This paper summarizes the clinical experience in the syndrome differentiation and treatment of rosacea using the method of venting heat and resolving stagnation. It is considered that the key pathogenesis of rosacea is the accumulation of heat with stagnation. Accordingly， the method of venting heat and resolving stagnation is proposed， which vents and disperses constraint heat by applying approaches such as dredging defensive qi， clearing qi， venting ying （营） level， and cooling blood， while eliminating stagnation and masses through regulating qi， resolving dampness， dispelling phlegm and removing stasis. In clinical practice， a core prescription for venting heat and resolving stagnation is formulated， with flexible modifications made according to the clinical characteristics of different rosacea subtypes， including erythematotelangiectatic， papulopustular， phymatous， and ocular types， thereby providing therapeutic insights for the treatment of rosacea with traditional Chinese medicine.

Background and aims As a ferroptosis inducer, sorafenib, a first-line treatment for hepatocellular carcinoma (HCC), has a significant antitumor effect. Nonetheless, HCC patients frequently develop sorafenib resistance. Here, we investigated the impacts of progestagen-associated endometrial protein (PAEP), which controls sorafenib resistance and tumorigenesis in HCC. Furthermore, we investigated the function of PAEP and the underlying molecular mechanisms that cause HCC ferroptosis when sorafenib is applied. Methods Western blot analysis, cell proliferation, colony formation and animal experiments were performed to investigate the function of PAEP in sorafenib resistance and tumorigenesis in HCC. We detected the levels of reactive oxygen species, iron, and malondialdehyde and preformed transmission electron microscopy to investigate the relationship between PAEP and ferroptosis. Co-immunoprecipitation (co-IP) assay was performed to investigate the underlying molecular mechanisms of PAEP that cause HCC ferroptosis. Results PAEP was significantly overexpressed in HCC tissues, and this was associated with a poor clinical prognosis. PAEP silencing dramatically reduced HCC cells’ malignant phenotype. We found that sorafenib-induced ferroptosis was more sensitive to HCC cells with PAEP knockdown. Furthermore, the orthotopic cell line-derived xenograft mouse model results showed that sorafenib sensitivity can be effectively increased in vivo by PAEP knockdown. We determined that transferrin (TF) was a PAEP target using the String database, and we further supported this finding with Co-IP analysis. Additionally, on sorafenib-induced ferroptosis in HCC cells, TF partially reversed the effects of PAEP knockdown. Conclusions Our research indicates that PAEP may be a potential biomarker for predicting sorafenib resistance in HCC and disruption of PAEP expression may be a potential cancer-directed therapeutic option for HCC.

ObjectiveTo investigate the protective effect of Qiju Dihuang Wan on diabetic retinopathy （DR） and its regulatory mechanism on the NOD-like receptor protein 3/Cysteinyl aspartate-specific proteinase-1/Gasdermin D （NLRP3/Caspase-1/GSDMD） signaling pathway. MethodsHuman retinal microvascular endothelial cells （HRMEC） were divided into the blank group， model group， and Qiju Dihuang Wan low- and high-dose groups. Except for the blank group， all groups were induced with 40 mmol·L^-1 high glucose， and the treatment groups were supplemented with 6% and 12% Qiju Dihuang Wan-containing serum， respectively， based on the induction. After 24 h of culture， the levels of interleukin （IL）-1β and IL-18 were measured by enzyme-linked immunosorbent assay （ELISA）， pyroptosis-related protein expression was detected by immunofluorescence and Western blot， and the mRNA levels of NLRP3/Caspase-1/GSDMD signaling pathway-related molecules were determined by real-time polymerase chain reaction （Real-time PCR）. The mice were randomly divided into the blank group， model group， Qiju Dihuang Wan low-， medium-， and high-dose groups （11， 22， 44 g·kg^-1·d^-1）， and calcium dobesilate group （0.13 g·kg^-1·d^-1）. Except for the blank group， all groups were intraperitoneally injected with streptozotocin to establish the DR model. After successful modeling， the treatment groups received corresponding doses of Qiju Dihuang Wan crude drug or calcium dobesilate suspension by gavage once daily， while the blank group and model group received an equal volume of normal saline， for 8 consecutive weeks. Fundus changes were examined by optical coherence tomography， optical coherence tomography angiography， and fundus fluorescein angiography. Retinal pathological morphology was observed by hematoxylin-eosin staining. Real-time PCR was used to detect the mRNA levels of NLRP3， Caspase‑1， GSDMD， IL‑1β， and IL‑18 in retinal tissue， and Western blot was used to detect the protein expression of NLRP3， ASC， cleaved Caspase‑1， and GSDMD‑N. ResultsCell experiments showed that compared with the blank group， the model group showed significantly decreased HRMEC viability （P<0.01）， and significantly increased levels of IL-1β， IL-18， as well as increased protein expression of NLRP3， cleaved Caspase-1， and GSDMD-N （P<0.01）. Compared with the model group， the above indicators were significantly reduced in the high-dose Qiju Dihuang Wan groups （P<0.05， P<0.01）. Animal experiments showed that compared with the blank group， the model group had elevated blood glucose （P<0.01）， decreased retinal thickness and vascular density （P<0.01）， up‑regulated mRNA expression of NLRP3， Caspase‑1， GSDMD， IL‑1β and IL‑18 in retinal tissue （P<0.01）， and up‑regulated protein expression of NLRP3， ASC， cleaved Caspase‑1 and GSDMD‑N （P<0.01）. Compared with the model group， the Qiju Dihuang Wan medium- and high‑dose groups showed decreased blood glucose （P<0.01）， increased retinal thickness and vascular density （P<0.01）， alleviated retinal pathological damage， and down‑regulated mRNA expression of NLRP3， Caspase‑1， GSDMD， IL‑1β， IL‑18， as well as protein expression of NLRP3， ASC， cleaved Caspase‑1， and GSDMD‑N （P<0.05， P<0.01）. ConclusionQiju Dihuang Wan may exert protective effects against diabetic retinopathy by inhibiting the activation of the NLRP3/Caspase-1/GSDMD signaling pathway and alleviating high glucose-induced retinal pyroptosis.

ObjectiveTo investigate the protective effect of Qiju Dihuang Wan on diabetic retinopathy （DR） and its regulatory mechanism on the NOD-like receptor protein 3/Cysteinyl aspartate-specific proteinase-1/Gasdermin D （NLRP3/Caspase-1/GSDMD） signaling pathway. MethodsHuman retinal microvascular endothelial cells （HRMEC） were divided into the blank group， model group， and Qiju Dihuang Wan low- and high-dose groups. Except for the blank group， all groups were induced with 40 mmol·L^-1 high glucose， and the treatment groups were supplemented with 6% and 12% Qiju Dihuang Wan-containing serum， respectively， based on the induction. After 24 h of culture， the levels of interleukin （IL）-1β and IL-18 were measured by enzyme-linked immunosorbent assay （ELISA）， pyroptosis-related protein expression was detected by immunofluorescence and Western blot， and the mRNA levels of NLRP3/Caspase-1/GSDMD signaling pathway-related molecules were determined by real-time polymerase chain reaction （Real-time PCR）. The mice were randomly divided into the blank group， model group， Qiju Dihuang Wan low-， medium-， and high-dose groups （11， 22， 44 g·kg^-1·d^-1）， and calcium dobesilate group （0.13 g·kg^-1·d^-1）. Except for the blank group， all groups were intraperitoneally injected with streptozotocin to establish the DR model. After successful modeling， the treatment groups received corresponding doses of Qiju Dihuang Wan crude drug or calcium dobesilate suspension by gavage once daily， while the blank group and model group received an equal volume of normal saline， for 8 consecutive weeks. Fundus changes were examined by optical coherence tomography， optical coherence tomography angiography， and fundus fluorescein angiography. Retinal pathological morphology was observed by hematoxylin-eosin staining. Real-time PCR was used to detect the mRNA levels of NLRP3， Caspase‑1， GSDMD， IL‑1β， and IL‑18 in retinal tissue， and Western blot was used to detect the protein expression of NLRP3， ASC， cleaved Caspase‑1， and GSDMD‑N. ResultsCell experiments showed that compared with the blank group， the model group showed significantly decreased HRMEC viability （P<0.01）， and significantly increased levels of IL-1β， IL-18， as well as increased protein expression of NLRP3， cleaved Caspase-1， and GSDMD-N （P<0.01）. Compared with the model group， the above indicators were significantly reduced in the high-dose Qiju Dihuang Wan groups （P<0.05， P<0.01）. Animal experiments showed that compared with the blank group， the model group had elevated blood glucose （P<0.01）， decreased retinal thickness and vascular density （P<0.01）， up‑regulated mRNA expression of NLRP3， Caspase‑1， GSDMD， IL‑1β and IL‑18 in retinal tissue （P<0.01）， and up‑regulated protein expression of NLRP3， ASC， cleaved Caspase‑1 and GSDMD‑N （P<0.01）. Compared with the model group， the Qiju Dihuang Wan medium- and high‑dose groups showed decreased blood glucose （P<0.01）， increased retinal thickness and vascular density （P<0.01）， alleviated retinal pathological damage， and down‑regulated mRNA expression of NLRP3， Caspase‑1， GSDMD， IL‑1β， IL‑18， as well as protein expression of NLRP3， ASC， cleaved Caspase‑1， and GSDMD‑N （P<0.05， P<0.01）. ConclusionQiju Dihuang Wan may exert protective effects against diabetic retinopathy by inhibiting the activation of the NLRP3/Caspase-1/GSDMD signaling pathway and alleviating high glucose-induced retinal pyroptosis.

Objectives:This study aimed to investigate the impact of quantitative flow ratio(QFR)-guided revascularization on outcome of elderly patients with coronary artery disease(CAD)undergoing valve surgery.Methods:We retrospectively analyzed 750 consecutive patients with angiographically confirmed CAD(≥50%stenosis)who underwent valve surgery at Zhongshan Hospital,Fudan University,between January 2016 and December 2021.According to the patients'ages,they were divided into the younger group(age<70 years old,n=532)and the elderly group(age≥70 years old,n=218).Revascularization strategies were evaluated using anatomical(angiography-based)and functional(QFR-based)criteria.Anatomical complete revascularization(CR)was defined as bypass grafting for all lesions with≥70%diameter stenosis in major coronary arteries or≥50%stenosis in the left main coronary artery.Functional CR referred bypass grafting for all lesions with QFR≤0.80.Incomplete revascularization(ICR)was defined as failure to meet CR criteria.According to the anatomical and functional definitions,the younger group and the elderly group were further divided into the incomplete revascularization subgroup and the complete revascularization subgroup respectively.Major adverse cardiovascular events(MACE),including death,myocardial infarction,repeat revascularization,and stroke,were assessed as the composite endpoint.Results:Over a follow-up of(3.7±1.8)years,the overall MACE rate was 13.3%.The younger group exhibited significantly lower MACE rates than the elderly group(10.7%vs.19.7%,P=0.001).In the younger group,anatomical ICR did not increase MACE risk(HR=1.46,95%CI:0.81-2.62,P=0.164),whereas functional ICR significantly increased MACE risk(HR=2.27,95%CI:1.24-4.15,P=0.001).In the elderly group,neither anatomical ICR(HR=1.22,95%CI:0.62-2.41,P=0.540)nor functional ICR(HR=1.52,95%CI:0.78-2.96,P=0.172)was associated with increased MACE risk.Conclusions:In patients undergoing valve surgery with CAD,functional ICR correlated with adverse outcomes in the younger group,whereas neither anatomical nor functional ICR significantly affected prognosis in elderly patients.These findings suggest that a moderately conservative revascularization strategy may be more appropriate for elderly populations.

Objective To explore the factors influencing the blood concentration of voriconazole in elderly hospitalized patients and inform the probability of attaining the target concentration in clinical practice.Methods Patients aged ≥65 years who were hospitalized in the First Affiliated Hospital of Anhui Medical University from January 2022 to December 2023 and underwent voriconazole blood concentration monitoring were enrolled.Their voriconazole blood concentrations and clinical data were collected.The patients were grouped according to the target effective concentration 0.5-5.0 mg/L of voriconazole recommended by the Chinese Pharmacological Society guidelines.Multivariate logistic regression analysis was used to determine the factors affecting the rate of achieving the target concentration.Results The 202 enrolled patients included 139 males and 63 females.A total of 244 voriconazole blood concentrations were available.The median age of the patients was 74(range:65-95)years.Voriconazole blood concentration ranged from 0.08 to 13.38 mg/L.The average concentration was(4.10±2.45)mg/L.The target effective blood concentration of voriconazole was achieved in 65.35％(132/202)of the patients.Logistic regression results showed that the dosage regimen,body weight,and hypoproteinemia(albumin＜25 g/L)were the main factors affecting voriconazole blood concentration.Conclusions The dosing regimen,body weight,and hypoproteinemia are the main influencing factors of voriconazole blood concentration.Relevant factors should be fully considered in clinical medication to ensure the safety and effectiveness of voriconazole.

Objective To examine the changing prevalence and antimicrobial resistance profiles of Burkholderia cepacia in 52 hospitals across China from 2015 to 2021.Methods A total of 9 261 strains of B.cepacia were collected from 52 hospitals between January 1,2015 and December 31,2021.Antimicrobial susceptibility of the strains was tested using Kirby-Bauer method or automated antimicrobial susceptibility testing systems according to a unified protocol.The results were interpreted according to the breakpoints released in the Clinical & Laboratory Standards Institute(CLSI)guidelines(2023 edition).Results A total of 9 261 strains of B.cepacia were isolated from all age groups,especially elderly patients.The proportion was 11.1％(1 032 strains)in children,significantly lower than the proportion in adults.About half(46.5％,4 310/9 261)of the strains were isolated from patients at least 60 years old and 42.3％(3 919/9 261)of the strains were isolated from young adults.Most isolates(71.1％)were isolated from sputum and respiratory secretions,followed by urine(10.7％)and blood samples(8.1％).B.cepacia isolates were highly susceptible to the five antimicrobial agents recommended in the CLSI M100 document(33rd edition,2023).B.cepacia isolates showed relatively higher resistance rates to meropenem and levofloxacin.However,the resistance rates to ceftazidime,trimethoprim-sulfamethoxazole,and minocycline remained below 8.1％.The percentage of B.cepacia strains resistant to levofloxacin was the highest compared to other antibiotics in any of the three age groups(from 12.4％in the patients＜18 years old to 20.6％in the patients aged 60 years or older).Conclusions B.cepacia is one of the clinically important non-fermenting gram-negative bacteria.Accurate and timely reporting of antimicrobial susceptibility test results and ongoing antimicrobial resistance surveillance are helpful for rational prescription of antimicrobial agents and proper prevention and control of nosocomial infections.

Objective To investigate changes in gut microbiota during diabetic nephropathy(DN)pro-gression using 16S rDNA sequencing technology.Methods A total of 90 male SD rats were randomly divided into a normal control group(n=10,no modeling,regular feeding)and a model group(diabetes model).The diabetes model was established by a single intraperitoneal injection of streptozotocin(STZ)at 60 mg/kg,with regular feeding.According to the feeding time after modeling,the rats were divided into 2-week,4-week,8-week,and 12-week model groups(fed for 2,4,8,and 12 weeks after model establishment),with 20 rats in each group.Blood urea nitrogen(BUN)was measured using the urease method,serum creatinine(Scr)was deter-mined by the picric acid method,and ELISA was used to detect urinary kidney injury molecule-1(KIM-1)and neutrophil gelatinase-associated lipocalin(NGAL)levels.HE,PAS,and Masson staining were used to observe renal tissue pathological changes.Gut microbiota was collected from the rats,and 16S rDNA gene sequencing was used to analyze the gut microbiota to understand changes in the gut microbiota.Results Compared with the normal control group,the levels of KIM-1 and NGAL in urine of rats in all model groups were significantly increased(P<0.05).Pathological staining results showed that,compared with the normal control group,rats in all model groups exhibited diffuse thickening of the glomerular basement membrane and pathological chan-ges such as local necrosis and vacuolar degeneration in renal tubular epithelial cells.16S rDNA sequencing re-sults indicated that the abundance and structure of intestinal microbiota in rats of all model groups changed.Compared with the normal control group,in the 8-week and 12-week model groups,the relative abundance of Bacteroides and Akkermansia decreased,while the relative abundance of Roseburia,Alloprevotella,Prevotel-laceae-Ga6A1,and Ruminococcaceae UCG-005 increased.Compared with the normal control group,in the 12-week model group,the abundance of Akkermansia decreased and that of Prevotellaceae-NK3B31 increased.Conclusion The abundance and structure of gut microbial community in DN rats under conventional feeding at different time points change significantly,further confirming the"gut-kidney axis"theory.

Objective:To construct a risk prediction model for early post-injury respiratory failure in patients with traumatic cervical spinal cord injury (TCSCI) and validate its efficacy.Methods:A retrospective cohort study was conducted to analyze the clinical data of 393 TCSCI patients admitted to Zhengzhou Central Hospital Affiliated to Zhengzhou University from January 2020 to October 2024, including 294 males and 99 females, aged 18-82 years [59(45, 72)years]. Among them, 76 patients had respiratory failure (19.3%). The patients were randomly divided into the training set ( n=275) and validation set ( n=118) at a ratio of 7∶3. According to the presence of respiratory failure within one week after admission, 275 patients in the training set were divided into respiratory failure group ( n=53) and non-respiratory failure group ( n=222). The demographic data, injury characteristics, laboratory test results, and imaging findings of the patients were collected. Risk factors were determined through univariate analysis and multivariate Logistic regression analysis and a nomogram prediction model was constructed. The area under the receiver operating characteristic (ROC) curve (AUC) and Hosmer-Lemeshow test were used to evaluate the discrimination and calibration of the model. Decision curve analysis (DCA) was plotted to evaluate the clinical effectiveness of the prediction model. Results:The results of the univariate analysis showed that there were significant differences in history of respiratory diseases, causes of injury, Glasgow coma scale (GCS), American Spinal Injury Association (ASIA) classification, ASIA-motor score (AMS), injury severity score (ISS), clinical pulmonary infection score (CPIS), hypoproteinemia and cervical vertebra fracture and dislocation between the respiratory failure group and non-respiratory failure group in the training set ( P<0.05). The results of multivariate Logistic regression analysis indicated that GCS, ASIA classification, CPIS, and hypoproteinemia were independent risk factors for early post-injury respiratory failure in TCSCI patients ( P<0.05). Based on the above four variables, a Logistic regression equation was constructed: Logit( P)=2.361-0.675×ASIA classification+0.419×CPIS-0.358×GCS+0.854×hypoproteinemia. In the prediction model established based on this equation, the AUC was 0.96 (95% CI 0.94, 0.99) in the training set and 0.89 (95% CI 0.82, 0.96) in the validation set. In the calibration curves of the training set and validation set, the prediction curve and reference curve were approximately overlapping, with the average absolute errors of 0.04 and 0.03. DCA results demonstrated that both the training and validation sets exhibited positive net benefits when threshold probabilities fell within ranges of 0%-78% and 0%-87%, respectively. Conclusion:The risk prediction model for early post-injury respiratory failure in TCSCI patients based on GCS, ASIA classification, CPIS and hypoproteinemia has good predictive efficacy and clinical practicability.

Objective:To investigate the prevalence of scoliosis among middle school students through school-based screening, and to analyze the correlations between axial trunk rotation (ATR) angle and Cobb angle among those with scoliosis considering gender, age, body mass index (BMI) and curve type, so as to provide references for early prevention and treatment.Methods:Random cluster sampling was used to enroll 9501 middle school students from 11 schools in the Hanyang District of Wuhan. They underwent a six-step scoliosis screening with a forward bending test, scoliometer measurements, and confirmatory X-ray examinations. The students exhibiting scoliosis were stratified by gender, age, BMI, and curve type. The correlation between ATR angle and Cobb angle was subsequently analyzed within each subgroup.Results:Scoliosis was observed in 358 of the students (150 boys and 208 girls), a positive screening rate of 3.8%. Moreover, the positive screening rate was significantly higher among the girls (4.8%) than among the boys (2.9%). There was a moderate Spearman correlation ( r=0.69) between the ATR and Cobb angles in 358 of the students with scoliosis, both the boys ( r=0.69) and the girls ( r=0.70). When it came to age, there was a positive correlation between the ATR and Cobb angles for students aged 13 to 16 irrespective of their BMI classification, except that there was no significant correlation between the two angles for those classified as obese. In terms of Peking Union Medical College (PUMC) classification, there was a positive correlation for those in types Ia, Ib, Ic, IIa, IIb, IIc and IId, but there was no significant correlation between the two angles for those in type III. Conclusions:Scoliosis is prevalent among the group of adolescents studied. Society, schools and parents need to prioritize prevention, heightened awareness, timely diagnosis and early treatment, particularly for girls. The ATR angle may serve as a practical surrogate for estimating Cobb angle severity in scoliosis screening for single-curve or double-curve cases. However, ATR measurements may yield false-negative results among those with triple-curve deformities or the obese, underscoring the need for supplementary diagnostic methods among such populations.