With the widespread adoption of low-dose CT screening and the extensive application of high-resolution CT, the detection rate of sub-centimeter lung nodules has significantly increased. How to scientifically manage these nodules while avoiding overtreatment and diagnostic delays has become an important clinical issue. Among them, lung nodules with a consolidation tumor ratio less than 0.25, dominated by ground-glass shadows, are particularly worthy of attention. The therapeutic challenge for this group is how to achieve precise and complete resection of nodules during surgery while maximizing the preservation of the patient's lung function. The "watershed topography map" is a new technology based on big data and artificial intelligence algorithms. This method uses Dicom data from conventional dose CT scans, combined with microscopic (22-24 levels) capillary network anatomical watershed features, to generate high-precision simulated natural segmentation planes of lung sub-segments through specific textures and forms. This technology forms fluorescent watershed boundaries on the lung surface, which highly fit the actual lung anatomical structure. By analyzing the adjacent relationship between the nodule and the watershed boundary, real-time, visually accurate positioning of the nodule can be achieved. This innovative technology provides a new solution for the intraoperative positioning and resection of lung nodules. This consensus was led by four major domestic societies, jointly with expert teams in related fields, oriented to clinical practical needs, referring to domestic and foreign guidelines and consensus, and finally formed after multiple rounds of consultation, discussion, and voting. The main content covers the theoretical basis of the "watershed topography map" technology, indications, operation procedures, surgical planning details, and postoperative evaluation standards, aiming to provide scientific guidance and exploration directions for clinical peers who are currently or plan to carry out lung nodule resection using the fluorescent microscope watershed analysis method.

The accumulation and spread of prion-like proteins is a key feature of neurodegenerative diseases (NDs) such as Alzheimer's disease, Parkinson's disease, or Amyotrophic Lateral Sclerosis. In a process known as 'seeding', prion-like proteins such as amyloid beta, microtubule-associated protein tau, α-synuclein, silence superoxide dismutase 1, or transactive response DNA-binding protein 43 kDa, propagate their misfolded conformations by transforming their respective soluble monomers into fibrils. Cellular and molecular evidence of prion-like propagation in NDs, the clinical relevance of their 'seeding' capacities, and their levels of contribution towards disease progression have been intensively studied over recent years. This review unpacks the cyclic prion-like propagation in cells including factors of aggregate internalization, endo-lysosomal leaking, aggregate degradation, and secretion. Debates on the importance of the role of prion-like protein aggregates in NDs, whether causal or consequent, are also discussed. Applications lead to a greater understanding of ND pathogenesis and increased potential for therapeutic strategies.
Humans ; Prions ; Neurodegenerative Diseases/pathology* ; Amyloid beta-Peptides ; Alzheimer Disease ; alpha-Synuclein ; tau Proteins ; Parkinson Disease

Objective:To assess the prevalence of dentinal hypersensitivity (DH) and related factors in urban adults in China.Methods:The study was designed as an observational, cross-sectional epidemiological study carried out in adults aged 18-69 years old in seven cities (Beijing, Shanghai, Wuhan, Chengdu, Xi′an, Guangzhou, and Harbin) of China. The study was conducted from March 2021 to May 2023. Patients were required to complete a questionnaire regarding the subjects′ socio-economic factors, dietary behavior, oral health behavior and personal antecedent factors. DH was clinically diagnosed by judging whether the tooth cold air stimulation provoked DH or not, and recorded by investigator pain rating Schiff score. Compare the findings of six cities (Harbin excluded) with a similar study conducted in 2008.Results:In total, 11 622 subjects from seven cities in China participated the study. Fifty two point two percent (6 072/11 622) of subjects reported DH in questionnaire, 36.7% (4 266/11 622) of subjects reported experiencing DH in response to cold air stimulation for at least one study tooth. Risk factors including age, sex, city, toothbrush method and acid reflux showed marked associations with DH ( P<0.05). The prevalence of DH of urban residents in six cities (Harbin excluded) was 33.7% (3 335/9 882), higher than that in 2008 [29.7%(2 354/7 939)]. Conclusions:Overall, DH was common among urban adults in China and the prevalence increased in recent years. Better understanding of DH and its associated factors should be considered in its prevention and management by dental professionals.

A Clinical pharmacist was fully involved in the anticoagulation drug treatment management process of a 104-year-old patient with a large area of cerebral infarction combined with chronic kidney disease stage Ⅴ and secondary deep vein thrombosis.After the patient was diagnosed with deep vein thrombosis,the clinical pharmacist comprehensively analyzed the patient's super-advanced age,history of atrial fibrillation,large area of cerebral infarction,extremely poor kidney function,deep vein thrombosis,and high bleeding risk indicated by the HAS-BLED score.They worked with the clinical doctor to develop an individualized anticoagulation treatment strategy for the patient.At the beginning of the treatment,warfarin was given to the patient at a daily dose of 1.25 mg,and the patient's coagulation indicators and kidney function were dynamically rechecked.The patient's blood creatinine level did not show significant changes throughout the anticoagulation treatment process.On the 8th day of medication,the patient's INR was 2.47,and the clinical pharmacist suggested adjusting the Warfarin to an alternate-day dose of 1.25 mg and 0.625 mg.Subsequently,the patient's INR was 2.41,and the condition improved,leading to discharge.Throughout the anticoagulation drug management process,the clinical pharmacist participated in the clinical decision-making for anticoagulant drug selection,provided professional medication guidance,and pharmacological monitoring to ensure the safe clinical use of drugs for special populations.

Immmunosuppressants are mainly used to reduce rejection after solid organ transplantation,so as to improve the success rate of organ transplantation.However,long-term use of immunosuppressants can also serious-ly impair the immune function of patients,thereby increasing the risk of viral infection and postoperative complica-tions,leading to transplant failure.Therefore,patients need to use both immunosuppressants and antiviral agents.If some immunosuppressants with antiviral effects are found,the patient's burden of taking medicines will be greatly reduced.Currently,the immunosuppressants with antiviral effect have been focused by researchers.The gradual re-vealing of the antiviral mechanism of these immunosuppressants will help to optimize the treatment plan of postope-rative rehabilitation of organ transplant recipients.Based on the mechanism of rejection of transplanted organ,this paper systematically describes the types of viruses which closely related to infection of organ transplant patients and the molecular mechanism of some immunosuppressants in antiviral aspects,which further provides a new idea for clinical prevention and treatment of viral infection due to organ transplantation.

H 1-antihistamines are widely used in the treatment of various allergic diseases, but there are still many challenges in the safe and rational use of H 1-antihistamines in pediatrics, and there is a lack of guidance on the prescription review of H 1-antihistamines for children.In this paper, suggestions are put forward from the indications, dosage, route of administration, pathophysiological characteristics of children with individual difference and drug interactions, so as to provide reference for clinicians and pharmacists.

OBJECTIVE: To study effects of Shenmai Injection on hypertensive heart failure and its mechanism for inhibiting myocardial fibrosis. METHODS: Salt-sensitive (Dahl/SS) rats were fed with normal diet (0.3% NaCl) and the high-salt diet (8% NaCl) to observe the changes in blood pressure and heart function, as the control group and the model group. Salt-insensitive rats (SS-13BN) were fed with the high-salt diet (8% NaCl) as the negative control group. After modeling, the model rats were randomly divided into heart failure (HF) group, Shenmai Injection (SMI) group and pirfenidone (PFD) group by a random number table, with 6 rats in each group. They were given sterilized water, SMI and pirfenidone, respectively. Blood pressure, cardiac function, fibrosis and related molecular expression were detected by sphygmomanometer, echocardiogram, enzyme linked immunosorbent assay (ELISA), hematoxylin-eosin staining, Masson staining, immunofluorescence and qPCR analysis. RESULTS: After high-salt feeding, compared with the control and negative control group, in the model group the blood pressure increased significantly, the left ventricular ejection fraction (LVEF) and left ventricular fraction shortening (LVFS) were significantly reduced, and the serum NT-proBNP concentration increased significantly (all P<0.05); furthermore, the arrangement of myocardial cells was disordered, the edema was severe, and the degree of myocardial fibrosis was also significantly increased (P<0.05); the protein and mRNA expressions of collagen type I (Col I) were up-regulated (P<0.05), and the mRNA expressions of transforming growth factor β 1 (TGF- β 1), Smad2 and Smad3 were significantly up-regulated (P<0.05). Compared with HF group, after intervention of Shenmai Injection, LVEF and LVFS increased, myocardial morphology was improved, collagen volume fraction decreased significantly (P<0.05), and the mRNA expressions of Col I, TGF- β 1, Smad2 and Smad3, as well as Col I protein expression, were all significantly down-regulated (all P<0.05). CONCLUSION Myocardial fibrosis is the main pathological manifestation of hypertensive heart failure, and Shenmai Injection could inhibit myocardial fibrosis and effectively improve heart failure by regulating TGF-β 1/Smad signaling pathway.
Rats ; Animals ; Stroke Volume ; Sodium Chloride ; Rats, Inbred Dahl ; Ventricular Function, Left ; Heart Failure ; Transforming Growth Factor beta1/metabolism* ; Hypertension ; Fibrosis ; RNA, Messenger

Nowadays potential preclinical drugs for the treatment of nonalcoholic steatohepatitis (NASH) have failed to achieve expected therapeutic efficacy because the pathogenic mechanisms are underestimated. Inactive rhomboid protein 2 (IRHOM2), a promising target for treatment of inflammation-related diseases, contributes to deregulated hepatocyte metabolism-associated nonalcoholic steatohepatitis (NASH) progression. However, the molecular mechanism underlying Irhom2 regulation is still not completely understood. In this work, we identify the ubiquitin-specific protease 13 (USP13) as a critical and novel endogenous blocker of IRHOM2, and we also indicate that USP13 is an IRHOM2-interacting protein that catalyzes deubiquitination of Irhom2 in hepatocytes. Hepatocyte-specific loss of the Usp13 disrupts liver metabolic homeostasis, followed by glycometabolic disorder, lipid deposition, increased inflammation, and markedly promotes NASH development. Conversely, transgenic mice with Usp13 overexpression, lentivirus (LV)- or adeno-associated virus (AAV)-driven Usp13 gene therapeutics mitigates NASH in 3 models of rodent. Mechanistically, in response to metabolic stresses, USP13 directly interacts with IRHOM2 and removes its K63-linked ubiquitination induced by ubiquitin-conjugating enzyme E2N (UBC13), a ubiquitin E2 conjugating enzyme, and thus prevents its activation of downstream cascade pathway. USP13 is a potential treatment target for NASH therapy by targeting the Irhom2 signaling pathway.

Objective:To understand the impact of intimate social networks and sexual networks on HIV-infection in men aged ≥50 years in Pengzhou, Sichuan Province, and provide reference for the formulation of HIV/AIDS prevention and control strategies in middle-aged and elderly people.Methods:A case-control study was conducted by an interview-style questionnaire survey in a case group consisted of 114 men aged ≥50 years and a control group consisted of 423 healthy men matched by age frequency in Pengzhou, Sichuan Province, from April 2019 to October 2020, and the influencing factors of HIV infection were identified by unconditional stepwise logistic regression analysis.Results:Among the 114 cases, 63.16% (72/114) and 96.49% (110/114) of men had intimate social network size and sexual network size ≥4 people, which were higher than the control group of 23.40% (99/423) and 11.58% (49/423) (all P<0.05).The overlap of intimate social network and sexual network was 49.12% (56/114) in the case group, which was lower than that in the control group (82.27%, 348/423)( P<0.05). Logistic regression analysis showed that the size of the intimate social network ≥4 people ( OR=8.66, 95 %CI: 2.01-37.30), the size of the sexual network ≥4 people ( OR=1 121.11, 95% CI: 28.38-4 429.61), the material support from the first intimate network member ( OR=6.39, 95% CI: 1.03-39.75), and multiple sexual partners ( OR=55.50, 95% CI: 6.22-494.96) were the risk factors of HIV-infection in men aged ≥50 years. Receiving health education about AIDS ( OR=0.07, 95% CI: 0.01-0.37), high sexual satisfaction with the first sexual partner and good personal relationship ( OR=0.02, 95% CI: 0.01-0.59; OR=0.01, 95% CI: 0.01-0.26), and the overlap between intimate social network and sexual network ( OR=0.02, 95% CI: 0.01-0.38) were the protective factors of HIV-infection in men aged ≥50 years. Conclusions:The overlap of intimate social network and sexual network can reduce the risk of HIV-infection in men aged ≥50 years. It is important to help middle-aged and elderly men to build good and stable intimate social and sexual networks to meet their social communication and sex demands and prevent HIV infection by reducing high riak sexual behaviors.

ObjectiveTo study the pathological process and changes of metabolites in myocardial tissue of heart failure induced by transverse aortic constriction （TAC） in rats. MethodRats were treated with TAC operation and divided into TAC-30 d group and TAC-60 d group， and sham operation group at the same period was set up as control. Echocardiography and pathological staining of myocardial tissue were performed on rats in each group. Enzyme-linked immunosorbent assay was used to determine the expression of amino-terminal pro-brain natriuretic peptide （NT-proBNP） and adenosine triphosphate （ATP） in serum. Liquid chromatography-mass spectrometry was used to observe the changes of metabolites and related pathways in myocardial tissue， the mobile phase consisted of 25 mmol·L^-1 ammonium acetate and 25 mmol·L^-1 ammonia hydroxide in water （A） and acetonitrile （B） for gradient elution （0-0.5 min， 95%B； 0.5-7 min， 95%-65%B； 7-8 min， 65%-40%B； 8-9 min， 40%B； 9-9.1 min， 40%-95%B； 9.1-12 min， 95%B）， electrospray ionization was used under positive and negative ion detection modes， acquisition range was m/z 70-1 050. ResultCompared with the sham-30 d group， the left ventricular internal diameter at end-systole （LVIDs） in TAC-30 d group was significantly decreased （P<0.01）， and left ventricular ejection fraction （LVEF）， fraction shortening （FS）， left ventricular end-diastolic posterior wall thickness （LVPWd）， left vebtricular end-systolic posterior wall thickness （LVPWs） were significantly increased （P<0.01）， there were cardiomyocyte arrangement disorder， edema， collagen fibre hyperplasia， the content of NT-probNP was significantly increased， while the content of ATP was significantly decreased （P<0.01）， and 15 metabolites with abnormal expression were involved in pyrimidine metabolic pathway， pantothenic acid and coenzyme A biosynthesis pathway. Compared with the sham-60 d group， LVEF and FS in the TAC-60 d group were significantly decreased （P<0.01）， and left ventricular internal diameter at end-diastole （LVIDd）， LVIDs and LVPWd were increased （P<0.05， P<0.01）， the edema of myocardial cells increased obviously， myocardium fibers degenerated， coagulation necrosis appeared， and a large amount of collagen fibers were deposited， the expression of NT-proBNP increased and the expression of ATP decreased （P<0.01）， there were 21 metabolites with abnormal expression， involving pyrimidine metabolic pathway， and starch and sucrose metabolic pathway. ConclusionAt 30 d after TAC， there are myocardial hypertrophy， lipid metabolism disorder， pyrimidine metabolism disorder and energy imbalance. At 60 d after TAC， there are heart failure， aggravation of lipid metabolism disorder， excessive activation of glucose metabolism， and continuous disorder of pyrimidine metabolism.