OBJECTIVE: Poxviruses are zoonotic pathogens that infect humans, mammals, vertebrates, and arthropods. However, the specific role of ticks in transmission and evolution of these viruses remains unclear. METHODS: Transcriptomic and metatranscriptomic raw data from 329 sampling pools of seven tick species across five continents were mined to assess the diversity and abundance of poxviruses. Chordopoxviral sequences were assembled and subjected to phylogenetic analysis to trace the origins of the unblasted fragments within these sequences. RESULTS: Fifty-eight poxvirus species, representing two subfamilies and 20 genera, were identified, with 212 poxviral sequences assembled. A substantial proportion of AT-rich fragments were detected in the assembled poxviral genomes. These genomic sequences contained fragments originating from rodents, archaea, and arthropods. CONCLUSION Our findings indicate that ticks play a significant role in the transmission and evolution of poxviruses. These viruses demonstrate the capacity to modulate virulence and adaptability through horizontal gene transfer, gene recombination, and gene mutations, thereby promoting co-existence and co-evolution with their hosts. This study advances understanding of the ecological dynamics of poxvirus transmission and evolution and highlights the potential role of ticks as vectors and vessels in these processes.
Animals ; Poxviridae/physiology* ; Ticks/virology* ; Phylogeny ; Transcriptome ; Evolution, Molecular ; Poxviridae Infections/virology* ; Genome, Viral

BACKGROUND: This study aimed to investigate programmed death-ligand 1 tumor proportion score in predicting the safety and efficacy of PD-1/PD-L1 antibody-based therapy in treating patients with advanced non-small cell lung cancer (NSCLC) in a real-world setting. METHODS: This retrospective, multicenter, observational study enrolled adult patients who received PD-1/PD-L1 antibody-based therapy in China and met the following criteria: (1) had pathologically confirmed, unresectable stage III-IV NSCLC; (2) had a baseline PD-L1 tumor proportion score (TPS); and (3) had confirmed efficacy evaluation results after PD-1/PD-L1 treatment. Logistic regression, Kaplan-Meier analysis, and Cox regression were used to assess the progression-free survival (PFS), overall survival (OS), and immune-related adverse events (irAEs) as appropriate. RESULTS: A total of 409 patients, 65.0% ( n = 266) with a positive PD-L1 TPS (≥1%) and 32.8% ( n = 134) with PD-L1 TPS ≥50%, were included in this study. Cox regression confirmed that patients with a PD-L1 TPS ≥1% had significantly improved PFS (hazard ratio [HR] 0.747, 95% confidence interval [CI] 0.573-0.975, P = 0.032). A total of 160 (39.1%) patients experienced 206 irAEs, and 27 (6.6%) patients experienced 31 grade 3-5 irAEs. The organs most frequently associated with irAEs were the skin (52/409, 12.7%), thyroid (40/409, 9.8%), and lung (34/409, 8.3%). Multivariate logistic regression revealed that a PD-L1 TPS ≥1% (odds ratio [OR] 1.713, 95% CI 1.054-2.784, P = 0.030) was an independent risk factor for irAEs. Other risk factors for irAEs included pretreatment absolute lymphocyte count >2.5 × 10 9 /L (OR 3.772, 95% CI 1.377-10.329, P = 0.010) and pretreatment absolute eosinophil count >0.2 × 10 9 /L (OR 2.006, 95% CI 1.219-3.302, P = 0.006). Moreover, patients who developed irAEs demonstrated improved PFS (13.7 months vs. 8.4 months, P <0.001) and OS (28.0 months vs. 18.0 months, P = 0.007) compared with patients without irAEs. CONCLUSIONS A positive PD-L1 TPS (≥1%) was associated with improved PFS and an increased risk of irAEs in a real-world setting. The onset of irAEs was associated with improved PFS and OS in patients with advanced NSCLC receiving PD-1/PD-L1-based therapy.
Humans ; Carcinoma, Non-Small-Cell Lung/metabolism* ; Male ; Female ; Retrospective Studies ; Middle Aged ; Lung Neoplasms/metabolism* ; Aged ; B7-H1 Antigen/metabolism* ; Programmed Cell Death 1 Receptor/metabolism* ; Adult ; Aged, 80 and over ; Immune Checkpoint Inhibitors/therapeutic use*

OBJECTIVE: To investigate short-term effectiveness of robot-assisted fracture reduction and fixation combined with arthroscopic exploration for posterolateral depressed tibial plateau fractures. METHODS: Between January 2022 and January 2024, 8 patients with posterolateral depressed tibial plateau fractures (Schatzker type Ⅲ) were treated using robot-assisted fracture reduction and fixation combined with arthroscopic exploration, with simultaneous treatment of concomitant ligament or meniscus tears. There were 3 males and 5 females with an average age of 54.1 years (range, 42-68 years). Injury mechanisms included traffic accidents (3 cases) and falls (5 cases). The time from injury to operation ranged from 2 to 4 days (mean, 3.1 days). Operation time, intraoperative blood loss, hospital stay duration, visual analogue scale (VAS) score for pain, and complications were recorded. Fracture healing and knee Rasmussen scores were assessed radiographically, while knee function was evaluated using range of motion and Hospital for Special Surgery (HSS) scores. RESULTS: All operations were successfully completed. The operation time was 108-129 minutes (mean, 120.1 minutes). The intraoperative blood loss was 10-100 mL (mean, 41.3 mL). The hospital stay duration was 4-7 days (mean, 5.6 days). All incisions healed by first intention without complication such as peroneal nerve injury, vascular damage, or infection. All patients were followed up 32-48 weeks (mean, 40 weeks). Radiographic follow-up confirmed that the knee Rasmussen scores rated as excellent in 8 patients and all fractures healed with the healing time of 12-16 weeks (mean, 13.5 weeks). The VAS score for pain was 2-4 (mean, 2.8) at discharge and improved to 0 at 1 month after operation. The knee range of motion was 80°-110° (mean, 96.1°) at discharge and increased to 135°-140° (mean, 137.9°) at 1 month after operation. At 3 months after operation, the HSS score was 91-94 (mean, 92.8), all graded as excellent. No severe complication, including implant failure, occurred during follow-up. CONCLUSION For posterolateral depressed tibial plateau fractures, the minimally invasive approach combining robot-assisted fracture reduction and fixation with arthroscopic exploration demonstrates multiple advantages, including shorter operation time, reduced intraoperative blood loss, excellent wound healing, fewer complications, and rapid recovery of knee function. This technique achieves satisfactory short-term effectiveness, while its long-term effectiveness requires further evaluation.
Humans ; Male ; Tibial Fractures/surgery* ; Female ; Middle Aged ; Adult ; Arthroscopy/methods* ; Minimally Invasive Surgical Procedures/methods* ; Fracture Fixation, Internal/methods* ; Aged ; Treatment Outcome ; Robotic Surgical Procedures/methods* ; Operative Time ; Range of Motion, Articular ; Fracture Healing ; Length of Stay ; Tibial Plateau Fractures

PURPOSE: The management of irreducible, sagittally unstable peritrochanteric fractures presents a significant challenge due to the inability to achieve closed reduction using conventional techniques. This study introduces a novel minimally invasive technique leveraging the mechanical advantage principle with long, angled hemostatic clamps. METHODS: A retrospective review was performed on 16 patients who sustained sagittally unstable peritrochanteric fractures and underwent a percutaneous hemostatic clamp leverage reduction procedure. INCLUSION CRITERIA: (1) Preoperative confirmation of fracture type as peritrochanteric fracture; (2) Intraoperative imaging confirms the presence of sagittal plane displacement at the fracture site; (3) Age > 18 years. EXCLUSION CRITERIA: (1) Open fractures, pathological fractures, and diabetes; (2) Long-term use of corticosteroids; (3) Patients with local skin or systemic conditions not suitable for surgery. Regular follow-ups at intervals of 6 - 8 weeks continued until evidence of bone consolidation was apparent in radiographic assessments. Evaluation of the alignment quality considered factors such as the re-establishment of the neck-shaft angle, the integrity of all cortical bone edges, and the rectification of any translational displacement, while the assessment of hip functionality was performed using the Harris scoring system. Statistical analysis of the relevant data was performed using SPSS 25.0 software. RESULTS: The average age of these 16 patients was 56.8 years (ranging from 25 to 81 years), consisting of 8 males and 8 females. According to the AO/OTA fracture classification, the cohort included 13 cases of type 31A, 2 cases of type 32A, and 1 case of type 32C. The time from hospital admission to the day of surgery ranged from 3 to 11 days, with an average of 5.1 days. Closed reduction was successfully implemented in all 10 instances, negating the necessity for transition to open reduction procedures. The mean operative duration was 105.8 min (range 80 - 180 min). Satisfactory results of the quality of reduction were determined by comparison with the normal side. The average Harris hip score was 94.1 (range 87 - 99), and the fracture healing time was 4.2 months (3 - 6 months). Implant failure and malunion were not observed. CONCLUSIONS This study provides an alternative, minimally invasive technique for reducing sagittally unstable, irreducible peritrochanteric fractures. This technique holds the potential to manage complex fractures with the same efficacy as is typically reserved for simple and easily reducible fractures.
Humans ; Male ; Female ; Retrospective Studies ; Minimally Invasive Surgical Procedures/methods* ; Aged ; Middle Aged ; Aged, 80 and over ; Hip Fractures/diagnostic imaging* ; Adult

Objective To study the trend of stroke mortality in Minhang District,Shanghai from 2012 to 2022 and to predict stroke mortality from 2023 to 2027.Methods Annual percentage change(APC)of stroke deaths in Minhang District,Shanghai from 2012 to 2022 was calculated,and then Joinpoint linear regression model was used to analyze the time trend of stroke deaths.A grey GM(1,1)model was constructed based on the stroke mortality rate in Minhang District,Shanghai from 2012 to 2022.The model was used to predict and analyze the stroke mortality rate in Minhang District,Shanghai from 2023 to 2027.The fitting effect of the model was evaluated using relative error and grade deviation.Results From 2012 to 2022,the overall mortality rate of stroke in Minhang District,Shanghai was on the rise for both males and females(total population:APC=2.50%,P<0.001;male:APC=3.41%,P<0.001;female:APC=1.46%,P=0.008).The grey GM(1,1)model was used to predict the increasing trend of stroke mortality rate in Minhang District from 2023 to 2027.The crude mortality rate of stroke in the entire population in 2027 would be 97.55/100000,with 112.31/100000 for males and 83.33/100000 for females.The fitting effect of the model was tested and evaluated to meet high requirements.Conclusion In the past decade,the mortality rate of stroke in Minhang District,Shanghai has shown a significant upward trend.The 5-year prediction results showed that the mortality rate will still on the rise year by year.

Near infrared spectroscopy(NIRS)has emerged as an indispensable analytical technology for quality monitoring in industrial and agricultural production.It is widely used in quantitative analysis in areas such as food,agriculture and medicine.To meet the requirements of industrial and agricultural production,it is particularly important to develop a NIRS quantitative analysis model that can predict the multicomponent of different samples.In this study,the multicomponent quantitative analysis model of NIRS based on convolution neural network(MulCoSpecNet)was proposed.MulCoSpecNet was composed of an encoding and decoding module,an expert module,a gate module,a multicomponent quantitative prediction module,and a hyperparameter optimizer.The spectral noise and random errors were mitigated,and the signal-to-noise ratio was enhanced through up-sampling and down-sampling in the encoding and decoding module.Diverse weightings were employed by the expert module and gate module to construct distinct sub-spectra.The model prediction accuracy and generalization ability were enhanced by the multicomponent quantitative prediction module,which employed convolutional and pooling operations.The hyperparameters in the hyperparameter space were synchronously optimized by the hyperparameter optimizer.By taking public NIRS datasets of grain and corn as examples,the prediction results of MulCoSpecNet were compared with partial least squares(PLS),extreme learning machine(ELM),support vector regression(SVM)and back propagation neural network(BP).The results showed that compared to PLS,the prediction accuracy of MulCoSpecNet to grain and corn were increased by 25.5%?45.2%and 10.0%?35.7%,respectively.Compared to ELM,the prediction accuracy of MulCoSpecNet were increased by 17.8%?38.6%and 18.2%?37.2%,respectively.Compared to SVM,the prediction accuracy of MulCoSpecNet were increased by 33.6%?47.0%and 31.3%?50.7%,respectively.Compared to BP,the prediction accuracy of MulCoSpecNet were increased by 2.0%?58.5%and 29.6%?48.6%,respectively.The issues of low prediction accuracy and poor generalization ability were effectively solved by the MulCoSpecNet,which was a NIRS multicomponent prediction model based on convolutional neural network.It provided a theoretical foundation for establishing non-destructive and high-precision NIRS multicomponent quantitative analysis model.

Objective To plan microwave antenna puncture direction effectively and realize personalized preoperative simulation by exploring microwave ablation(MWV)outcomes of lung cancer based on real anatomical model.Methods Firstly,a personalized MWA simulation model consisting of the lung tissue,tumor and vascular system was constructed based on the lung CT data of real patients.Secondly,the MWA effect was simulated by coupling 2 physical fields including an electromagnetic field and a biological heat transfer field,so as to determine the volume of the ablation thermocoagulation zone and the temperature distribution of the lung tissue.Finally,the effects of the vascularized network on the ablation results were quantitatively evaluated in terms of conductivity and blood perfusion,and the ablation results were analyzed with different distances between the large vessels and the antennae(5 and 10 mm from the antennae tips)and puncture angles(large vessels parallelling or intersecting with the antennae tips).Results The vascularized network reduced the volume of the thermocoagulation zone by 0.5％to 3.7％,and blood perfusion made the ablation temperature and the volume of the thermocoagulation zone decreased significantly.The cooling effect gradually diminished with the increase of the distance between the large vessels and the antenna.With the same treatment parameters,the thermocoagulation zone formed when the large vessels paralleled with the antenna was obviously larger than that when the vessles intersected with the antenna.Conclusion Personalized MWA simulation analysis based on real CT data contributes to clarifying the temperature distribution and damage estimation close to the actual situation,which provides guidance and reference for precise treatment of the lung tumor and determination of microwave antenna puncture direction.[Chinese Medical Equipment Journal,2024,45(9):27-34]

Background and purpose:Primary adrenal intravascular large B-cell lymphoma(IVLBCL)is rare and highly aggressive.Unfortunately,comprehensive and sufficient understanding of the disease is lacking.This study investigated the clinicopathological and molecular genetic characteristics of adrenal IVLBCL.Methods:Adrenal IVLBCL cases diagnosed from 2012 to 2023 were collected from Department of Pathology,Fudan University Shanghai Cancer Center.The clinical and histopathological features,immunophenotype,treatment and prognosis were analyzed.The molecular genetic characteristics were detected using next-generation sequencing(NGS).This study was approved by the Ethics Committee of Fudan University Shanghai Cancer Center(Ethics number:050432-4-2307E).Results:All of the 5 patients were male,with median age 52 years(ranged 50-82 years).Two cases had low-grade fever,1 case had abdominal pain,1 case was found by physical examination,and the information of the remaining one was unknown.Peripheral blood test showed elevated serum lactate dehydrogenase in 2 cases and adrenal dysfunction in 2 cases.On initial diagnosis,imaging tests displayed adrenal enlargement or masses with increased fluorodeoxyglucose(FDG)uptake.Bilateral adrenal glands were involved in 4 cases and only the right adrenal gland was involved in the other case.Morphologically,large atypical lymphocytes were confined to blood vessels,and fibrinous necrosis was observed in some cases.Immunohistochemical study revealed that CD20 was positive in all cases.Ki-67 proliferation index was high,all above 80%.80%(4/5)of the cases were of non-germinal-center B-cell-like(non-GCB)phenotype,100%(4/4)of the cases had MYC/BCL2 double expression.Endothelial cell markers staining indicated that most of the tumor cells were confined within the blood vessels in all cases.Follow-up data were available in 3 patients.One patient who underwent only surgical resection died 5 months after diagnosis,one achieved complete remission after surgery plus R-CHOP,and the other diagnosed by biopsy achieved a partial remission after R-CHOP.The 1-year overall survival rate was 66.7%,and overall survival was 5-87 months.NGS testing in 1 case showed missense mutations in MYD88 V217F,TP53,CDH1,ARID1B,MSH3,MLH3,PTPRK,CD22 and FLCN.Conclusion:Adrenal IVLBCL is rare and tends to occur in the middle-aged and elderly male.The majority of our patients were non-GCB phenotype,often accompanied by MYC/BCL2 double expression,and MYD88 non-L265P mutation was detected.Early diagnosis of adrenal IVLBCL is difficult due to its diverse clinical symptoms and lack of specificity.It is of great importance to accumulate more cases and further understand the clinicopathological and molecular genetic characteristics of this rare disease,which might not only help with early diagnosis,timely treatment and improvement of prognosis,but also provide a theoretical basis for further understanding the pathogenesis and development of the disease and exploring therapeutic targets.

Objective:To evaluate the relationship between the Geriatric Nutritional Risk Index (GNRI) and postoperative pulmonary complications (PPCs) in elderly patients undergoing thoracoscopic lung resection.Methods:Two hundred and ninety-one elderly patients of either sex, aged ≥60 yr, of American Society of Anesthesiologists Physical Status classificationⅠ-Ⅲ, undergoing elective thoracoscopic lung resection at Xuzhou Cancer Hospital from July 2022 to September 2023, were selected. Patients were divided into high GNRI group or low GNRI group based on the optimal cutoff value of GNRI (represented as a continuous variable) determined by the receiver operating characteristic curve to predict PPCs. The occurrence of PPCs was compared between the two groups within the first 7 postoperative days. The relationship between GNRI and PPCs was evaluated by the logistic regression analysis. The nonlinear correlation between GNRI score (expressed as a continuous variable) and PPCs was investigated by the restricted cubic spline. The accuracy of the GNRI, Assess Respiratory Risk in Surgical Patients in Catalonia (ARISCAT) score, and combination of the two in predicting the occurrence of PPCs was evaluated by the areas under the ROC curve (95% confidence interval[ CI]). Results:A total of 269 patients were finally included, with 114 in high GNRI group (GNRI≥100.9) and 155 in low GNRI group (GNRI<100.9). Compared with high GNRI group, the incidence of PPCs was significantly increased compared with low GNRI group (42.6% vs 16.7%, P<0.001). The multivariate logistic regression analysis showed that low GNRI was a risk factor for PPCs, while elevated GNRI score was a protective factor for PPCS in elderly patients undergoing thoracoscopic lung resection ( P<0.05). The restricted cubic spline showed a linear correlation between GNRI score and PPCs ( P=0.947). The areas under the receiver operating characteristic curves of the GNRI, ARISCAT score, and combination of the two in predicting PPCs were 0.646 (95% CI 0.589-0.704), 0.619 (95% CI 0.564-0.674) and 0.708 (95% CI 0.647-0.769), respectively. Conclusions:Low GNRI is an independent risk factor for PPCs in elderly patients undergoing thoracoscopic lung resection, while elevated GNRI score is a protective factor. The combination of GNRI and ARISCAT score can predict the occurrence of PPCs.

This study aims to investigate the mechanism of berberine in regulating the metabolism network via clock-controlled genes represented by brain and muscle arnt-like 1(BMAL1) to ameliorate insulin resistance(IR) of hepatocytes in vitro. The HepG2 cell model of dexamethasone-induced IR(IR-HepG2) was established and treated with 5, 10, and 20 μmol·L~(-1) berberine, respectively, for 24 h. The glucose oxidase method and cell counting kit-8(CCK-8) assay were employed to measure extracellular glucose concentration and cell viability, respectively. Periodic acid-Schiff(PAS) staining and lipid fluorescence method were used to detect glycogen and lipids. The immunofluorescence(IF) assay was employed to detect the nuclear localization of BMAL1 and circadian locomotor output cycles kaput(CLOCK) in IR-HepG2 cells. Western blot was employed to determine the protein levels of BMAL1, CLOCK, period circadian clock 2(PER2), cryptochrome circadian regulator 1(CRY1), Rev-Erbα, carbohydrate response element-binding protein(ChREBP), peroxisome proliferator-activated receptors alpha and gamma(PPARα/γ), sterol regulatory element-binding protein 1C(SREBP-1C), mammalian target of rapamycin(mTOR), protein kinase B(Akt), glycogen synthase kinase-3β(GSK3β), acetyl coenzyme A carboxylase 1(ACC1), fatty acid synthase(FASN), carnitine palmitoyltransferase 1α(CPT1α), nicotinamide phosphoribosyltransferase(NAMPT), silent information regulator 1(SIRT1), adiponectin(ADPN), insulin receptor substrate 2(IRS2), and phosphatidylinositol 3-kinase regulatory subunit p85(PI3Kp85). In addition, the levels of phosphorylated adenosine monophosphate-activated protein kinase alpha(AMPKα), Akt, GSK3β, BMAL1, and mTOR were determined. Furthermore, 20 μmol·L~(-1) CLK8 was added to measure the glucose consumption as well as the protein levels of ChREBP, PPARα, and mTOR in IR-HepG2 cells. The results showed that berberine increased the glucose consumption, lowered the lipid levels, increased the expression and nuclear localization of BMAL1 and CLOCK, and up-regulated the level of BMAL1 in IR-HepG2 cells. Furthermore, berberine up-regulated the levels of ADPN, IRS2, PI3Kp85, p-Akt(Ser473)/Akt, p-mTOR(Ser2448)/mTOR, PPARα, and CPT1α, and down-regulated the levels of p-GSK3β(Ser9)/GSK3β, ChREBP, SREBP-1C, ACC1, and FASN. The addition of CLK8 reduced glucose consumption in IR-HepG2 cells, up-regulated the ChREBP level, and down-regulated PPARα and mTOR levels by inhibiting the BMAL1 and CLOCK interaction. In summary, berberine regulated glucose and lipid metabolism via clock-controlled genes with BMAL1 at the core to ameliorate IR of hepatocytes.
Humans ; Hepatocytes/drug effects* ; Lipid Metabolism/drug effects* ; Glucose/metabolism* ; Berberine/pharmacology* ; Insulin Resistance ; Hep G2 Cells ; CLOCK Proteins/genetics* ; ARNTL Transcription Factors/genetics*