Impact of examined lymph node number on lymph node status and prognosis in FIGO stage IB-IIA cervical squamous cell carcinoma: A population-based study.

Objective: We aimed to investigate the association of examined lymph node (ELN) number with lymph node status and long-term survival in FIGO stage IB-IIA cervical squamous cell carcinoma(CSCC) and to determine the minimum number of ELN associated with survival improvement. Method: Data from the Surveillance, Epidemiology, and End Results Program (SEER) database of FIGO stage IB-IIA CSCC patients undergoing hysterectomy and pelvic lymphadenectomy in 2004-2016 were analyzed to explore the relationship between ELN number and lymph node status and overall survival (OS) by using the multivariable approach. The estimated probability of falsely identifying a patient as node-negative and the hazard ratios (HRs) for each ELN was fitted with a LOWESS smoother, and the structural breakpoints were determined. X-tile software was used to determine the optimal cutoff value for ELNs. Results: A total of 2627 patients were analyzed. The optimal cutoff value of the ELN number was identified as 7 based on the results of X-tile software. The structural breakpoints according to the associations between the number of ELNs and the estimated risk of false-negative lymph node dissection and HRs for overall survival were 9 and 8, respectively. The multivariate analysis indicated that ELN number was an independent prognostic factor for OS, both as a continuous or categorical variable. To further explore the effect of more ELNs on survival, another cutoff value of 17 was chosen to compare the survival curves of patients. The multivariate-adjusted COX model showed that patients with ELN<8 had a significantly higher risk of death than those with ELN8-17 (HR=1.447, 95% CI =1.075-1.947, p=0.015), but there was no significant difference in overall survival between patients with ELN>17 and patients with ELN8-17 (HR=0.822, 95%CI =0.665-1.016, p=0.070). Conclusion: A sufficient number of ELNs was associated with better long-term survival in FIGO stage IB-IIA CSCC. At least 8 ELNs need to be examined for prognostic stratification. Excessive lymph node dissection (ELN>17) may not confer additional survival benefits.

The 5'-end motif of Senecavirus A cDNA clone is genetically modified in 36 different ways for uncovering profiles of virus recovery.

Senecavirus A (SVA) is an emerging picornavirus. Its genome is one positive-sense, single-stranded RNA. The viral protein (VPg) is covalently linked to the extreme 5' end of the SVA genome. A complex hairpin-pseudoknot-hairpin (HPH) RNA structure was computationally predicted to form at the 5' end of the SVA genome. A total of three extra "U" residues (UUU) served as a linker between the HPH structure and the VPg, causing putative UUU-HPH formation at the extreme 5' end of the SVA genome. It is unclear how the UUU-HPH structure functions. One SVA cDNA clone (N0) was constructed previously in our laboratory. Here, the N0 was genetically tailored for reconstructing a set of 36 modified cDNA clones (N1 to N36) in an attempt to rescue replication-competent SVAs using reverse genetics. The results showed that a total of nine viruses were successfully recovered. Out of them, five were independently rescued from the N1 to N5, reconstructed by deleting the first five nucleotides (TTTGA) one by one from the extreme 5' end of N0. Interestingly, these five viral progenies reverted to the wild-type or/and wild-type-like genotype, suggesting that SVA with an ability to repair nucleotide defects in its extreme 5' end. The other four were independently rescued from the N26 to N29, containing different loop-modifying motifs in the first hairpin of the HPH structure. These four loop-modifying motifs were genetically stable after serial passages, implying the wild-type loop motif was not a high-fidelity element in the first hairpin during SVA replication. The other genetically modified sequences were demonstrated to be lethal elements in the HPH structure for SVA recovery, suggesting that the putative HPH formation was a crucial cis-acting replication element for SVA propagation.

The radiomic-clinical model using the SHAP method for assessing the treatment response of whole-brain radiotherapy: a multicentric study.

OBJECTIVE: To develop and validate a pretreatment magnetic resonance imaging (MRI)-based radiomic-clinical model to assess the treatment response of whole-brain radiotherapy (WBRT) by using SHapley Additive exPlanations (SHAP), which is derived from game theory, and can explain the output of different machine learning models. METHODS: We retrospectively enrolled 228 patients with brain metastases from two medical centers (184 in the training cohort and 44 in the validation cohort). Treatment responses of patients were categorized as a non-responding group vs. a responding group according to the Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) criteria. For each tumor, 960 features were extracted from the MRI sequence. The least absolute shrinkage and selection operator (LASSO) was used for feature selection. A support vector machine (SVM) model incorporating clinical factors and radiomic features wase used to construct the radiomic-clinical model. SHAP method explained the SVM model by prioritizing the importance of features, in terms of assessment contribution. RESULTS: Three radiomic features and three clinical factors were identified to build the model. Radiomic-clinical model yielded AUCs of 0.928 (95%CI 0.901-0.949) and 0.851 (95%CI 0.816-0.886) for assessing the treatment response in the training cohort and validation cohort, respectively. SHAP summary plot illustrated the feature's value affected the feature's impact attributed to model, and SHAP force plot showed the integration of features' impact attributed to individual response. CONCLUSION: The radiomic-clinical model with the SHAP method can be useful for assessing the treatment response of WBRT and may assist clinicians in directing personalized WBRT strategies in an understandable manner. KEY POINTS: • Radiomic-clinical model can be useful for assessing the treatment response of WBRT. • SHAP could explain and visualize radiomic-clinical machine learning model in a clinician-friendly way.

Tolerance of Senecavirus A to Mutations in Its Kissing-Loop or Pseudoknot Structure Computationally Predicted in 3' Untranslated Region.

Senecavirus A (SVA) is an emerging virus that belongs to the genus Senecavirus in the family Picornaviridae. Its genome is a positive-sense and single-stranded RNA, containing two untranslated regions (UTRs). The 68-nt-long 3' UTR is computationally predicted to possess two higher-order RNA structures: a kissing-loop interaction and an H-type-like pseudoknot, both of which, however, cannot coexist in the 3' UTR. In this study, we constructed 17 full-length SVA cDNA clones (cD-1 to -17): the cD-1 to -7 contained different point mutations in a kissing-loop-forming motif (KLFM); the cD-8 to -17 harbored one single or multiple point mutations in a pseudoknot-forming motif (PFM). These 17 mutated cDNA clones were independently transfected into BSR-T7/5 cells for rescuing recombinant SVAs (rSVAs), named rSVA-1 to -17, corresponding to cD-1 to -17. The results showed that the rSVA-1, -2, -3, -4, -5, -6, -7, -9, -13, and -15 were successfully rescued from their individual cDNA clones. Moreover, all mutated motifs were genetically stable during 10 viral passages in vitro. This study unveiled viral abilities of tolerating mutations in the computationally predicted KLFM or PFMs. It can be concluded that the putative kissing-loop structure, even if present in the 3' UTR, is unnecessary for SVA replication. Alternatively, if the pseudoknot formation potentially occurs in the 3' UTR, its deformation would have a lethal effect on SVA propagation.

Cross-sectional study on risk factors associated with porcine epidemic diarrhea virus infection in pig farms in Junan county, China.

Porcine epidemic diarrhea (PED) is a highly contagious, intestinal infectious disease in pigs, characterized by severe diarrhea, vomiting and dehydration. PED is widely epidemic in China as well as in many eastern Asian and America countries, causing tremendous losses in pig industry. However, little was known about the disease frequency and the associated risk factors of PED in pig farms. A cross-sectional study was conducted to estimate the herd prevalence and to identify the potential risk factors of porcine epidemic diarrhea virus (PEDV) infection of pig farms (≥100 pigs) in Junan county, China. A two-stage random sampling strategy was adopted, and a total of 751 fecal samples from suckling piglets of 82 farms were collected and tested by RT-PCR and sequencing for PEDV. Meanwhile, information on the putative risk factors of PEDV infection of those farms were collected in forms of questionnaires, followed by a descriptive analysis, univariable and multivariable logistic regression analysis. The results showed that the herd-level true prevalence of PEDV infection of pig farms in Junan was 35.16 % (95 %CI: 22.91-53.89); there were two variables significantly associated with PEDV infection, which were 'having more than 1000 slaughter pigs per annum' (OR = 5.42, 95 %CI: 1.19-24.72), and 'Weaning at 21-25 days' old' (OR = 4.50, 95 %CI:1.25-16.20). The research suggested that PED was highly endemic in pig farms in Junan county; larger herd size and weaning at an earlier age were potential risk factors associated with PEDV infection in pig farms in Junan. This study set an example in the research on herd-level prevalence of PEDV infection and risk factors associated with PEDV infection, and the results were of practical significance for the future planning of prevention and control of PED in Junan or other areas of China.

The Efficacy and Safety of Continuous Intravenous Endostar Treatment Combined With Concurrent Chemoradiotherapy in Patients With Locally Advanced Cervical Squamous Cell Carcinoma: A Randomized Controlled Trial.

OBJECTIVE: To investigate the short-term efficacy and safety of Endostar combined with concurrent chemoradiotherapy in the treatment of locally advanced cervical squamous cell carcinoma (LACSC). METHODS: A total of 91 patients with LACSC admitted to the First Affiliated Hospital of Anhui Medical University from June 2019 to December 2020 were randomly assigned to either the experimental group (n = 48) or control group (n = 43). The control group received radiotherapy for cervical cancer and paclitaxel combined with platinum chemotherapy (CCRT), and the experimental group received Endostar continuous intravenous infusion of anti-angiogenic therapy plus CCRT. The short-term efficacy, common clinical indicators, tumor indicators, changes in serum vascular endothelial growth factor-A (VEGF-A), and the occurrence of adverse events (AEs) were explored after treatment. RESULTS: Compared with the control group, the complete response (CR) rate in the experimental group was significantly increased (83.33% vs 65.12%, P < 0.05). Both routine indicators and tumor indicators in the two groups were significantly decreased compared to before treatment. Compared with the control group, patients in the experimental group had higher incidences of neutropenia, hypertension, and infection, but lower incidence of nausea. After treatment, the serological expression of VEGF-A was significantly decreased in both groups. CONCLUSION: Endostar combined with CCRT in the treatment of LACSC can further improve the efficacy of CR rate and significantly reduce serum tumor indicators and VEGF-A levels, with mild and controllable AEs. Endostar combined with CCRT is expected to be a new treatment regimen for LACSC.

Clinical Validation of Two Recombinase-Based Isothermal Amplification Assays (RPA/RAA) for the Rapid Detection of African Swine Fever Virus.

African swine fever (ASF), caused by African swine fever virus (ASFV), is a devastating infectious disease of domestic pigs and wild boars, and has tremendous negative socioeconomic impact on the swine industry and food security worldwide. It is characterized as a notifiable disease by World Organisation for Animal Health (OIE). No effective vaccine or treatment against ASF has so far been available. Early detection and rapid diagnosis are of potential significance to control the spread of ASF. Recombinase-based isothermal amplification assay, recombinase polymerase amplification (RPA) developed by TwistDx (Cambridge, United Kingdom) or recombinase-aided amplification (RAA) by Qitian (Wuxi, China), is becoming a molecular tool for the rapid, specific, and cost-effective identification of multiple pathogens. In this study, we aim to investigate if RPA/RAA can be a potential candidate for on-site, rapid and primary detection of ASFV. A panel of 152 clinical samples previously well-characterized by OIE-recommended qPCR was enrolled in this study, including 20 weak positive (Ct value ≥ 30) samples. This panel was consisted of different types, such as EDTA-blood, spleen, lung, lymph node, kidney, tonsil, liver, brain. We evaluated two recombinase-based isothermal amplification assays, RPA or RAA, by targeting the ASFV B646L gene (p72), and validated the clinical performance in comparison with OIE real-time PCR. Our result showed that the analytical sensitivity of RPA and RAA was as 93.4 and 53.6 copies per reaction, respectively at 95% probability in 16 min, at 39°C. They were universally specific for all 24 genotypes of ASFV and no cross reaction to other pathogens including Classical swine fever virus (CSV), Foot-and-mouth disease virus (FMDV), Pseudorabies virus, Porcine circovirus 2 (PCV2), Porcine Reproductive and respiratory syndrome virus (PPRSV). The results on detection of various kinds of clinical samples indicated an excellent diagnostic agreement between RPA, RAA and OIE real-time PCR method, with the kappa value of 0.960 and 0.973, respectively. Compared to real-time PCR, the specificity of both RPA and RAA was 100% (94.40% ∼ 100%, 95% CI), while the sensitivity was 96.59% (90.36% ∼ 99.29%, 95% CI) and 97.73% (92.03% ∼ 99.72%, 95% CI), respectively. Our data demonstrate that the developed recombinase-based amplification assay (RPA/RAA), promisingly equipped with field-deployable instruments, offers a sensitive and specific platform for the rapid and reliable detection of ASFV, especially in the resource-limited settings for the purpose of screening and surveillance of ASF.

Complete Genome Sequence of a Novel Senecavirus A Isolate from an Asymptomatic Pig in China.

Senecavirus A (SVA) is the single member of the genus Senecavirus of the family Picornaviridae Here, we report a complete genome sequence of SVA strain GX2018-92, which was isolated from an asymptomatic piglet in China. This virus genome consists of 7,280 nucleotides and will be available to further study the epidemiology of porcine SVA.

[Changes of Skin Temperature of Acupoint Regions of the Governor Meridian after Moxibustion Stimulation].

OBJECTIVE: To observe changes of skin temperature along the Governor Vessel (GV) after moxibustion stimulation. METHODS: A total of 36 healthy volunteer subjects were recruited in the present study. The skin temperature of Mingmen (GV 4), Dazhui (GV 14), Shenzhu (GV 12), Zhiyang (GV 9), Zhongshu (GV 7), Yaoyangguan (GV 3) regions and their bilateral control sites (1.5 cun lateral to GV 4) was detected by using a Thermo Tracer TH 9100. RESULTS: Following moxibustion stimulation of GV 4 region, a marked infrared radiant track along the central part of the back covering the GV was observed in the healthy volunteer subjects, and the skin temperature levels of both GV 4 and its bilateral control points were significantly increased (P < 0.001). The skin temperature of GV 4 was remarkably higher than those of both left and right control points (P < 0.001). After moxibustion stimulation, the average skin temperature levels of GV 9, GV 7, GV 4 and GV 3 were all up-regulated in comparison with pre-moxibustion (P < 0.01). CONCLUSION: Moxibustion stimulation of Mingmen (GV 4) can induce an infrared radiant track along the central part of the back covering the GV and raise skin temperature of acupoint areas of the GV.

[Effect of Electroacupuncture Stimulation of Acupoints at the Distal Limbs on Heart Function of Volunteers with Acute Hypoxia].

OBJECTIVE: To observe the effect of electroacupuncture (EA) stimulation of different acupoints at the distal ends of the limbs on cardiac function in volunteers with acute hypoxia, so as to determine if its actions are realized by way of segmental innervations or meridians. METHODS: Twenty healthy volunteers were divided into control, Quze (PC 3), Shousanli (LI 10), Guangming (GB 37) and Zusanli (ST 36) groups (both PC 3 and LI 10 are innervated by spinal C3-C6, and both ST 36 and GB 37 innervated by L5-S1). Acute hyoxia (simulating the conditions of about 5,000 m height above the sea level) was induced by asking the volunteers to inhale low-oxygen gas mixture (10.8% O2 + 89.2% N2) for 30 min, when, the participants' cardiac output (CO), heart rate (HR), left cardiac work (LOW), left ventricular ejection time (LVET)were measured using a ICG Monitor and EA stimulation (10 Hz/20 Hz, 1-2 V) was also conducted for 20 min following inhaling low-oxygen for 10 min. RESULTS: Before low-oxygen inhale, the levels of CO, HR, LCW and LVET ratios (test value/basic value) of the control, PC 3, LI 10, ST 36 and GB 37 groups were comparable (P > 0.05). After inhaling low-oxygen gas mixture for 10 min, the levels of CO, HR, and LCW ratios were significantly increased, and the LVET ratios were notably decreased in the five groups (P < 0.05). Compared with the 10 min-low-oxygen inhale of the same one group, CO and HR ratios at both EA 10 min and 20 min in the PC 3 and ST 36 groups, LCW ratios at EA 10 min in both PC 3 and ST 36 groups were notably down-regulated (P < 0.05), while the LVET ratios of both PC 3 and ST 36 groups was significantly prolonged (P < 0.05). No significant changes of CO, HR, LCW and LVET ratios were found in the LI 10 and GB 37 groups after EA for 10 min and 20 min (P > 0.05). CONCLUSION: EA stimulation of Quze (PC 3) and Zusanli (ST 36), but not Shousanli (LI 10) and Guangming (GB 37) can lower CO, HR and LCW levels and increase LVET in volunteer subjects undergoing acute hypoxia, suggesting that the therapeutic effect of EA maybe not rely on the segmental innervations, but rather, depend on the meridians to which the acupoints belong.

Complete Genome Sequence of a Field Isolate of Classical Swine Fever Virus Belonging to Subgenotype 2.1b from Hunan Province, China.

We report the complete genome sequence of a field isolate of classical swine fever virus (CSFV), Hunan 23/2013, belonging to the predominant subgenotype 2.1b. This strain was originally isolated from diseased pigs in Hunan Province, China. This report will help in understanding the molecular diversity of CSFV stains circulating in China and in selecting and developing a suitable vaccine candidate for CSF control.

Complete genome sequence of a classical Swine Fever virus isolate belonging to a new subgenotype, 2.1c, from guangxi province, china.

The complete genome sequence of a field isolate of classical swine fever strain (CSFV), GXF29/2013, was determined in this study. This strain was originally isolated from infected pigs in Guangxi Province, China. The most significant difference in the amino acid sequence of the polyprotein from subgenotypes 2.1a and 2.1b is an SPA→APV amino acid substitution at positions 88 and 90 in the E2 protein.

Variations in energy metabolism along the pericardium meridian and its relationship with visceral function adjustments during electroacupuncture.

BACKGROUND: Electroacupuncture (EA) is a traditional Chinese medicine treatment guided by meridian theory. As it gradually gains more worldwide acceptance, a clarification of its mechanisms is extremely urgent. We observed variations in transcutaneous oxygen pressure/carbon dioxide pressure (tcpO2/tcpCO2) and microcirculation blood perfusion units (BPU) along the pericardium meridian, and cardiac function during EA at Neiguan (PC6) to explore variations in energy metabolism and its relationship with visceral function adjustments during EA. METHODS: Twenty-two healthy volunteers participated in this study. Three channel laser Doppler flowmetry and tcpO2/tcpCO2 detection systems were used to detect tcpO2/tcpCO2 and microcirculation BPU along the pericardium meridian. A hemodynamic monitor was used to detect cardiac function. RESULTS: In the normal state, the microcirculatory BPU along the pericardium meridian were significantly higher than that of their bilateral corresponding control points (p < 0.05). During EA at PC6, the values of the microcirculatory BPU along the pericardium meridian did not vary, and few increased. In the normal state, the values of tcpO2 along the pericardium meridian were significantly higher than those of their bilateral corresponding control points (p < 0.05). In addition, the values of tcpCO2 along the pericardium meridian were lower than those of their bilateral corresponding control points. In comparison with the normal state, EA could decrease tcpO2 along the meridian significantly (p < 0.05) and increase tcpCO2. During EA at PC6 in healthy volunteers treated by artificial acute mild hypoxia, cardiac output and cardiac index (p < 0.05) decreased and systemic vascular resistance increased significantly (p < 0.05). CONCLUSIONS: In the normal state, the values of microcirculatory BPU and tcpO2 along the pericardium meridian were both higher than those of their bilateral corresponding control points. Energy metabolism was vigorous along the meridian. During EA, the decrease in oxygen partial pressure along the pericardium meridian might be a result of strengthened energy metabolism of associated tissue and increased oxygen consumption. The variations in energy metabolism along the pericardium meridian during the course of EA had a close relationship with visceral function adjustments. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTRTRC13003193.