Objective: To establish a real-time quality control scheme based on the median (MD-IC) of internal control cycle threshold value in negative samples (NEG-IC-CT), so as to monitor anomalies such as progressive drift in nucleic acid testing system not covered by conventional internal quality control (IQC) in blood center nucleic acid laboratories, and to verify its feasibility. Methods: The internal control CT values of 54 426 negative samples were retrospectively collected. These samples were from four reagent batches of the two new and old equipment sets during the operation of the Wantai nucleic acid testing system in our blood center. The daily median of NEG-IC-CT values was used as the research indicator. Control limits were calculated using median absolute deviation (MAD) to construct the Median-MAD quality control chart. The monitoring performance of this scheme for the operation status of the testing system was simultaneously evaluated. Results: Statistical analysis showed significant differences in NEG-IC-CT value distribution between the new and old equipment sets, as well as between the two different reagent batches of the old equipment (P<0.000 1). The NEG-IC-CT value performance of the two different reagent batches of the new equipment was no significant difference in distribution (P>0.05). This scheme identified three typies of distinct anomalies. The out-of-control events observed with the old equipment in both the O1 and O2 reagent batches suggested potential performance decay due to equipment aging. The unreported change of reagent batch in time of Phase B with new equipment caused a stepwise drift on the quality control chart. In the later stage of Phase A with the new equipment, an alert was triggered, indicating potential quality risks associated with practices such as the mixed use of the remaining reagents and extremely long operator working hours. Conclusion: The realtime quality control scheme based on NEG-IC-CT value established in this study has been preliminarily validated for its monitoring effectiveness in nucleic acid testing in our blood center. This scheme performed well in detecting differences among testing systems and reagent batches, serving as an effective supplement to routine internal quality control. It can provide an intuitive and effective evaluation method for monitoring the performance of the nucleic acid testing process at blood center.

ObjectiveTo investigate the molecular mechanisms by which Wenyang Jiedu granules （WYJD） alleviate influenza A virus （IAV）-induced pneumonia based on single-cell transcriptome sequencing. MethodsThirty female BALB/c mice were randomly divided into a blank control group （Control）， IAV group， and WYJD low-， medium-， and high-dose groups （WYJD-L， WYJD-M， WYJD-H； 2.925， 5.85， 11.7 g·kg^-1， n=6）. Except for the Control group， all other groups were intranasally inoculated with IAV subtype H1N1 （A/PR/8/34） to establish an infection model. Two hours after modeling， drug administration was initiated and continued for 5 consecutive days， with daily monitoring of body weight and general condition. On day 6， mice were sacrificed and samples were collected. Lung index was calculated， and histopathological examination of lung tissue was performed. Lung tissues from the Control， IAV， and WYJD-H groups were subjected to single-cell transcriptome sequencing （n=3）， focusing on type I alveolar epithelial cells （AT1） to analyze changes in gene expression and signaling pathways. Western blot was used to detect the expression changes of relevant proteins to validate the single-cell sequencing results. ResultsCompared with the Control group， the IAV group exhibited significantly decreased body weight （P<0.05） and significantly increased lung index （P<0.05）. Compared with the IAV group， all WYJD-treated groups exhibited significantly increased body weight （P<0.01） and significantly decreased lung index （P<0.01）. Single-cell sequencing analysis revealed that WYJD inhibited overactivation of interferon and inflammatory signaling pathways in AT1 cells after IAV infection， including interferon-γ response， interferon-α response， tumor necrosis factor-α/nuclear factor-κB （TNF-α/NF-κB）， and interleukin-6/Janus kinase/signal transducer and activator of transcription 3 （IL-6/JAK/STAT3） pathways. Compared with the Control group， the number of AT1 cells in the IAV group showed a decreasing trend. Compared with the IAV group， the WYJD-H group showed an increasing trend， although neither difference was statistically significant. Further analysis of AT1 cell subpopulation gene expression showed that， compared with the Control group， the IAV group exhibited increased expression of pro-apoptotic genes FAS cell surface death receptor （FAS） and cyclin-dependent kinase inhibitor 1A （CDKN1A）， a significant increase in tumor protein p53 （Tp53） expression （P<0.05）， and significant decreases in expression of the AT1 marker gene advanced glycosylation end-product-specific receptor （AGER） and membrane structural gene caveolin1 （CAV1） （P<0.05， P<0.01）. Compared with the IAV group， the WYJD-H group showed significantly decreased expression of FAS， CDKN1A， and Tp53 （P<0.05， P<0.01）， and significantly increased expression of AGER and CAV1 （P<0.05， P<0.01）. Regarding interferon response-related genes， compared with the Control group， the IAV group showed increased expression of interferon-stimulated gene 15 （ISG15）， interferon-induced protein with tetratricopeptide repeats 3 （IFIT3）， signal transducer and activator of transcription 2 （STAT2）， bone marrow stromal cell antigen 2 （BST2）， and C-X-C motif chemokine ligand 10 （CXCL10）， with a significant increase in 2′，5′-oligoadenylate synthetase-like protein 1 （OASL1） （P<0.05）. Compared with the IAV group， the WYJD-H group showed significantly decreased expression of all the above genes， with highly significant differences for ISG15， IFIT3， STAT2， BST2， and OASL1 （P<0.01）， and a significant difference for CXCL10 （P<0.05）. Among inflammation-related genes， compared with the Control group， the IAV group showed significantly increased expression of intercellular adhesion molecule 1 （ICAM1）， tumor necrosis factor alpha-induced protein 3 （TNFAIP3）， keratin 8 （KRT8）， tumor necrosis factor receptor superfamily member 1A （TNFRSF1A）， and TNFRSF1B （P<0.01）， and increased expression of NFKBIA， a negative regulator of NF-κB （P<0.05）. Compared with the IAV group， the WYJD-H group showed significantly decreased expression of KRT8 and TNFRSF1B （P<0.05）， while ICAM1， NFKBIA， TNFAIP3， and TNFRSF1A showed decreasing trends without statistical significance. Western blot validation showed that， compared with the Control group， protein expression levels of ISG15， FAS， p53， and phosphorylated p65 （p-p65） in lung tissue of the IAV group were significantly increased （P<0.05， P<0.01）. Compared with the IAV group， the WYJD-H group showed significantly decreased expression of these proteins （P<0.05， P<0.01）. ConclusionWYJD may alleviate viral pneumonia by targeting gene expression in AT1 cells， inhibiting overactivated interferon and inflammatory signaling pathways after IAV infection， and downregulating pro-apoptotic signaling， thereby reducing alveolar epithelial injury.

Objective The aim of this study was to analysis the incidence and mortality of malignant tumors in the cancer registration area of Kunming City in 2020,as well as the trend of changes from 2016 to 2020.Methods The malignant tumor data of 12 cancer registration areas in Kunming in 2020 that met the quality criteria were used to analyze the crude incidence,crude mortali-ty,age-standardized incidence/mortality rate by Chinese standard population(ASIRC/ASMRC)of malignant tumors in different gen-ders and regions.The annual percentage change(APC)was calculated using Joinpoint 5.3.0.0 software,the incidence and mortality trends of malignant tumors from 2016 to 2020 were evaluated.Results In 2020,the crude incidence and ASIRC of malignant tumors in cancer registration areas of Kunming City were 234.27/100,000 and 141.68/100,000,respectively.The ASIRC of males was high-er than that of females(146.94/100,000 vs.137.33/100,000,Z=3.459,P<0.001),and that of rural areas was higher than that of urban areas(146.37/100,000 vs.134.09/100,000,Z=-4.462,P<0.001).The crude mortality and ASMRC of malignant tumors were 135.67/100,000 and 73.18/100,000,respectively.The ASMRC of males was higher than that of females(91.65/100,000 vs.55.43/100,000,Z=19.260,P<0.001),and that of rural areas was higher than that of urban areas(76.27/100,000 vs.70.00/100,000,Z=-3.359,P<0.001).There were 81.39%of new cases and 90.36%of deaths of malignant tumors occurred in the popu-lation aged 50 and above.The top 5 cancer incidence in the Kunming City were lung cancer,colorectal cancer,breast cancer,liver cancer and prostate cancer.The top 5 cancer mortality were lung cancer,liver cancer,colorectal cancer,prostate cancer and stomach cancer.The ASIRC(APC=-3.05%,95%CI:-5.91%--0.10%,P=0.046)and ASMRC(APC=-5.47%,95%CI:-8.52%--2.32%,P=0.012)of malignant tumors in urban areas of Kunming showed a downward trend.Conclusions From 2016 to 2020,the ASIRC and ASMRC of malignant tumors in urban areas of Kunming showed a downward trend,but there was no significant changing trend in rural tumor registration areas.Rural areas are key areas for the prevention and treatment of malignant tumors in Kunming city;Lung cancer,colorectum cancer,liver cancer and prostate cancer are the key types of cancer for prevention and treatment.

Objective The aim of this study was to analysis the incidence and mortality of malignant tumors in the cancer registration area of Kunming City in 2020,as well as the trend of changes from 2016 to 2020.Methods The malignant tumor data of 12 cancer registration areas in Kunming in 2020 that met the quality criteria were used to analyze the crude incidence,crude mortali-ty,age-standardized incidence/mortality rate by Chinese standard population(ASIRC/ASMRC)of malignant tumors in different gen-ders and regions.The annual percentage change(APC)was calculated using Joinpoint 5.3.0.0 software,the incidence and mortality trends of malignant tumors from 2016 to 2020 were evaluated.Results In 2020,the crude incidence and ASIRC of malignant tumors in cancer registration areas of Kunming City were 234.27/100,000 and 141.68/100,000,respectively.The ASIRC of males was high-er than that of females(146.94/100,000 vs.137.33/100,000,Z=3.459,P<0.001),and that of rural areas was higher than that of urban areas(146.37/100,000 vs.134.09/100,000,Z=-4.462,P<0.001).The crude mortality and ASMRC of malignant tumors were 135.67/100,000 and 73.18/100,000,respectively.The ASMRC of males was higher than that of females(91.65/100,000 vs.55.43/100,000,Z=19.260,P<0.001),and that of rural areas was higher than that of urban areas(76.27/100,000 vs.70.00/100,000,Z=-3.359,P<0.001).There were 81.39%of new cases and 90.36%of deaths of malignant tumors occurred in the popu-lation aged 50 and above.The top 5 cancer incidence in the Kunming City were lung cancer,colorectal cancer,breast cancer,liver cancer and prostate cancer.The top 5 cancer mortality were lung cancer,liver cancer,colorectal cancer,prostate cancer and stomach cancer.The ASIRC(APC=-3.05%,95%CI:-5.91%--0.10%,P=0.046)and ASMRC(APC=-5.47%,95%CI:-8.52%--2.32%,P=0.012)of malignant tumors in urban areas of Kunming showed a downward trend.Conclusions From 2016 to 2020,the ASIRC and ASMRC of malignant tumors in urban areas of Kunming showed a downward trend,but there was no significant changing trend in rural tumor registration areas.Rural areas are key areas for the prevention and treatment of malignant tumors in Kunming city;Lung cancer,colorectum cancer,liver cancer and prostate cancer are the key types of cancer for prevention and treatment.

BACKGROUND:More and more scholars are investigating the mechanism of hypoxia-inducible factor-1α in regulating bone homeostasis and oral and maxillofacial diseases to provide new targets and strategies for the treatment of related disorders,but there is no relevant review.OBJECTIVE:To summarize the regulatory potential of hypoxia-inducible factor-1α in a variety of oral and maxillofacial diseases and bone homeostasis with the aim of providing a new research direction for oral and maxillofacial bone tissue engineering.METHODS:A literature review was conducted in databases such as PubMed,Web of Science and CNKI,for articles Published from 2003 to 2024.The keywords were"hypoxia inducible factor-1α,oral cavity,bone formation,osteoclast,angiogenesis,oxidative stress,tissue engineering,periodontitis,pulpitis,temporomandibular joint osteoarthritis"in Chinese and English.Finally,84 articles were included for review.RESULTS AND CONCLUSION:(1)Hypoxia-inducible factor-1α is essential in promoting bone tissue regeneration,facilitating osteogenic-angiogenic coupling,and mitigating damage from oxidative stress in bone tissue.(2)Increasing levels of hypoxia-inducible factor-1α in tissue cells reduces inflammation in periodontitis and promotes periodontal tissue remodeling,pulp regeneration,and involves in joint remodeling after temporomandibular joint osteoarthritis.(3)By stabilizing the level of hypoxia-inducible factor-1α in tissue cells,the micronutrient-carrying biomaterial promotes bone marrow mesenchymal stem cells to migrate and attach to the bone defect area,coupling angiogenesis and osteogenesis to achieve bone regeneration.(4)How to increase the level of hypoxia-inducible factor-1α in oral and maxillofacial tissues using bioactive materials to achieve bone regeneration at maxillofacial bone defects remains to be investigated.

Aim To investigate the effect of cumulative non-high density lipoprotein cholesterol/high density lip-oprotein cholesterol(non-HDLC/HDLC)exposure on atherosclerotic cardiovascular disease(ASCVD).Methods A prospective cohort study was conducted.A total of 50 777 employees of Kailuan Group who participated in three physical examinations in 2006-2007,2008-2009 and 2010-2011 were selected as the study subjects.Groups were divided into Q1,Q2,Q3 and Q4 according to the cumulative non-HDLC/HDLC exposure quartiles.Kaplan-Meier curve was used to calculate the cumulative incidence of ASCVD in different cumulative non-HDLC/HDLC groups,and Log-rank test was used to compare the differences among groups.Cox proportional risk model was used to analyze the effect of cumulative non-HDLC/HDLC exposure on ASCVD.Results The average follow-up was(10.19±2.21)years,and 5 003 new cases of ASCVD occurred.The cumulative incidence of ASCVD in groups Q1 to Q4 was 6.49％,8.71％,10.86％and 14.85％,respectively(Log-rank P＜0.01).Multivariate Cox regression analysis showed that compared with group Q1,the HR(95％CI)of ASCVD in groups Q2,Q3 and Q4 were 1.13(1.03～1.24),1.18(1.07～1.29),1.22(1.12～1.34),respectively;the HR(95％CI)of myocardial infarction were 1.15(0.87～1.53),1.44(1.10～1.88),1.67(1.29～2.17),respectively;the HR(95％CI)of revascularization were 1.21(0.99～1.49),1.31(1.07～1.60)and 1.49(1.22～1.81),respectively;the HR(95％CI)of ischemic stroke were 1.17(1.03～1.32),1.17(1.04～1.33)and 1.21(1.06～1.37),respectively;but the above association was not found when heart failure and atrial fibrillation were used as the outcome events.The restricted cubic spline showed that cumulative non-HDLC/HDLC values were line-arly associated with the risk of ASCVD.Conclusion Cumulative non-HDLC/HDLC exposure was positively associated with the risk of ASCVD.

Objective To investigate the influence of Liraglutide on carotid intima-media thickness(CIMT)and serum Sirtuin protein 6(SIRT6)in patients with type 2 diabetes mellitus(T2DM)complicated with carotid atherosclerosis(CAS).Methods A total of 120 hospitalized patients with T2DM complicated with CAS were enrolled in this study from the Department of Endocrinology of Affiliated Renhe Hospital of China Three Gorges University and Yiling Hospital of Yichang City from July 2022 to January 2024.All the patients were randomly divided into Liraglutide(Lir,n=59)group and control(Con,n=61)group.Lir group was treated with Liraglutide combined with current hypoglycemic regimen.Con group was adjusted based on the original hypoglycemic scheme.The expression of serum SIRT6 and CIMT were compared between the two groups before and after treatment.Results After 24 weeks treatment,the fasting plasma glucose(FPG),2-hour postprandial blood glucose(2 hPG),glycatde hemoglobin A1c(HbA1c)and high sensitivity C-reactive protein(hs-CRP)levels were all decreased in both groups(P<0.05 or P<0.01).BMI,TC,TG,LDL-C,plasminogen activator inhibitor-1(PAI-1)and CIMT were significantly lower(P<0.05),while SIRT6 and superoxide dismutase(SOD)was significantly higher in the Lir group after treatment(P<0.05).Pearson or Spearman correlation analysis showed that CIMT was positively correlated with BMI,FPG,2 hPG,HbA1c,TC,TG,LDL-C,hs-CRP,PAI-1,DM duration(r=0.322,0.218,0.202,0.610,0.363,0.238,0.343,0.558,0.183,0.371,P<0.05 or P<0.01),and negatively correlated with SIRT6,SOD and HDL-C(r=-0.525,-0.432,-0.207,P<0.05 or P<0.01).SIRT6 was negatively correlated with BMI,HbA1c,TC,LDL-C,hs-CRP and PAI-1(r=-0.320,-0.550,-0.408,-0.422,-0.769,-0.224,P<0.05 or P<0.01),and positively correlated with SOD(r=0.550,P<0.01).Multiple stepwise regression showed that hs-CRP and SOD were independent influencing factors for SIRT6.HbA1c and SIRT6 were influencing factors for CIMT of T2DM patients.Conclusions Liraglutide could improve glucose and lipid metabolism,increase serum SIRT6 and decrease CIMT.

Objective To explore the traditional Chinese medicine(TCM)syndrome characteristics of patients with Chikungunya hemorrhagic fever and to provide empirical data to support the application of TCM in diagnosing and treating Chikungunya hemorrhagic fever.Methods A cross-sectional survey was conducted to collect clinical data(sex,age,days since onset,and comorbidity underlying disease conditions)and TCM with four-examination information(symptoms,tongue manifestations,and pulse manifestations)from 255 patients with Chikungunya hemorrhagic fever who visited Lecong Hospital of Shunde,Foshan,the Third People's Hospital of Shunde District of Foshan,Shunde Hospital of Southern Medical University Affiliated Chencun Hospital between July 23 and July 29,2025.Factor and cluster analyses were used to summarize TCM syndrome characteristics and analyze core pathogenesis in conjunction with clinical features.Results Among the 255 patients with Chikungunya hemorrhagic fever,131 were male and 124 were female,with a age of(49.05±17.93)years and a disease duration of(3.26±1.78)days.Among the four types of examination information in TCM,35 items exhibited a frequency exceeding 10%.The most prevalent symptoms were arthralgia(180 patients,70.59%),exanthem(153 patients,60.00%),fatigue(99 patients,38.82%),anhidrosis(98 patients,38.43%),pruritus(96 patients,37.65%),and fever(92 patients,36.08%).Tongue and pulse manifestations were primarily white fur(155 patients,60.78%),pink tongue(111 patients,43.53%),slippery pulse(143 patients,56.08%),and greasy fur(134 patients,52.53%).Patients with disease onset≤3 d had a higher incidence of arthralgia,fatigue,fever,aversion to cold,generalized muscle pain,aversion to wind,insomnia,headache,sweating,low-grade fever,poor appetite,loose stool,hyperhidrosis,and red tongue than those with disease onset≥4 d(P<0.05).Patients with disease onset≥4 d had a higher incidence of pink tongue and thick fur than those with disease onset≤3 d(P<0.05).The syndrome elements in patients with Chikungunya hemorrhagic fever predominantly manifested on the defensive exterior,with involvement of the sinew-bone joints,skin-muscle,and spleen.Pathogenic factors were primarily characterized by external winds,dampness,and heat.Factor and cluster analysis result indicated three TCM pathogenesis progression patterns:imbalance of the defensive exterior with wind-dampness conflict and heat transformation;dampness-heat flowing into muscles and meridians causing joint obstruction and qi blood stasis;and dampness-heat congelation resulting in qi mechanism obstruction,consumption of body fluids,and infiltration of the skin.Conclusion Patients with Chikungunya hemorrhagic fever primarily present with fever,joint pain,and rashes.In TCM,this condition falls under the category of"dampness-warmth"syndrome.Its etiology is attributed to pathogens,with transmission occurring through mosquito bites.The core pathogenesis of TCM is the invasion of the defensive exterior and dampness-toxic heat accumulation.The therapeutic principles focus on clearing heat pathogens,resolving dampness pathogens,dispersing wind pathogens,and promoting the resolution of rashes.

Objective To analyze the proportion and clinicopathological characteristics of HER2-positive breast cancer patients with BRCA1/2 pathogenic variants, and their response to neoadjuvant anti-HER2 targeted therapy. Methods The clinicopathological data of 531 breast cancer patients with germline BRCA1/2 pathogenic variants (201 with BRCA1 variants and 330 with BRCA2 variants) were analyzed. Results Among the 201 BRCA1 and 330 BRCA2 variants, 17 (8.5%) and 42 (12.7%) HER2-positive breast cancer cases were identified, respectively, accounting for 11.1% of all BRCA1/2-mutated breast cancers. Compared with BRCA1/2-mutated HR-positive/HER2-negative patients, HER2-positive patients did not present any significant differences in clinicopathological features; however, compared with triple-negative breast cancer patients, HER2-positive patients had a later onset age and lower tumor grade. Among the 17 patients who received neoadjuvant anti-HER2 targeted therapy, 10 cases achieved pCR (58.8%), whereas 7 cases did not (41.2%). Conclusion HER2-positive breast cancer accounts for more than 10% of BRCA1/2-mutated patients. Approximately 40% of these patients fail to achieve pCR after neoadjuvant targeted therapy. This phenomenon highlights the possibility of combining anti-HER2 targeted agents with poly (adenosine diphosphate-ribose) polymerase inhibitors.

BACKGROUND:Bone defects can directly affect the success rate and long-term stability of dental implants.Studies have shown that salidroside has the ability to promote the proliferation and differentiation of osteoblasts,but less is reported on its pathways related to osteogenic differentiation. OBJECTIVE:To investigate the effects of salidroside on the proliferation and differentiation of MC3T3-E1 cells and the expression of related genes and proteins through in vitro cell experiments. METHODS:Cell counting kit-8 test and alkaline phosphatase test were used to determine the optimal concentration of salidroside(0.5,1,5,10,and 50 μmol/L)in promoting the proliferation and differentiation of MC3T3-E1 cells.There were four groups in the experiment:control group,salidroside group,salidroside+LY294002 group,and LY294002 group,which were cultured with osteogenic induction solution,osteogenic induction solution containing 10 μmol/L salidroside,osteogenic induction solution containing 10 μmol/L salidroside+10 μmol/L LY294002,and osteogenic induction solution containing 10 μmol/L LY294002,respectively.The effects of salidroside and LY294002,an inhibitor of the PI3K/Akt signaling pathway,on the expressions of genes and proteins related to osteogenesis were observed. RESULTS AND CONCLUSION:Cell counting kit-8 assay and alkaline phosphatase assay showed that salidroside promoted the proliferation of MC3T3-E1 cells most significantly at 10 μmol/L.Compared with the control group,salidroside could promote mineralization,promote cell adhesion,reduce cell death,increase mRNA expression of Runx-2,osteocalcin and osteopontin(P<0.01),and increase protein expression of Runx-2 and p-Akt(P<0.01).However,the addition of LY294002 reversed the above results.These findings indicate that salidroside can promote the mineralization of MC3T3-E1 cells and the expression of osteogenesis-related genes and proteins,which may be related to the activation of PI3K/Akt signaling pathway.