[Application effect of a dual release system of androgen and its antagonist in the repair of full-thickness burn wounds in mice].

Objective: To explore the optimal ratio of dihydrotestosterone and hydroxyflutamide (hereinafter referred to as DH), construct a dual release system of androgen and its antagonist, and analyze the application effect of this system in the repair of full-thickness burn wounds in mice. Methods: This study was an experimental study. The HaCaT cells were divided into blank group (without drug culture), low baseline group, medium baseline group, and high baseline group according to the random number table (the same grouping method below), and the last three groups of cells were cultured by adding three different ratios of DH. Under a medium ratio, the mass of dihydrotestosterone in the three baseline groups from low to high was 1.4, 2.8, and 4.0 µg, respectively, and the mass of hydroxyflutamide was 1.2, 1.6, and 2.0 µg, respectively. On this basis, under a small ratio, the mass of dihydrotestosterone was reduced by half and the mass of hydroxyflutamide was increased by half; under a large ratio, the mass of dihydrotestosterone was increased by half and the mass of hydroxyflutamide was reduced by half. After culture of 2 days, the cell proliferation level was detected by cell counting kit 8 (n=4). Sixteen 6-8-week-old male BALB/c mice were used to establish a full-thickness burn wound on the back and divided into blank group, small ratio group, medium ratio group, and large ratio group, with 4 mice in each group. On post injury day (PID) 7, normal saline containing different ratios of DH was locally dropped to the wounds of mice in the last three groups of mice (the total mass of DH in the three ratio groups from small to large was 127.5, 165.0, and 202.5 µg, respectively, and the mass ratios of dihydrotestosterone to hydroxyflutamide (hereinafter referred to as drug mass ratio) were 8∶9, 8∶3, and 8∶1, respectively), afterwards, the administration was repeated every 48 hours until PID 27; normal saline was dropped to the wound of mice in blank group at the aforementioned time points. The wound healing status on PID 0 (immediately), 7, 14, 21, and 28 was observed, and the wound healing rates on PID 7, 14, 21, and 28 were calculated (n=4). On PID 28, the wound tissue was taken, which was stained with hematoxylin and eosin for observing re-epithelialization and with Masson for observing collagen fibers, and the proportion of collagen fibers was analyzed (n=3). Twenty 6-8-week-old male BALB/c mice were used to establish a full-thickness burn wound on the back and divided into ordinary scaffold group, small proportion scaffold group, medium proportion scaffold group, and large proportion scaffold group (with 5 mice in each group). On PID 7, the wound was continuously dressed with a polycaprolactone scaffold without drug and a polycaprolactone scaffold containing DH with a drug mass ratio of 1∶3, 1∶1, or 3∶1 (i.e. the dual release system of androgen and its antagonist, with total mass of DH being about 1.7 mg) prepared by using electrospinning technology until the end of the experiment. Histopathological analyses of tissue (n=3) at the same time points as those in the previous animal experiment were performed. On PID 7 and 14, the wound exudates were collected and the relative abundance of bacterial communities was analyzed using 16S ribosomal RNA high-throughput sequencing (n=3). Results: After culture of 2 days, under a small ratio, the proliferation levels of HaCaT cells in low baseline group and high baseline group were significantly higher than the level in blank group (P<0.05). As the time after injury prolonged, the wounds of all four groups of mice continued to shrink. On PID 14, the wound healing rate of mice in large ratio group was 72.5% (61.7%, 75.1%), which was close to 53.3% (49.5%, 64.4%) in blank group (P>0.05); the wound healing rates of mice in small and medium ratio groups were 74.2% (71.0%, 84.2%) and 70.4% (65.1%, 74.4%), respectively, which were significantly higher than the rate in blank group (with both Z values being -2.31, P<0.05). On PID 21, the wound healing rate of mice in small ratio group was significantly higher than that in blank group (Z=-2.31, P<0.05). On PID 28, the wounds of mice in the three ratio groups were completely re-epithelialized and the epidermis was thicker than that in blank group; compared with that in blank group, the collagen fiber content in the wound tissue of mice in the three ratio groups was higher and arranged more orderly, and the proportions of collagen fibers in the wound tissue of mice in small and large ratio groups were significantly increased (P<0.05). On PID 28, the wounds of mice in ordinary scaffold group were partially epithelialized, while the wounds of mice in the three proportion scaffold groups were almost completely epithelialized. Among them, the wounds of mice in small proportion scaffold group had the thickest epidermis. The proportion of collagen fibers in the wound tissue of mice in small proportion scaffold group was significantly increased compared with that in ordinary scaffold group (P<0.05). On PID 7, the bacterial communities with high relative abundance in the wound exudation of mice in the four groups included bacteria of Corynebacterium, Staphylococcus, and Rhodococcus. On PID 14, the bacterial communities with high relative abundance in the wound exudation of mice in the four groups included bacteria of Stenotrophomonas, Rhodococcus, and Staphylococcus, and the number of bacterial species in the wound exudation of mice in the three proportion scaffold groups was more than that in ordinary scaffold group. Conclusions: When the drug mass ratio is relatively small, DH has the effect of promoting the proliferation of HaCaT cells. The ratio of 8∶9 is the optimal mass ratio of dihydrotestosterone to hydroxyflutamide, and DH with this mass ratio can promote re-epithelialization and collagen deposition of full-thickness burn wounds in mice, and promote wound healing. The constructed dual release system of androgen and its antagonist with DH in a 1∶3 drug mass ratio contributes to the re-epithelialization and collagen deposition of the full-thickness burn wounds in mice, and can improve the diversity of wound microbiota.

[International comparison and assessment of the quality of drug clinical trial implementation in China based on scientific regulatory system].

With the rapid development of clinical research and the continuous enhancement of innovation capability in China, the quality of clinical research under China's scientific regulatory system has drawn widespread attention. This study evaluated the quality results of China's drug clinical trials implementation, compared the scientific regulatory systems of clinical research quality between China and the United States, analyzed real-world clinical application on the approval of new anti-tumor drugs through clinical trials, in order to analyze China's status and level of clinical trial implementation quality in the international industry, and explore the advantages and value of China's clinical research scientific regulation by collecting clinical trial data inspections disclosed by regulatory agencies in both China and the United States, as well as verifying information on the approval of new anti-tumor drugs.

Unconventional exciton evolution from the pseudogap to superconducting phases in cuprates.

Electron quasiparticles play a crucial role in simplifying the description of many-body physics in solids with surprising success. Conventional Landau's Fermi-liquid and quasiparticle theories for high-temperature superconducting cuprates have, however, received skepticism from various angles. A path-breaking framework of electron fractionalization has been established to replace the Fermi-liquid theory for systems that show the fractional quantum Hall effect and the Mott insulating phenomena; whether it captures the essential physics of the pseudogap and superconducting phases of cuprates is still an open issue. Here, we show that excitonic excitation of optimally doped Bi2Sr2CaCu2O8+δ with energy far above the superconducting-gap energy scale, about 1 eV or even higher, is unusually enhanced by the onset of superconductivity. Our finding proves the involvement of such high-energy excitons in superconductivity. Therefore, the observed enhancement in the spectral weight of excitons imposes a crucial constraint on theories for the pseudogap and superconducting mechanisms. A simple two-component fermion model which embodies electron fractionalization in the pseudogap state provides a possible mechanism of this enhancement, pointing toward a novel route for understanding the electronic structure of superconducting cuprates.

[A multicenter epidemiological study of acute bacterial meningitis in children].

Objective: To analyze the clinical epidemiological characteristics including composition of pathogens , clinical characteristics, and disease prognosis acute bacterial meningitis (ABM) in Chinese children. Methods: A retrospective analysis was performed on the clinical and laboratory data of 1 610 children <15 years of age with ABM in 33 tertiary hospitals in China from January 2019 to December 2020. Patients were divided into different groups according to age,<28 days group, 28 days to <3 months group, 3 months to <1 year group, 1-<5 years of age group, 5-<15 years of age group; etiology confirmed group and clinically diagnosed group according to etiology diagnosis. Non-numeric variables were analyzed with the Chi-square test or Fisher's exact test, while non-normal distrituction numeric variables were compared with nonparametric test. Results: Among 1 610 children with ABM, 955 were male and 650 were female (5 cases were not provided with gender information), and the age of onset was 1.5 (0.5, 5.5) months. There were 588 cases age from <28 days, 462 cases age from 28 days to <3 months, 302 cases age from 3 months to <1 year of age group, 156 cases in the 1-<5 years of age and 101 cases in the 5-<15 years of age. The detection rates were 38.8% (95/245) and 31.5% (70/222) of Escherichia coli and 27.8% (68/245) and 35.1% (78/222) of Streptococcus agalactiae in infants younger than 28 days of age and 28 days to 3 months of age; the detection rates of Streptococcus pneumonia, Escherichia coli, and Streptococcus agalactiae were 34.3% (61/178), 14.0% (25/178) and 13.5% (24/178) in the 3 months of age to <1 year of age group; the dominant pathogens were Streptococcus pneumoniae and the detection rate were 67.9% (74/109) and 44.4% (16/36) in the 1-<5 years of age and 5-<15 years of age . There were 9.7% (19/195) strains of Escherichia coli producing ultra-broad-spectrum ß-lactamases. The positive rates of cerebrospinal fluid (CSF) culture and blood culture were 32.2% (515/1 598) and 25.0% (400/1 598), while 38.2% (126/330)and 25.3% (21/83) in CSF metagenomics next generation sequencing and Streptococcus pneumoniae antigen detection. There were 4.3% (32/790) cases of which CSF white blood cell counts were normal in etiology confirmed group. Among 1 610 children with ABM, main intracranial imaging complications were subdural effusion and (or) empyema in 349 cases (21.7%), hydrocephalus in 233 cases (14.5%), brain abscess in 178 cases (11.1%), and other cerebrovascular diseases, including encephalomalacia, cerebral infarction, and encephalatrophy, in 174 cases (10.8%). Among the 166 cases (10.3%) with unfavorable outcome, 32 cases (2.0%) died among whom 24 cases died before 1 year of age, and 37 cases (2.3%) had recurrence among whom 25 cases had recurrence within 3 weeks. The incidences of subdural effusion and (or) empyema, brain abscess and ependymitis in the etiology confirmed group were significantly higher than those in the clinically diagnosed group (26.2% (207/790) vs. 17.3% (142/820), 13.0% (103/790) vs. 9.1% (75/820), 4.6% (36/790) vs. 2.7% (22/820), χ2=18.71, 6.20, 4.07, all P<0.05), but there was no significant difference in the unfavorable outcomes, mortility, and recurrence between these 2 groups (all P>0.05). Conclusions: The onset age of ABM in children is usually within 1 year of age, especially <3 months. The common pathogens in infants <3 months of age are Escherichia coli and Streptococcus agalactiae, and the dominant pathogen in infant ≥3 months is Streptococcus pneumoniae. Subdural effusion and (or) empyema and hydrocephalus are common complications. ABM should not be excluded even if CSF white blood cell counts is within normal range. Standardized bacteriological examination should be paid more attention to increase the pathogenic detection rate. Non-culture CSF detection methods may facilitate the pathogenic diagnosis.

[The clinical value of multi-target stool fecal immunochemical test-DNA in early screening and diagnosis for colorectal cancer].

Objective: To investigate the clinical diagnostic value of multi-target stool fecal immunochemical test-DNA (FIT-DNA) test in colorectal cancer (CRC) and advanced adenoma (AA). Methods: A total of 235 patients who were undergoing colonoscopy or colorectal cancer surgery in the Cancer Hospital, Chinese Academy of Medical Sciences from April 2021 to January 2022 were prospectively enrolled. There were 141 males and 94 females, with an average age of (55±13) years (22-86). The patients were divided into two groups, including 215 patients who were first diagnosed but not treated (86 cases of CRC, 12 cases of AA, 25 cases of non-advanced adenoma, 8 cases of hyperplastic or other polyps and 84 apparently healthy cases) and 20 patients in the intervention group (2 cases with a history of CRC surgery, 6 cases with a history of endoscopic surgery, 4 non-CRC patients with special diseases and 8 cases with a history of neoadjuvant chemoradiotherapy). Fresh stool samples were collected before intestinal preparation or surgery for FIT-DNA test using the matching kit for sample processing and nucleic acid purification. KRAS mutation and methylation of BMP3 and NDRG4 genes were detected by fluorescence probe method, and FIT method was employed to detect fecal occult blood. Colonoscopy or pathological biopsy results were used as the gold standard. And the screening and diagnostic efficacy of FIT-DNA test for colorectal cancer and advanced adenoma were evaluated by receiver operating curve (ROC). Results: The sensitivity of FIT-DNA test for early colorectal cancer and advanced adenoma was 7/7 and 8/12, respectively. And the negative predictive value was 98.1% (104/106) and 93.7% (104/111), respectively. The overall screening sensitivity for both early colorectal cancer and advanced adenoma was 15/19, and the negative predictive value was 96.3% (104/108). Besides, the area under the curves (AUCs) were 0.982 (95%CI: 0.960-1.000, P<0.05), 0.758 (95%CI: 0.592-0.924, P<0.05) and 0.841 (95%CI: 0.724-0.957, P<0.05), respectively. Moreover, the diagnostic sensitivity of FIT-DNA test was 98.8% (85/86) for colorectal cancer, 8/12 for advanced adenoma, and 94.9% (93/98) for both colorectal cancer and advanced adenoma, with a specificity of 88.9% (104/117). The AUCs were 0.968 (95%CI: 0.937-0.997, P<0.05), 0.758 (95%CI: 0.592-0.924, P<0.05) and 0.942 (95%CI: 0.905-0.979, P<0.05), respectively. After the inclusion of intervention group, the overall diagnostic sensitivity and specificity of FIT-DNA test was 91.6% (98/107) and 89.1% (114/128), respectively. Conclusion: FIT-DNA test has a high early screening and diagnostic efficacy for colorectal cancer.

[Research progress on the characteristics of artemisia pollen allergens and related pollinosis].

In recent years, the morbidity of pollinosis has been increasing year by year. Anemophilous flower pollen is the most important allergen causing pollinosis, among which artemisia pollen is one of the most common airborne allergens. In this paper, based on the immune biology characteristics of major sensitization protein components of artemisia pollen, and from the perspective of immunology, the main pathogenic mechanism of action and clinical characteristics of artemisia pollen are elaborated to provide the reference basis for the development of accurate and effective artemisia pollen disease prevention and control strategy, hoping to provide patients with scientific and effective prevention and control suggestions.

[Progress on clinical trials of common gastrointestinal cancer drugs in China from 2012 to 2021].

Objective: Systematically summarize the research progress of clinical trials of gastric cancer oncology drugs and the overview of marketed drugs in China from 2012 to 2021, providing data and decision-making evidence for relevant departments. Methods: Based on the registration database of the drug clinical trial registration and information disclosure platform of Food and Drug Administration of China and the data query system of domestic and imported drugs, the information on gastric cancer drug clinical trials, investigational drugs and marketed drugs from January 1, 2012 to December 31, 2021 was analyzed, and the differences between Chinese and foreign enterprises in terms of trial scope, trial phase, treatment lines and drug type, effect and mechanism studies were compared. Results: A total of 114 drug clinical trials related to gastric tumor were registered in China from 2012 to 2021, accounting for 3.7% (114/3 041) of all anticancer drug clinical trials in the same period, the registration number showed a significant growth rate after 2016 and reached its peak with 32 trials in 2020. Among them, 85 (74.6%, 85/114) trials were initiated by Chinese pharmaceutical enterprise. Compared with foreign pharmaceutical enterprise, Chinese pharmaceutical enterprise had higher rates of phase I trials (35.3% vs 6.9%, P=0.001), but the rate of international multicenter trials (11.9% vs 67.9%, P<0.001) was relatively low. There were 76 different drugs involved in relevant clinical trials, of which 65 (85.5%) were targeted drugs. For targeted drugs, HER2 is the most common one (14 types), followed by PD-1 and multi-target VEGER. In the past ten years, 3 of 4 marketed drugs for gastric cancer treatment were domestic and included in the national medical insurance directory. Conclusions: From 2012 to 2021, China has made some progress in drug research and development for gastric carcinoma. However, compared with the serious disease burden, it is still insufficient. Targeted strengthening of research and development of investment in many aspects of gastric cancer drugs, such as new target discovery, matured target excavating, combination drug development and early line therapy promotion, is the key work in the future, especially for domestic companies.

[Comparison of early outcome between one-stage hybrid technique and frozen elephant thunk technique in the treatment of Stanford A aortic dissection involving the arch].

Objective: To analyze the early outcome of one-stage hybrid technique in the treatment of Stanford type-A aortic dissection involving the arch and compare its therapeutic efficacy with the classical frozen elephant trunk technique (FET). Methods: A total of 106 patients with Stanford type-A aortic dissection involving the arch in Department of Cardiac and Vascular Surgery, 1st Affiliated Hospital of Soochow University from October 2015 to October 2019 was collected. All patients in this group were treated with one-stage hybrid technique (modified arch debranching technique) without deep hypothermia circulation. Meanwhile, 30 patients with Stanford type A dissection involving the arch who underwent FET from January 2014 to September 2015 were collected. The therapeutic effects of the two surgical methods were analyzed and compared. Results: The age [M (Q1, Q3)] of 106 patients in hybrid group was 49.0 (40.0, 55.0) years, including 89 males and 17 females. The age [M(Q1, Q3)] of 30 patients in FET group was 49.5 (41.5, 65.3) years, including 24 males and 6 females. The time [M(Q1, Q3)] of using ventilator in hybrid group was 56.0 (38.0, 72.0) h, which was shorter than 127.0 (92.0, 145.0) h in FET group (P<0.001). The incidence of cerebral infarction in hybrid group was 2.8% (3 cases), which was lower than 13.3% (4 cases) in FET group (P=0.042); the incidence of postoperative renal insufficiency in hybrid group was 7.5% (8 cases), which was lower than 23.3% (7 cases) in FET group (P=0.023); the ICU time [M (Q1, Q3)] in hybrid group was 8.0 (6.0, 10.0) d, which was shorter than 14.0 (8.3, 24.0) d in FET group (P<0.001). Conclusion: Compared with FET, one-stage hybrid technology is safer and more effective in the treatment of Stanford type A aortic dissection involving the arch. Its short-term therapeutic efficacy appears good.

[Drug-resistant gene polymorphisms in Plasmodium falciparum isolated from Bioko Island, Equatorial Guinea in 2018 and 2019].

OBJECTIVE: To investigate the genetic polymorphisms of Plasmodium falciparum multidrug resistance protein 1 (PfMDR1), chloroquine resistance transporter (PfCRT) and Kelch 13 (PfK13) genes in Bioko Island, Equatorial Guinea, so as to provide insights into the development of the malaria control strategy in local areas. METHODS: A total of 85 peripheral blood samples were collected from patients with Plasmodium falciparum infections in Bioko Island, Equatorial Guinea in 2018 and 2019, and genomic DNA was extracted. The PfMDR1, PfCRT and PfK13 genes were amplified using a nested PCR assay. The amplification products were sequenced, and the gene sequences were aligned. RESULTS: There were no mutations associated with artemisinin resistance in PfK13 gene in Bioko Island, Equatorial Guinea, while drug-resistant mutations were detected in PfMDR1 and PfCRT genes, and the proportions of PfMDR1_N86Y, PfMDR1_Y184F and PfCRT_K76T mutations were 35.29% (30/85), 72.94% (62/85) and 24.71% (21/85), respectively. CONCLUSIONS: There are mutations in PfMDR1, PfCRT and PfK13 genes in P. falciparum isolates from Bioko Island, Equatorial Guinea.

COVID-19-Associated Myelitis Involving the Dorsal and Lateral White Matter Tracts: A Case Series and Review of the Literature.

Coronavirus disease 2019 (COVID-19) myelitis is a rare condition, most commonly presenting with nonenhancing central expansile cord T2 signal changes. A single case report has also described longitudinal involvement of the dorsal columns. We present 5 cases of COVID-19-associated myelitis with tract-specific involvement of the dorsal and lateral columns and discuss potential pathophysiologic pathways for this unique pattern.

Development of the Soft X-ray AGM-AGS RIXS beamline at the Taiwan Photon Source.

We report on the development of a high-resolution and highly efficient beamline for soft X-ray resonant inelastic X-ray scattering (RIXS) located at the Taiwan Photon Source. This beamline adopts an optical design that uses an active grating monochromator (AGM) and an active grating spectrometer (AGS) to implement the energy compensation principle of grating dispersion. Active gratings are utilized to diminish defocus, coma and higher-order aberrations, as well as to decrease the slope errors caused by thermal deformation and optical polishing. The AGS is mounted on a rotatable granite platform to enable momentum-resolved RIXS measurements with scattering angles over a wide range. Several high-precision instruments developed in-house for this beamline are described briefly. The best energy resolution obtained from this AGM-AGS beamline was 12.4 meV at 530 eV, achieving a resolving power of 4.2 × 104, while the bandwidth of the incident soft X-rays was kept at 0.5 eV. To demonstrate the scientific impact of high-resolution RIXS, we present an example of momentum-resolved RIXS measurements on a high-temperature superconducting cuprate, i.e. La2-xSrxCuO4. The measurements reveal the A1g buckling phonons in superconducting cuprates, opening a new opportunity to investigate the coupling between these phonons and charge-density waves.

Highly efficient solid-state Raman yellow-orange lasers created by enhancing the cavity reflectivity.

A new, to the best of our knowledge, output coupler (OC) with enhancement of the cavity reflectivity is proposed to remarkably elevate the output powers and efficiencies of diode-pumped Nd:GdVO4/KGW Raman yellow-orange lasers. The cavity reflectivity is effectively increased by using the double-sided dichroic coating on the OC. In comparison with the conventional single-sided coating, the conversion efficiency can be boosted from 15% to 26.3% in the experiment of a yellow laser at 578.8 nm, and the maximum output power can be increased from 5.7 to 10.5 W in the quasi-continuous-wave mode with 50% duty cycle and frequency of 500 Hz. Furthermore, in the operation of an orange laser at 588 nm, the maximum output power can be improved from 5.6 to 7.0 W by replacing the conventional OC with the new one.

[Progress on clinical trials of cancer drugs in China, 2020].

Objective: To explore the latest progress of oncology drug clinical trials in China under COVID-19, as well as to provide decision-making evidence for related stakeholders. Research progress of oncology drug trials and approved cancer drugs in China in 2020 were systematically summarized and compared with 2019. Methods: Information Disclosure Platform for Drug Clinical Studies and China Food and Drug Administration Query System for Domestic and Imported Drug were searched for registered clinical trials and approved oncology drugs, respectively. The trial scope, stage, drug type, effect and mechanism of domestic and global pharmaceutical enterprises were compared between 2019 and 2020. Results: A total of 722 cancer drug trials registered in China in 2020, with an annual growth rate of 52.3%, accounting for 28.3% of all registered trials. Among them, 603 (83.5%) trials were initiated by domestic pharmaceutical enterprises, and 105 (14.5%) were international multicenter trials, phase I trials accounted for 44.5%. For all those trials, there were 458 cancer drug varieties, with an annual growth rate of 36.7%, and 361 (85.8%) were developed by domestic enterprises. Most of the investigational products were therapeutic innovative drugs (77.1%), major in tumor treatment (92.8%). In terms of mechanism, targeted drugs were the most popular, accounting for 76.6%, and programmed cell death-1 (PD-1) and epithelial growth factor receptor (EGFR) were the most common targets. In addition, there were 19 anticancer drugs from 17 companies approved in China in 2019, with 10 drugs from domestic companies. Lung cancer and breast cancer are the most common indications for both registered trials and marketed drugs. No statistically significant differences were found between 2020 and 2019 in terms of the distribution of trial sponsor, scope and stage, as well as the distribution of drug type, effect and mechanism (P>0.05). Conclusions: During the Covid-19 epidemic period, clinical trials of oncology drugs in China progress smoothly and maintain a high growth rate. Series of innovative products obtained by domestic enterprises in 2020 is the main driving force of development of oncology drug clinical trials in China.

Establishing peripheral PD-L1 as a prognostic marker in hepatocellular carcinoma patients: how long will it come true?

Background The prognostic role of intratumoral programmed cell death ligand 1 (PD-L1) expression in hepatocellular carcinoma (HCC) has been investigated by several meta-analyses. However, the prognostic value of pretreatment peripheral PD-L1 (PPPD-L1) level in HCC remains undetermined. Thus, this systemic review aimed to establish PPPD-L1 as a new prognostic marker in HCC according to available evidence. Methods Case–control studies investigating the prognostic role of PPPD-L1 in HCC were systemically sought in the database of PubMed and Web of Science until March 25th, 2020. Our main concern is survival results, including overall survival (OS), disease-free survival (DFS), and progression-free survival (PFS). The combined results were summarized in narrative form according to data extracted from each included study. Results Finally, nine studies published from 2011 to 2019, were incorporated into this systemic review. Among these, six studies evaluated the PD-L1 expression by enzyme-linked immunosorbent assay (ELISA) from blood serum, and three studies evaluated the PD-L1 expression by flow cytometric analysis from peripheral blood mononuclear cells (PBMC). According to the extracted evidence, high PPPD-L1 expression, measured in either blood serum or PBMC, is associated with poor OS, poor DFS, and poor PFS. Meanwhile, PPPD-L1 was also correlated with enlarged tumor size and more likely with advanced tumor stage as well as vascular invasion. Conclusion High PPPD-L1 level is associated with increased mortality rate and increased recurrence rate in HCC. As a convenient serum marker, PPPD-L1 could be a promising marker of prognosis in HCC patients (AU)

[Induction of hepatocellular carcinoma in B6C3 (F1) mice chronicly exposed to trichloroethylene with enhanced acetylation of histone H2AK9ac and SET expression in the liver tissue].

Objective: To establish an animal model of trichloroethylene (TCE) -induced liver cancer following chronic exposure and to understand the changes in SET expression and histone acetylation, potentially serving as a molecular mechanism for TCE-induced hepatocarcinogenesis. Methods: B6C3 mice at 6 weeks were treated with TCE at a series of doses (500, 1000 and 2000 mg/kg) by gastric gavage, with corn oil used as the negative control and carbon tetrachloride (CCl(4)) as the positive control. The serum and liver were sampled for the determination of biochemical indexes and pathological examination after 56 weeks of chemical exposure. Western blot was used to determine the levels of SET, H2AK9ac and HDAC1 expression. Results: The overall survival rate of the mice in various groups was 90.4% (141/156) , with no statistical difference between groups (P>0.05) . Compared with the negative control, the organ coefficient for the liver in the high dose TCE group and the positive control group were significantly increased (P<0.05) . The levels of ALT, AST, LDH and BUN in the all the three TCE groups and the positive control were significantly higher than those in the negative control (P<0.01) . CREA levels in the 1000 and 2000 mg/kg TCE groups were significantly higher than those in the negative control (P<0.05) . Statistical increases in the incidence of hepatocellular carcinoma and the activities of ALT and AST in various doses of TCE-exposed mice as compared with the control were observed (P<0.01) , in a dose-dependent manner. In the 1000 and 2000 mg/kg of TCE treated mice, levels of SET and H2AK9ac were increased (P<0.05) , while HDAC1 was decreased (P<0.05) , Compared to the tissue adjacent to liver cancer, in the 1000 and 2000 mg/kg TCE groups, the levels of SET were increased (P<0.05) , while HDAC1 was decreased (P<0.05) , and H2AK9ac increased in the 2000 mg/kg group. Conclusion: The hepatocellular carcinoma mouse model induced by chronic exposure to trichloroethylene was successfully established, with enhanced SET protein expression and H2AK9ac in the hepatic tissue.

Establishing peripheral PD-L1 as a prognostic marker in hepatocellular carcinoma patients: how long will it come true?

BACKGROUND: The prognostic role of intratumoral programmed cell death ligand 1 (PD-L1) expression in hepatocellular carcinoma (HCC) has been investigated by several meta-analyses. However, the prognostic value of pretreatment peripheral PD-L1 (PPPD-L1) level in HCC remains undetermined. Thus, this systemic review aimed to establish PPPD-L1 as a new prognostic marker in HCC according to available evidence. METHODS: Case-control studies investigating the prognostic role of PPPD-L1 in HCC were systemically sought in the database of PubMed and Web of Science until March 25th, 2020. Our main concern is survival results, including overall survival (OS), disease-free survival (DFS), and progression-free survival (PFS). The combined results were summarized in narrative form according to data extracted from each included study. RESULTS: Finally, nine studies published from 2011 to 2019, were incorporated into this systemic review. Among these, six studies evaluated the PD-L1 expression by enzyme-linked immunosorbent assay (ELISA) from blood serum, and three studies evaluated the PD-L1 expression by flow cytometric analysis from peripheral blood mononuclear cells (PBMC). According to the extracted evidence, high PPPD-L1 expression, measured in either blood serum or PBMC, is associated with poor OS, poor DFS, and poor PFS. Meanwhile, PPPD-L1 was also correlated with enlarged tumor size and more likely with advanced tumor stage as well as vascular invasion. CONCLUSION: High PPPD-L1 level is associated with increased mortality rate and increased recurrence rate in HCC. As a convenient serum marker, PPPD-L1 could be a promising marker of prognosis in HCC patients.

[Disease burden of colorectal cancer in China: any changes in recent years?]

Objective: To update the disease burden of colorectal cancer (CRC) in Chinese population by integrating the latest multi-source evidences. Methods: Groups of data from GLOBOCAN, series of Chinese Cancer Registry Annual Report (annual report), Cancer Incidence in Five Continents (CI5), Global Burden of Disease Project 2017 (GBD), China Death Cause Surveillance Datasets and China Health Statistical Yearbooks (yearbook) were used to extract the information. Data on incidence, mortality, disability-adjusted life year (DALY) and percentage distribution of sub-location of CRC were used to analyze the latest disease burden in China, and age-standardized rates by world standard population were mainly used. Joinpoint Trend Analysis Software 4.7.0.0 was applied for time trend analysis. Data related to the economic burden of CRC in China were gathered by literature review. Results: (1) Current status: according to the latest annual report, the incidence and mortality rates of CRC were 17.1 per 100 000 and 7.9 per 100 000, respectively among the covered registration sites in 2015. The incidence ratios of male to female and that of urban to rural were 1.5 and 1.4, with the mortality ratios were 1.6 and 1.4, respectively. Similar to data from the annual report, the mortality rate was reported as 6.9 per 100 000 in 2017 by the surveillance data sets. Data from the GBD project showed that, the DALYs caused by CRC in China in 2017 was 4.254 million person years (doubled compared with that of 1990), accounting for 22.4% of the global burden of CRC. (2) Time trends: according to the annual reports, from 2009 to 2015, the incidence rate and mortality rate of CRC in China decreased by 10.2% and 9.5%, respectively. The same trend was also observed in urban sites, but was opposite in rural areas (increased 20.0% in incidence and 15.2% in mortality). Results from the Joinpoint analysis showed that the averaged annual percentage change (AAPC) was estimated as -1.6% (P<0.05) in the national mortality rate. Similarly, in the incidence and mortality rates of urban sites appeared as AAPC=-1.5% and -1.4% (all P<0.05), but inversely in the incidence rate from the rural sites as AAPC=3.3% (P<0.05). The yearbook data showed a 9.8% increase in urban and 20.6% increase in rural on the mortality in 2017 when compared with 2004, but the Joinpoint analysis showed no statistical significance (P<0.05). (3) Distribution of sub-location of CRC: the annual report showed that among all the new CRC cases in China in 2015, colon, rectal and anal cancer accounted for 49.6%, 49.2% and 1.2%, respectively, while the proportions were 51.3%, 47.6% and 1.1%, respectively in 2009. The proportion of colon cancer was continuously higher in the urban (>52%) than that in the rural areas (<44%). The CI5 Ⅺ data showed that ascending and sigmoid colons were more commonly seen among all the colon cancers. (4) Economic burden: the average annual growth rate of the medical expenditure per CRC patient in China ranged from 6.9% to 9.2%, and the 1-year out-of-pocket expenditure of a newly diagnosed patient accounted for about 60% of their previous-year household income. Conclusions: In China, the overall disease burden of CRC might have been decreased slightly but generally remained stable in the last several years, however, the rising burden appeared in the rural areas should not be ignored. In consistent with findings from a previous review, men and people from the urban areas are considered the target populations for CRC. The finding of higher proportion of colon cancer in urban areas suggests the impact of development of socioeconomic and medical technologies on CRC development and detection. The economic burden of CRC continued to grow.

High-power diode-pumped Nd:GdVO4/KGW Raman laser at 578 nm.

A diode-pumped neodymium-doped gadolinium vanadate (Nd:GdVO4) laser is developed as a compact efficient yellow light at 578 nm by means of intracavity stimulated Raman scattering (SRS) in a potassium gadolinium tungstate (KGW) crystal and the second-harmonic generation in a lithium triborate crystal. The SRS process with a shift of 768cm-1 is achieved by setting the polarization of the fundamental wave along the Ng axis of the KGW crystal. The self-Raman effect arising from the Nd:GdVO4 crystal is systematically explored by employing two kinds of coating specification for the output coupler. With a specific coating on the output coupler to suppress the self-Raman effect, the maximum output power at 578 nm can reach 3.1 W at a pump power of 32 W. Moreover, two different lengths for the Nd:GdVO4 crystal are individually used to verify the influence of the self-Raman effect on the lasing efficiency.