Objective:To analyze the correlation of monocyte/high density lipoprotein ratio(MHR),neutrophil/lymphocyte ratio(NLR),platelet/lymphocyte ratio(PLR)and bone density,bone metabolism markers in elderly essential hypertension with osteoporosis(OP)patients.Methods:This study was a retrospective study,198 elderly essential hypertension patients who were admitted in our hospital from January 2022 to June 2024 were selected.According to the patient's bone mass test results,patients were divided into normal bone mass group(n=79),osteopenia group(n=68)and OP group(n=51).MHR,NLR,PLR,bone density(left hip,left femoral neck and lumbar spine L1-L4)and bone metabolism markers were compared among three groups,the correlation of MHR,NLR,PLR and bone density,bone metabolism markers were analyzed by Pearson correlation.Results:MHR,NLR,PLR in normal bone mass group,osteopenia group and OP group increased in turn(P＜0.05).The left hip,left femoral neck and lumbar spine L1-L4 bone density in normal bone mass group,osteopenia group,OP group decreased in turn(P＜0.05).25-hydroxyvitamin D[25(OH)D]in normal bone mass group,osteopenia group and OP group decreased in turn,alkaline phosphatase(ALP)and parathyroid hormone(PTH)increased in turn(P＜0.05).MHR,NLR and PLR were negatively correlated with left hip bone density,left femoral neck bone density,lumbar spine L1-L4 bone density,25(OH)D and positively correlated with PTH and ALP(P＜0.05).Conclusion:The increase of MHR,NLR and PLR in elderly essential hypertension with OP patients can affect bone mineral density and bone metabolism.

AIM To investigate the effects of Yunpi Tongchang Formula on intestinal mucosal barrier damage in rats with opioid-induced constipation(OIC)of Spleen-Kidney Yang Deficiency Syndrome.METHODS In contrast to the 10 rats of the blank group,the 50 rats of the modeling group were induced into models of OIC of Spleen-Kidney Yang Deficiency Pattern by 7 days consecutive administration of both subcutaneous loperamide injection and alternating gavage of activated carbon ice water and vinegar.Following successful modeling,rats were randomly allocated into the model group,the mosapride citrate tablet group(1.35 mg/kg),and the high-dose,medium-dose,and low-dose Yunpi Tongchang Formula groups(15.12,7.56,3.78 g/kg),with 8 mice in each group.Upon the completion of the 14 days treatment,the rats had their TCM Syndrome scores assessed;their fecal water content,initial black stool excretion time,and small intestine propulsion rate measured;their colon tissue morphology observed by HE staining;their serum levels of IL-6,TNF-α,and IL-1β detected by ELISA;their expressions of occludin and zonula occludens-1(ZO-1)in colon tissues detected by immunohistochemistry;their mRNA expressions of MyD88,TLR4 and NF-κB p65 in the colon tissues detected by RT-qPCR;and their protein expressions of MyD88,TLR4 and NF-κB p65 in the colon tissues detected by Western blot.RESULTS Compared to the blank group,the model group had higher TCM Syndrome scores(P＜0.01);lower fecal water content and small intestine propulsion rate(P＜0.05,P＜0.01);longer initial black stool excretion time(P＜0.01);more mucosal edema in colon tissue,obvious inflammatory infiltration,and glandular disorder;increased serum levels of IL-6,TNF-α and IL-1 β(P＜0.05);decreased colon expressions of ZO-1 and occludin(P＜0.01);and increased mRNA and protein expressions of TLR4,MyD88 and NF-κB p65(P＜0.01).Compared to the model group,both the medium-dose Yunpi Tongchang Formula group and the mosapride citrate tablet group demonstrated effectively reduced TCM syndrome scores(P＜0.01);increased fecal water content and small intestine propulsion rate(P＜0.05,P＜0.01);and shorter initial black stool excretion time(P＜0.01);improved colon mucosal edema and inflammatory infiltration;decreased serum levels of IL-6,TNF-α and IL-1β(P＜0.01);upregulated protein expressions of ZO-1 and occludin(P＜0.01);and downregulated mRNA and protein expressions of TLR4,MyD88 and NF-κB p65(P＜0.05,P＜0.01).CONCLUSION Yunpi Tongchang Formula significantly ameliorates constipation symptoms in OIC rat models of Spleen-Kidney Yang Deficiency Syndrome because of its efficacy in attenuating intestinal inflammation and preserving the integrity of intestinal epithelial barrier structure,with its mechanistic action in downregulating TLR4/MyD88/NF-κB signaling pathway activation.

OBJECTIVE To investigate the changes of air aerosols in the digestive endoscope cleaning and disinfec-tion room under real working conditions and observe the purification effects of aerosols under different ventilation and disinfection modes.METHODS Under the real working conditions(with both the air conditioner and recircu-lating air disinfection machine under the working mode),the air samples were collected every 1 hour from 8:00 to 16:00 from the digestive endoscope cleaning and disinfection room of Ren Ji Hospital,Shanghai Jiao Tong U-niversity School of Medicine from May 2023 to Oct.2023;the contents of particulate matters(PM)and microor-ganisms in the air were detected.At the busiest moment of the cleaning and disinfection room,the air was respec-tively sampled from the cleaning and disinfection room with the working condition modes of air condition systems,recirculating air disinfection machine or natural ventilation before the starting of systems and after the work for 0.5 hour,1 hour and 2 hours.The contents of PMs and microorganisms were detected.RESULTS The PM0.5 con-centrations during various time periods met the Grade 9 ISO clean room standard(≤35,200 particles/L)under the real working conditions,and the content of airborne viable particles also conformed to the Class Ⅲ environmental requirements(≤500 CFU/m3).All of the three ventilation and disinfection methods showed certain effects on purification of the con-tents of PM0.5 and microorganisms after the ventilation for 2 hours,the contents of PMs and microorganisms of the air disinfection machine group decreased most remarkably,followed by the air conditioner group,the natural ventilation group the least.There were no significant differences in the PM concentration and the content of microorganisms among the three groups at the time points;there were only significant differences in the PM concentration and the content of mi-croorganisms of the air disinfection machine group after the ventilation for 2 hours,0.5 hour and 1 hour(P＜0.05).CONCLUSIONS Both the air conditioning systems and recirculating air disinfection machine under the working con-dition mode have certain effect on purification of the contents of PM and microorganisms,and the specific effect need to be further studied.The implementation of multicenter dynamic surveillance with the help of intelli-gent techniques may provide reference for the optimization of ventilation and disinfection strategies.

Objective:To analyze the correlation of monocyte/high density lipoprotein ratio(MHR),neutrophil/lymphocyte ratio(NLR),platelet/lymphocyte ratio(PLR)and bone density,bone metabolism markers in elderly essential hypertension with osteoporosis(OP)patients.Methods:This study was a retrospective study,198 elderly essential hypertension patients who were admitted in our hospital from January 2022 to June 2024 were selected.According to the patient's bone mass test results,patients were divided into normal bone mass group(n=79),osteopenia group(n=68)and OP group(n=51).MHR,NLR,PLR,bone density(left hip,left femoral neck and lumbar spine L1-L4)and bone metabolism markers were compared among three groups,the correlation of MHR,NLR,PLR and bone density,bone metabolism markers were analyzed by Pearson correlation.Results:MHR,NLR,PLR in normal bone mass group,osteopenia group and OP group increased in turn(P＜0.05).The left hip,left femoral neck and lumbar spine L1-L4 bone density in normal bone mass group,osteopenia group,OP group decreased in turn(P＜0.05).25-hydroxyvitamin D[25(OH)D]in normal bone mass group,osteopenia group and OP group decreased in turn,alkaline phosphatase(ALP)and parathyroid hormone(PTH)increased in turn(P＜0.05).MHR,NLR and PLR were negatively correlated with left hip bone density,left femoral neck bone density,lumbar spine L1-L4 bone density,25(OH)D and positively correlated with PTH and ALP(P＜0.05).Conclusion:The increase of MHR,NLR and PLR in elderly essential hypertension with OP patients can affect bone mineral density and bone metabolism.

Numerous studies have shown that depression is main-ly associated with the abnormal expression of connexin 43(Cx43)in astrocytes(Astro)and its mediated dysfunction of gap junction(GJ).However,the molecular mechanism of post-translational modifications targeting Cx43 to regulate neuroin-flammation-associated depression is still unclear.Post-transla-tional modifications of Cx43 mainly include phosphorylation of specific amino acid sites by PKC,PKA,PKG,MAPK and PTK,and protein degradation of Cx43 through the K48/K63 polyubiq-uitylation and deubiquitination pathways,which ultimately lead to protein degradation through K48/K63 polyubiquitination and deubiquitination.These modifications are ultimately involved in the regulation of neuroinflammatory responses through the associ-ation of GJ function.In this paper,we systematically review the role of Cx43 post-translational modifications in neuroinflamma-tion,with the aim of further exploring the potential application of targeting these modifications to modulate the inflammatory re-sponse mechanism in improving depressive symptoms.

Numerous studies have shown that depression is main-ly associated with the abnormal expression of connexin 43(Cx43)in astrocytes(Astro)and its mediated dysfunction of gap junction(GJ).However,the molecular mechanism of post-translational modifications targeting Cx43 to regulate neuroin-flammation-associated depression is still unclear.Post-transla-tional modifications of Cx43 mainly include phosphorylation of specific amino acid sites by PKC,PKA,PKG,MAPK and PTK,and protein degradation of Cx43 through the K48/K63 polyubiq-uitylation and deubiquitination pathways,which ultimately lead to protein degradation through K48/K63 polyubiquitination and deubiquitination.These modifications are ultimately involved in the regulation of neuroinflammatory responses through the associ-ation of GJ function.In this paper,we systematically review the role of Cx43 post-translational modifications in neuroinflamma-tion,with the aim of further exploring the potential application of targeting these modifications to modulate the inflammatory re-sponse mechanism in improving depressive symptoms.

Objective To investigate the distribution and antimicrobial resistance profiles of clinically isolated Haemophilus influenzae and Moraxella catarrhalis in hospitals across China from 2015 to 2021,and provide evidence for rational use of antimicrobial agents.Methods Data of H.influenzae and M.catarrhalis strains isolated from 2015 to 2021 in CHINET program were collected for analysis,and antimicrobial susceptibility testing was performed by disc diffusion method or automated systems according to the uniform protocol of CHINET.The results were interpreted according to the CLSI breakpoints in 2022.Beta-lactamases was detected by using nitrocefin disk.Results From 2015 to 2021,a total of 43 642 strains of Haemophilus species were isolated,accounting for 2.91％of the total clinical isolates and 4.07％of Gram-negative bacteria in CHINET program.Among the 40 437 strains of H.influenzae,66.89％were isolated from children and 33.11％were isolated from adults.More than 90％of the H.influenzae strains were isolated from respiratory tract specimens.The prevalence of β-lactamase was 53.79％in H.influenzae strains.The H.influenzae strains isolated from children showed higher resistance rate than the strains isolated from adults.Overall,779 strains of H.influenzae did not produce β-lactamase but were resistant to ampicillin(BLNAR).Beta-lactamase-producing strains showed significantly higher resistance rates to these antimicrobial agents than the β-lactamase-nonproducing strains.Of the 16 191 M.catarrhalis strains,80.06％were isolated from children and 19.94％isolated from adults.M.catarrhalis strains were mostly susceptible to both amoxicillin-clavulanic acid and cefuroxime,evidenced by resistance rate lower than 2.0％.Conclusions The emergence of antibiotic-resistant H.influenzae due to β-lactamase production poses a challenge for clinical anti-infective treatment.Therefore,it is very important to implement antibiotic resistance surveillance for H.influenzae and guide rational antibiotic use.All local clinical microbiology laboratories should actively improve antibiotic susceptibility testing and strengthen antibiotic resistance surveillance for H.influenzae.

Objective:To investigate the mechanism of natural antigen B(nAgB)to protect Immune thrombocytopenia(ITP)mouse model by influencing autophagy.Methods:Twenty-eight female BALB/c mice aged 8-10 weeks were randomly divided into four groups.7 mice of each group were immunized intraperitoneally,the control group was treated with PBS as the control group;ITP group was treated with anti-CD41 monoclonal antibody(anti-CD41Ab)only;nAgB group was treated with nAgB intraperitoneal injection for 5d;nAgB+ITP group was treated with nAgB intraperitoneal injection for 5d,then treated with anti-CD41 Ab.The peripheral blood platelet count in each group was tested;and the spleen and liver should be isolated and weighed,the organ index was calculated;qRT-PCR was used to detect spleen microtubule-associated protein 1 light chain 3(LC3),p62,Beclin-1 mRNA expression levels.Western blot was used to detect the protein expression level of spleen LC3 Ⅱ/LC3 Ⅰ,p62,Beclin-1.Results:Compared with the control group,mice in the ITP group showed a significant decrease in blood PLT count[(102.1±17.9)× 109/L vs(485.4±185.2)×109/L,P＜0.01],a significant increase in spleen index(P＜0.01),mice in the nAgB group showed a significant increase in blood PLT count,rising to(1051±127.6)× 109/L on the 3 day after modeling.Compared with the ITP group,mice in the nAgB+ITP group showed a significant increase in PLT count on the 1 day of anti-CD41 Ab administration[(428.6±131.6)× 109/L vs(102.1±17.9)×109/L,P＜0.05],however,the spleen index was significantly decreased(P＜0.05).qRT-PCR and Western blot results showed that compared with the control group,the mRNA and protein expression levels of spleen LC3,p62 and Beclin-1 were increased in the ITP group of mice(P＜0.05,P＜0.01).Compared with the ITP group,the nAgB+ITP group could significantly decrease mRNA levels of spleen LC3,p62 and Beclin-1(P＜0.05,P＜0.01),and also significantly decrease the protein expression levels of LC3 Ⅱ/LC3 Ⅰ,p62 and Beclin-1(P＜0.05,P＜0.01).Conclusion:nAgB inhibits the transcription and expression levels of autophagy-related genes and regulates immune intolerance,thereby protecting ITP mouse models.

Objective:To investigate the mechanism of natural antigen B(nAgB)to protect Immune thrombocytopenia(ITP)mouse model by influencing autophagy.Methods:Twenty-eight female BALB/c mice aged 8-10 weeks were randomly divided into four groups.7 mice of each group were immunized intraperitoneally,the control group was treated with PBS as the control group;ITP group was treated with anti-CD41 monoclonal antibody(anti-CD41Ab)only;nAgB group was treated with nAgB intraperitoneal injection for 5d;nAgB+ITP group was treated with nAgB intraperitoneal injection for 5d,then treated with anti-CD41 Ab.The peripheral blood platelet count in each group was tested;and the spleen and liver should be isolated and weighed,the organ index was calculated;qRT-PCR was used to detect spleen microtubule-associated protein 1 light chain 3(LC3),p62,Beclin-1 mRNA expression levels.Western blot was used to detect the protein expression level of spleen LC3 Ⅱ/LC3 Ⅰ,p62,Beclin-1.Results:Compared with the control group,mice in the ITP group showed a significant decrease in blood PLT count[(102.1±17.9)× 109/L vs(485.4±185.2)×109/L,P＜0.01],a significant increase in spleen index(P＜0.01),mice in the nAgB group showed a significant increase in blood PLT count,rising to(1051±127.6)× 109/L on the 3 day after modeling.Compared with the ITP group,mice in the nAgB+ITP group showed a significant increase in PLT count on the 1 day of anti-CD41 Ab administration[(428.6±131.6)× 109/L vs(102.1±17.9)×109/L,P＜0.05],however,the spleen index was significantly decreased(P＜0.05).qRT-PCR and Western blot results showed that compared with the control group,the mRNA and protein expression levels of spleen LC3,p62 and Beclin-1 were increased in the ITP group of mice(P＜0.05,P＜0.01).Compared with the ITP group,the nAgB+ITP group could significantly decrease mRNA levels of spleen LC3,p62 and Beclin-1(P＜0.05,P＜0.01),and also significantly decrease the protein expression levels of LC3 Ⅱ/LC3 Ⅰ,p62 and Beclin-1(P＜0.05,P＜0.01).Conclusion:nAgB inhibits the transcription and expression levels of autophagy-related genes and regulates immune intolerance,thereby protecting ITP mouse models.

Objectives: Hypoparathyroidism (HP) is a rare endocrine disorder caused by parathyroid hormone (PTH) defi ciency. The PTH is a candidate gene for familial isolated hypoparathyroidism (FIH). This study aimed to investigate the pathogenicity of two novel rare variants (RVs) ofPTH through in vitro functional study. Methods: Targeted next-generation sequencing was used to identify candidate gene mutations. Clinical data were retrospectively collected. Wild-type (WT) PTH was used as a template for site-directed mutagenesis to create mutant eukaryotic expression plasmids, which were transfected into cells. Treated with or without 4-phenylbu tyric acid (4-PBA), the levels of intact PTH (iPTH) and PTH (1-84) were measured by chemiluminescence, and protein expression was assessed using Western blotting. Results: Two patients carrying PTH mutations (c.154G > A: p.Val52Ile, c.270G > T: p.Leu90Phe) were identified.Patient 1, a 45-year-old male, presented with carpal and pedal numbness, muscle cramps, and low serum calcium (1.29 mmol/L). Patient 2, a 12-year-old female, had muscle twitches, convulsions, low calcium (1.50 mmol/L), and iPTH of 4 pg/mL. The iPTH or PTH (1-84) levels in the medium transfected with mutant Val52Ile and Leu90Phe PTH decreased by 31%–38%, and 51%–96% compared to WT (allP < 0.05), which were not rescued by 4-PBA. No significant changes in intracellular PTH expression were observed. Conclusions In this study, two novel RVs of PTH(Val52Ile and Leu90Phe) were identified that may impair hormone synthesis and secretion. Our study has broadened the mutation spectrum of the PTH and shed light on potential mechanisms underlying FIH.