, peak diastolic flow rate, and blood flow rate of the left second intercostal IMA were 1.9±0.3 mm, 66.8±17.7 cm/s, 6.4 (0.0, 9.7) cm/s, 19.7±9.4 mL/min; and those of the right one were 2.1±0.3 mm, 69.7±18.5 cm/s, 6.0 (0.0, 9.2) cm/s and 22.8±11.5 mL/min, respectively. IMA vessel diameter and blood flow were greater on the right than those on the left side in the same individual (P<0.01). In univariate analysis, sex and body surface area were the factors that influenced the size of the IMA vessel among different individuals, and by linear regression analysis, the size of the IMA vessel was only related to body surface area among different individuals. On univariate analysis, diabetes mellitus was the only factor affecting IMA blood flow, with a mean reduction in blood flow of 18.4% (left) and 21.7% (right) in the diabetic group (P<0.05). Conclusion    Preoperative evaluation of the IMA using ultrasound over the parasternal second intercostal space is easy, noninvasive, and has a high success rate. The internal diameter of the IMA is positively correlated with body surface area, and blood flow is significantly reduced in patients with diabetes.

Objective:To analyze the electrophysiological characteristics and influencing factors of peripheral neuropathy in Parkinson's disease(PD)patients.Methods:Totally 68 PD patients and 30 controls were selected for neuroelectrophysiological evaluation, including items such as limb motor nerve terminal latency(LP)and amplitude and sensory nerve conduction velocity(SCV)and amplitude.Age, sex, serum folate, vitamin B 12, homocysteine and hemoglobin levels were also recorded for the two groups.The Hoehn-Yahr scale was used to assess patients and levodopa daily doses and levodopa equivalent daily doses were calculated.According to the criteria for neuroelectrophysiological abnormalities, 31 PD patients were found to have peripheral neuropathy and 37 PD patients did not have peripheral neuropathy. Results:In PD patients, a total of 952 peripheral nerves were examined, with 21.7% having motor nerve involvement(118/544)and 72.8%(297/of 408)having sensory nerve involvement.In the control group, a total of 420 peripheral nerves were examined, with 4.2%(10/240)having motor nerve involvement and 26.1%(47/180)having sensory nerve involvement.Compared with the control group, the wave amplitudes of motor nerve terminals were reduced in the PD group for the ulnar nerve( t=2.172/2.345, right/left), median nerve( t=2.104/2.543, right/left), and tibial nerve( t=2.340/2.444, right/left)(all P<0.05); compared with the control group, the wave amplitudes of sensory nerve terminals of the ulnar nerve( Z=3.535/3.439, right/ left), median nerve( Z=3.076/2.937, right/left), and peroneal nerve( Z=2.795/2.795, right/left)were all reduced in the PD group(all P<0.05); compared with the control group, sensory conduction velocities of the ulnar nerve( t=2.326/2.487, right/left), median nerve( t=3.269/2.386, right/left), and peroneal nerve( t=2.551/2.418, right/left)were prolonged(all P<0.05). The rate of abnormalities with the sensory nerve terminal wave amplitude( χ2=149.814, P<0.001)was higher than that of abnormalities with motor nerve terminal wave amplitude in PD patients; the rate of abnormalities with the sensory nerve terminal wave amplitude( χ2=58.364, P<0.001)was higher than that of abnormalities with sensory conduction velocities.Logistic regression analysis showed that increased folic acid( OR=0.825, 95% CI: 0.637-0.990)and vitamin B 12( OR=0.996, 95% CI: 0.991-1.000)were protective factors for PD peripheral neuropathy; H-Y score, levodopa daily dose( OR=1.009, 95% CI: 1.003-1.015), and increased homocysteine( OR=1.151, 95% CI: 1.041-1.273)were risk factors for PD peripheral neuropathy.After excluding confounding factors, H-Y classification( OR=3.213, 95% CI: 1.342-7.713)remained an independent risk factor for peripheral nerve injury in PD patients. Conclusions:In PD patients with peripheral neuropathy, both motor nerves and sensory nerves are involved, sensory nerves are more significantly involved, and axonal damage is more important than myelin loss; increased H-Y classification is an independent risk factor for peripheral nerve injury in PD patients.

Objective:To master the epidemic trend of human brucellosis in Qinghai Province, so as to provide basis for scientific prevention and control of the disease.Methods:In 2019 and 2020, at the national and provincial brucellosis monitoring sites in Qinghai Province, a total of 18 counties (cities and districts, hereinafter referred to as counties), no less than 400 serum samples were sampled every year for brucellosis Rose-Bengal plate agglutination test (RBPT) and serum tube agglutination test (SAT), which would be tested and judged according to the criteria of "Diagnosis for Brucellosis" (WS 269-2019).Results:In 2019, a total of 1 612 people were monitored in national brucellosis monitoring sites, 93 were RBPT positive, 54 were SAT positive, 54 were diagnosed, and the prevalence rate was 3.35% (54/1 612). In 2020, 1 677 people were monitored in national brucellosis monitoring sites, 151 were RBPT positive, 80 were SAT positive, 80 were diagnosed, and the prevalence rate was 4.77% (80/1 677). There were significant differences in RBPT positive rate, SAT positive rate and prevalence rate among national monitoring sites between the two years (χ 2 = 12.52, 4.24, 4.24, P < 0.05). In 2019, a total of 6 043 people were monitored in provincial brucellosis monitoring sites, 128 were RBPT positive, 91 were SAT positive, 87 were diagnosed, and the prevalence rate was 1.44% (87/6 043). In 2020, 5 664 people were monitored, 108 were RBPT positive, 59 were SAT positive, 52 were diagnosed, and the prevalence rate was 0.92% (52/5 664). There was no significant difference in RBPT positive rate among provincial monitoring sites between the two years (χ 2 = 0.66, P = 0.416), and the differences in SAT positive rate and prevalence rate were statistically significant among provincial monitoring sites between the two years (χ 2 = 4.98, 14.57, P < 0.05). Conclusion:In 2019 and 2020, there are human brucellosis in national and provincial brucellosis monitoring sites in Qinghai Province.

Objective:To investigate the expression and clinical significance of peptide/histidine transporter solute carrier family 15 member 4 (SLC15A4) in peripheral blood mononuclear cells (PBMCs) of patients with systemic lupus erythematosus (SLE).Methods:Fifty-five patients with SLE were divided into active SLE group and stable SLE group according to SLE disease activity index (SLEDAI) score, and 13 healthy volunteers were used as controls. The expression of SLC15A4 in PBMCs were detected by Western blot method. Moreover, the correlation between the expression of SLC15A4 and clinical and laboratory parameters of SLE patients were analyzed. The expression of SLC15a4 in the three groups was compared based on one-way analysis of variance (ANOVA), and the correlation between SLC15A4 expression level and clinical indicators was analyzed by Pearson correlation.Results:The expression levels of SLC15A4 in active SLE group, stable SLE group and healthy control group were (0.96±0.19), (0.88±0.14), (0.78±0.24), respectively. The expression level of SLC15A4 in SLE with active disease was higher than that in healthy controls ( F=4.47, P=0.015). In addition, the expression of SLC15A4 in PBMCs of SLE patients was positively correlated with the quantity of anti-double stranded DNA (anti-dsDNA) antibody, erythrocyte sedimentation rate (ESR) and systemic lupus erythematosus disease activity index (SLEDAI) ( r=0.29, P=0.031; r=0.36, P=0.007; r=0.32, P=0.017, respectively). However, the expression of SLC15A4 in PBMCs had no significant correlation with 24-h urinary protein ( r=0.45, P=0.127) and C3 ( r=0.20, P=0.133). Conclusion:SLC15A4 is involved in the pathogenesis of SLE and its expression in PBMCs of SLE patients can be used as an index to evaluate disease activity.