FHPM: Fine-grained Huge Page Management For Virtualization

As more data-intensive tasks with large footprints are deployed in virtual machines (VMs), huge pages are widely used to eliminate the increasing address translation overhead. However, once the huge page mapping is established, all the base page regions in the huge page share a single extended page table (EPT) entry, so that the hypervisor loses awareness of accesses to base page regions. None of the state-of-the-art solutions can obtain access information at base page granularity for huge pages. We observe that this can lead to incorrect decisions by the hypervisor, such as incorrect data placement in a tiered memory system and unshared base page regions when sharing pages. This paper proposes FHPM, a fine-grained huge page management for virtualization without hardware and guest OS modification. FHPM can identify access information at base page granularity, and dynamically promote and demote pages. A key insight of FHPM is to redirect the EPT huge page directory entries (PDEs) to new companion pages so that the MMU can track access information within huge pages. Then, FHPM can promote and demote pages according to the current hot page pressure to balance address translation overhead and memory usage. At the same time, FHPM proposes a VM-friendly page splitting and collapsing mechanism to avoid extra VM-exits. In combination, FHPM minimizes the monitoring and management overhead and ensures that the hypervisor gets fine-grained VM memory accesses to make the proper decision. We apply FHPM to improve tiered memory management (FHPM-TMM) and to promote page sharing (FHPM-Share). FHPM-TMM achieves a performance improvement of up to 33% and 61% over the pure huge page and base page management. FHPM-Share can save 41% more memory than Ingens, a state-of-the-art page sharing solution, with comparable performance

Cervical HPV infection in Yueyang, China: a cross-sectional study of 125,604 women from 2019 to 2022

ObjectiveHuman papillomavirus (HPV) infection is currently the main cause of cervical cancer and precancerous lesions in women. The aim of this study was to investigate the epidemiological characteristics of HPV genotypes among women in Yueyang city and to provide a basis for the prevention and treatment of cervical cancer in this city.MethodsA cross-sectional study was conducted on 125,604 women who had received treatment from eight hospitals in Yueyang city from September 2019 to September 2022. Analysis of the prevalence of HPV in patients.ResultsThe prevalence of HPV was 20.5% (95%CI: 20.2–20.7%), of which the high-risk type (HR-HPV) accounted for 17.5% (95%CI: 17.3–17.7%) and the low-risk type (LR-HPV) accounted for 5.0% (95%CI: 4.9–5.1%). Among the HR-HPV subtypes, the top five in prevalence, from the highest to the lowest, were HPV52 (5.1%), HPV16(2.7%), HPV58 (2.6%), HPV53 (2.4%), and HPV51 (1.7%). The main LR-HPV infection types were HPV81 (2,676 cases, OR = 2.1%; 95%CI, 2.0–2.1%). Among the infected patients, 19,203 cases (OR = 74.3%; 95%CI, 73.8–74.9%) had a single subtype, 4,673 cases (OR = 18.1%; 95%CI, 17.6–18.6%) had two subtypes, and 1957 cases (OR = 7.6%; 95%CI, 7.3–7.9%) had three or more subtypes. HPV prevalence is highest among women <25 years, 55–64 years and ≥ 65 years of age.ConclusionThe prevalence of HPV in women in Yueyang city was 20.5%, with HR-HPV being dominant. As women aged <25 years, 55–64 years, and ≥ 65 years are at a relatively higher risk, more attention should be paid to them for prevention and control of HPV infections

Study on the second personalized chair ⁃ side education to change the knowledge, attitude, and practice of patients with periodontitis

Objective To explore the application effect of secondary personalized chairside education on changing the knowledge and behavior of patients with oral periodontal disease. Methods A total of 124 patients experiencing initial periodontal disease were selected. Sixty⁃two patients were observed in the observation group, and 62 patients were observed in the control group. After the doctor checked and determined the periodontal condition of the patients, the nurse conducted a targeted, personalized secondary one⁃on⁃one chairside mission for the observation group; in the control group, the nurses provided routine one⁃to⁃one health education to the patients before treatment. Statistical analysis was conducted to assess periodontal knowledge mastery, self ⁃ care behaviors, rate of return for periodontal treatment and patient satisfaction after 3 months. The plaque index and scale index were statistically analyzed before and 3 months after treatment. Results No statistical difference was found in the general data between the two groups of patients (P > 0.05); however, the degree of mastery of periodontal knowledge in the observation group was higher than that in the control group. The degrees of mastery of the clinical manifestations, hazards and treatment methods were 96.7% , 93.5% , and 91.9% in the observation group and 72.5% , 48.3% , and 69.3% in the control group, respectively; the difference was statistically significant (P < 0.05). The patients in the observation group were more likely than those in the control group to brush more than 2 times daily, use dental floss and use an interdental brush; 100%, 96.7%, and 77.4% of patients in the observation group and 80.6%, 56.4%, and 40.3% of patients in the control group participated in these oral health care behaviors, respectively. The difference was statistically significant (P < 0.05). The rate of recovery and patient satisfaction were higher in the observation group than in control group at 3 months; the rate of recovery and patient satisfaction were 80.6% and 96%, in the observation group and 41.9% and 88.7% in the control group, respectively. The difference was statistically significant (P < 0.05). After 3 months, the plaque index in the observation group was lower than that in the control group (1.71 ± 1.12, 2.35 ± 0.78), and the difference was statistically significant (P < 0.05). Conclusion Secondary personalized chairside education can significantly improve the patient s cognition of the disease, allow the formation of accurate oral health awareness, and change the patients bad oral hygiene habits and medical behavior. Thus, this method is an effective oral health education method and can change the knowledge and beliefs of patients with oral periodontitis

Safety and efficacy of allogeneic bone marrow mesenchymal stem cells for treatment of canine leukopenia induced by canine parvovirus infection

ABSTRACT: This study aims to establish a therapy strategy for canine leukopenia induced by canine parvovirus (CPV) infection through intravenous infusion of allogeneic bone marrow mesenchymal stem cells (BMMSCs) and to evaluate the therapeutic effect of BMMSCs on canine parvovirus. Forty healthy 2-month-old dogs were randomly divided into four groups including the BMMSC treatment group (A), conventional treatment group (B), CPV infection group (C), and a normal control group (D). Then the A, B, and C groups were orally infected with CPV (103.25 TCID50/mL) at 1mL/kg, and the D group received the same dose of saline. After the onset of infection, Group A received mesenchymal stem cells (MSCs) and rehydration as the treatment; Group B was treated with anti-inflammatory therapeutics and rehydration; and Group C and D were injected with the same dose of physiological saline. The level of leukocytes rebounded significantly after the treatment with BMMSCs and returned to reference numbers on Day 3 after treatment, which was significantly higher than that in the conventional treatment group. The concentrations of IL-2 and IFN-α were gradually increased during the treatment, and the BMMSC treatment group exhibited significantly higher IL-2 and IFN-α concentrations than the conventional treatment group on Days 3 and 4. The expression of the virus in the blood gradually decreased during the treatment, and the BMMSC treatment group displayed a faster decrease than the conventional treatment group. These results showed the advantages of BMMSC treatment over conventional treatment. This study provides a new BMMSC treatment strategy for canine leukopenia induced by CPV infection and reveals the mechanism by which BMMSC increases leukocytes after CPV infection

Karyotype Analysis of Gazania rigens Varieties

For studying species origin, systematic evolution and phylogenetic relationship of Gazania rigens, four different G. rigens varieties, with different flower colors, were subjected to chromosome karyotype analysis. The somatic chromosome number in three varieties ‘Hongwen’, ‘Xingbai’ and ‘Richu’ was 2n = 10, while in ‘Zhongguo Xunzhangju’ it was 2n = 20. We speculate that the cardinal number of chromosomes in G. rigens plants is x = 5, in which case ‘Zhongguo Xunzhangju’ is a tetraploid. The karyotype formulae of ‘Hongwen’, ‘Xingbai’ and ‘Richu’ were 2n = 8m + 2sm, 2n = 8m  + 2sm and 2n = 10m respectively. The karyotype formula of ‘Zhongguo Xunzhangju’ was 2n = 18m + 2sm. The asymmetrical karyotype coefficients of the four G. rigens varieties ranged from 53.80% to 58.84%. Only ‘Richu’ had a ‘1A’ karyotype, while the others were relatively symmetric ‘2A’. Karyotype analysis indicates that the three introduced varieties have a close genetic relationship

Comparison of Dosimetric Gains Provided by Intensity-Modulated Radiotherapy, Volume-Modulated Arc Therapy, and Helical Tomotherapy for High-Grade Glioma

Purpose. Because of the poor prognosis for high-grade glioma (HGG) patients, it is important to increase the dose of the tumor to improve the efficacy while minimizing the dose of organs at risk (OARs). Thus, we evaluated the potential dosimetric gains of helical tomotherapy (HT) versus intensity-modulated radiotherapy (IMRT) or volume-modulated arc therapy (VMAT) for high-grade glioma (HGG). Methods. A total of 42 HGG patients were retrospectively selected who had undergone helical tomotherapy; then, IMRT and VMAT plans were generated and optimized for comparison after contouring crucial neuronal structures for neurogenesis and neurocognitive function. IMRT and VMAT were optimized with the Eclipse treatment planning system (TPS) (Version 11.0.31) and HT using TomoTherapy Hi-Art Software (Version 2.0.7) (Accuray, Madison, WI, USA). All three techniques were optimized for simultaneously delivering 60 Gy to planning target volume (PTV) 1 and 50-54 Gy to PTV2. We also analyzed the homogeneity index (HI) and conformity index (CI) of PTVs and organ at risk (OAR) sparing. Results. There was no significant difference in the PTV coverage among IMRT, VMAT, or HT. As for the HI, HT plans (PTV1 HI: 0.09±0.03, PTV2 HI: 0.17±0.05) had the best homogeneity when compared to IMRT plans (PTV1 HI: 0.10±0.04, PTV2 HI: 0.18±0.04) and VMAT plans (PTV1 HI: 0.11±0.03, PTV2 HI: 0.20±0.03). The CI value of HT (PTV1 CI: 0.98±0.03, PTV2: 0.98±0.05) was closest to the optimal value. Except for the IMRT and VMAT groups, there were statistically significant differences between the other two groups of the CI values in both PTV1 and PTV2. The other comparison values were statistically significant except for the optic nerve, and VMAT had the best sparing of the optic chiasm. The mean and max doses of OARs declined significantly in HT. Conclusions. For high-grade glioma patients, HT had superior outcomes in terms of PTV coverage and OAR sparing as compared with IMRT/VMAT

Human papillomavirus infections among women with cervical lesions and cervical cancer in Yueyang, China: a cross-sectional study of 3674 women from 2019 to 2022

Abstract Purpose To investigate the distribution of the incidence and genotypes of human papillomavirus (HPV) among women with cervical cancer (CC) and precancerous cervical lesions in Yueyang City, China, to develop prevention and control strategies for CC. Methods A total of 3674 patients with cervical lesions and cervical cancer who attended 7 hospitals in Yueyang City between September 2019 and September 2022 were included. They included 1910 cervical intraepithelial neoplasia (CIN) I, 718 CIN II, 576 CIN II and 470 CC, respectively. The HPV genotyping of the above patients was detected by Real time-PCR in the laboratory department of each hospital. Results The total HPV prevalence was 74.69% (95% CI 73.28–76.09%) in 3674 patients. The incidence of high- and low-risk HPV was 73.46% and 7.21%, respectively. The prevalence of HPV in CIN I, CIN II, CIN III, and invasive CC (ICC) groups was 66.65% (1273/1910, 95% CI 64.53–68.77%), 80.78% (580/718, 95% CI 77.89–83.67%), 83.88% (483/576, 95% CI 80.84–86.87%), and 86.81% (408/470, 95% CI 83.74–89.88%), respectively. The top three HPV subtypes in ICC are HPV16, HPV52, and HPV58. The prevalence of HPV 16 increased with increasing disease severity, with this genotype being present in 12.57%, 20.89%, 36.98%, and 50.85% of CIN I, CIN II, CIN III, and ICC cases, respectively (p < 0.001). Single HPV infection was predominant in cervical lesions, with a prevalence of 48.50% (95% CI 46.89–50.12%). The HPV prevalence varied by age, being highest among women with ICC, CIN I, CIN II and CIN III aged ≥ 60 years, 50–59 years, 40–49 years, and 40–49 years, respectively. Conclusion The prevalence of HPV in patients with cervical lesions in Yueyang City was very high, with HPV 16, 52, 58, 53, and 51 being the five most common HPV genotypes in patients with cervical lesions

Efficacy and safety of GST-HG171 in adult patients with mild to moderate COVID-19: a randomised, double-blind, placebo-controlled phase 2/3 trialResearch in context

Summary: Background: GST-HG171 is a potent, broad-spectrum, orally bioavailable small-molecule 3C like protease inhibitor that has demonstrated greater potency and efficacy compared to Nirmatrelvir in pre-clinical studies. We aimed to evaluate the efficacy and safety of orally administered GST-HG171 plus Ritonavir in patients with coronavirus disease 2019 (COVID-19) infected with emerging XBB and non-XBB variants. Methods: This randomised, double-blind, placebo-controlled phase 2/3 trial was conducted in 47 sites in China among adult patients with mild-to-moderate COVID-19 with symptoms onset ≤72 h. Eligible patients were randomised 1:1 to receive GST-HG171 (150 mg) plus Ritonavir (100 mg) or corresponding placebo tablets twice daily for 5 days, with stratification factors including the risk level of disease progression and vaccination status. The primary efficacy endpoint was time to sustained recovery of clinical symptoms within 28 days, defined as a score of 0 for 11 COVID-19-related target symptoms for 2 consecutive days, assessed in the modified intention-to-treat (mITT) population. This trial was registered at ClinicalTrials.gov (NCT05656443) and Chinese Clinical Trial Registry (ChiCTR2200067088). Findings: Between Dec 19, 2022, and May 4, 2023, 1525 patients were screened. Among 1246 patients who underwent randomisation, most completed basic (21.2%) or booster (74.9%) COVID-19 immunization, and most had a low risk of disease progression at baseline. 610 of 617 who received GST-HG171 plus Ritonavir and 603 of 610 who received placebo were included in the mITT population. Patients who received GST-HG171 plus Ritonavir showed shortened median time to sustained recovery of clinical symptoms compared to the placebo group (13.0 days [95.45% confidence interval 12.0–15.0] vs. 15.0 days [14.0–15.0], P = 0.031). Consistent results were observed in both SARS-CoV-2 XBB (45.7%, 481/1053 of mITT population) and non-XBB variants (54.3%, 572/1053 of mITT population) subgroups. Incidence of adverse events was similar in the GST-HG171 plus Ritonavir (320/617, 51.9%) and placebo group (298/610, 48.9%). The most common adverse events in both placebo and treatment groups were hypertriglyceridaemia (10.0% vs. 14.7%). No deaths occurred. Interpretation: Treatment with GST-HG171 plus Ritonavir has demonstrated benefits in symptom recovery and viral clearance among low-risk vaccinated adult patients with COVID-19, without apparent safety concerns. As most patients were treated within 2 days after symptom onset in our study, confirming the potential benefits of symptom recovery for patients with a longer duration between symptom onset and treatment initiation will require real-world studies. Funding: Fujian Akeylink Biotechnology Co., Ltd