OBJECTIVE: To observe the effects of moxibustion at "Xinshu" (BL15) and "Feishu" (BL13) on myocardial transferrin receptor 1 (TfR1), ferroptosis suppressor protein 1 (FSP1), atrial natriuretic peptide (ANP), and typeⅠcollagen myocardial collagen fibers (CollagenⅠ) in rats with chronic heart failure (CHF), and to explore the mechanism of moxibustion for ameliorating myocardial fibrosis and improving cardiac function in CHF. METHODS: Fifty SD rats were randomly divided into a normal group (n=10) and a modeling group (n=40). The CHF model was established in the modeling group by ligating the left anterior descending coronary artery. After successful modeling, the rats were randomly divided into a model group (n=9), a moxibustion group (n=8), a rapamycin (RAPA) group (n=9), and a moxibustion+RAPA group (n=9). In the moxibustion group, moxibustion was delivered at bilateral "Feishu"(BL13) and "Xinshu" (BL15), 15 min at each point in each intervention, once daily, for 4 consecutive weeks. In the RAPA group, RAPA solution was administered intraperitoneally at a dose of 1 mg/kg, once daily for 4 consecutive weeks. In the moxibustion+RAPA group, RAPA solution was administered intraperitoneally after moxibustion. Ejection fraction (EF) and left ventricular fractional shortening (FS) were measured after modeling and intervention. After intervention, morphology of cardiac muscle was observed using HE staining and Masson's trichrome staining. Total iron content in myocardial tissue was detected using a colorimetric method. Western blot and qPCR were adopted to detect the protein and mRNA expression of TfR1, FSP1, ANP, and CollagenⅠ in myocardial tissue. RESULTS: Compared with the normal group, the EF and FS values decreased (P<0.01); necrosis, edema, degeneration, and arrangement disorder were presented in cardiomyocytes; inflammatory cells were obviously infiltrated, the structure of myocardial fibers was disarranged, the collagen fibers were obviously deposited and fibrosis increased (P<0.01); the total iron content and the protein and mRNA expression of TfR1, ANP, and CollagenⅠ in myocardial tissue were elevated (P<0.01), while the protein and mRNA expression of FSP1 were reduced (P<0.01) in the model group. Compared with the model group, the moxibustion group showed that EF and FS increased (P<0.01); myocardial cell morphology was improved, and myocardial fibrosis was alleviated (P<0.01); the total iron content and the protein and mRNA expression of TfR1, ANP, and CollagenⅠ in myocardial tissue decreased (P<0.01), while the protein and mRNA expression of FSP1 increased (P<0.01, P<0.05). Compared with the model group, the myocardial fibrosis was increased (P<0.05); the total iron content and the protein and mRNA expression of TfR1, ANP, CollagenⅠ in myocardial tissue were increased (P<0.01), while protein and mRNA expression of FSP1 decreased (P<0.01) in the RAPA group. When compared with the RAPA group and the moxibustion + RAPA group, EF and FS were elevated (P<0.01, P<0.05); myocardial cells were improved in morphology, the total iron content and the protein and mRNA expression of TfR1, ANP, and CollagenⅠ in myocardial tissue decreased (P<0.01), while protein and mRNA expression of FSP1 increased (P<0.01) in the moxibustion group. In comparison with the moxibustion + RAPA group, the RAPA group showed the decrease in EF and FS (P<0.01), the worsened myocardial fibrosis (P<0.01), the increase in the total iron content and the protein and mRNA expression of TfR1, ANP, and CollagenⅠ in myocardial tissue (P<0.01), and the decrease in the protein and mRNA expression of FSP1 (P<0.01). CONCLUSION Moxibustion at "Feishu" (BL13) and "Xinshu" (BL15) can slow down the process of myocardial fibrosis and improve cardiac function in CHF rats. The mechanism of moxibustion may be related to inhibiting ferroptosis through regulating autophagy.
Animals ; Rats ; Heart Failure/physiopathology* ; Moxibustion ; Rats, Sprague-Dawley ; Male ; Receptors, Transferrin/genetics* ; Myocardium/metabolism* ; Acupuncture Points ; Humans ; Chronic Disease/therapy* ; Antigens, CD/metabolism*

In recent years,significant breakthroughs have been achieved in the immunotherapy for Alzheimer's disease.In line with global advancements,two anti-amyloid-β monoclonal antibodies have been approved and successfully launched in China for clinical use.Lecanemab and Donanemab were officially used in June 2024 and April 2025 in China,respectively.In order to standardize the rational and safe application of anti-amyloid-β monoclonal antibodies for Alzheimer's disease in China,this article integrates recom-mendations from the clinical trials and real-world experience from the author's team and domestic peers to further update the recom-mendations for the clinical use of anti-amyloid-β monoclonal antibody based on the 2024 version.It includes indications for therapy,pre-treatment evaluation and preparation,administration protocols and safety measures during treatment,and post-treatment monitor-ing strategies.

Intraoperative cell salvage (IOCS) has been widely applied as an important blood conservation measure in surgical operations. However, there is currently a lack of clinical practice guidelines for the implementation of IOCS in patients with malignant tumors. This report aims to provide clinicians with recommendations on the use of IOCS in patients with malignant tumors based on the review and assessment of the existed evidence. Data were derived from databases such as PubMed, Embase, the Cochrane Library and Wanfang. The guideline development team formulated recommendations based on the quality of evidence, balance of benefits and harms, patient preferences, and health economic assessments. This study constructed seven major clinical questions. The main conclusions of this guideline are as follows: 1) Compared with no perioperative allogeneic blood transfusion (NPABT), perioperative allogeneic blood transfusion (PABT) leads to a more unfavorable prognosis in cancer patients (Recommended); 2) Compared with the transfusion of allogeneic blood or no transfusion, IOCS does not lead to a more unfavorable prognosis in cancer patients (Recommended); 3) The implementation of IOCS in cancer patients is economically feasible (Recommended); 4) Leukocyte depletion filters (LDF) should be used when implementing IOCS in cancer patients (Strongly Recommended); 5) Irradiation treatment of autologous blood to be reinfused can be used when implementing IOCS in cancer patients (Recommended); 6) A careful assessment of the condition of cancer patients (meeting indications and excluding contraindications) should be conducted before implementing IOCS (Strongly Recommended); 7) Informed consent from cancer patients should be obtained when implementing IOCS, with a thorough pre-assessment of the patient's condition and the likelihood of blood loss, adherence to standardized internally audited management procedures, meeting corresponding conditions, and obtaining corresponding qualifications (Recommended). In brief, current evidence indicates that IOCS can be implemented for some malignant tumor patients who need allogeneic blood transfusion after physician full evaluation, and LDF or irradiation should be used during the implementation process.

Objective: To analyze the prevalence and the risk factors of fungal sepsis in 25 neonatal intensive care units (NICU) among preterm infants in China, and to provide a basis for preventive strategies of fungal sepsis. Methods: This was a second-analysis of the data from the "reduction of infection in neonatal intensive care units using the evidence-based practice for improving quality" study. The current status of fungal sepsis of the 24 731 preterm infants with the gestational age of <34⁺⁰ weeks, who were admitted to 25 participating NICU within 7 days of birth between May 2015 and April 2018 were retrospectively analyzed. These preterm infants were divided into the fungal sepsis group and the without fungal sepsis group according to whether they developed fungal sepsis to analyze the incidences and the microbiology of fungal sepsis. Chi-square test was used to compare the incidences of fungal sepsis in preterm infants with different gestational ages and birth weights and in different NICU. Multivariate Logistic regression analysis was used to study the outcomes of preterm infants with fungal sepsis, which were further compared with those of preterm infants without fungal sepsis. The 144 preterm infants in the fungal sepsis group were matched with 288 preterm infants in the non-fungal sepsis group by propensity score-matched method. Univariate and multivariate Logistic regression analysis were used to analyze the risk factors of fungal sepsis. Results: In all, 166 (0.7%) of the 24 731 preterm infants developed fungal sepsis, with the gestational age of (29.7±2.0) weeks and the birth weight of (1 300±293) g. The incidence of fungal sepsis increased with decreasing gestational age and birth weight (both P<0.001). The preterm infants with gestational age of <32 weeks accounted for 87.3% (145/166). The incidence of fungal sepsis was 1.0% (117/11 438) in very preterm infants and 2.0% (28/1 401) in extremely preterm infants, and was 1.3% (103/8 060) in very low birth weight infants and 1.7% (21/1 211) in extremely low birth weight infants, respectively. There was no fungal sepsis in 3 NICU, and the incidences in the other 22 NICU ranged from 0.7% (10/1 397) to 2.9% (21/724), with significant statistical difference (P<0.001). The pathogens were mainly Candida (150/166, 90.4%), including 59 cases of Candida albicans and 91 cases of non-Candida albicans, of which Candida parapsilosis was the most common (41 cases). Fungal sepsis was independently associated with increased risk of moderate to severe bronchopulmonary dysplasia (BPD) (adjusted OR 1.52, 95%CI 1.04-2.22, P=0.030) and severe retinopathy of prematurity (ROP) (adjusted OR 2.55, 95%CI 1.12-5.80, P=0.025). Previous broad spectrum antibiotics exposure (adjusted OR=2.50, 95%CI 1.50-4.17, P<0.001), prolonged use of central line (adjusted OR=1.05, 95%CI 1.03-1.08, P<0.001) and previous total parenteral nutrition (TPN) duration (adjusted OR=1.04, 95%CI 1.02-1.06, P<0.001) were all independently associated with increasing risk of fungal sepsis. Conclusions: Candida albicans and Candida parapsilosis are the main pathogens of fungal sepsis among preterm infants in Chinese NICU. Preterm infants with fungal sepsis are at increased risk of moderate to severe BPD and severe ROP. Previous broad spectrum antibiotics exposure, prolonged use of central line and prolonged duration of TPN will increase the risk of fungal sepsis. Ongoing initiatives are needed to reduce fungal sepsis based on these risk factors.
Infant ; Infant, Newborn ; Humans ; Birth Weight ; Intensive Care Units, Neonatal ; Retrospective Studies ; Tertiary Care Centers ; Infant, Extremely Low Birth Weight ; Gestational Age ; Infant, Extremely Premature ; Sepsis/epidemiology* ; Retinopathy of Prematurity/epidemiology* ; Bronchopulmonary Dysplasia/epidemiology*

OBJECTIVE: To compare the efficiency and effect of establishing rat peri-implantitis model by traditional cotton thread ligation and local injection of Porphyromonas gingivalis lipopolysaccharide (LPS) around the implant, as well as the combination of the two methods. METHODS: Left side maxillary first molars of 39 male SD rats were extracted, and titanium implants were implanted after four weeks of healing. After 4 weeks of implant osseointegration, 39 rats were randomly divided into 4 groups. Cotton thread ligation (n=12), local injection of LPS around the implant (n=12), and the two methods combined (n=12) were used to induce peri-implantitis, the rest 3 rats were untreated as control group. All procedures were conducted under 5% isoflurane inhalation anesthesia. The rats were sacrificed 2 weeks and 4 weeks after induction through carbon dioxide asphyxiation method. The maxilla of the rats in the test groups were collected and marginal bone loss was observed by micro-CT. The gingival tissues around the implants were collected for further real time quantitative PCR (RT-qPCR) analysis, specifically the expression of tumor necrosis factor-alpha (TNF-α) as well as interleukin-1β (IL-1β). The probing depth (PD), bleeding on probing (BOP) and gingival index (GI) of each rat in the experimental group were recorded before induction of inflammation and before death. RESULTS: After 4 weeks of implantation, the osseointegration of implants were confirmed. All the three test groups showed red and swollen gums, obvious marginal bone loss around implants. After 2 weeks and 4 weeks of inflammation induction, PD, GI and BOP of the three test groups increased compared with those before induction, but only BOP was statistically significant among the three test groups (P < 0.05). At the end of 2 weeks of inflammation induction, marginal bone loss was observed at each site in the cotton thread ligation group and the combined group. At each site, the bone resorption in the combined group was greater than that in the cotton thread ligation group, but the difference was not statistically significant (P > 0.05), bone resorption was observed at some sites of some implants in LPS local injection group. At the end of 4 weeks of inflammation induction, marginal bone loss was observed at all sites in each group. The marginal bone loss in the cotton thread ligation group and the combined group was greater than that in the LPS local injection group, and the difference was statistically significant (P < 0.05). At the end of 2 weeks and 4 weeks of induction, the expression of TNF-α and IL-1β in the test groups were higher than those in the control group (P < 0.05). CONCLUSION Compared with local injection of LPS around the implant, cotton thread ligature and the two methods combined can induce peri-implantitis in rats better and faster.
Animals ; Male ; Rats ; Alveolar Bone Loss/etiology* ; Dental Implants/adverse effects* ; Inflammation ; Lipopolysaccharides ; Peri-Implantitis/pathology* ; Rats, Sprague-Dawley ; Tumor Necrosis Factor-alpha

Acyl-CoA synthetase long chain family member 5 (ACSL5), is a member of the acyl-CoA synthetases (ACSs) family that activates long chain fatty acids by catalyzing the synthesis of fatty acyl-CoAs. The dysregulation of ACSL5 has been reported in some cancers, such as glioma and colon cancers. However, little is known about the role of ACSL5 in acute myeloid leukemia (AML). We found that the expression of ACSL5 was higher in bone marrow cells from AML patients compared with that from healthy donors. ACSL5 level could serve as an independent prognostic predictor of the overall survival of AML patients. In AML cells, the ACSL5 knockdown inhibited cell growth both in vitro and in vivo. Mechanistically, the knockdown of ACSL5 suppressed the activation of the Wnt/β-catenin pathway by suppressing the palmitoylation modification of Wnt3a. Additionally, triacsin c, a pan-ACS family inhibitor, inhibited cell growth and robustly induced cell apoptosis when combined with ABT-199, the FDA approved BCL-2 inhibitor for AML therapy. Our results indicate that ACSL5 is a potential prognosis marker for AML and a promising pharmacological target for the treatment of molecularly stratified AML.
Humans ; Antineoplastic Agents/therapeutic use* ; Apoptosis ; beta Catenin/metabolism* ; Biomarkers, Tumor/metabolism* ; Cell Line, Tumor ; Coenzyme A Ligases/metabolism* ; Leukemia, Myeloid, Acute/metabolism* ; Lipoylation ; Prognosis ; Wnt Signaling Pathway

COVID-19 has been prevalent for three years. The virulence of SARS-CoV-2 is weaken as it mutates continuously. However, elderly patients, especially those with underlying diseases, are still at high risk of developing severe infections. With the continuous study of the molecular structure and pathogenic mechanism of SARS-CoV-2, antiviral drugs for COVID-19 have been successively marketed, and these anti-SARS-CoV-2 drugs can effectively reduce the severe rate and mortality of elderly patients. This article reviews the mechanism, clinical medication regimens, drug interactions and adverse reactions of five small molecule antiviral drugs currently approved for marketing in China, so as to provide advice for the clinical rational use of anti-SARS-CoV-2 in the elderly.

Objective:To provide data support for the improvement of aeromedical support by summarizing the disease characteristics and analyzing the change pattern of disease spectrum for the temporarily grounded military flying personnel assessed in the annual physical examination.Methods:The clinical data of military flying personnel who were assessed as temporary grounding in the annual physical examination in Air Force Healthcare Center for Special Services Hangzhou from 2012 to 2021 were retrospectively analyzed. They were divided into 2012—2016 group and 2017—2021 group with a 5-year span. The distributions of disease, age and aircraft type were statistically compared between 2 groups of temporarily grounded military flying personnel.Results:A total of 522 flying personnel, aged from 23-55 years and flew 100-20 000 h, were enrolled. There were 242 cases in 2012—2016 group and 280 cases in 2017—2021 group. Compared with 2012—2016 group, 2017—2021 group was found 9 new diseases. Among the top 10 diseases in 2017—2021 group, the proportion of pulmonary nodules, hypertension, diabetes, abnormal tumor indicators, positive fecal occult blood was increased, and the proportion of thyroid nodules, abnormal liver function, arrhythmia was decreased. There was a significant difference in the age distribution between 2 groups of temporarily grounded military flying personnel ( χ2=20.97, P<0.001). The proportion of flying personnel aged ≥40 years old was increased in 2017—2021 group. The proportion of fighter-trainer pilots and bomb-transporter flying personnel increased in 2017—2021 group, and the difference was significant ( χ2=14.66, P=0.001). Conclusions:In recent years, more diseases, mostly occult diseases, are found in the disease spectrum of the temporarily grounded military flying personnel. Since some insidious diseases require more time to observe their convalescent effect and the influence to flight but the routine phone follow-up is called within 2 months of discharge, so a long-term and effective follow-up mechanism is suggested.

Objective:To provide data support for the improvement of aeromedical support by summarizing the disease characteristics and analyzing the change pattern of disease spectrum for the temporarily grounded military flying personnel assessed in the annual physical examination.Methods:The clinical data of military flying personnel who were assessed as temporary grounding in the annual physical examination in Air Force Healthcare Center for Special Services Hangzhou from 2012 to 2021 were retrospectively analyzed. They were divided into 2012—2016 group and 2017—2021 group with a 5-year span. The distributions of disease, age and aircraft type were statistically compared between 2 groups of temporarily grounded military flying personnel.Results:A total of 522 flying personnel, aged from 23-55 years and flew 100-20 000 h, were enrolled. There were 242 cases in 2012—2016 group and 280 cases in 2017—2021 group. Compared with 2012—2016 group, 2017—2021 group was found 9 new diseases. Among the top 10 diseases in 2017—2021 group, the proportion of pulmonary nodules, hypertension, diabetes, abnormal tumor indicators, positive fecal occult blood was increased, and the proportion of thyroid nodules, abnormal liver function, arrhythmia was decreased. There was a significant difference in the age distribution between 2 groups of temporarily grounded military flying personnel ( χ2=20.97, P<0.001). The proportion of flying personnel aged ≥40 years old was increased in 2017—2021 group. The proportion of fighter-trainer pilots and bomb-transporter flying personnel increased in 2017—2021 group, and the difference was significant ( χ2=14.66, P=0.001). Conclusions:In recent years, more diseases, mostly occult diseases, are found in the disease spectrum of the temporarily grounded military flying personnel. Since some insidious diseases require more time to observe their convalescent effect and the influence to flight but the routine phone follow-up is called within 2 months of discharge, so a long-term and effective follow-up mechanism is suggested.

Amyloid β-protein(Aβ) deposition in the brain is directly responsible for neuronal mitochondrial damage of Alzheimer's disease(AD) patients. Mitophagy, which removes damaged mitochondria, is a vital mode of neuron protection. Ginsenoside Rg_1(Rg_1), with neuroprotective effect, has displayed promising potential for AD treatment. However, the mechanism underlying the neuroprotective effect of Rg_1 has not been fully elucidated. The present study investigated the effects of ginsenoside Rg_(1 )on the autophagy of PC12 cells injured by Aβ_(25-35) to gain insight into the neuroprotective mechanism of Rg_1. The autophagy inducer rapamycin and the autophagy inhi-bitor chloroquine were used to verify the correlation between the neuroprotective effect of Rg_1 and autophagy. The results showed that Rg_1 enhanced the viability and increased the mitochondrial membrane potential of Aβ-injured PC12 cells, while these changes were blocked by chloroquine. Furthermore, Rg_(1 )treatment increased the LC3Ⅱ/Ⅰ protein ratio, promoted the depletion of p62 protein, up-regulated the protein levels of PINK1 and parkin, and reduced the amount of autophagy adaptor OPTN, which indicated the enhancement of autophagy. After the silencing of PINK1, a key regulatory site of mitophagy, Rg_1 could not increase the expression of PINK1 and parkin or the amount of NDP52, whereas it can still increase the LC3Ⅱ/Ⅰ protein ratio and promote the depletion of OPTN protein which indicated the enhancement of autophagy. Collectively, the results of this study imply that Rg_1 can promote autophagy of PC12 cells injured by Aβ, and may reduce Aβ-induced mitochondrial damage by promoting PINK1-dependent mitophagy, which may be one of the key mechanisms of its neuroprotective effect.
Amyloid beta-Peptides/toxicity* ; Animals ; Ginsenosides/pharmacology* ; Humans ; Mitophagy/physiology* ; PC12 Cells ; Protein Kinases/metabolism* ; Rats ; Ubiquitin-Protein Ligases/metabolism*