Mortality Burden of Liver Cancer in China: An Observational Study From 2008 to 2020.

Background and Aims: China accounts for nearly half of liver cancer deaths globally. A better understanding of the current liver cancer mortality will be helpful to establishing priorities for intervention and to decreasing the disease burden of liver cancer. The study aimed to explore and predict the mortality burden of liver cancer in China. Methods: Data were extracted from the Disease Surveillance Point system of the Chinese Center for Disease Control and Prevention from 2008 to 2020. Crude and age-standardized liver cancer mortality rates were reported by sex, urban or rural residence, and region. Trends in liver cancer mortality rates from 2008 to 2020 were estimated as average annual percentage change (AAPC). The changing trend of live cancer mortality in the future is also predicted. Results: In 2020, the crude mortality of liver cancer was 25.57/100,000, and males and people lived in rural areas had higher age-standardized liver cancer mortality rates than females and people lived in people in urban areas. Crude mortality and age-standardized mortality rates in southwest provinces (Guangxi, Sichuan, Tibet) and in a northeast province (Heilongjiang) were higher than that in other provinces, and age-specific mortality rates increased with age. From 2008 to 2020, liver cancer mortality rates decreased, but people under 50 years of age had a higher AAPC than those over 50 years of age, possibly because of the adoption of hepatitis B virus vaccination in newborns and children. Furthermore, the mortality of liver cancer in 2021-2030 is predicted to have a downward trend. Conclusions: Liver cancer mortality rates declined in China from 2008 to 2020. Future interventions to control liver cancer mortality need to focus on people of male sex, older age, and living in rural areas or less developed provinces.

Prevalence and risk evaluation of cardiovascular disease in the newly diagnosed prostate cancer population in China: A nationwide, multi-center, population-based cross-sectional study.

BACKGROUND: Cardiovascular disease (CVD) has emerged as the leading cause of death from prostate cancer (PCa) in recent decades, bringing a great disease burden worldwide. Men with preexisting CVD have an increased risk for major adverse cardiovascular events when treated with androgen deprivation therapy (ADT). The present study was aimed to explore the prevalence and risk evaluation of CVD among people with newly diagnosed PCa in China. METHODS: Clinical data of newly diagnosed PCa patients were retrospectively collected from 34 centers in China from 2010 to 2022 through convenience sampling. CVD was defined as myocardial infarction, arrhythmia, heart failure, stroke, ischemic heart disease, and others. CVD risk was estimated by calculating Framingham risk scores (FRS). Patients were accordingly divided into low-, medium-, and high-risk groups. χ2 or Fisher's exact test was used for comparison of categorical variables. RESULTS: A total of 4253 patients were enrolled in the present study. A total of 27.0% (1147/4253) of patients had comorbid PCa and CVD, and 7.2% (307/4253) had two or more CVDs. The enrolled population was distributed in six regions of China, and approximately 71.0% (3019/4253) of patients lived in urban areas. With imaging and pathological evaluation, most PCa patients were diagnosed at an advanced stage, with 20.5% (871/4253) locally progressing and 20.5% (871/4253) showing metastasis. Most of them initiated prostatectomy (46.6%, 1983/4253) or regimens involving ADT therapy (45.7%, 1944/4253) for prostate cancer. In the present PCa cohort, 43.1% (1832/4253) of patients had hypertension, and half of them had poorly controlled blood pressure. With FRS stratification, as expected, a higher risk of CVD was related to aging and metabolic disturbance. However, we also found that patients with treatment involving ADT presented an originally higher risk of CVD than those without ADT. This was in accordance with clinical practice, i.e., aged patients or patients at advanced oncological stages were inclined to accept systematic integrative therapy instead of surgery. Among patients who underwent medical castration, only 4.0% (45/1118) received GnRH antagonists, in stark contrast to the grim situation of CVD prevalence and risk. CONCLUSIONS: Prostate cancer patients in China are diagnosed at an advanced stage. A heavy CVD burden was present at the initiation of treatment. Patients who accepted ADT-related therapy showed an original higher risk of CVD, but the awareness of cardiovascular protection was far from sufficient.

RETINOBLASTOMA RELATED 1 switches mitosis to meiosis in rice.

The transition from mitosis to meiosis is a critical event in the reproductive development of all sexually reproducing species. However, the mechanisms that regulate this process in plants remain largely unknown. Here, we find that the rice (Oryza sativa L.) protein RETINOBLASTOMA RELATED 1 (RBR1) is essential to the transition from mitosis to meiosis. Loss of RBR1 function results in hyper-proliferative sporogenous-cell-like cells (SCLs) in the anther locules during early stages of reproductive development. These hyper-proliferative SCLs are unable to initiate meiosis, eventually stagnating and degrading at late developmental stages to form pollen-free anthers. These results suggest that RBR1 acts as a gatekeeper of entry into meiosis. Furthermore, cytokinin content is significantly increased in rbr1 mutants, whereas the expression of type-B response factors, particularly LEPTO1, is significantly reduced. Given the known close association of cytokinins with cell proliferation, these findings imply that hyper-proliferative germ cells in the anther locules may be attributed to elevated cytokinin concentrations and disruptions in the cytokinin pathway. Using a genetic strategy, the association between germ cell hyper-proliferation and disturbed cytokinin signaling in rbr1 has been confirmed. In summary, we reveal a unique role of RBR1 in the initiation of meiosis; our results clearly demonstrate that the RBR1 regulatory module is connected to the cytokinin signaling pathway and switches mitosis to meiosis in rice.

Trends in Mortality of Cirrhosis in China: An Analysis of the China Death Surveillance Database from 2008 to 2020.

Background and Aims: China accounts for 14.9% of total cirrhosis deaths worldwide. A detailed and comprehensive understanding of the contemporary status of cirrhosis mortality in China is crucial for establishing strategies for intervention and decreasing the disease burden of cirrhosis worldwide. The study aimed to report the cirrhosis mortality rates in our whole country or province over time. Methods: Mortality data from 2008 to 2020 were retrieved from the Disease Surveillance Point System (DSPs) of the Chinese Center for Disease Control and Prevention. The crude mortality rate and age-standardized mortality rate of patients with cirrhosis were stratified by sex, residential location, and region. The average annual percentage change (AAPC) in cirrhosis mortality rates from 2008 to 2020 was also calculated. Results: The crude mortality rate of cirrhosis was 4.57/100,000 people in 2020. Compared with females and individuals living in urban areas, males and people living in rural areas had greater age-standardized mortality. The crude mortality rate and age-standardized mortality rate in provinces in Southwest China (Guangxi, Yunnan, Guizhou, and Qinghai) were greater than those in other provinces. Moreover, with increasing age, the age-specific mortality rate increased significantly. From 2008 to 2020, the mortality rate of cirrhosis in China decreased except for in males aged 50-59 years, females aged 45-49 years and females aged 80-84 years. Conclusions: The mortality rate of patients with cirrhosis in China decreased from 2008 to 2020. In the future, interventions of cirrhosis mortality control need to pay more attention to all males, females aged 45-49 and 80-84 years, and people living in rural areas and in provinces in Southwest China.

Chromosome ends initiate homologous chromosome pairing during rice meiosis.

During meiotic prophase I, chromosomes undergo large-scale dynamics to allow homologous chromosome pairing, prior to which chromosome ends attach to the inner nuclear envelope and form a chromosomal bouquet. Chromosome pairing is crucial for homologous recombination and accurate chromosome segregation during meiosis. However, the specific mechanism by which homologous chromosomes recognize each other is poorly understood. Here, we investigated the process of homologous chromosome pairing during early prophase I of meiosis in rice (Oryza sativa) using pooled oligo probes specific to an entire chromosome or chromosome arm. We revealed that chromosome pairing begins from both ends and extends towards the center from early zygotene through late zygotene. Genetic analysis of both trisomy and autotetraploidy also showed that pairing initiation is induced by both ends of a chromosome. However, healed ends that lack the original terminal regions on telocentric and acrocentric chromosomes cannot initiate homologous chromosome pairing, even though they may still enter the telomere clustering region at the bouquet stage. Furthermore, a chromosome that lacks the distal parts on both sides loses the ability to pair with other intact chromosomes. Thus, the native ends of chromosomes play a crucial role in initiating homologous chromosome pairing during meiosis and likely have a substantial impact on genome differentiation.

Pien Tze Huang Inhibits Proliferation of Colorectal Cancer Cells through Suppressing PNO1 Expression and Activating p53/p21 Signaling Pathway.

OBJECTIVE: To explore the regulatory effect of Pien Tze Huang (PZH) on targeting partner of NOB1 (PNO1) and it's down-stream mediators in colorectal cancer (CRC) cells. METHODS: Quantitative polymerase chain reaction was performed to determine mRNA levels of PNO1, TP53, and CDKN1A. Western blotting was performed to determine protein levels of PNO1, p53, and p21. HCT-8 cells were transduced with a lentivirus over-expressing PNO1. Colony formation assay was used to detect cell survival in PNO1 overexpression of HCT-8 cells after PZH treatment. Cell-cycle distribution, cell viability and cell apoptosis were performed to identify the effect of PNO1 overexpression on cell proliferation and apoptosis of HCT-8 cells after PZH treatment. Xenograft BALB/c nude mice bearing HCT116 cells transduced with sh-PNO1 or sh-Ctrl lentivirus were evaluated. Western blot assay was performed to detect PNO1, p53, p21 and PCNA expression in tumor sections. Terminal deoxynucleotidyl transferase dUTP nick end labling (TUNEL) assay was used to determine the apoptotic cells in tissues. RESULTS: PZH treatment decreased cell viability, down-regulated PNO1 expression, and up-regulated p53 and p21 expressions in HCT-8 cells (P<0.05). PNO1 overexpression attenuated the effects of PZH treatment, including the expression of p53 and p21, cell growth, cell viability, cell cycle arrest and cell apoptosis in vitro (P<0.05). PNO1 knockdown eliminated the effects of PZH treatment on tumor growth, inhibiting cell proliferation inhibition and apoptosis induction in vivo (P<0.05). Similarly, PNO1 knockdown attenuated the effects of PZH treatment on the down-regulation of PNO1 and up-regulation of p53 and p21 in vivo (P<0.05). CONCLUSION: The mechanism by which PZH induces its CRC anti-proliferative effect is at least in part by regulating the expression of PNO1 and its downstream targets p53 and p21.

Cuproptosis-Related Gene Signature Contributes to Prognostic Prediction and Immunosuppression in Multiple Myeloma.

Cuproptosis is a type of programmed cell death triggered by accumulation of intracellular copper which was considered closely related to tumor progression. The study of cuproptosis in multiple myeloma (MM) is however limited. To determine the prognostic significance of cuproptosis-related gene signature in MM, we interrogated gene expression and overall survival with other available clinical variables from public datasets. Four cuproptosis-related genes were included to establish a prognostic survival model by least absolute shrinkage and selection operator (LASSO) Cox regression analysis, which showed a good performance on prognosis prediction in both training and validation cohorts. Patients with higher cuproptosis-related risk score (CRRS) exhibited worse prognosis compared with lower risk score. Survival prediction capacity and clinical benefit were elevated after integrating CRRS to existing prognostic stratification system (International Staging System, ISS or Revised International Staging System, RISS) both on 3-year and 5-year survival. Based on CRRS groups, functional enrichment analysis and immune infiltration in bone marrow microenvironment revealed correlation between CRRS and immunosuppression. In conclusion, our study found that cuproptosis-related gene signature is an independent poor prognostic factor and functions negatively on immune microenvironment, which provides another perspective on prognosis assessment and immunotherapy strategy in MM.

CT-guided microcoil localization of pulmonary nodules before VATS: clinical experience in 1059 patients.

OBJECTIVE: To retrospectively evaluate the efficacy and safety of CT-guided microcoil localization of pulmonary nodules before video-assisted thoracoscopic surgery (VATS). METHODS: A total of 1059 consecutive patients with 1331 pulmonary nodules treated between July 2018 and April 2021 were included in this study. Of the 1331 nodules, 1318 were localized using the tailed method and 13 were localized using the non-tailed method. The localization technical success rate and complications of the microcoil localization procedure were assessed. Univariate and multivariate logistic regression analyses were used to determine potential risk factors for technical failure, pneumothorax, and pulmonary hemorrhage. RESULTS: The technical success rate of the localization procedure was 98.4% (1310/1331 nodules). Nodule location in the lower lobes (p = 0.015) and need for a longer needle path (p < 0.001) were independent predictors of technical failure. All localization procedure-related complications were minor (grade 1 or 2) adverse events, with the exception of one grade 3 complication. The most common complications were pneumothorax (302/1331 nodules [22.7%]) and pulmonary hemorrhage (328/1331 nodules [24.6%]). Male sex (p = 0.001), nodule location in the middle (p = 0.003) and lower lobes (p = 0.025), need for a longer needle path (p < 0.001), use of transfissural puncture (p = 0.042), and simultaneous multiple localizations (p < 0.001) were independent risk factors for pneumothorax. Female sex (p = 0.015), younger age (p = 0.023), nodules location in the upper lobes (p = 0.011), and longer needle path (p < 0.001) were independent risk factors for pulmonary hemorrhage. CONCLUSIONS: CT-guided microcoil localization of pulmonary nodules before VATS using either the tailed or non-tailed method is effective and safe. CLINICAL RELEVANCE STATEMENT: CT-guided microcoil localization of pulmonary nodules before VATS resection is effective and safe when using either the tailed or non-tailed method. Nodules requiring transfissural puncture and multiple nodules requiring simultaneous localizations can also be successfully localized with this method. KEY POINTS: • Pre-VATS CT-guided microcoil localization of pulmonary nodules by tailed or non-tailed method was effective and safe. • When the feasible puncture path was beyond the scope of wedge resection, localization could be performed using the non-tailed method. • Although transfissural puncture and simultaneous multiple localization were independent risk factors for pneumothorax, they remained clinically feasible.

Population pharmacokinetics of antibacterial agents in the older population: a literature review.

INTRODUCTION: Older individuals face an elevated risk of developing bacterial infections. The optimal use of antibacterial agents in this population is challenging because of age-related physiological alterations, changes in pharmacokinetics (PK) and pharmacodynamics (PD), and the presence of multiple underlying diseases. Therefore, population pharmacokinetics (PPK) studies are of great importance for optimizing individual treatments and prompt identification of potential risk factors. AREA COVERED: Our search involved keywords such as 'elderly,' 'old people,' and 'geriatric,' combined with 'population pharmacokinetics' and 'antibacterial agents.' This comprehensive search yielded 11 categories encompassing 28 antibacterial drugs, including vancomycin, ceftriaxone, meropenem, and linezolid. Out of 127 studies identified, 26 (20.5%) were associated with vancomycin, 14 (11%) with meropenem, and 14 (11%) with piperacillin. Other antibacterial agents were administered less frequently. EXPERT OPINION: PPK studies are invaluable for elucidating the characteristics and relevant factors affecting the PK of antibacterial agents in the older population. Further research is warranted to develop and validate PPK models for antibacterial agents in this vulnerable population.

The influence of varus and valgus deviation on the contact area of patellofemoral joint in healthy knees.

OBJECT: Varus-valgus lower alignment is a risk factor for patellofemoral osteoarthritis, but malalignment alone affect not only the tibiofemoral joint but also the patellofemoral joint. The aim of the present study was to analyse the contact area of patellofemoral joint in varus alignment and valgus alignment of healthy subjects using magnetic resonance imaging. METHODS: Twenty-six healthy subjects with valgus lower limb alignment (Group I, n = 26) and twenty-six volunteers with varus lower limb alignment (Group II, n = 26) was performed. An MRI scan was used to capture and measure the patellofemoral joint articular cartilage contact area at different degrees of knee flexion (20°, 40°,60°) in passive movement. All subjects were categorized on the basis of the global limb alignment and mechanical alignment of the femur and tibia. Varus alignment is hip-knee-ankle angle ≥ 3°; and valgus alignment is hip-knee-ankle angle ≥ - 3°. To obtain medial facet contact area and lateral facet contact area for each slice, the length of each respective line of contact was multiplied by the 5 mm slice thickness. RESULTS: The overall joint contact area increased from 168.0 ± 20.5 mm2 at 20° knee flexion to 334.4 ± 30.5 mm2 at 60° knee flexion in group (I) The overall joint contact area increased from 178.0 ± 18.9 mm2 at 20° knee flexion to 328.9 ± 27.2 mm2 at 60° knee flexion in group (II) There was a significant difference in lateral facet contact area between group I and group II at 40° of knee flexion. There was significantly different in medial facet contact area between group I and group II at 20° and 40° of knee flexion. CONCLUSIONS: Throughout the knee movement, the contact area on the lateral facet of the patellofemoral joint was greater in the valgus group. In the early phase of knee flexion, the contact area of the medial patellofemoral joint was larger in the varus group. Lower alignment is an important factor in patellofemoral joint degeneration.

Optical Temperature Sensing Based on Linear Change of Luminescence Intensity Ratio in Y2O3: Tm3+, Eu3+ Phosphors.

In this work, Y2O3: Tm3+, Eu3+ phosphors were made by homogeneous precipitation with urea as precipitator. The emission spectra varying with temperature of Y2O3: Tm3+, Eu3+ phosphors were measured and analyzed. Analysis show that the luminescence of Eu3+ represents a normal thermal quenching change, while that of Tm3+ exhibits slow thermal enhancement phenomenon. In the temperature range of 303-503 K, the luminescence of Tm3+ showed a trend of first strengthening and then weakening. The reason for this phenomenon of Tm3+ is that there is energy transfer from Eu3+ to Tm3+, and the energy transfer efficiency increases gradually with temperature. Meanwhile, the luminescence of Tm3+ also have thermal quenching effect. Under the combined influence of thermal quenching and energy transfer, the luminescence of Tm3+ first becomes stronger and then then becomes weaker. According to the calculation, the luminescence intensity ratio (LIR) of Tm3+ and Eu3+ conforms to the linear empirical formula with increasing temperature. The relative sensitivity of phosphors decreases with Eu3+ concentration increased, and the maximum Sr reaches 0.460% K-1 (1% Tm3+, 0.3% Eu3+, at 303 K). Moreover, the temperature cycle test present that the LIR of phosphors has good repeatability.

A de novo evolved gene contributes to rice grain shape difference between indica and japonica.

The role of de novo evolved genes from non-coding sequences in regulating morphological differentiation between species/subspecies remains largely unknown. Here, we show that a rice de novo gene GSE9 contributes to grain shape difference between indica/xian and japonica/geng varieties. GSE9 evolves from a previous non-coding region of wild rice Oryza rufipogon through the acquisition of start codon. This gene is inherited by most japonica varieties, while the original sequence (absence of start codon, gse9) is present in majority of indica varieties. Knockout of GSE9 in japonica varieties leads to slender grains, whereas introgression to indica background results in round grains. Population evolutionary analyses reveal that gse9 and GSE9 are derived from wild rice Or-I and Or-III groups, respectively. Our findings uncover that the de novo GSE9 gene contributes to the genetic and morphological divergence between indica and japonica subspecies, and provide a target for precise manipulation of rice grain shape.

Contact area and pressure changes of patellofemoral joint during stair ascent and stair descent.

PURPOSE: To investigate the differences of patellofemoral joint pressure and contact area between the process of stair ascent and stair descent. METHODS: The finite element models of 9 volunteers without disorders of knee (9 males) to estimate patellar cartilage pressure during the stair ascent and the stair descent. Simulations took into account cartilage morphology from magnetic resonance imaging, joint posture from weight-bearing magnetic resonance imaging, and ligament model. The three-dimension models of the patella, femur and tibia were developed with the medical image processing software, Mimics 11.1. The ligament was established by truss element of the non-linear FE solver. The equivalent gravity direction (-z direction) load was applied to the whole end of femur (femoral head) according to the body weight of the volunteers, and the force of patella was observed. A paired-samples t-test or Wilcoxon rank sum test to make comparisons between stair ascent and stair descent. Statistical analyses were performed using SPSS 22.0 using a P value of 0.05 to indicate significance. RESULTS: During the stair descent (knee flexion at 30°), the contact pressure of the patella was 2.59 ± 0.06Mpa. The contact pressure of femoral trochlea cartilage was 2.57 ± 0.06Mpa. During the stair ascent (knee flexion at 60°), the contact pressure with patellar cartilage was 2.82 ± 0.08Mpa. The contact pressure of the femoral trochlea cartilage was 3.03 ± 0.11Mpa. The contact area between patellar cartilage and femoral trochlea cartilage was 249.27 ± 1.35mm2 during the stair descent, which was less than 434.32 ± 1.70mm2 during the stair ascent. The area of high pressure was located in the lateral area of patella during stair descent and the area of high pressure was scattered during stair ascent. CONCLUSION: There are small change in the cartilage contact pressure between stair ascent and stair descent, indicating that the joint adjusts the contact pressure by increasing the contact area.

Thrombopoietin level predicts the response to avatrombopag treatment for persistent thrombocytopenia after haploidentical haematopoietic stem cell transplantation.

Persistent thrombocytopenia (PT) has an unsatisfactory response to therapy after haploidentical haematopoietic stem cell transplantation (haplo-HSCT). We retrospectively evaluated the safety and efficacy of avatrombopag treatment in 69 patients with PT following haplo-HSCT and assessed whether baseline thrombopoietin (TPO) levels could predict treatment response. Overall response (OR) and complete response (CR) were defined as increased platelet levels to over 20 × 109/L or 50 × 109/L independent of platelet transfusion during or within 7 days of the end of avatrombopag treatment, respectively. The incidences of OR and CR were 72.5% and 58.0%, with a median of 11 and 29 days to OR and CR, respectively. ROC analysis suggested that the optimally discriminant baseline TPO level threshold for both OR and CR to avatrombopag was ≤ 1714 pg/mL. In multivariate analysis, a lower baseline TPO level (P = 0.005) was a significant independent factor of response to avatrombopag. For patients resistant to other TPO receptor agonists (TPO-RAs), 9/16 (56.3%) exhibited a response after switching to avatrombopag. Avatrombopag was well tolerated, and responders achieved improved overall survival (79.0% vs. 91.1%, P = 0.001). In conclusion, avatrombopag is a potential safe and effective treatment for PT after haplo-HSCT, and lower baseline TPO levels predicted a better response.

Trends of Mortality in End-Stage Liver Disease - China, 2008-2020.

Introduction: Liver cancer and cirrhosis represent the most prevalent forms of end-stage liver diseases (ESLDs). Notably, in China, deaths attributed to ESLDs contribute significantly to the global mortality rate of these disorders. Enhanced comprehension of the mortality profile associated with ESLDs in China could provide crucial insights into intervention prioritization, which could in turn help reduce the overall global burden of these diseases. Methods: Data were obtained from China's Disease Surveillance Points system. The presentation includes both crude and age-standardized mortality rates, stratified by sex, residential location, and region. Using Joinpoint Regression, trends in annual mortality rates were estimated from the period of 2008 to 2020 and expressed as the average annual percentage change (AAPC). Results: In 2020, the gross mortality rate of ESLD stood at 30.08 cases per 100,000 individuals. A higher age-standardized ESLD mortality rate was observed in males and rural populations in comparison to their female and urban counterparts, respectively. Noticeably, the highest mortality rates associated with liver cancer and cirrhosis were reported in South and Southwest China, respectively. A positive correlation was noticed between age-specific ESLD mortality rates and advancing age. Interestingly, an annual decrease in the ESLD mortality rate was observed from 2008 to 2020. In urban contexts, the AAPC of cirrhosis was noted to be higher than that of liver cancer. Conclusions: The mortality rate associated with ESLDs in China decreased between 2008 and 2020. Nevertheless, the death burden attributable to ESLD continues to be alarmingly high. Future initiatives should prioritize the reduction of ESLD mortality in particular populations: males, elderly individuals, and those residing in rural regions of South and Southwest China. The emphasis of future interventions should be placed on antiviral therapy for adults diagnosed with viral hepatitis, and on the prevention of hepatitis B virus (HBV) infection across all demographics.

Genotype-phenotype correlation of deletions and duplications of 4p: case reports and literature review.

Structural rearrangements of chromosome 4p gives rise to a group of rare genomic disorders that mainly result in two different clinical entities: Wolf-Hirschhorn syndrome (WHS) and partial 4p trisomy. The severity of the phenotype depends on the size of the deletion or locus duplication. Here, we present two unrelated individuals with a copy number variation of chromosome 4p. Inverted duplication deletions (inv dup-del) in 4p are particularly rare. Case 1 describes a 15-year-old girl with a 1.055 Mb deletion of terminal 4p, distal to the recognized critical region of WHS, and a large duplication of 9.6 Mb in size from 4p16.3 to p16.1. She had postnatal development delay, intellectual disability (especially pronounced in speech), seizure/electroencephalogram anomalies, and facial dysmorphic features. This unusual chromosomal imbalance resulted in the WHS phenotype rather than the 4p trisomy syndrome phenotype. Case 2 describes a 21-month-old boy with a 1.386 Mb terminal 4p deletion who presented with slight developmental delay, borderline intellectual disability, and seizures. Combined with previous reported cases of 4 pter del-dup or pure 4p terminal deletions, our observations suggest that terminal chromosome 4p deletion is more pathogenic than the concomitant partial 4p duplication, and some regions of the 4p terminal may have regulatory effects on the remaining region of 4p. About nine cases have been reported thus far to date, and our study delineates further genotype-phenotype correlations about terminal 4p duplication-deletions for predicting disease prognosis and patient counseling.

Correlation between scalp high-frequency oscillations and prognosis in patients with benign epilepsy of childhood with centrotemporal spikes.

AIMS: The study aimed to explore whether high-frequency oscillations (HFOs) can predict seizure risk and atypical manifestations of benign epilepsy of childhood with centrotemporal spikes (BECTS). METHODS: We recruited 60 patients and divided them into three groups: (1) seizure-free BECTS, (2) active typical BECTS, and (3) active atypical forms of BECTS. Electroencephalogram was used to record the number, location, average amplitude, and duration of spikes, and spike ripples were analyzed using time-frequency technology. Multivariable logistic regression analysis was used to investigate independent predictive factors for prognosis. RESULTS: The number of sleep spike ripples, rather than spikes, was an independent risk factor for the active period of the disease (odds ratio [OR] = 4.714, p = 0.003) and atypical forms of BECTS (OR = 1.455, p = 0.049); the optimal thresholds for the spike ripple rate were >0 (area under the curve [AUC] = 0.885, sensitivity = 96.15%, specificity = 73.33%) and >0.6/min (AUC = 0.936, sensitivity = 84.21%, specificity = 96.15%), respectively. Furthermore, in typical BECTS, the spike ripple rate showed significant negative correlations with time since the last seizure (ρ = -0.409, p = 0.009) and age (ρ = -0.379, p = 0.016), while the spike rate did not. CONCLUSION: Spike ripple was a marker for distinguishing typical and atypical forms of BECTS and reflected the risk of seizure recurrence better than the spike alone. The present findings might assist clinicians in BECTS treatment.

Development of a Crystal Digital RT-PCR for the Detection of Atypical Porcine Pestivirus.

Atypical porcine pestivirus (APPV), a newly discovered virus, is associated with the type A-II congenital tremor (CT) in neonatal piglets. APPV distributes throughout the world and causes certain economic losses to the swine industry. The specific primers and probe were designed targeting the 5' untranslated region (UTR) of APPV to amplify a 90 bp fragment, and the recombinant standard plasmid was constructed. After optimizing the concentrations of primers and probe, annealing temperature, and reaction cycles, a crystal digital RT-PCR (cdRT-PCR) and real-time quantitative RT-PCR (qRT-PCR) were successfully established. The results showed that the standard curves of the qRT-PCR and the cdRT-PCR had R2 values of 0.999 and 0.9998, respectively. Both methods could specifically detect APPV, and no amplification signal was obtained from other swine viruses. The limit of detection (LOD) of the cdRT-PCR was 0.1 copies/µL, and that of the qRT-PCR was 10 copies/µL. The intra-assay and inter-assay coefficients of variation of repeatability and reproducibility were less than 0.90% for the qRT-PCR and less than 5.27% for the cdRT-PCR. The 60 clinical tissue samples were analyzed using both methods, and the positivity rates of APPV were 23.33% by the qRT-PCR and 25% by the cdRT-PCR, with a coincidence rate of 98.33%. The results indicated that the cdRT-PCR and the qRT-PCR developed here are highly specific, sensitive methods for the rapid and accurate detection of APPV.

Predicting short-term and long-term mortalities from sepsis in patients who receive allogeneic haematopoietic stem cell transplantation.

Patients who receive allogeneic haematopoietic stem cell transplantation (allo-HSCT) may develop sepsis, which result in a highly intensive care unit admission rate and mortality. Therefore, short-term and long-term prognostic models for sepsis after allo-HSCT are urgently needed. We enrolled patients receiving allo-HSCT who developed sepsis after allo-HSCT at Peking University People's Hospital between 2012 and 2021, including 287 patients who received allo-HSCT in 2018-2021 in the derivation cohort, and 337 patients in 2012-2017 in the validation cohort. Multivariate logistic regression analysis was used to identify prognostic factors, and these identified factors were incorporated into two scoring models. Seven independent factors (acute graft-versus-host disease (GVHD), chronic GVHD (cGVHD), total bilirubin, lactate dehydrogenase (LDH) and organ dysfunction [renal, lung and heart]) were included in the 6-month prognostic model, and six factors (cGVHD, C-reactive protein, LDH, organ dysfunction [lung, neurologic and coagulation]) were included in the 14-day prognostic model. The area under the receiver operating characteristic curves, calibration plots and decision curve analysis demonstrated the robust predictive performance of the models, better than the Sequential Organ Failure Assessment score. Early identification of patients with high risk of 6-month and 14-day death may allow clinicians to provide timely treatments and improve the therapeutic effects.

The burden of hepatitis C virus in the world, China, India, and the United States from 1990 to 2019.

Background and aim: Hepatitis C virus infection can lead to an enormous health burden worldwide. Investigating the changes in HCV-related burden between different countries could provide inferences for disease management. Hence, we aim to explore the temporal tendency of the disease burden associated with HCV infection in China, India, the United States, and the world. Methods: Detailed data on the total burden of disease related to HCV infection were collected from the Global Burden of Disease (GBD) 2019 database. Joinpoint regression models were used to simulate the optimal joinpoints of annual percent changes (APCs). Further analysis of the age composition of each index over time and the relationship between ASRs and the socio-demographic Index (SDI) were explored. Finally, three factors (population growth, population aging, and age-specific changes) were deconstructed for the changes in the number of incidences, deaths, and DALYs. Results: It was estimated that 6.2 million new HCV infections, 0.54 million HCV-related deaths, and 15.3 million DALYs worldwide in 2019, with an increase of 25.4, 59.1, and 43.6%, respectively, from 1990, are mainly due to population growth and aging. China experienced a sharp drop in age-standardized rates in 2019, the United States showed an upward trend, and India exhibited a fluctuating tendency in the burden of disease. The incidence was increasing in all locations recently. Conclusion: HCV remains a global health concern despite tremendous progress being made. The disease burden in China improved significantly, while the burden in the United States was deteriorating, with new infections increasing recently, suggesting more targeted interventions to be established to realize the 2030 elimination goals.