Objective To investigate the health status of workers exposed to noise in a brewery in Beijing and to analyze the relationship between hearing loss and blood pressure. Methods A total of 949 noise-exposed workers in a brewery who participated in occupational health examination were selected as the investigation subjects. A survey was conducted to investigate the pure tone hearing threshold and abnormal blood pressure of the workers with different characteristics, and to analyze the relationship between the two. Results Among the noise-exposed workers, the detection rates of hearing abnormality, hypertension, and increased systolic and diastolic blood pressure were 73.55%, 52.37%, 43.84% and 46.47%, respectively. The detection rates of hearing abnormality, indicators of hypertension, high frequency hearing threshold abnormality and increased binaural high frequency hearing threshold on average in males were higher than those in females (P < 0.05). Except that there was no statistically significant difference in weighted values of the better ear’s hearing thresholds among different working age groups (P> 0.05), the detection rates of other hearing abnormality, indicators of hypertension, speech frequency hearing threshold abnormality, high frequency hearing threshold abnormality，increased binaural high frequency hearing threshold on average and the weighted value of the better ear's hearing threshold all increased or had an increasing trend with the increase of age or working years (P< 0.05). The detection rates of hypertension in the groups with high frequency hearing threshold abnormality and increased binaural high frequency hearing threshold on average were higher than those in the normal group (P＜0.05). Conclusion The noise-exposed workers in the brewery have hearing impairment, which is related to the occurrence of hypertension. It is recommended to strengthen the publicity and education on noise protection and take protective measures to reduce the occurrence of occupational noise injury.

Objectives:To analyze the consistency of evaluating left ventricular hemodynamics (HDF) based on single plane and multi plane cine sequences of magnetic resonance mitral valve orifice.Methods:A prospective study was conducted on 48 healthy adults, and two methods were used to measure the mitral valve diameter and calculate HDF parameters. The first method was to measure the diameter of the mitral valve opening in the left ventricular three chamber cine sequence; The second method is to measure the mitral valve diameter using cine sequences of two chamber, three chamber, and four chamber hearts, and then take the average value. Paired t-tests were used to compare the differences in HDF measured by two methods, and Pearson correlation coefficient ( r), intra group correlation coefficient ( ICC), and Bland-Altman analysis were used to test the consistency and reproducibility of the two methods. Results:The root mean square (RMS) of longitudinal HDF calculated using single plane and multi plane mitral valve diameters were [(17.28±4.41)% vs (17.21±4.61)%] ( P=0.379) for the entire cardiac cycle, [(21.45±5.54)% vs (21.49±5.68)%] ( P=0.646) for systolic phase, and [(12.78±4.10)% vs (12.54±4.24)%] ( P=0.106) for diastolic phase, respectively. The difference in the calculation results of HDF parameters related to ventricular function was not statistically significant (all P>0.05), and there was good consistency ( r=0.924-0.996, ICC=0.924-0.995). The two HDF parameters related to atrial function were sensitive to the measurement method of mitral valve orifice diameter [RMS of longitudinal HDF during active atrial emptying: (3.26±1.51)% vs (3.32±1.55)%, P=0.006; longitudinal HDF pulse during active atrial emptying: (-2.60±1.28)% vs (-2.76±1.30)%, P<0.001]. Conclusions:The ventricular function related HDF parameters obtained from the analysis of mitral valve orifice diameter using single plane and multi plane methods have good consistency, and can be evaluated using relatively simple single plane methods for left ventricular HDF.

Objective To construct a management program for upper limb lymphedema prevention in postopera-tive breast cancer patients and to evaluate its effectiveness.Methods The first draft of the upper limb lymphede-ma prevention and management protocol for postoperative breast cancer patients was constructed on the basis of ev-idence summaries and qualitative interviews,and 2 rounds of correspondence were conducted in December 2022.Using the convenience sampling method,patients undergoing surgery for malignant tumours in the breast surgery de-partment of a tertiary-level hospital in Zhengzhou City were selected as the study subjects,and 58 patients admitted from January to March 2023 were included in the experimental group according to the time of their first visit.57 patients admitted from July to December 2022 were included in the control group and were given routine care.The rates of lymphedema occurrence,upper limb function score and patients'adherence to lymphedema prevention be-haviours after 1,3,and 6 months of intervention were compared between the 2 groups.Results The valid ques-tionnaire recovery rates of the 2 rounds of expert correspondence were 92.59％and 100％,and the authority coeffi-cients of the experts were 0.940 and 0.950,and the Kendall's harmony coefficients were 0.228 and 0.254,respec-tively(P＜0.00 1).The coefficients of variation of the 2nd round of correspondence were 0.07～0.24.The final draft of the programme included 5 first-level entries,12 second-level entries,and 32 third-level entries.During the appli-cation of the programme,a total of 5 cases were dislodged,and 55 cases were finally included in each of the ex-perimental and control groups.The results of repeated measures ANOVA showed that there was an interaction ef-feet between the upper limb function scores and lymphedema prevention behavior compliance scores before inter-vention and at 1,3,and 6 months after discharge between the 2 groups(P＜0.05).Simple effects analysis showed that at 1,3,and 6 months after discharge,the upper limb function score and lymphedema prevention behavior com-pliance score of the experimental group were better than those of the control group,and the differences were sta-tistically significant(P＜0.05).At 6 months post-intervention,the difference in the occurrence of lymphedema was statistically significant when comparing the 2 groups(P=0.032).Adverse events such as subcutaneous bruising and falls did not occur in either group.Conclusion The upper limb lymphoedema prevention and management pro-gramme for postoperative breast cancer patients constructed in this study is scientific,feasible and safe,and can ef-fectively reduce the incidence of lymphoedema in patients and improve their quality of life.

Objective To investigate the effect of COX6B2 expression in gastric cancer tissues on the patients'long-term prognosis and its underlying mechanism.Methods Based on the public databases and the medical records of patients,we analyzed the expression level of COX6B2 in gastric cancer and adjacent tissues and its influence on long-term prognosis of the patients.Enrichment analysis were used to predict the possible role of COX6B2 in gastric cancer.The effects of lentivirus-mediated COX6B2 knockdown on biological behaviors of gastric cancer cells were examined using CCK-8 assay,flow cytometry,and Western blotting.Results TCGA database and the results of immunohistochemistry,Western blotting and real-time PCR all demonstrated a significantly higher expression of COX6B2 in gastric cancer tissues(P<0.05).Kaplan-Meier plotter database and Kaplan-Meier curves showed that the patients with high COX6B2 expression had significantly shorter postoperative survival(P<0.05).A high expression of COX6B2 in gastric cancer tissues was closely correlated with clinicopathologic stage,CEA and CA19-9(P<0.05).A high expression of COX6B2,CEA level≥5 μg/L and CA19-9 level≥37 kU/L were independent risk factors affecting postoperative 5-year survival rate of gastric cancer patients(P<0.05),and COX6B2 expression level had a predictive value for long-term prognosis of the patients(P<0.05).GO and KEGG enrichment analyses showed that COX6B2 was mainly involved in the regulation of cell cycle.In the in vitro cell experiment,COX6B2 overexpression significantly promoted gastric cancer cell proliferation,increased the percentage of G1/S phase cells and inhibited the cellular expressions of p53 and p21(P<0.05).Conclusions COX6B2 is highly expressed in gastric cancer and is closely correlated with a poor long-term prognosis of the patients possibly by promoting gastric cancer cell proliferation and regulating cell cycle.

Objective To investigate the effect of COX6B2 expression in gastric cancer tissues on the patients'long-term prognosis and its underlying mechanism.Methods Based on the public databases and the medical records of patients,we analyzed the expression level of COX6B2 in gastric cancer and adjacent tissues and its influence on long-term prognosis of the patients.Enrichment analysis were used to predict the possible role of COX6B2 in gastric cancer.The effects of lentivirus-mediated COX6B2 knockdown on biological behaviors of gastric cancer cells were examined using CCK-8 assay,flow cytometry,and Western blotting.Results TCGA database and the results of immunohistochemistry,Western blotting and real-time PCR all demonstrated a significantly higher expression of COX6B2 in gastric cancer tissues(P<0.05).Kaplan-Meier plotter database and Kaplan-Meier curves showed that the patients with high COX6B2 expression had significantly shorter postoperative survival(P<0.05).A high expression of COX6B2 in gastric cancer tissues was closely correlated with clinicopathologic stage,CEA and CA19-9(P<0.05).A high expression of COX6B2,CEA level≥5 μg/L and CA19-9 level≥37 kU/L were independent risk factors affecting postoperative 5-year survival rate of gastric cancer patients(P<0.05),and COX6B2 expression level had a predictive value for long-term prognosis of the patients(P<0.05).GO and KEGG enrichment analyses showed that COX6B2 was mainly involved in the regulation of cell cycle.In the in vitro cell experiment,COX6B2 overexpression significantly promoted gastric cancer cell proliferation,increased the percentage of G1/S phase cells and inhibited the cellular expressions of p53 and p21(P<0.05).Conclusions COX6B2 is highly expressed in gastric cancer and is closely correlated with a poor long-term prognosis of the patients possibly by promoting gastric cancer cell proliferation and regulating cell cycle.

Objective To investigate the mechanism of sanguinarine(SA)for alleviating ulcerative colitis(UC)induced by dextran sodium sulfate(DSS)in mice.Methods Male C57BL/6 mouse models of 3.5%DSS-induced UC were randomized for treatment with 1,5 and 10 mg/kg SA by gavage,400 mg/kg sulfasalazine by gavage,or 10 mg/kg SA combined with intraperitoneal injection of 30 mg/kg ML385(a Nrf2 inhibitor).The changes in intestinal inflammation was assessed by monitoring weight changes,disease activity index(DAI)score,colon length measurement,and HE staining.After the treatments,the colon tissues were collected for detection of malondialdehyde(MDA)content using colorimetry,mRNA expressions of inflammatory factors using RT-qPCR,and the expressions of Nrf2,HO-1,Keap-1,p-p65,p65,occludin,and ZO-1 proteins were detected using Western blotting.Results SA treatment obviously alleviated weight loss,colon length shortening and DAI score increase and ameliorated structural destruction of the colon glands and colonic crypts in mice with DSS-induced UC.SA intervention significantly decreased the levels of TNF-α,IL-1β and IL-6 mRNA and lowered ROS and MDA levels in the colon tissue of UC mice.The mouse models receiving SA treatment showed significantly increased expressions of Nrf2,HO-1,occludin and ZO-1 and lowered expressions of Keap-1 and P-P65 in the colon tissue without significant changes of p65 expression,and these changes were SA dose-dependent.Treatment with ML385 obviously attenuated the effect of high-dose SA for improving UC in the mouse models.Conclusion SA can improve UC-like enteritis in mice possibly by activating the Nrf2 pathway and inhibiting the NF-κB pathway in the colon tissue.

Objective To investigate the effect of acupuncture on the inflammatory changes of α7 nicotinic acetylcholine receptors(α7 nicotinic acetylcholine receptors,α7nAChRs)in rats with chronic migraine(CM).Methods Adult male SD rats were randomly divided into control group(VEH group),model group(NTG group),acupuncture group(TA group),α7nAChRs antagonist group(MLA group)and α7nAChRs agonist group(TA group)according to basic pain threshold.The rat model of CM was established by repeated subcutaneous injection of nitroglycerin(NTG)at the neck and back every other day.TA group and MLA group received acupuncture treatment one hour before NTG injection,20 minutes every day for 9 consecutive days.The MLA group was intraperitoneally injected with α7nAChRs antagonist MLA half an hours before acupuncture,and the PNU group was intraperitoneally injected with α7nAChRs agonist PNU-282987 half an hours before NTG injection,both groups were injected continuously for 9 days.The changes of paw withdrawal mechanical threshold(Paw Withdrawal Mechanical Threshold,PWMT)and tail-flick latency(Tail-Flick Latency,TFL)were detected by Von Frey and thermal radiation pain meter.The contents of inflammatory factors IL-1β,TNF-α and TGF-β in TNC and serum were determined by ELISA.The relative fluorescence intensity and co-expression of GFAP and α7nAChRs in TNC were detected by immunofluorescence dual labeling method.Results Compared with VEH group,PWMT and TFL in NTG group were significantly decreased(P<0.05 or P<0.01),the contents of IL-1β(P<0.01)and TNF-α(P<0.01,P<0.05)in serum and TNC were significantly increased;and in TNC,the astrocytes were activated significantly(P<0.01),while the relative fluorescence intensity of α7nAChRs and the co-expression of GFAP and α7nAChRs were significantly decreased(P<0.05,P<0.01).Compared with NTG group,PWMT and TFL in TA group were increased(P<0.05 or P<0.01),the contents of IL-1β(P<0.01)and TNF-α(P<0.01,P<0.05)in serum and TNC were increased;and in TNC,the relative fluorescence intensity of GFAP was significantly decreased(P<0.01),however the relative fluorescence intensity of α7nAChRs and the co-expression of GFAP and α7nAChRs were significantly increased(P<0.01).Compared with MLA group,PWMT and TFL in TA groups and PNU groups were significantly increased(P<0.05 or P<0.01).The contents of IL-1β(P<0.05)and TNF-α(P<0.01)in serum and TNC of TA group were increased,while the contents of TGF-β(P<0.05)were decreased.The contents of IL-1β in serum and TNC of PNU group were decreased(P<0.01,P<0.05),while the contents of TGF-β(P<0.01)were significantly increased.Conclusions Acupuncture can effectively relieve CM inflammatory response and hypersensitivity to pain,and its anti-inflammatory and analgesic effects may be related to the up-regulation of α7nAChRs expression.

Objective To investigate the mechanism of sanguinarine(SA)for alleviating ulcerative colitis(UC)induced by dextran sodium sulfate(DSS)in mice.Methods Male C57BL/6 mouse models of 3.5%DSS-induced UC were randomized for treatment with 1,5 and 10 mg/kg SA by gavage,400 mg/kg sulfasalazine by gavage,or 10 mg/kg SA combined with intraperitoneal injection of 30 mg/kg ML385(a Nrf2 inhibitor).The changes in intestinal inflammation was assessed by monitoring weight changes,disease activity index(DAI)score,colon length measurement,and HE staining.After the treatments,the colon tissues were collected for detection of malondialdehyde(MDA)content using colorimetry,mRNA expressions of inflammatory factors using RT-qPCR,and the expressions of Nrf2,HO-1,Keap-1,p-p65,p65,occludin,and ZO-1 proteins were detected using Western blotting.Results SA treatment obviously alleviated weight loss,colon length shortening and DAI score increase and ameliorated structural destruction of the colon glands and colonic crypts in mice with DSS-induced UC.SA intervention significantly decreased the levels of TNF-α,IL-1β and IL-6 mRNA and lowered ROS and MDA levels in the colon tissue of UC mice.The mouse models receiving SA treatment showed significantly increased expressions of Nrf2,HO-1,occludin and ZO-1 and lowered expressions of Keap-1 and P-P65 in the colon tissue without significant changes of p65 expression,and these changes were SA dose-dependent.Treatment with ML385 obviously attenuated the effect of high-dose SA for improving UC in the mouse models.Conclusion SA can improve UC-like enteritis in mice possibly by activating the Nrf2 pathway and inhibiting the NF-κB pathway in the colon tissue.

As confusion mounts over RNA isoforms involved in phenotypic plasticity, aberrant CpG methylation-mediated disruption of alternative splicing is increasingly recognized as a driver of intratumor heterogeneity (ITH). Protease serine 3 (PRSS3), possessing four splice variants (PRSS3-SVs; PRSS3-V1-V4), is an indispensable trypsin that shows paradoxical effects on cancer development. Here, we found that PRSS3 transcripts and their isoforms were divergently expressed in lung cancer, exhibiting opposing functions and clinical outcomes, namely, oncogenic PRSS3-V1 and PRSS3-V2 versus tumor-suppressive PRSS3-V3, by targeting different downstream genes. We identified an intragenic CpG island (iCpGI) in PRSS3. Hypermethylation of iCpGI was mediated by UHRF1/DNMT1 complex interference with the binding of myeloid zinc finger 1 (MZF1) to regulate PRSS3 transcription. The garlic-derived compound diallyl trisulfide cooperated with 5-aza-2'-deoxycytidine to exert antitumor effects in lung adenocarcinoma cells through site-specific iCpGI demethylation specifically allowing MZF1 to upregulate PRSS3-V3 expression. Epigenetic silencing of PRSS3-V3 via iCpGI methylation (iCpGIm) in BALF and tumor tissues was associated with early clinical progression in patients with lung cancer but not in those with squamous cell carcinoma or inflammatory disease. Thus, UHRF1/DNMT1-MZF1 axis-modulated site-specific iCpGIm regulates divergent expression of PRSS3-SVs, conferring nongenetic functional ITH, with implications for early detection of lung cancer and targeted therapies.

ObjectiveTo observe the intervention effect of Chaihu and Longgu Mulitang （CLMT） on rat depression model prepared by chronic unpredictable mild stress （CUMS） based on cyclic adenosine monophosphate （cAMP）/protein kinase A （PKA）/cAMP-response element-binding protein （CREB）-brain-derived neurotrophic factor （BDNF） signaling pathway. MethodSixty SD rats were divided into normal group， model group， and CLMT low-， medium- and high-dose groups and fluoxetine group （positive control） according to random number table. They， except the normal group， were treated with CUMS for 49 days to prepare the rat depression model. The CLMT low-， medium- and high-dose groups were given 2.89， 5.78 11.56 g·kg^-1 of CHMD granules， respectively， and the fluoxetine group was given 2.06 mg·kg^-1 of fluoxetine hydrochloride on the 29^th day. The normal group and the model group received equal volume of normal saline for 21 days. The behavioral performance of rats were observed by open field test and forced swim test. The levels of 5-hydroxytryptamine （5-HT）， norepinephrine （NE） and cAMP in rat hippocampus were measured by enzyme-linked immunosorbent assay （ELISA）. The mRNA expressions of PKA， CREB， and BDNF in rat hippocampus were detected by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）， and the protein expressions of PKA and BDNF were detected by Western blot. Immunohistochemistry was used to determine the expression of CREB， and hematoxylin and eosin （HE） staining and Nissl staining were used to observe the morphological changes of hippocampus. ResultCompared with the conditions in the normal group， the immobility time of the model group in the forced swim test was increased （P<0.01） and the total movement distance， residence time in central area， number of entries in central area and movement distance in central area were decreased （P<0.01）. Additionally， the contents of 5-HT， NE and cAMP in hippocampus of the model group as well as the protein expressions of PKA， BDNF and CRE，the mRNA expressions of BDNF and CREB were lower than those in the normal group （P<0.01）. Compared with the model group， the CLMT groups had reduced immobility time （P<0.01）， elevated total movement distance， residence time in central area， number of entries in central area and movement distance in central area （P<0.05， P<0.01）， up-regulated contents of 5-HT， NE and cAMP in hippocampus （P<0.05， P<0.01）， and up-regulated protein expressions of PKA， BDNF and CREB and mRNA expressions of BDNF and CREB （P<0.01）. HE staining and Nissl staining showed that CLMT significantly improved the neuronal structure in rat hippocampus. ConclusionCLMT alleviates the anxiety and depression of rats. These effects may be mediated by regulating monoamine neurotransmitters 5-HT and NE in hippocampus of depressed rats， activating cAMP/PKA/CREB/BDNF signaling pathway， up-regulating the expression of BDNF and protecting hippocampal structure and function .