Lung function benefits of traditional Chinese medicine Qiju granules against fine particulate air pollution exposure: a randomized controlled trial.

Introduction: Multiple targets are considered as the causes of ambient fine particulate matter [aerodynamic diameters of < 2.5 µm (PM2.5)] induced lung function injury. Qiju granules are derived from the traditional Chinese medicine (TCM) formula known as Qi-Ju-Di-Huang-Wan (Lycium, Chrysanthemum, and Rehmannia Formula, QJDHW), which has been traditionally used to treat symptoms such as cough with phlegm, dry mouth and throat, and liver heat. This treatment approach involves attenuating inflammation, oxidative stress, and fibrosis response. This study investigated the effects of Qiju granules on protecting lung function against PM2.5 exposure in a clinical trial. Methods: A randomized, double-blinded, and placebo-controlled trial was performed among 47 healthy college students in Hangzhou, Zhejiang Province in China. The participants were randomly assigned to the Qiju granules group or the control group based on gender. Clinical follow-ups were conducted once every 2 weeks during a total of 4 weeks of intervention. Real-time monitoring of PM2.5 concentrations in the individually exposed participants was carried out. Data on individual characteristics, heart rate (HR), blood pressure (BP), and lung function at baseline and during the follow-ups were collected. The effects of PM2.5 exposure on lung function were assessed within each group using linear mixed-effect models. Results: In total, 40 eligible participants completed the scheduled follow-ups. The average PM2.5 level was found to be 64.72 µg/m3 during the study period. A significant negative correlation of lung function with PM2.5 exposure concentrations was observed, and a 1-week lag effect was observed. Forced expiratory volume in one second (FEV1), peak expiratory flow (PEF), maximal mid-expiratory flow (MMEF), forced expiratory flow at 75% of forced vital capacity (FVC) (FEF75), forced expiratory flow at 50% of FVC (FEF50), and forced expiratory flow at 25% of FVC (FEF25) were significantly decreased due to PM2.5 exposure in the control group. Small airway function was impaired more seriously than large airway function when PM2.5 exposure concentrations were increased. In the Qiju granules group, the associations between lung function and PM2.5 exposure were much weaker, and no statistical significance was observed. Conclusion: The results of the study showed that PM2.5 exposure was associated with reduced lung function. Qiju granules could potentially be effective in protecting lung functions from the adverse effects of PM2.5 exposure. Clinical Trial Registration: identifier: ChiCTR1900021235.

Early hyperbaric oxygen therapy through regulating the HIF-1α signaling pathway attenuates Neuroinflammation and behavioral deficits in a mouse model of Sepsis-associated encephalopathy.

BACKGROUND: Sepsis-associated encephalopathy (SAE) presents a significant clinical challenge, associated with increased mortality and healthcare expenses. Hyperbaric oxygen therapy (HBOT), involving inhaling pure or highly concentrated oxygen under pressures exceeding one atmosphere, has demonstrated neuroprotective effects in various conditions. However, the precise mechanisms underlying its protective actions against sepsis-associated brain injury remain unclear. This study aimed to determine whether HBOT protects against SAE and to elucidate the impact of the hypoxia-inducible factor-1α (HIF-1α) signaling pathway on SAE. METHODS: The experiment consisted of two parts. In the first part, C57BL/6 J male mice were divided into five groups using a random number table method: control group, sham surgery group, sepsis group, HBOT + sepsis group, and HBOT + sham surgery group. In the subsequent part, C57BL/6 J male mice were divided into four groups: sepsis group, HBOT + sepsis group, HIF-1α + HBOT + sepsis group, and HIF-1α + sepsis group. Sepsis was induced via cecal ligation and puncture (CLP). Hyperbaric oxygen therapy was administered at 1 h and 4 h post-CLP. After 24 h, blood and hippocampal tissue were collected for cytokine measurements. HIF-1α, TNF-α, IL-1ß, and IL-6 expression were assessed via ELISA and western blotting. Microglial expression was determined by immunofluorescence. Blood-brain barrier permeability was quantified using Evans Blue. Barnes maze and fear conditioning were conducted 14 days post-CLP to evaluate learning and memory. RESULTS: Our findings reveal that CLP-induced hippocampus-dependent cognitive deficits coincided with elevated HIF-1α and increased TNF-α, IL-1ß, and IL-6 levels in both blood and hippocampus. Observable activation of microglial cells in the hippocampus and increased blood-brain barrier (BBB) permeability were also evident. HBOT mitigated HIF-1α, TNF-α, IL-1ß, and IL-6 levels, attenuated microglial activation in the hippocampus, and significantly improved learning and memory deficits in CLP-exposed mice. Additionally, these outcomes were corroborated by injecting a lentivirus that overexpressed HIF-1α into the hippocampal region of the mice. CONCLUSION: HIF-1α escalation induced peripheral and central inflammatory factors, promoting microglial activation, BBB impairment, and cognitive dysfunction. However, HBOT ameliorated these effects by reducing HIF-1α levels in Sepsis-Associated Encephalopathy.

Production of 1,4-Butanediol from Succinic Acid Using Escherichia Coli Whole-Cell Catalysis.

The widespread attention towards 1,4-butanediol (BDO) as a key chemical raw material stems from its potential in producing biodegradable plastics. However, the efficiency of its biosynthesis via current bioprocesses is limited. In this study, a dual-pathway approach for 1,4-BDO production from succinic acid was developed. Specifically, a double-enzyme catalytic pathway involving carboxylic acid reductase and ethanol dehydrogenase was proposed. Optimization of the expression levels of the pathway enzymes led to a significant 318 % increase in 1,4-BDO titer. Additionally, the rate-limiting enzyme MmCAR was engineered to enhance the kcat/KM values by 50 % and increase 1,4-BDO titer by 46.7 %. To address cofactor supply limitations, an NADPH and ATP cycling system was established, resulting in a 48.9 % increase in 1,4-BDO production. Ultimately, after 48 hours, 1,4-BDO titers reached 201 mg/L and 1555 mg/L in shake flask and 5 L fermenter, respectively. This work represents a significant advancement in 1,4-BDO synthesis from succinic acid, with potential applications in the organic chemical and food industries.

A paired measles-rubella catch-up campaign in Sichuan China to stop an outbreak and strengthen local immunization programs.

BACKGROUND: China has been working towards measles elimination, but in 2017, measles outbreaks occurred in Ganzi and Aba prefectures of Sichuan province, representing 95% of all provincial cases and jeopardizing measles elimination. METHODS: During March and April 2017, high-performing prefectures were paired with outbreak and other interested counties to jointly conduct a measles-rubella (MR) catch-up campaign, build population immunity, and strengthen the counties' programs. RESULTS: House-to-house search identified 88,383 children in Ganzi that lacked MCV vaccination; 85,144 (96.34%) were vaccinated. Search identified 33,683 children in Aba who were not vaccinated against measles; 33,074 (98.19%) were vaccinated. The supporting prefectures helped install Immunization Information Systems and enroll unvaccinated children into the immunization program.The outbreak ended within a month and incidence has remained low for the subsequent six years. CONCLUSION: A paired catch-up campaign represents an effective model of using measles elimination strategies to strengthen local immunization programs for long-term program effectiveness.

Dapagliflozin prevents kidney podocytes pyroptosis via miR-155-5p/HO-1/NLRP3 axis modulation.

Diabetic nephropathy (DN) is a significant clinical microvascular complication associated with diabetes mellitus (DM), and end-stage diabetes giving rise to kidney failure is developing into the major etiological factor of chronic kidney failure. Dapagliflozin is reported to limit podocyte damage in DM, which has proven to protect against renal failure. Mounting evidence has demonstrated that pyroptosis is associated with DM progression. Nevertheless, whether pyroptosis causes DN and the underlying molecular pathways remain obscure. In this study, we aimed to explore the antipyroptotic attributes of dapagliflozin and elucidate the underlying mechanisms of kidney damage in diabetes. In vivo, experiments were conducted in streptozotocin (STZ)-induced type 2 diabetic mice, which were administered dapagliflozin via gavage for 6 weeks. Subsequently, the specific organizational characteristics and expression of pyroptosis-related genes were evaluated. Intragastric dapagliflozin administration markedly reduced renal tissue injury. Meanwhile, dapagliflozin also attenuated the expression level of pyroptosis associated genes, including ASC, cleaved Caspase-1, GSDMD N-termini, NLRP3, IL-18, and IL-1ß in renal tissue of dapagliflozin-treated animals. Similar antipyroptotic effects were observed in palmitic acid (PA)-treated mouse podocytes. We also found that heme oxygenase 1 (HO-1) enhanced the protection of mouse podocyte clone 5 cells (MPC5). Moreover, miR-155-5p inhibition increased pyroptosis in PA-treated MPC5 cells, suggesting that miR-155-5p acts as an endogenous stimulator that increases HO-1 expression and reduces pyroptosis. Hence, our findings imply that dapagliflozin inhibits podocyte pyroptosis via the miR-155-5p/HO-1/NLRP3 axis in DM. Furthermore, dapagliflozin substitution may be regarded as an effective strategy for preventing pyroptosis in the kidney, including a therapeutic option for treating pyroptosis-related DN.

Phosphatidic acid interacts with an HD-ZIP transcription factor GhHOX4 to influence its function in fiber elongation of cotton (Gossypium hirsutum).

Upland cotton, the mainly cultivated cotton species in the world, provides over 90% of natural raw materials (fibers) for the textile industry. The development of cotton fibers that are unicellular and highly elongated trichomes on seeds is a delicate and complex process. However, the regulatory mechanism of fiber development is still largely unclear in detail. In this study, we report that a homeodomain-leucine zipper (HD-ZIP) IV transcription factor, GhHOX4, plays an important role in fiber elongation. Overexpression of GhHOX4 in cotton resulted in longer fibers, while GhHOX4-silenced transgenic cotton displayed a "shorter fiber" phenotype compared with wild type. GhHOX4 directly activates two target genes, GhEXLB1D and GhXTH2D, for promoting fiber elongation. On the other hand, phosphatidic acid (PA), which is associated with cell signaling and metabolism, interacts with GhHOX4 to hinder fiber elongation. The basic amino acids KR-R-R in START domain of GhHOX4 protein are essential for its binding to PA that could alter the nuclear localization of GhHOX4 protein, thereby suppressing the transcriptional regulation of GhHOX4 to downstream genes in the transition from fiber elongation to secondary cell wall (SCW) thickening during fiber development. Thus, our data revealed that GhHOX4 positively regulates fiber elongation, while PA may function in the phase transition from fiber elongation to SCW formation by negatively modulating GhHOX4 in cotton.

Effectiveness of a single low-dose computed tomography screening for lung cancer: A population-based perspective cohort study in China.

The purpose of this perspective cohort study was to evaluate the effectiveness of low-dose computed tomography (LDCT) screening for lung cancer in China. This study was conducted under the China Urban Cancer Screening Program (CanSPUC). The analysis was based on participants aged 40 to 74 years from 2012 to 2019. A total of 255 569 eligible participants were recruited in the study. Among the 58 136 participants at high risk of lung cancer, 20 346 (35.00%) had a single LDCT scan (defined as the screened group) and 37 790 (65.00%) not (defined as the non-screened group). Overall, 1162 participants were diagnosed with lung cancer at median follow-up time of 5.25 years. The screened group had the highest cumulative incidence of lung cancer and the non-screened group had the highest cumulative lung cancer mortality and all-cause cumulative mortality. We performed inverse probability weighting (IPW) to account for potential imbalances, and Cox proportional hazards model to estimate the weighted association between mortality and LDCT scans. After IPW adjusted with baseline characteristics, the lung cancer incidence density was significantly increased (37.0% increase) (HR1.37 [95%CI 1.12-1.69]), lung cancer mortality was decreased (31.0% decrease) (HR0.69 [95%CI 0.49-0.97]), and the all-cause mortality was significantly decreased (23.0% lower) (HR0.77 [95% CI 0.68-0.87]) in the screened group. In summary, a single LDCT for lung cancer screening will reduce the mortality of lung cancer and all-cause mortality in China.

Evaluation of therapeutic benefits of botulinum toxin for foot dystonia associated with Parkinson's disease.

BACKGROUND: Foot dystonia occurs in patients with Parkinson's disease (PD) and leads to pain, malformation, and difficulty with walking. Botulinum toxin injections may be effective for foot dystonia, but the extent of improvement and effects on motor function are unclear. METHODS: In this study, we performed botulinum toxin injections for foot dystonia in 25 patients with PD. At 3 weeks and 3 months post-infection, we assessed changes in plantar pressure distribution utilizing the Pressure Plate system; dystonia using the Modified Ashworth Spasm score; pain using the visual analog scale (VAS) score; and lower extremity function using the Calf-raise Senior (CRS) test, Timed Up and Go (TUG) test, and gait parameters (eg, stride length, step length). RESULTS: We found improved Modified Ashworth Spasm score (p < 0.01) and VAS score (p < 0.01) post-injection. CRS test score (3 weeks, p = 0.006; 3 months, p = 0.068), stride length (3 weeks, p = 0.012; 3 months, p = 0.715), and step length (3 weeks, p = 0.011; 3 months, p = 0.803) also improved. Plantar pressure distribution improved after botulinum toxin injection (metatarsal 1, 3 weeks, p = 0.031; 3 months, p = 0.144; metatarsal 2, 3 weeks, p = 0.049; 3 months, p = 0.065; metatarsal 3, 3 weeks, p = 0.002; 3 months, p = 0.017; metatarsal 4, 3 weeks, p = 0.017; 3 months, p = 0.144; medial heel, 3 weeks, p = 0.01; 3 months, p = 0.395; lateral heel, 3 weeks, p = 0.035; 3 months, p = 0.109). CONCLUSION: Botulinum toxin injection for foot dystonia in patients with PD can reduce spasms and pain and normalize plantar pressure distribution, which improves balance and lower extremity function.

First-principles studies on the electronic and photocatalytic water splitting properties of surface functionalized Y2C-based MXenes.

Recently, MXenes, an emerging family of two-dimensional (2D) materials, have attracted increasing interest for photocatalytic water splitting due to their various excellent physical and chemical properties, such as large specific surface area, good hydrophilicity, and remarkable light absorption ability. However, the photocatalysts of MXenes with symmetric structures are limited by rapid recombination of photo-generated carriers and the prerequisite of a large band gap no less than 1.23 eV. Differently, Janus MXenes with different surface functional groups facilitate the separation of photo-generated electrons and holes with the help of the intrinsic electric field. And, at the same time, there is no prerequisite for the band gap of Janus MXene photocatalysts as long as they possess appropriate band edge positions. Here, we explored the structural, electronic and photocatalytic water splitting properties of symmetric Y2CT2 and Janus Y2CTT' MXenes (T, T' = H, F, Cl, OH) using the density functional theory (DFT) method. Our calculations show that all the investigated Y2CT2 are not suitable photocatalysts for photocatalytic water splitting at all pH values (pH = 0, 7, and 14). In contrast, all the investigated Janus Y2CTT' MXenes are good water splitting photocatalysts with high optical absorption coefficients and remarkable solar-to-hydrogen (STH) efficiencies larger than 18% at pH = 14. Moreover, the STH efficiencies are larger than 18% even at all investigated pH values for Y2CHCl (18.5-22.6%), Y2 CFCl (∼18.7%), and Y2 C(OH)Cl (∼19.4%). Based on the first-principles calculations, we here for the first time propose an easy strategy to design Janus MXene photocatalyst candidates with possible high STH efficiency according to the electronic properties of their symmetric counterparts. Our study is helpful for the future design of Janus MXenes and more generally Janus 2D photocatalysts for water splitting with high STH efficiency.

A comparative study on the features of breast sclerosing adenosis and invasive ductal carcinoma via ultrasound and establishment of a predictive nomogram.

Objective: To analyze the clinical and ultrasonic characteristics of breast sclerosing adenosis (SA) and invasive ductal carcinoma (IDC), and construct a predictive nomogram for SA. Materials and methods: A total of 865 patients were recruited at the Second Hospital of Shandong University from January 2016 to November 2022. All patients underwent routine breast ultrasound examinations before surgery, and the diagnosis was confirmed by histopathological examination following the operation. Ultrasonic features were recorded using the Breast Imaging Data and Reporting System (BI-RADS). Of the 865 patients, 203 (252 nodules) were diagnosed as SA and 662 (731 nodules) as IDC. They were randomly divided into a training set and a validation set at a ratio of 6:4. Lastly, the difference in clinical characteristics and ultrasonic features were comparatively analyzed. Result: There was a statistically significant difference in multiple clinical and ultrasonic features between SA and IDC (P<0.05). As age and lesion size increased, the probability of SA significantly decreased, with a cut-off value of 36 years old and 10 mm, respectively. In the logistic regression analysis of the training set, age, nodule size, menopausal status, clinical symptoms, palpability of lesions, margins, internal echo, color Doppler flow imaging (CDFI) grading, and resistance index (RI) were statistically significant (P<0.05). These indicators were included in the static and dynamic nomogram model, which showed high predictive performance, calibration and clinical value in both the training and validation sets. Conclusion: SA should be suspected in asymptomatic young women, especially those younger than 36 years of age, who present with small-size lesions (especially less than 10 mm) with distinct margins, homogeneous internal echo, and lack of blood supply. The nomogram model can provide a more convenient tool for clinicians.

The association of body mass index and weight waist adjustment index with serum ferritin in a national study of US adults.

BACKGROUND: Abnormal serum ferritin levels are associated with a variety of diseases. Meanwhile, abnormal serum ferritin is influenced by a variety of risk factors, but its correlation with obesity remains poorly described. OBJECTIVE: This study aimed to investigate the association of body mass index (BMI) and weight waist adjustment index (WWI) with serum ferritin in US adults. METHODS: Participants in this study took part in the National Health and Nutrition Examination Survey (NHANES) prior to the pandemic from 2017 to March 2020. Serum ferritin was used as the sole response variable and BMI and WWI were used as independent variables. Multiple linear regression was used to assess the relationship between serum ferritin and the independent variables, and smoothed curve fitting and threshold effects analysis were performed to assess the presence of non-linear relationships. To validate the sensitive individuals for the correlation between the independent and the dependent variables, a subgroup analysis was performed. RESULTS: A final total of 7552 participants were included in this study. Both independent variables had a positive relationship with serum ferritin, with effect values of (ß = 0.68, 95% CI: 0.17-1.19) when BMI was the independent variable and (ß = 8.62, 95% CI: 3.53-13.72) when WWI was the independent variable in the fully adjusted model. This positive association between the two obesity-related indexes and serum ferritin became more significant as BMI and WWI increased (P for trend < 0.001). In subgroup analyses, the positive association between the independent variables and serum ferritin was more pronounced in participants who were male, 40-59 years old, white, and had diabetes and hypertension. In addition, smoothed curve fitting and threshold effects analysis demonstrated a linear positive association of BMI and WWI with serum ferritin. CONCLUSIONS: In the US adult population, while there was a linear positive association of WWI and BMI with serum ferritin, the effect values between WWI and serum ferritin were more significant. Male, 40-59 years old, white, participants with diabetes and hypertension should be cautious that higher WWI might entail a risk of higher serum ferritin levels.

[Diagnostic Efficacy of 68Ga-Labeled Prostate-Specific Membrane Antigen and 18F-Labeled Sodium Fluoride PET/CT in Prostate Cancer With Bone Metastasis].

Objective To compare the efficiency of 68Ga-labeled prostate-specific membrane antigen (68Ga-PSMA-11) and 18F-labeled sodium fluoride (18F-NaF) PET/CT in the diagnosis of bone metastasis in the patients with prostate cancer.Methods The prostate cancer patients suspected of bone metastasis who underwent 68Ga-PSMA-11 PET/CT and 18F-NaF PET/CT from January 2018 to January 2021 were included in this study.The number of lesions,maximum standardized uptake value (SUVmax),and tumor-to-background (T/B) ratio were compared between the two methods.Results 18F-NaF PET/CT detected more metastases than 68Ga-PSMA-11 PET/CT (310 vs.264,P<0.001).The median SUVmax[23.2 (16.4,33.4) vs.4.1 (2.5,5.6)] and median T/B ratio[7.0 (4.9,9.9) vs.6.7 (3.7,9.6)] of 18F-NaF PET/CT were higher than those of 68Ga-PSMA-11 PET/CT (all P<0.001).With the number of lesions as the indicator,the sensitivity,specificity,accuracy,positive predictive value,and negative predictive value of 18F-NaF PET/CT were 100.0%,92.0%,92.0%,98.7%,and 100.0% respectively,and those of 68Ga-PSMA-11 PET/CT were 85.2%,94.0%,79.2%,98.9%,and 50.5%,respectively.Conclusion 18F-NaF PET/CT is superior to 68Ga-PSMA-11 PET/CT in the detection of bone metastases of prostate cancer.

Evaluation of the effectiveness of hospital infection prevention and control based on the SMART principle. / 基于SMART原则的医院感染预防与控制效果评价.

OBJECTIVES: Hospital infection not only increases patient suffering and mortality, but also causes huge economic losses. It is urgent to take effective measures to improve the situation of hospital infection and focus on hand hygiene and disinfection. The SMART principle is to follow the principles of specificity, measurability, attainability, relevance, and timeliness when setting goals. This study aims to use the SMART principle in the prevention and control of hospital infection, to take a series of measures on the hospital infection such as hand hygiene, and to evaluate the implementation effect. METHODS: This study is a retrospective study. From January to June 2020, the SMART principle was used to carry out intervention for infection prevention and control in the Xiangya International Medical Department, Central South University, and implement the infection prevention and control quality improvement plan. Using indicator data as targeting measurement standard, we established evaluation indicators for hospital infection prevention and control knowledge awareness and hand hygiene compliance rate as the process monitoring, surgical site infection rate and catheter-related urinary tract infection rate as the result monitoring. The evaluation indicators after intervention (July 2020 to June 2021) were compared with those before intervention (January 2019 to December 2019). RESULTS: Fifty-one medical staff working in the Xiangya International Medical Department were included. There were 12 doctors and 39 nurses, and 6 males and 45 females. The age ranged from 21 to 57 (30.2±7.1) years. After the intervention, the awareness of hospital infection prevention and control knowledge and hand hygiene compliance rate of medical staff were significantly higher than those before the intervention (both P<0.05), but there were no significant differences in surgical site infection rate and catheter-related urinary tract infection rate before and after intervention (both P>0.05). After the intervention, the awareness of hospital infection prevention and control knowledge and hand hygiene compliance rate of medical staff in the internal and surgical wards were higher than those before the intervention (all P<0.05). The awareness of hospital infection prevention and control knowledge of medical staff in surgical wards was low but improved significantly. The compliance rate of hand hygiene of medical staff in internal wards was high and improved significantly. After the intervention, the awareness of hospital infection prevention and control knowledge and hand hygiene compliance rate of male and female medical staff were higher than those before the intervention (all P<0.05), both of which were significantly higher in males than in females. After the intervention, the awareness of hospital infection prevention and control knowledge and hand hygiene compliance rate for medical staff aged less than 30 years old and 30 to 40 years old were higher than those before the intervention (all P<0.05). Medical staff aged 30 to 40 years had a low awareness of hospital infection prevention and control knowledge, but both indicators improved most significantly. After the intervention, the awareness of hospital infection prevention and control knowledge of doctors and nurses was increased (both P<0.05). The awareness of doctors improved more significantly, and the hand hygiene compliance rate of nurses improved (P<0.05). After the intervention, the awareness of hospital infection prevention and control knowledge and hand hygiene compliance rate of medical staff with primary and intermediate professional titles were higher than those before the intervention (all P<0.05), and the improvement was more significant for medical staff with intermediate professional titles. CONCLUSIONS: Based on the SMART principle management method, the implementation of quality improvement plans combined with various domestic and international evaluation standards for infection prevention and control can effectively improve the awareness of infection control knowledge and hand hygiene compliance rate of medical staff, strengthen the prevention and control of hospital infection, and further ensure the safety of patients.

Dapagliflozin alleviates renal podocyte pyroptosis via regulation of the HO­1/NLRP3 axis.

Diabetic nephropathy is one of the most significant complications of diabetes, resulting in increased patient mortality. Dapagliflozin is an inhibitor of sodium­glucose cotransporter 2 that has an important protective effect on the kidney. Recent studies showed that pyroptosis is involved in the advancement of diabetic nephropathy (DN). However, the potential molecular mechanisms underlying the association between pyroptosis and renal podocyte injury in DN remain unclear. Thus, the present study investigated the anti­pyroptotic function of dapagliflozin in podocytes and further clarified the potential mechanisms. In this study, a model of lipid metabolism disturbance was established through palmitic acid (PA) induction in a mouse podocyte clone 5 (MPC5) cell line. MPC5 PA­induced pyroptosis was measured by ELISA, western blotting, quantitative PCR and Hoechst 33342/propidium iodide double­fluorescence staining. The protective role of HO­1 was measured using knockdown and overexpression experiments. It was found that dapagliflozin attenuated the expression of pyroptosis­related proteins, including nucleotide oligomerization domain­like receptor thermal protein domain associated protein 3, apoptosis­associated speck­like protein containing a caspase activation and recruitment domain, caspase­1, IL­18 and IL­1ß in the PA group. Meanwhile, the heme oxygenase 1 (HO­1) expression level decreased within PA, an effect that was reversed by dapagliflozin. Furthermore, the expression of pyroptosis­related proteins and inflammatory cytokines was reduced following HO­1 overexpression. Therefore, these results suggested that dapagliflozin ameliorates MPC5 pyroptosis by mediating HO­1, which has a protective effect on diabetic nephropathy.

Establishment of a facial nerve trunk crush injury model and evaluation of facial nerve self-healing in rats.

INTRODUCTION/AIMS: To facilitate further investigation into the mechanisms of facial nerve regeneration, a simple and reliable model of facial nerve crush injury is essential. Nevertheless, the establishment of such models lacks standardization and repeatability, while the healing capacity of the nerve is often overlooked, potentially affecting future studies. METHODS: We made facial nerve trunk crush injury models with different pressing times and detected the changes from the distal nerves to the motoneurons via behavior analysis, electrophysiological test, and histomorphometry analysis. RESULTS: It revealed a particular capacity for self-healing following facial nerve crush damage because there was almost no facial motoneuron apoptosis in the MC group during the observation period, and rats in MC group had total facial paralysis in behavioral tests following surgery and varying degrees of recovery 28 days postoperatively with no treatments. As the pressing time increased, the latency, wave amplitude, nerve fiber damage degree, nerve axon ratio, myelin thickness, electroneurograph (ENoG) value, ultrastructural damage, abnormal morphological changes, and the buccal muscle atrophy of each MC group gradually increased or got worse during the observation period. However, after 28 postoperative days, only the ENoG values of the M10min and M12min groups were beyond 90%, indicating no self-healing. DISCUSSION: It suggests that a stable model of peripheral facial palsy may be created by applying a 12.5 cm mosquito clamped to the facial nerve trunk for at least 10 min, which laid the foundation for the subsequent research to objectively evaluate facial nerve regeneration.

[Causes of False-Positive Results in 68Ga-Labeled Fibroblast Activation Protein Inhibitor PET/CT Imaging].

Objective To investigate the causes of false-positive results in the 68Ga-labeled fibroblast activation protein inhibitor (68Ga-FAPI-04) PET/CT imaging. Methods The imaging data of 547 patients undergoing 68Ga-FAPI-04 PET/CT examination in the Department of Nuclear Medicine of the Affiliated Hospital of Southwest Medical University from September 2020 to May 2021 were retrospectively collected.Two experienced nuclear medicine diagnostic physicians analyzed the clinical data,relevant imaging examinations,laboratory examinations,pathological results and follow-up results of the patients with false-positive results. Results The 68Ga-FAPI-04 PET/CT imaging of 547 patients showed false-positive results in 99 (18.1%) patients,including 56 males and 43 females.The postoperative pathological examination confirmed false-positive results in 13 patients,including 1 patient of thyroiditis,2 patients of pulmonary tuberculosis,1 patient of bone tuberculosis,2 patients of pulmonary inflammatory pseudotumor,1 patient of pulmonary sarcoidosis,1 patient of pulmonary benign fibroma,1 patient of organic pneumonia,2 patients of renal angiomyolipoma,1 patient of mass pancreatitis,and 1 patient of pancreatic mucinous cystadenoma.The medical history,relevant imaging examination,and long-term follow-up confirmed false-positive results in 86 patients.Specifically,the false-positive uptake in the neck,chest,abdomen,bone joint,and skin occurred in 8 (9.3%),13 (15.1%),5 (5.8%),57 (66.3%),and 3 (3.5%) patients,respectively.Inflammation-related uptake appeared in 83 (83.8%) patients with false-positive imaging results,of which arthritis (23 patients) and osteophyte (29 patients) were the most common.Sixteen (16.2%) patients showed the false-positive uptake related to fibroblasts. Conclusion 68Ga-FAPI-04 PET/CT imaging will show non-malignant tumor false-positive results,which are mainly associated with inflammation and fibroblasts.

Yield and cost of government-organized colorectal cancer screening in young high-risk population in Northeast China.

Guidelines for colorectal cancer (CRC) screening recommend screening at age 40 for high-risk population in China. However, the yield and cost of CRC screening in younger population are lacking. This analysis aimed to evaluate the yield and cost of CRC screening in high-risk 40- to 54-year-olds. Individuals aged 40-54 years who were determined to have a high risk of CRC were recruited from December 2012 to December 2019. We calculated odds ratios (OR) and 95% confidence intervals (CI) for the detection rate of colorectal lesions among the three age groups and further calculated number of colonoscopies needed to screen (NNS) to detect one advanced lesion and cost of each group. The detection rates of advanced colorectal neoplasm in men aged 45-49 years (OR = 2.00, 95% CI: 0.93-4.30) and 50-54 years (OR = 2.19, 95% CI: 1.04-4.62) were higher than that aged 40-44 years. The detection rates of colorectal adenoma in women aged 50-54 years was higher than that aged 40-44 years (OR = 1.64, 95% CI: 1.23-2.19). Among the male screening population, NNS and cost to detect one advanced lesion in participants aged 45-49 years were similar to that aged 50-54 years, saving approximately half endoscopic resources and financial expenses compared with screening that aged 40-44 years. From the perspective of screening results and costs, it might be beneficial to delay the starting age of screening by gender. This study may provide reference for optimizing CRC screening strategies.

Viral metagenomics of the gut virome of diarrheal children with Rotavirus A infection.

Diarrhea is a leading cause of morbidity and mortality in children worldwide and represents a major dysbiosis event. Rotavirus has been recognized as a global leading pathogen of diarrhea. This study is aimed at investigating differences in the gut virome between diarrheal children and healthy controls. In 2018, 76 diarrheal fecal samples and 27 healthy fecal samples in Shanghai and 40 diarrheal fecal samples and 19 healthy fecal samples in Taizhou were collected to investigate the composition of the gut virome. Viral metagenomic analyses revealed that the alpha diversity of the diarrheal virome was not significantly different from that of the healthy virome, and the beta diversity had a significant difference between diarrheal and healthy children. The diarrheal virome was mainly dominated by the families Adenoviridae, Astroviridae, Caliciviridae, and Picornaviridae. Meanwhile, the healthy virome also contains phages, including Microviridae and Caudovirales. The high prevalence of diverse enteric viruses in all samples and the little abundance of Microviridae and Caudovirales in diarrheal groups were identified. The study introduced a general overview of the gut virome in diarrheal children, revealed the compositional differences in the gut viral community compared to healthy controls, and provided a reference for efficient treatments and prevention of virus-infectious diarrhea in children.

A population-based cross-sectional study on the situation of cervical cancer screening in Liaoning, China.

BACKGROUND: Cervical cancer (CC) screening is currently recognized as an effective intervention for CC. Previous studies found that the proportion of screening was low in China, especially in Liaoning. Therefore, we performed a population-based cross-sectional survey to investigate the situation of cervical cancer screening and analyze their related factors for providing a decision-making basis for sustainable and effective development of cervical cancer screening. METHODS: This population-based cross-sectional study involved aged 30 to 69 years in nine counties/districts in Liaoning from 2018 to 2019. Data were collected using the quantitative data collection methods, and analyzed in SPSS version 22.0. RESULTS: Overall, only 22.37% of 5334 respondents reported having ever been screened for cervical cancer in past 3 years, and 38.41% of respondents reported having the willingness for cervical cancer screening in next 3 years. In the rate of CC screening, multilevel analysis indicated that age, marital status, education level, type of occupation, medical insurance, family income, place of residence and regional economic level had a significant impact on proportion of screening. In the rate of CC screening willingness, multilevel analysis indicated that age, family income, health status, place of residence, regional economic level and CC screening still had a significant impact, but marital status, education level and medical insurance type had no significant impact. There was no significant difference in marital status, education level and medical insurance type after the factors of CC screening were added in the model. CONCLUSION: Our study found both proportion of screening and willingness were at a low level, and age, economic and regional factors were the main factors for implementation of CC screening in China. In the future, targeted policies should be formulated according to the characteristics of different groups of people, and reduce the gap in the current health service capacity between different regions.

ICOS/ICOSLG and PD-1 Co-Expression is Associated with the Progression of Colorectal Precancerous- Carcinoma Immune Microenvironment.

Purpose: This study aimed to investigate the expression of inducible T-cell co-stimulator (ICOS) and its ligand (ICOSLG), along with their association with clinicopathological features and influence on the immune profile in colorectal cancer (CRC). Patients and Methods: The Cancer Genome Atlas Colorectal Adenocarcinoma cohorts were used. We also analyzed 131 clinical samples of colon lesions, including precancerous lesions (hyperplastic polyps, low-grade dysplasia, and high-grade dysplasia) and CRC tissues. We conducted immunohistochemical (IHC) assays and multiple IHC (mIHC) of CD4+, Foxp3+ tumor-infiltrating lymphocytes (TILs), and PD-1/PD-L1 immune checkpoints in precancerous lesions and CRC samples from our patient subsets to determine changes and correlations in ICOS and ICOSLG expression during progression through the adenoma-carcinoma pathway. Results: High expression of ICOS and ICOSLG was a significant factor in CRC in multiple analyses and was positively correlated with CD4+/Foxp3+ TIL density and PD-1/PD-L1 expression, which increased with the sequential progression of lesions from precancerous tissues to carcinoma. Multivariable logistic regression analysis suggested that the location and expression level of ICOS/ICOSLG may be involved in precancerous-carcinoma progression. The co-expression status of PD-1 and ICOS/ ICOSLG could stratify patients with colorectal lesions into three groups of low, moderate, and high risk of progression. According to this classification and mIHC assays, we found a strong correlation between increased PD-1+ICOS+ or PD-1+ICOSLG+ co-expression and CRC, which might be deemed an independent factor in carcinogenesis. Conclusion: Increased ICOS/ICOSLG expression may be associated with the progressive formation of Foxp3+ TILs in the immune microenvironment and may further promote the development of the abnormal cytology of colorectal lesions from precancerous neoplasia to CRC. Our findings support the interpretation that enhanced co-expression of PD-1+ICOS+ or PD-1+ICOSLG+ contributes to the immune-active microenvironment of the colorectal adenoma-carcinoma sequence.