A 71-year-old male presented with esophageal cancer and severe aortic valve regurgitation. Treatment strategies for such patients are controversial. Considering the risks of cardiopulmonary bypass and potential esophageal cancer metastasis, we successfully performed transcatheter aortic valve implantation and minimally invasive three-incision thoracolaparoscopy combined with radical resection of esophageal cancer (McKeown) simultaneously in the elderly patient who did not require neoadjuvant treatment. This dual minimally invasive procedure took 6 hours and the patient recovered smoothly without any surgical complications.

ObjectiveThis study aims to investigate the molecular mechanism by which Guizhi Fulingwan （GFW） inhibits ferroptosis in endometriosis （EMT） through the regulation of the hypoxia inducible factor-1α/heme oxygenase 1 （HIF-1α/HO-1） signaling pathway. MethodsMachine learning was employed to identify ferroptosis-related biomarkers associated with EMT. Network pharmacology was utilized to identify the active components of GFW and its potential therapeutic targets against EMT， including core targets. Functional enrichment analysis was conducted to explore the biological processes， molecular functions， cellular components， and signaling pathways associated with the potential targets. An EMT rat model was established via autologous transplantation. Thirty female Sprague-Dawley （SD） rats were randomly divided into five groups： sham-operated， model， positive control （dienogest at 0.2 mg·kg^-1）， low-dose GFW （2.5 g·kg^-1）， and high-dose GFW （5 g·kg^-1）. After modeling， the rats received their respective treatment by oral gavage for 28 consecutive days， while the sham and model groups received equal volumes of distilled water. Serum and ectopic endometrial tissues were collected. Hematoxylin and eosin （HE） staining was employed to evaluate morphological alterations in ectopic lesions. Quantitative real-time polymerase chain reaction （Real-time PCR） and Western blot were conducted to assess mRNA and protein expression of HIF-1α， HO-1， glutathione peroxidase 4 （GPX4）， spermidine/spermine N1-acetyltransferase （SAT1）， and prostaglandin-endoperoxide synthase 2 （PTGS2）. Tissue levels of malondialdehyde （MDA）， glutathione （GSH）， and ferrous iron （Fe²⁺） were quantified using commercial assay kits. Serum levels of interleukin-6 （IL-6） and transforming growth factor-β₁ （TGF-β₁） were measured via enzyme-linked immunosorbent assay （ELISA）. ResultsFive ferroptosis-related biomarkers in EMT were identified： ALOX12， CHAC1， SAT1， AST1， and HO-1. Network pharmacology analysis revealed 42 active components of GFW and 192 potential therapeutic target genes related to EMT treatment， with FOS， JUN， HO-1 identified as core targets. Functional enrichment analysis indicated that the potential targets were primarily involved in oxidative stress response and reactive oxygen species metabolism and were enriched in the HIF-1 signaling pathway. Compared to the sham-operated group， the model group exhibited significant increases in both mRNA and protein expression of HIF-1α， HO-1， and PTGS2， as well as elevated tissue levels of Fe²⁺ and MDA. Conversely， GSH levels and the expression of GPX4 and SAT1 were markedly reduced， and serum levels of IL-6 and TGF-β₁ levels were significantly higher （P<0.01）. Compared with the model group， all GFW-treated groups showed significant downregulation of HIF-1α and HO-1， reduced Fe²⁺ levels， and downregulated expression of MDA， PTGS2， IL-6， and TGF-β₁. Meanwhile， GSH， GPX4， and SAT1 expression levels were significantly increased （P<0.05， P<0.01）， effectively ameliorating iron overload and oxidative stress， thereby demonstrating therapeutic efficacy in EMT， with the high-dose GFW demonstrating the most pronounced therapeutic effects. ConclusionGFW exerts therapeutic effects on endometriosis by regulating the HIF-1α/HO-1 signaling pathway to rectify iron metabolism disorders and attenuate free iron-induced oxidative damage. It upregulates the antioxidative defense system to inhibit lipid peroxidation cascades and modulates inflammatory cytokine networks. These effects collectively disrupt the pathological interaction between ferroptosis and chronic inflammation， providing a novel theoretical foundation for the clinical application of GFW in EMT treatment.

Objective To investigate the therapeutic efficacy of Erchen Decoction plus Sanzi Yangqin Decoction in the treatment of elderly patients with acute exacerbation of chronic obstructive pulmonary disease(COPD)of phlegm-dampness accumulation in lung syndrome,and to explore its possible therapeutic mechanism through the interleukin 33/soluble growth stimulation expressed gene 2(IL-33/ST2)signaling pathway.Methods A prospective trial was conducted on 92 elderly patients with acute exacerbation of COPD of phlegm-dampness accumulation in lung syndrome who were treated in Haikou Hospital of Traditional Chinese Medicine from January 2021 to June 2023.The patients were randomly divided into the control group and the observation group according to the random number table method,with 46 cases in each group.The control group was treated with conventional western medicine,while the observation group was treated with Erchen Decoction plus Sanzi Yangqin Decoction on the basis of treatment for the control group,and the course of treatment covered two weeks.The changes of traditional Chinese medicine(TCM)syndrome scores,lung function indicators,white blood cell count(WBC),neutrophil percentage(Neut%),and serum IL-33,ST2,interleukin 6(IL-6)and interleukin 8(IL-8)levels of patients in the two groups before and after the treatment were observed,and the clinical efficacy and medication safety of the patients in the two groups were evaluated.Results(1)After two weeks of treatment,the total effective rate of the observation group was 86.96%(40/46)and that of the control group was 67.39%(31/46),and the intergroup comparison(tested by chi-square test)showed that the therapeutic effect of the observation group was significantly superior to that of the control group(P<0.05).(2)After treatment,the TCM syndrome scores such as dyspnea,suppression in the chest,cough and expectoration in the two groups were decreased compared with those before treatment(P<0.05),and the decrease in the observation group was significantly superior to that in the control group(P<0.01).(3)After treatment,the lung function indicators such as forced vital capacity(FVC),forced expiratory volume in one second(FEV1),and peak expiratory flow(PEF)of the two groups all improved compared with those before treatment(P<0.05),and the improvement in the observation group was significantly superior to that in the control group(P<0.01).(4)After treatment,the levels of inflammatory indicators such as WBC,Neut%,and serum IL-33,ST2,IL-6 and IL-8 in the two groups were all decreased compared with those before treatment(P<0.05),and the decrease in the observation group was significantly superior to that in the control group(P<0.01).(5)The total incidence of adverse reactions in both groups was all 8.70%(4/46),and the intergroup comparison showed that the difference was not statistically significant(P>0.05).Conclusion The clinical efficacy of Erchen Decoction plus Sanzi Yangqin Decoction in the treatment of elderly patients with acute exacerbation of COPD of phlegm-dampness accumulation in lung syndrome is remarkable,and it is effective on improving the TCM syndromes,related inflammatory indicators and lung function.Its mechanism may be related to the reduction of the patients'serum IL-33 level,the inhibition of IL-33/ST2 signaling pathway and the expression of related inflammatory factors,so as to inhibit inflammatory response and improve the progression of COPD.

BACKGROUND:Satisfactory clinical results have been achieved in the treatment of Sanders Ⅲ calcaneal fractures by percutaneous compression fixation with three-dimensional frame screws.However,whether the stability of minimally invasive plate internal fixation can be achieved in terms of biomechanics,and the advantages and disadvantages after comparison are still unknown. OBJECTIVE:To investigate the fixation effect of different internal fixation devices on Sanders Ⅲ calcaneal fractures by finite element analysis. METHODS:A finite element model of Sanders Ⅲ calcaneal fracture was made based on CT data of a 26-year-old healthy male volunteer.The calcaneal fracture models were fixed by minimally invasive three-dimensional frame screws and minimally invasive Y-plate.The longitudinal loads of 350 and 700 N were applied respectively.The displacement and stress distribution of the two models were analyzed,and the stability of each model was compared. RESULTS AND CONCLUSION:(1)The peak stress of bone block and implant in the minimally invasive three-dimensional frame screw model was significantly lower than that in the minimally invasive minimally invasive plate model.The average stress of bone block and implant in the three-dimensional frame screw model was also significantly lower than that in the minimally invasive plate model.(2)The maximum displacement of the two models was located at the medial side of the articular surface of the posterior talus,and the maximum displacement of the three-dimensional frame screw model was smaller than that of the minimally invasive plate model.(3)The longitudinal displacement between the anterior fragment and the medial fragment of the minimally invasive plate model was smaller,and the transverse and vertical displacement between the medial fragment and the middle fragment of the three-dimensional group screw model was smaller.(4)It is concluded that both of the two internal fixation models can provide satisfactory fixation effect.The three-dimensional frame screw model can provide better transverse and vertical stability with more uniform stress distribution and smaller comprehensive displacement of bone fragments,while the minimally invasive plate has more advantages in maintaining longitudinal stability.

Dental caries is the local destruction of hard tooth tissue caused by acidic byproducts generated by cariogenic bacteria,primarily Streptococcus mutans,which ferment free sugars in the presence of host factors,dietary components,and environmental conditions.A main feature of dental caries is the formation of dental plaque biofilm,which significantly improves the resistance of bacteria to drugs and host immunity.Traditional anti-caries drugs mainly exert anti-biofilm functions indirectly through antibacterial activities.However,they tend to interfere with the symbiotic microbiota while inhibiting cariogenic bacteria,which may cause imbalance within the oral microbial system.With increasing attention paid to the homeostasis of oral microbiota,new types of anti-caries drugs have been developed,such as natural extracts,artificially synthesized small molecules,and oligonucleotides.They act on key targets to inhibit the formation of biofilm substrates or regulate the interactions between oral microorganisms,thereby efficiently inhibiting biofilm formation.These drugs do not have bactericidal effects.Nevertheless,they exert indirect antimicrobial effects by interfering with biofilm substrate formation or microbial interactions.The optimization of delivery carriers,combination drug therapy,and biomimetic design further enhance the efficacy of these new types of anti-caries drugs.This article provides a review of the prevention and treatment principles and key targets of dental plaque biofilm.We also discussed the types,mechanisms of action,and development trends of relevant drugs.

OBJECTIVE: To compare and analyze the effect of unplanned versus planned admission to the intensive care unit (ICU) on the prognosis of high-risk patients after surgery, so as to provide a clinical evidence for clinical medical staff to evaluate whether the postoperative patients should be transferred to ICU or not after surgery. METHODS: The clinical data of patients who were transferred to ICU after surgery admitted to the Affiliated Hospital of Guizhou Medical University from January to December in 2021 were retrospectively analyzed, including gender, age, body mass index, past history (whether combined with hypertension, diabetes, pulmonary disease, cardiac disease, renal failure, liver failure, hematologic disorders, tumor, etc.), acute physiology and chronic health evaluation II (APACHE II), elective surgery, pre-operative hospital consultation, length of surgery, worst value of laboratory parameters within 24 hours of ICU admission, need for invasive mechanical ventilation (IMV), duration of IMV, length of ICU stay, total length of hospital stay, ICU mortality, in-hospital mortality, and survival status at 30th day postoperative. The unplanned patients were further divided into the immediate transfer group and delayed transfer group according to the timing of their ICU entrance after surgery, and the prognosis was compared between the two groups. Cox regression analysis was used to find the independent risk factors of 30-day mortality in patients transferred to ICU after surgery. RESULTS: Finally, 377 patients were included in the post-operative admission to the ICU, including 232 in the planned transfer group and 145 in the unplanned transfer group (42 immediate transfers and 103 delayed transfers). Compared to the planned transfer group, patients in the unplanned transfer group had higher peripheral blood white blood cell count (WBC) at the time of transfer to the ICU [×10⁹/L: 10.86 (7.09, 16.68) vs. 10.11 (6.56, 13.27)], longer total length of hospital stay [days: 23.00 (14.00, 34.00) vs. 19.00 (12.00, 29.00)], and 30-day post-operative mortality was higher [29.66% (43/145) vs. 17.24% (40/232)], but haemoglobin (Hb), arterial partial pressure of carbon dioxide (PaCO₂), oxygenation index (PaO₂/FiO₂), and IMV requirement rate were lower [Hb (g/L): 95.00 (78.00, 113.50) vs. 98.00 (85.00, 123.00), PaCO₂ (mmHg, 1 mmHg ≈ 0.133 kPa): 36.00 (29.00, 41.50) vs. 39.00 (33.00, 43.00), PaO₂/FiO₂ (mmHg): 197.00 (137.50, 283.50) vs. 238.00 (178.00, 350.25), IMV requirement rate: 82.76% (120/145) vs. 93.97% (218/232)], all differences were statistically significant (all P < 0.05). Kaplan-Meier survival curve showed that the 30-day cumulative survival rate after surgery was significantly lower in the unplanned transfer group than in the planned transfer group (Log-Rank test: χ² = 7.659, P = 0.006). Univariate Cox regression analysis showed that unplanned transfer, APACHE II score, whether deeded IMV at transfer, total length of hospital stay, WBC, blood K⁺, and blood lactic acid (Lac) were associated with 30-day mortality after operation (all P < 0.05). Multifactorial Cox analysis showed that unplanned transfer [hazard ratio (HR) = 2.45, 95% confidence interval (95%CI) was 1.54-3.89, P < 0.001], APACHE II score (HR = 1.03, 95%CI was 1.00-1.07, P = 0.031), the total length of hospital stay (HR = 0.86, 95%CI was 0.83-0.89, P < 0.001), the need for IMV on admission (HR = 4.31, 95%CI was 1.27-14.63, P = 0.019), highest Lac value within 24 hours of transfer to the ICU (HR = 1.17, 95%CI was 1.10-1.24, P < 0.001), and tumor history (HR = 3.12, 95%CI was 1.36-7.13, P = 0.007) were independent risk factors for patient death at 30 days post-operative, and the risk of death was 2.45 times higher in patients unplanned transferred than in those planned transferred. Subgroup analysis showed that patients in the delayed transfer group had significantly longer IMV times than those in the immediate transfer group [hours: 43.00 (11.00, 121.00) vs. 17.50 (2.75, 73.00), P < 0.05]. CONCLUSIONS The 30-day mortality, WBC and total length of hospital stay were higher in patients who were transferred to ICU after surgery, and PaO₂/FiO₂ was lower. Unplanned transfer, oncology history, use of IMV, APACHE II score, total length of hospital stay, and Lac were independent risk factors for patient death at 30 days postoperatively, and patients with delayed transfer to ICU had longer IMV time.
Humans ; Retrospective Studies ; Respiration, Artificial ; Hospitalization ; Prognosis ; Intensive Care Units

OBJECTIVE: To explore the genetic basis of three children with unexplained mental retardation/developmental delay. METHODS: Peripheral venous blood samples were collected for routine G-banding karyotyping analysis and chromosomal microarray analysis (CMA). Whole exome sequencing (WES) was also carried out for patient 3. RESULTS: The karyotypes of the 3 children were normal. The result of CMA analysis of patient 1 was arr[GRCh37]: 2q22/3(145 128 071-145 159 029)×1, with a 31 kb deletion, which was predicted to be a pathogenic copy number variation. The deletion has involved exons 8 to 10 of the ZEB2 gene. Patient 2 was arr[hg19]:2q22.3 (145 071 457-146 881 759)×1, with a 1.81 Mb deletion involving the ZEB2 and GTDC1 genes. Patient 3 was arr[GRCh37]: 9p23p23(11 698 261-12 106 261)×1, with a 408 kb deletion containing no disease-associated gene. WES has identified a c.2102C>A (p.Ser701*) variant in exon 8 of the ZEB2 gene, which was included in ClinVar database and rated as pathogenic, and verified by Sanger sequencing as a de novo variant. CONCLUSION For the substantial clinical and genetic heterogeneity of Mowat-Wilson-syndrome, CMA and WES are helpful to identify the etiology of children with developmental delay/mental retardation of unknown causes, particularly those with peculiar facial features and multiple congenital malformations.
Child ; DNA Copy Number Variations ; Facies ; Glycosyltransferases/genetics* ; Hirschsprung Disease ; Humans ; Intellectual Disability/genetics* ; Microcephaly/genetics*

Lingguizhugan Decoction (LGZG) has been investigated in basic studies, with satisfactory effects on insulin resistance in non-alcoholic fatty liver disease (NAFLD). This translational approach aimed to explore the effect and underlying mechanism of LGZG in clinical setting. A randomized, double-blinded, placebo-controlled trial was performed. A total of 243 eligible participants with NAFLD were equally allocated to receive LGZG (two groups: standard dose and low dose) or placebo for 12 weeks on the basis of lifestyle modifications. The primary efficacy variable was homeostasis model assessment of insulin resistance (HOMA-IR). Analyses were performed in two populations in accordance with body mass index (BMI; overweight/obese, BMI ⩾ 24 kg/m²; lean, BMI < 24 kg/m²). For overweight/obese participants, low-dose LGZG significantly decreased their HOMA-IR level compared with placebo (-0.19 (1.47) versus 0.08 (1.99), P = 0.038). For lean subjects, neither dose of LGZG showed a superior effect compared with placebo. Methylated DNA immunoprecipitation sequencing and real-time qPCR found that the DNA N6-methyladenine modification levels of protein phosphatase 1 regulatory subunit 3A (PPP1R3A) and autophagy related 3 (ATG3) significantly increased after LGZG intervention in overweight/obese population. Low-dose LGZG effectively improved insulin resistance in overweight/obese subjects with NAFLD. The underlying mechanism may be related to the regulation of DNA N6-methyladenine modification of PPP1R3A and ATG3. Lean subjects may not be a targeted population for LGZG.
Humans ; Non-alcoholic Fatty Liver Disease/drug therapy* ; Overweight/drug therapy* ; Insulin Resistance ; Obesity/drug therapy* ; China ; DNA/therapeutic use*

Pulmonary arteriovenous malformations (PAVMs) can induce cryptogenic stroke and are also an important cause of stroke in young adults. The risk of ischemic stroke increases with age in patients with PAVMs. Contrast echocardiography can be used for early screening of PAVMs, especially in young patients with cryptogenic stroke. After treatment, patients with PAVMs have a reduced risk of ischemic stroke. This article summarizes the etiology, pathogenesis, diagnosis and treatment of PAVMs by retrieving studies on PAVMs and ischemic stroke, in order to improve the understanding of PAVMs and avoid misdiagnosis and missed diagnosis.