Background Pulmonary heart disease (PHD) is a critical cardiopulmonary disease in high-altitude areas, with pulmonary hypertension (PH) as its central pathological basis. Cold and hypoxia are vital environmental characteristics of high-altitude regions; however, their joint effect on the hospitalization risk for PHD and the underlying biological mechanisms remain unclear. Objective To evaluate the associations of cold, hypoxia, and their joint exposure with PHD hospitalization risk, and to investigate PH-related pathological changes induced by combined cold and hypoxic exposure and the intervention effects of γ-aminobutyric acid (GABA) in rats. Methods Based on hospitalization data for 92986 PHD cases from 333 hospitals in Gansu Province (2018–2022), a generalized additive model (GAM) with a quasi-Poisson distribution was used to assess the associations between daily mean temperature, atmospheric oxygen content (AOC) and the daily number of PHD hospitalizations. Four joint exposure categories were constructed using the fifth percentile of temperature (P₅, −7.90℃) and AOC grades (high or low) to assess the associations between different exposure combinations and daily PHD hospital admissions. To further investigate PH-related pathological changes and the intervention effects of GABA, 24 specific-pathogen-free male Sprague–Dawley rats were randomly assigned to four groups (n=6): normal temperature and normoxia control group (NC), combined cold and hypoxia exposure group (CH), combined exposure plus low-dose GABA intervention group (CHL), and combined exposure plus high-dose GABA intervention group (CHH). After 5 weeks, pulmonary hemodynamics and vascular remodeling were evaluated. Gut microbiota and inflammatory cytokines in lung tissue were assessed using 16S rRNA sequencing and enzyme-linked immunosorbent assay (ELISA), respectively. Results Each 1 g·m⁻³ decrease in AOC and each 1 ℃ decrease in daily mean temperature were associated with 2.6% (RR=1.026, 95%CI: 1.024, 1.027) and 1.8% (RR=1.018, 95%CI: 1.015, 1.020) increases in PHD hospitalization risk, respectively. Compared with the non-low-temperature and high-AOC group, the low-temperature and low-AOC group had the highest risk estimate (RR=1.673, 95%CI: 1.567, 1.785). Animal experiments demonstrated that, compared with the NC group, rats in the CH group showed shortened pulmonary artery acceleration time (PAT) and increased mean pulmonary artery pressure (MPAP), right ventricular hypertrophy index (RVHI), pulmonary arterial wall thickness, and α-smooth muscle actin (α-SMA) expression (P<0.05). The Observed Species and Chao1 indices of the gut microbiota were significantly lower in the CH group than in the NC group (P<0.05), while levels of tumor necrosis factor-alpha (TNF-α) and interleukin-1beta (IL-1β) in lung tissue were elevated (P<0.05). GABA intervention improved selected hemodynamic, vascular remodeling, and inflammatory indices. Conclusion Decreases in daily mean temperature and AOC are associated with an increased risk of PHD hospitalization, with the highest risk estimate observed in the low-temperature and low-AOC group. Animal experiments suggest that combined cold and hypoxic exposure induce PH-related pathological changes accompanied by alterations in the gut microbiota and pulmonary inflammation. GABA may partially ameliorate these changes.

Objective: To assess the association between the metabolic score for insulin resistance index (METS-IR) and overactive bladder (OAB) in the US population，so as to explore the potential of METS-IR as a predictive tool for OAB risk and to provide insights for early screening and intervention strategies. Methods: Based on the data from the National Health and Nutrition Examination Survey (NHANES) 2005-2018，a cross-sectional design was employed，and multivariate logistic regression models were used to analyze the association between METS-IR and OAB. METS-IR was analyzed both as a continuous variable and categorized into quartiles. To further validate the association between METS-IR and OAB across diverse populations，subgroup analyses were conducted in participants stratified by clinical characteristics. Smooth curve fitting was employed to test the linearity of the METS-IR-OAB relationship. Results: Elevated METS-IR was associated with an increased risk of OAB (P<0.001)，and this positive correlation remained stable when METS-IR was categorized into quartiles (P<0.001). Subgroup analyses revealed that the association between METS-IR and OAB was more pronounced in females，participants younger than 55 years，and non-diabetic individuals (P<0.05). Furthermore，smooth curve fitting confirmed a linear positive correlation between METS-IR and OAB，with this linear relationship observed in both diabetic and non-diabetic groups. Conclusion: This study，based on the NHANES 2005-2018 database，found a linear positive correlation between METS-IR and OAB.

Objective To explore the impact of suture configuration and fixation type on the biome-chanical strength of rotator cuff repair,using a factorial design study.Methods Sixteen fresh-frozen porcine shoulder samples were randomized into an anchorless double-row suture bridge transosseous su-tures(DS)group,an anchored double-row suture bridge transosseous-equivalent(DE)group,an an-chorless X-BOX construct transosseous sutures(XS)group,and an anchored X-BOX construct transos-seous-equivalent(XE)group,each of four,according to suture configuration(double-row suture bridge,traditional X-BOX construct)and fixation type(suture anchors,transosseous sutures).Then,their fatigue resistance(first-cycle excursion,gap length difference ratio,and the percentage of ex-posed footprints)and the failure strength(the maximum failure load and the re-tear type)were mea-sured using a biomechanical material testing machine.Results Different suture configurations affected failure strength(F=39.559,P<0.001),with the double-row suture bridge groups(693.07±58.35 N,746.76±138.57 N)showing significantly higher failure strength,compared to the traditional X-BOX groups(462.90±18.91 N,421.43±90.76 N).However,the fixation type did not significantly im-pact failure strength(F=1.161,P=0.302).Moreover,the suture configuration influenced the gap differ-ence ratio(F=7.781,P=0.016),but had no significant correlation with other fatigue resistance indica-tors(P>0.05).Meanwhile,failure strength and fatigue resistance were not correlated with fixation type,and the interaction between suture and fixation type(P>0.05).The incidence of failure types for the four suture configurations was as follows:Type I tendon tear:XS>XE>DS=DE;type II tendon tear:DS>XE>XS=DE;fixing material-related failure:DE>DS=XE=XS.Conclusion The failure strength and gap formation ratio in rotator cuff repair under fatigue loading are influenced by suture configuration,whereas no significant association has been observed with respect to fixation method,whether using transosseous sutures or suture anchors.

Objective To explore the impact of suture configuration and fixation type on the biome-chanical strength of rotator cuff repair,using a factorial design study.Methods Sixteen fresh-frozen porcine shoulder samples were randomized into an anchorless double-row suture bridge transosseous su-tures(DS)group,an anchored double-row suture bridge transosseous-equivalent(DE)group,an an-chorless X-BOX construct transosseous sutures(XS)group,and an anchored X-BOX construct transos-seous-equivalent(XE)group,each of four,according to suture configuration(double-row suture bridge,traditional X-BOX construct)and fixation type(suture anchors,transosseous sutures).Then,their fatigue resistance(first-cycle excursion,gap length difference ratio,and the percentage of ex-posed footprints)and the failure strength(the maximum failure load and the re-tear type)were mea-sured using a biomechanical material testing machine.Results Different suture configurations affected failure strength(F=39.559,P<0.001),with the double-row suture bridge groups(693.07±58.35 N,746.76±138.57 N)showing significantly higher failure strength,compared to the traditional X-BOX groups(462.90±18.91 N,421.43±90.76 N).However,the fixation type did not significantly im-pact failure strength(F=1.161,P=0.302).Moreover,the suture configuration influenced the gap differ-ence ratio(F=7.781,P=0.016),but had no significant correlation with other fatigue resistance indica-tors(P>0.05).Meanwhile,failure strength and fatigue resistance were not correlated with fixation type,and the interaction between suture and fixation type(P>0.05).The incidence of failure types for the four suture configurations was as follows:Type I tendon tear:XS>XE>DS=DE;type II tendon tear:DS>XE>XS=DE;fixing material-related failure:DE>DS=XE=XS.Conclusion The failure strength and gap formation ratio in rotator cuff repair under fatigue loading are influenced by suture configuration,whereas no significant association has been observed with respect to fixation method,whether using transosseous sutures or suture anchors.

Objective To establish and evaluate a rapid detection method for SARS-CoV-2 based on reverse transcriptase-recombinase aided amplification(RT-RAA)combined with the clustered regularly interspaced short palindromic repeats(CRISPR)/Cas12a system.Methods RT-RAA primers and CRISPR-derived RNA(crRNA)were designed based on the nucleocapsid(N)gene of SARS-CoV-2 from NCBI database.The detection system was optimized with magnesium acetate(MgAc)concentration,RT-RAA reaction tempera-ture and time and LbCas12a reaction temperature.The sensitivity and specificity of the method were evaluated using recombinant plas-mids(100-106 copies/μL)and other respiratory pathogens.The RT-RAA-CRISPR/Cas12a method was compared with RT-PCR by tes-ting 70 clinical samples in parallel.Results The optimized RT-RAA-CRISPR/Cas12a assay could detect SARS-CoV-2 within 50 min at 37 ℃.The limit of detection was 10 copies/μL for the fluorescence-based method and 1×102 copies/μL for the lateral flow assay.The method specifically detected SARS-CoV-2 without cross-reactivity to other respiratory pathogens.The results of testing 70 clinical samples using RT-RAA-CRISPR/Cas12a showed agreement of 100％with those of RT-PCR.Conclusion The established RT-RAA-CRISPR/Cas12a assay for SARS-CoV-2 detection is rapid,cost-effective,highly sensitive and specific.It can be performed by less experienced personnel and no expensive equipment is required,thus it may provide a new approach for rapid clinical diagnosis and large-scale on-site screening of SARS-CoV-2.

Humans ; Asthma/drug therapy* ; Biological Therapy

Objective To investigate the prevalence of single nucleotide polymorphisms (SNPs) of artemisinin resistance-related Pfubp1 and Pfap2mu genes in Plasmodium falciparum isolates from Bioko Island, Equatorial Guinea, so as to to provide baseline data for the formulation of malaria control strategies in Bioko Island. Methods A total of 184 clinical blood samples were collected from patients with P. falciparum malaria in Bioko Island, Equatorial Guinea from 2018 to 2020, and genomic DNA was extracted. The Pfubp1 and Pfap2mu gene SNPs of P. falciparum were determined using a nested PCR assay and Sanger sequencing, and the gene sequences were aligned. Results There were 159 wild-type P. falciparum isolates (88.83%) from Bioko Island, Equatorial Guinea, and 6 SNPs were identified in 20 Pfubp1-mutant P. falciparum isolates (11.17%), in which 4 non-synonymous mutations were detected, including E1516G, K1520E, D1525E, E1528D. There was only one Pfubp1gene mutation site in 19 Pfubp1-mutant P. falciparum isolates (95.00%), in which non-synonymous mutations accounted for 68.42% (13/19). D1525E and E1528D were identified as major known epidemic mutation sites in the Pfubp1 gene associated with resistance to artemisinin-based combination therapies (ACTs). At amino acid position 1525, there were 178 wild-type P. falciparum isolates (99.44%) and 1 mutant isolate (0.56%), with such a mutation site identified in blood samples in 2018, and at amino acid position 1528, there were 167 wild-type P. falciparum isolates (93.30%) and 12 mutant isolates (6.70%). The proportions of wild-type P. falciparum isolates were 95.72% (134/140), 79.25% (126/159) and 95.83% (161/168) in the target amplification fragments of the three regions in the Pfap2mu gene (Pfap2mu-inner1, Pfap2mu-inner2, Pfap2mu-inner3), respectively. There were 16 different SNPs identified in all successfully sequenced P. falciparum isolates, in which 7 non-synonymous mutations were detected, including S160N, K199T, A475V, S508G, I511M, L595F, and Y603H. There were 7 out of 43 Pfap2mu-mutant P. falciparum isolates (16.28%) that harbored only one gene mutation site, in which non-synonymous mutations accounted for 28.57% (2/7). For the known delayed clearance locus S160N associated with ACTs, there were 143 wild-type (89.94%) and 16 Pfap2mu-mutant P. falciparum isolates (10.06%). Conclusions Both Pfubp1 and Pfap2mu gene mutations were detected in P. falciparum isolates from Bioko Island, Equatorial Guinea from 2018 to 2020, with a low prevalence rate of Pfubp1 gene mutation and a high prevalence rate of Pfap2mu gene mutation. In addition, new mutation sites were identified in the Pfubp1 (E1504E and K1520E) and Pfap2mu genes (A475V and S508G).

Objective:To evaluate artificial intelligence constructed by deep convolutional neural network (DCNN) for the site identification in upper gastrointestinal endoscopy.Methods:A total of 21 310 images of esophagogastroduodenoscopy from the Cancer Hospital of Chinese Academy of Medical Sciences from January 2019 to June 2021 were collected. A total of 19 191 images of them were used to construct site identification model, and the remaining 2 119 images were used for verification. The performance differences of two models constructed by DCCN in the identification of 30 sites of the upper digestive tract were compared. One model was the traditional ResNetV2 model constructed by Inception-ResNetV2 (ResNetV2), the other was a hybrid neural network RESENet model constructed by Inception-ResNetV2 and Squeeze-Excitation Networks (RESENet). The main indices were the accuracy, the sensitivity, the specificity, positive predictive value (PPV) and negative predictive value (NPV).Results:The accuracy, the sensitivity, the specificity, PPV and NPV of ResNetV2 model in the identification of 30 sites of the upper digestive tract were 94.62%-99.10%, 30.61%-100.00%, 96.07%-99.56%, 42.26%-86.44% and 97.13%-99.75%, respectively. The corresponding values of RESENet model were 98.08%-99.95%, 92.86%-100.00%, 98.51%-100.00%, 74.51%-100.00% and 98.85%-100.00%, respectively. The mean accuracy, mean sensitivity, mean specificity, mean PPV and mean NPV of ResNetV2 model were 97.60%, 75.58%, 98.75%, 63.44% and 98.76%, respectively. The corresponding values of RESENet model were 99.34% ( P<0.001), 99.57% ( P<0.001), 99.66% ( P<0.001), 90.20% ( P<0.001) and 99.66% ( P<0.001). Conclusion:Compared with the traditional ResNetV2 model, the artificial intelligence-assisted site identification model constructed by RESENNet, a hybrid neural network, shows significantly improved performance. This model can be used to monitor the integrity of the esophagogastroduodenoscopic procedures and is expected to become an important assistant for standardizing and improving quality of the procedures, as well as an significant tool for quality control of esophagogastroduodenoscopy.

Objective:To investigate the role of lncRNA H19 in evaluating prognosis and regulating radioresistance of colon cancer, aiming to provide a new potential target for the diagnosis and treatment of colon cancer.Methods:The value of lncRNA H19 in the clinicopathological parameters and prognosis of colon cancer was assessed based on bioinformatics technology. The expression of lncRNA H19 in HCT116 and SW620 cells was regulated through siRNA and overexpression plasmid transfection, respectively. The effect of regulating lncRNA H19 expression on the proliferation, DNA synthesis, radiosensitivity and cell cycle of colon cancer cells after X-ray irradiation were detected by CCK8, EdU, cell clonogenic survival assay and flow cytometry.Results:The expression of lncRNA H19 was significantly upregulated in colon cancer tissues and correlated with poor prognosis in colon cancer patients. LncRNA H19, as a high-risk gene for colon cancer, had a significant advantage for prognostic assessment of colon cancer (AUC=0.816). Furthermore, the expression of lncRNA H19 was upregulated after X-ray irradiation in colon cancer cells. Knockdown of lncRNA H19 (siRNA-H19) significantly increased the radiosensitivity in HCT116 cells, while overexpression of lncRNA H19 (H19-OE) enhanced the radioresistance in SW620 cells. Moreover, flow cytometry revealed that the G 2/M phase arrest induced by X-ray irradiation was obviously aggravated after siRNA-H19 treatment in colon cancer cells, which suggested that lncRNA H19 might regulate the radiosensitivity by inhibiting cell cycle progression. Conclusion:LncRNA H19 plays a key role in the prognostic assessment and regulating the radiosensitivity in colon cancer, which can be used as a potential target for improving radiosensitivity of colon cancer radiotherapy.

Although targeted, immune and other therapeutic strategies have become the first-line standard therapy for patients with advanced lung cancer, acquired drug resistance is still inevitable in most cases. The advent of antibody-drug conjugates (ADC) provides a new choice. ADC is a new anticancer drug formed by the coupling of targeted anti-tumor monoclonal antibodies and cytotoxic drugs. Compared with chemotherapeutic drugs, ADC has the advantages of high tolerance, accurate target recognition and little effect on non-cancer cells, and has shown good clinical benefits in the treatment of a variety of malignant tumors. This article reviews the application of ADC in advanced non-small cell lung cancer.