Bronchiolar adenoma (BA) is a rare type of lung tumor characterized by bilayered epithelial cells having a continuous basal layer and a luminal layer. It resembles mucinous adenocarcinoma (MA) on frozen section, with difficulty in distinguishing the basal layer. Immunohistochemistry is the best choice for verifying the diagnosis. This study aimed to comprehensively characterize three cases of BA-combined carcinoma using clinical, histopathological, and genetic features. BA and carcinoma sections were subjected to next-generation sequencing, respectively. It was hypothesized that while different mutation forms matched different regions, BA and lung adenocarcinoma shared the same gene mutation when they co-occurred in the same location. BA with extensive carcinoma is extremely rare and presents diagnostic challenges due to its overlap with conditions such as MA. Because of its distinctive morphological characteristics, BA may be regarded as a low-grade malignancy, particularly during a confusing evaluation. A multifaceted examination of clinical, radiological, immunohistochemical, and genetic data is necessary for an accurate diagnosis.

Background: Reduction of immunosuppression (ROI) remains the mainstay of treatment for BK virus infection (BKVI) in kidney transplantation (KT). This review explored the role of intravenous immunoglobulin (IVIG) and mammalian target of rapamycin inhibitor (mTORi) regimens as alternative therapies for KT recipients with BKVI, focusing on viral clearance and graft-related outcomes. Methods: An electronic search was conducted for articles examining IVIG or mTORi use in treating BKVI among adult and/or pediatric KT recipients. Meta-analyses of proportions were performed for relevant outcomes. Results: Twenty-seven studies (13 evaluating IVIG and 14 evaluating mTORi) were included; all but three enrolled only adult participants. In IVIG studies, the pooled viral clearance rate was 76.4% (95% confidence interval [CI], 64.2%–85.5%), with numerically higher clearance for IVIG after ROI compared to IVIG with ROI (87.0% vs. 66.1%). Overall graft survival was 84.7% (95% CI, 70.7%–92.7%), with numerically higher survival in IVIG after ROI than in IVIG with ROI (93.6% vs. 78.4%). Pooled histological clearance and graft rejection rates were 82.8% and 14.5%, respectively. In mTORi studies, the pooled viral clearance rate was 68.0% (95% CI, 58.0%–76.7%) and overall graft survival was 89.1% (95% CI, 82.7%–93.4%), with no significant difference between patients with and without prior ROI. Histological clearance and graft rejection rates were 59.8% and 8.6%, respectively. Conclusions IVIG and mTORi regimens appear to be feasible alternatives to ROI in KT recipients with BKVI, achieving viral clearance while maintaining graft survival. Future randomized controlled trials are needed to further define their role and strengthen current evidence with higher-quality data.

Background: Kidney transplant recipients (KTRs) are at risk of coronavirus disease 2019 (COVID-19) complications and mortality. This study examined factors associated with moderate, severe, or critical COVID-19 infection among KTRs during the Omicron-predominant period. Methods: This single-center retrospective study included KTRs aged ≥18 years diag-nosed with COVID-19 between January 1, 2022, and December 31, 2023. Mild infection was defined as symptomatic illness without lower respiratory tract infection (LRTI);moderate infection as LRTI without hypoxia; severe infection as oxygen saturation <94% on room air; and critical infection as respiratory failure, septic shock, or multiple organ dysfunction. We compared the characteristics of KTRs with asymptomatic or mild COVID-19 versus those with moderate to critical disease. Logistic regression analysis was performed to identify factors associated with moderate to critical illness. Results: Most KTRs (94.4%) had received three or more vaccine doses. Of 603 episodes of COVID-19 infection during the study period, 554 (91.9%) were asymptomatic or mild, while 49 (8.1%) were moderate to critical. Multivariate analysis revealed that older age (adjusted odds ratio [aOR], 1.037; 95% confidence interval [CI], 1.006–1.069) and longer symptom duration before seeking care (aOR, 1.288; 95% CI, 1.155–1.436) were associated with higher odds of moderate to critical disease. Protective factors included receiving a vaccine booster within the past year (aOR, 0.414; 95% CI, 0.212–0.809) and higher glomerular filtration rate (aOR, 0.971; 95% CI, 0.956–0.986). Conclusions KTRs should seek care early if infected with COVID-19 and keep their COVID-19 vaccine boosters updated within 1 year of the last dose.

Background: Kidney transplant recipients (KTRs) are at risk of coronavirus disease 2019 (COVID-19) complications and mortality. This study examined factors associated with moderate, severe, or critical COVID-19 infection among KTRs during the Omicron-predominant period. Methods: This single-center retrospective study included KTRs aged ≥18 years diag-nosed with COVID-19 between January 1, 2022, and December 31, 2023. Mild infection was defined as symptomatic illness without lower respiratory tract infection (LRTI);moderate infection as LRTI without hypoxia; severe infection as oxygen saturation <94% on room air; and critical infection as respiratory failure, septic shock, or multiple organ dysfunction. We compared the characteristics of KTRs with asymptomatic or mild COVID-19 versus those with moderate to critical disease. Logistic regression analysis was performed to identify factors associated with moderate to critical illness. Results: Most KTRs (94.4%) had received three or more vaccine doses. Of 603 episodes of COVID-19 infection during the study period, 554 (91.9%) were asymptomatic or mild, while 49 (8.1%) were moderate to critical. Multivariate analysis revealed that older age (adjusted odds ratio [aOR], 1.037; 95% confidence interval [CI], 1.006–1.069) and longer symptom duration before seeking care (aOR, 1.288; 95% CI, 1.155–1.436) were associated with higher odds of moderate to critical disease. Protective factors included receiving a vaccine booster within the past year (aOR, 0.414; 95% CI, 0.212–0.809) and higher glomerular filtration rate (aOR, 0.971; 95% CI, 0.956–0.986). Conclusions KTRs should seek care early if infected with COVID-19 and keep their COVID-19 vaccine boosters updated within 1 year of the last dose.

Background: Kidney transplant recipients (KTRs) are at risk of coronavirus disease 2019 (COVID-19) complications and mortality. This study examined factors associated with moderate, severe, or critical COVID-19 infection among KTRs during the Omicron-predominant period. Methods: This single-center retrospective study included KTRs aged ≥18 years diag-nosed with COVID-19 between January 1, 2022, and December 31, 2023. Mild infection was defined as symptomatic illness without lower respiratory tract infection (LRTI);moderate infection as LRTI without hypoxia; severe infection as oxygen saturation <94% on room air; and critical infection as respiratory failure, septic shock, or multiple organ dysfunction. We compared the characteristics of KTRs with asymptomatic or mild COVID-19 versus those with moderate to critical disease. Logistic regression analysis was performed to identify factors associated with moderate to critical illness. Results: Most KTRs (94.4%) had received three or more vaccine doses. Of 603 episodes of COVID-19 infection during the study period, 554 (91.9%) were asymptomatic or mild, while 49 (8.1%) were moderate to critical. Multivariate analysis revealed that older age (adjusted odds ratio [aOR], 1.037; 95% confidence interval [CI], 1.006–1.069) and longer symptom duration before seeking care (aOR, 1.288; 95% CI, 1.155–1.436) were associated with higher odds of moderate to critical disease. Protective factors included receiving a vaccine booster within the past year (aOR, 0.414; 95% CI, 0.212–0.809) and higher glomerular filtration rate (aOR, 0.971; 95% CI, 0.956–0.986). Conclusions KTRs should seek care early if infected with COVID-19 and keep their COVID-19 vaccine boosters updated within 1 year of the last dose.

Background: Kidney transplant recipients (KTRs) are at risk of coronavirus disease 2019 (COVID-19) complications and mortality. This study examined factors associated with moderate, severe, or critical COVID-19 infection among KTRs during the Omicron-predominant period. Methods: This single-center retrospective study included KTRs aged ≥18 years diag-nosed with COVID-19 between January 1, 2022, and December 31, 2023. Mild infection was defined as symptomatic illness without lower respiratory tract infection (LRTI);moderate infection as LRTI without hypoxia; severe infection as oxygen saturation <94% on room air; and critical infection as respiratory failure, septic shock, or multiple organ dysfunction. We compared the characteristics of KTRs with asymptomatic or mild COVID-19 versus those with moderate to critical disease. Logistic regression analysis was performed to identify factors associated with moderate to critical illness. Results: Most KTRs (94.4%) had received three or more vaccine doses. Of 603 episodes of COVID-19 infection during the study period, 554 (91.9%) were asymptomatic or mild, while 49 (8.1%) were moderate to critical. Multivariate analysis revealed that older age (adjusted odds ratio [aOR], 1.037; 95% confidence interval [CI], 1.006–1.069) and longer symptom duration before seeking care (aOR, 1.288; 95% CI, 1.155–1.436) were associated with higher odds of moderate to critical disease. Protective factors included receiving a vaccine booster within the past year (aOR, 0.414; 95% CI, 0.212–0.809) and higher glomerular filtration rate (aOR, 0.971; 95% CI, 0.956–0.986). Conclusions KTRs should seek care early if infected with COVID-19 and keep their COVID-19 vaccine boosters updated within 1 year of the last dose.

Objective To establish a rapid,sensitive,and specific multiplex PCR detection method for the simultaneous detection of Cryptosporidium,Eimeria,and bovine parvovirus.Methods Specific primers targeting the SSU rRNA genes of Cryptosporidium and Eimeria,as well as the VP2 gene of bovine parvovirus were designed and the corresponding recombinant plasmid standards were constructed.To establish the multiplex PCR method,the reaction conditions were optimized using temperature gradient PCR and single-variable control methods.The sensitivity,specificity,reproducibility,and clinical application of the protocol were evaluated.Results The optimal annealing temperature was found to be 60.5℃,and the forward and reverse primer concentrations were determined to be 0.2 μmol/L for Eimeria,and 0.4 μmol/L for Cryptosporidium and bovine parvovirus.The assay demonstrated high sensitivity,with detection limits of 243,260,and 3 110 copies for the recombinant plasmid standards of Cryptosporidium,Eimeria,and bovine parvovirus,respectively.Specificity testing showed no cross-reactivity with ten common bovine pathogens,including Salmonella,bovine viral diarrhea virus,and bovine rotavirus.Consistent intra-and inter-batch results confirmed the strong reproducibility of the method.Clinical application to 81 diarrhea samples from various regions in the Ganzi Prefecture,Sichuan,revealed positivity rates of 18.52%(15/81)for Cryptosporidium,34.57%(28/81)for Eimeria,and 18.52%(15/81)forbovineparvovirus,withamixedinfectionrateof3.7%(3/81).Conclusions Themultiplex PCR method established in this study offers a reliable tool for differential diagnosis and epidemiological investigation of the three common diarrheal pathogens in yaks.

Objective To explore the mechanism of acupuncture's effect on hippocampal neuron apoptosis in a post-traumatic stress disorder(PTSD)rat model via the reactive oxygen species(ROS)/c-Jun N-terminal kinase(JNK)/p53 pathway.Methods Thirty rats were randomly divided into normal control group(NC group),PTSD rat model group(PTSD group)and electroacupuncture intervention group(EA group),with 10 rats in each group.The results of behavioral test(open field experiment and elevated cross maze experiment)were compared.The terminal deoxynucleotidyl trans-ferase dUTP nick-end labeling(TUNEL)staining method was used to detect hippocampal neuron apoptosis in each group.DHE fluorescence staining was employed to measure ROS levels in the brain tissue of each group.The content of Ros index[malondialdehyde(MDA),superoxide dismutase(SOD)and glutathione(GSH)]in brain tissue of each group was detected.Western blot analysis was per-formed to determine the protein expression levels of JNK,p-JNK,p53 and PUMA in hippocampal tissue.Results The total movement distance of rats in the PTSD group was significantly shorter,and the total number of uprightand central cell entry times were significantly shorter than those in the NC group(P＜0.05).The total distance moved by rats in the EA group was significantly longer,and the total number of upright and central lattice entry times were significantly higher than those in the PTSD group(P＜0.05).The percentage of times and time of entering the open arm in the PTSD group was significantly lower,and the anxiety index was significantly higher than that in the NC group(P＜0.05).The percentage of times and time of entering the open arm in the EA group was significantly higher,and the anxiety index was significantly lower than that in the PTSD group(P＜0.05).The neuronal apoptosis rate of the PTSD group was significantly higher than that of the NC group(P＜0.05);the neuronal apoptosis rate in the EA group was significantly lower than that in the PTSD group(P＜0.05).The mean fluorescence intensity of ROS in brain tissue of the PTSD group was significantly higher than that of the NC group(P＜0.05);the mean fluorescence intensi-ty of ROS in the EA group was significantly lower than that in the PTSD group(P＜0.05).The MDA content in brain tissue of the PTSD group was significantly higher,and SOD activity and GSH content were significantly lower than those of the NC group(P＜0.05);the MDA content in the brain tissue of the EA group was significantly lower,and the SOD activity and GSH content were sig-nificantly higher than those of the PTSD group(P＜0.05).The p-JNK/JNK and the expression levels of p53 and PUMA in brain tissue of the PTSD group were significantly higher than those of the NC group(P＜0.05);the p-JNK/JNK and the expression levels of p53 and PUMA in the brain tissue of the EA group were significantly lower than those of the PTSD group(P＜0.05).Conclusion Acu-puncture can inhibit hippocampal neuron apoptosis and relieve fear symptoms in PTSD rats,possibly through the activation of the ROS/JNK/p53 pathway.

Insufficient alveolar bone thickness increases the risk of periodontal dehiscence and fenestration, especially in orthodontic tooth movement. Abaloparatide (ABL), a synthetic analog of human PTHrP (1-34) and a clinical medication for treating osteoporosis, has recently demonstrated its potential in enhancing craniofacial bone formation. Herein, we show that intraoral submucosal injection of ABL, when combined with mechanical force, promotes in situ alveolar bone thickening. The newly formed bone is primarily located outside the original compact bone, implying its origin from the periosteum. RNA sequencing of the alveolar bone tissue revealed that the focal adhesion (FA) pathway potentially mediates this bioprocess. Local injection of ABL alone enhances cell proliferation, collagen synthesis, and phosphorylation of focal adhesion kinase (FAK) in the alveolar periosteum; when ABL is combined with mechanical force, the FAK expression is upregulated, in line with the accomplishment of the ossification. In vitro, ABL enhances proliferation, migration, and FAK phosphorylation in periosteal stem cells. Furthermore, the pro-osteogenic effects of ABL on alveolar bone are entirely blocked when FAK activity is inhibited by a specific inhibitor. In summary, abaloparatide combined with mechanical force promotes alveolar bone formation via FAK-mediated periosteal osteogenesis. Thus, we have introduced a promising therapeutic approach for drug-induced in situ alveolar bone augmentation, which may prevent or repair the detrimental periodontal dehiscence, holding significant potential in dentistry.
Osteogenesis/drug effects* ; Periosteum/cytology* ; Parathyroid Hormone-Related Protein/administration & dosage* ; Animals ; Focal Adhesion Protein-Tyrosine Kinases/metabolism* ; Alveolar Process/drug effects* ; Cell Proliferation/drug effects* ; Phosphorylation ; Rats ; Male ; Humans ; Focal Adhesion Kinase 1/metabolism* ; Cell Movement/drug effects*

AIM:To investigate the regulatory mechanism of silent information regulator 6(Sirt6)on nuclear factor E2-related factor 2(Nrf2)/heme oxygenase-1(HO-1)signaling pathway and ferroptosis in skeletal muscle aging in-duced by D-galactose(D-Gal)in mice.METHODS:A D-Gal-induced mouse aging model was established and randomly divided into control and D-Gal groups.In vitro,D-Gal-treated C2C12 mouse myoblasts were treated with ferroptosis ago-nist erastin(Era)and inhibitor ferrostatin-1(Fer-1),Sirt6 agonist MDL-800 and inhibitor OSS-128167,and Nrf2 siRNA.Mouse body weight and forelimb relative grip strength were monitored.RT-qPCR and Western blot were used to measure the expression of Sirt6,Nrf2,HO-1,P53,P21,P16,muscle ring finger protein 1,muscle atrophy F-box,solute carrier family 7 member 11,and glutathione peroxidase 4 in gastrocnemius muscle and myoblasts.Hematoxylin-eosin staining was performed to examine muscle fiber diameter.Levels of reactive oxygen species(ROS),mitochondrial ROS,mitochon-drial membrane potential,senescence-associated β-galactosidase activity,glutathione,lipid peroxidation,and Fe2? con-centration were measured in myoblasts and myotubes.Immunofluorescence staining was used to detect myosin heavy chain(MyHC)expression in myotubes.RESULTS:Mice in the D-Gal group exhibited significant reductions in body weight and forelimb grip strength(P<0.01),upregulation of aging and muscle atrophy markers,and decreased mRNA and pro-tein levels of ferroptosis markers and Sirt6(P<0.01).Additionally,gastrocnemius muscle fiber diameter significantly de-creased(P<0.01).In D-Gal-treated myoblasts and myotubes,aging and muscle atrophy markers were elevated(P<0.01),MyHC expression was reduced,and protein levels of ferroptosis-related markers,Sirt6,Nrf2,and HO-1 were de-creased(P<0.05 or P<0.01).Fer-1 pre-treatment alleviated these changes(P<0.05 or P<0.01).MDL-800 significantly improved D-Gal-induced aging and muscle atrophy in myoblasts and myotubes,while increasing the expression of ferropto-sis-related proteins(P<0.05 or P<0.01).However,the addition of Erastin abolished the beneficial effects of MDL-800(P<0.05 or P<0.01).Following Nrf2 siRNA transfection,the ability of MDL-800 to improve ferroptosis and the quality of myotube formation was significantly diminished(P<0.05 or P<0.01).CONCLUSION:Sirt6 inhibits ferroptosis in myo-blasts through the Nrf2/HO-1 signaling pathway,thereby alleviating age-related changes in myoblasts and the decline in myotube formation quality,which is beneficial for improving skeletal muscle aging.