Objective:To conduct a comparative analysis of the oxygen depletion and oxygen effect of FLASH irradiation and conventional irradiation by direct measurement of oxygen content.Methods:The oxygen content in different tissues and organs of mice was measured using a phosphorescent probe. A subcutaneous xenograft tumor model in mice was established, to receive electron-beam irradiation at different doses and dose rates. The oxygen depletion of tumor and normal tissue was analyzed, and tumor control was evaluated. The oxygen depletion of conventional irradiation and FLASH irradiation was further analyzed using an in vitro model. The survival fraction (SF) of normal cells after conventional irradiation and FLASH irradiation was calculated using colony formation assay under different partial pressures of oxygen, and the data were fitted to the oxygen enhancement ratio (OER) curve. Results:The mean oxygen content of subcutaneous xenograft tumor in mice was 1.28%, suggesting hypoxia. The mean oxygen content of normal tissue ranged from 3.51% to 6.53%, suggesting physioxia. In animal experiments, oxygen depletion was not observed during conventional irradiation. High-dose-rate (20 Gy/s) and ultra-high-dose-rate (FLASH, 40 Gy/s) irradiation produced oxygen depletion. During FLASH irradiation, with the increase of oxygen content, the oxygen depletion was 0.1-0.2 mm Hg/Gy for tumor tissue and 0.19-0.21 mm Hg/Gy for skin tissue, which tended to stabilize. FLASH irradiation maintained equivalent tumor control compared to conventional irradiation. The tumoricidal effect was significantly enhanced with the increase of oxygen content in the tissue ( t=3.46, P<0.01). In in vitro experiments, the mean oxygen depletion rate was about 0.16 mm Hg/Gy for conventional irradiation and 0.16-0.18 mm Hg/Gy for FLASH irradiation, which did not change significantly with the increase of oxygen content. FLASH irradiation was associated with an oxygen effect. When the partial pressure of oxygen decreased from physioxia to hypoxia, the OER value significantly reduced. Conclusions:Normal tissues and organs are in physioxia, which exhibits a lower oxygen content than that in the air. FLASH irradiation can consume a proportion of oxygen, producing an oxygen effect. When oxygen content decreases, the oxygen depletion rate slows down after FLASH irradiation.

Objective:To conduct a comparative analysis of the oxygen depletion and oxygen effect of FLASH irradiation and conventional irradiation by direct measurement of oxygen content.Methods:The oxygen content in different tissues and organs of mice was measured using a phosphorescent probe. A subcutaneous xenograft tumor model in mice was established, to receive electron-beam irradiation at different doses and dose rates. The oxygen depletion of tumor and normal tissue was analyzed, and tumor control was evaluated. The oxygen depletion of conventional irradiation and FLASH irradiation was further analyzed using an in vitro model. The survival fraction (SF) of normal cells after conventional irradiation and FLASH irradiation was calculated using colony formation assay under different partial pressures of oxygen, and the data were fitted to the oxygen enhancement ratio (OER) curve. Results:The mean oxygen content of subcutaneous xenograft tumor in mice was 1.28%, suggesting hypoxia. The mean oxygen content of normal tissue ranged from 3.51% to 6.53%, suggesting physioxia. In animal experiments, oxygen depletion was not observed during conventional irradiation. High-dose-rate (20 Gy/s) and ultra-high-dose-rate (FLASH, 40 Gy/s) irradiation produced oxygen depletion. During FLASH irradiation, with the increase of oxygen content, the oxygen depletion was 0.1-0.2 mm Hg/Gy for tumor tissue and 0.19-0.21 mm Hg/Gy for skin tissue, which tended to stabilize. FLASH irradiation maintained equivalent tumor control compared to conventional irradiation. The tumoricidal effect was significantly enhanced with the increase of oxygen content in the tissue ( t=3.46, P<0.01). In in vitro experiments, the mean oxygen depletion rate was about 0.16 mm Hg/Gy for conventional irradiation and 0.16-0.18 mm Hg/Gy for FLASH irradiation, which did not change significantly with the increase of oxygen content. FLASH irradiation was associated with an oxygen effect. When the partial pressure of oxygen decreased from physioxia to hypoxia, the OER value significantly reduced. Conclusions:Normal tissues and organs are in physioxia, which exhibits a lower oxygen content than that in the air. FLASH irradiation can consume a proportion of oxygen, producing an oxygen effect. When oxygen content decreases, the oxygen depletion rate slows down after FLASH irradiation.

ObjectiveThis study aimed to evaluate the clinical efficacy of Ruyi Zhenbaowan（RYZBW）in the treatment of initial and early knee osteoarthritis （KOA） through a prospective multicenter，randomized，double-blind，and placebo-parallel controlled trial. MethodFrom October 13^th， 2021 to December 25^th， 2021， 240 KOA subjects meeting the acceptance criteria were enrolled in 15 sub-centers including Wangjing Hospital， Chinese Academy of Chinese Medical Sciences， and they were randomly divided into observation group and control group， with 120 cases in each group. The intervention measures for the observation group were RYZBW + health education， and the intervention measures for the control group were RYZBW placebo + health education. The intervention period in both groups was four weeks， and they were followed up for four weeks after the intervention. The primary outcome measure was the total score of Western Ontario and McMaster University Osteoarthritis Index score （WOMAC score）， and the secondary outcome measures were the response rate of visual scale （VAS） pain score， WOMAC sub item scores （joint pain， joint stiffness， and joint function）， quality of life （SF-12） score， and traditional Chinese medicine （TCM） syndrome score. Result（1） Efficacy evaluation. The marginal model results showed that the observation group was better than the control group in improving the WOMAC total score and WOMAC pain score in the treatment of KOA with RYZBW， and the difference was statistically significant （P<0.05）. There was no significant difference between the two groups in improving VAS score response rate， WOMAC function score， WOMAC stiffness score， SF12-PCS （quality of life-physical health） score， SF12-MCS （quality of life-mental health） score， and TCM syndrome score. （2） Subgroup analysis. ① In terms of VAS score response rate， the response rate of the observation group was higher than that of the control group for subjects with baseline VAS score of （4， 5］， and the difference was statistically significant （P<0.05）. ② In terms of TCM syndrome score， for subjects aged ［56， 60］ and ［61， 65］， the decrease in total TCM syndrome score in the observation group was better than that in the control group， and the difference was statistically significant （P<0.05）. ConclusionTibetan medicine RYZBW has good clinical efficacy in improving WOMAC total score， VAS score response rate， WOMAC pain score， WOMAC function score， and TCM syndrome score for patients with initial and early KOA， which can fill the lack of Tibetan medicine RYZBW in the treatment of KOA and make a demonstration study for the inheritance and development of ethnic medicine.

Objective:To compare the effects on DNA strand break induced by ultra-high dose rate (FLASH) electron beam and conventional irradiation, and investigate whether FLASH effect was correlated with a reduction of radiation response.Methods:Aqueous pBR322 plasmid was treated with FLASH (125 Gy/s) and conventional irradiation (0.05 Gy/s) under physioxia (4% O 2) and normoxia (21% O 2). Open circle DNA and linear DNA were detected by agarose gel electrophoresis, and the plasmid DNA damage was quantified with an established mathematical model to calculate the relative biological effect (RBE) of DNA damage. In some experiments, Samwirin A (SW) was applied to scavenge free radicals generated by ionizing radiation. Results:Under physioxia, the yields of DNA strand breakage induced by both FLASH and conventional irradiation had a dose-dependent manner. FLASH irradiation could significantly decrease radiation-induced linear DNA compared with conventional irradiation ( t=5.28, 5.79, 7.01, 7.66, P<0.05). However, when the aqueous plasmid was pretreated with SW, there was no difference of DNA strand breakage between FLASH and conventional irradiation ( P>0.05). Both of the yields of open circle DNA and linear DNA had no difference caused by FLASH and conventional radiotherapy at normoxia, but were significantly higher than those under physioxia. In addition, the yields of linear DNA and open circle DNA induced by FLASH irradiation per Gy were (2.78±0.03) and (1.85±0.17) times higher than those of conventional irradiation, respectively. Conclusions:FLASH irradiation attenuated radiation-induced DNA damage since a low production yield of free radical in comparison with conventional irradiation, and hence the FLASH effect was correlated with oxygen content.

By analyzing the epidemic characteristics of influenza during the COVID-19 epidemic in Jiangsu Province from 2020 to 2022, it found that 90 721 influenza-like case samples were collected in Jiangsu Province from 2020 to 2022, of which 6 732 were nucleic acid-positive samples, with an average positive detection rate of 7.4% in three years. The annual positive detection rate presented a U-shaped distribution, with positive detection rates of 4.4%, 3.2% and 14.7%, respectively, with statistically significant differences ( χ2=12 126.00, P<0.001). During the seasonal peak period of influenza from 2020 to 2022, there was a significant decrease in the intensity of the two influenza activity peaks that occurred before the virus became fully prevalent in the population. The first peak occurred from January to February 2020, and the positive detection rate of influenza nucleic acid decreased from 54.4% (317/583) in the third week to 2.1% (12/584) in the eighth week, with a statistically significant difference ( χ2=394.49 , P<0.001) . The second occurred in December 2022, and the positive detection rate of influenza nucleic acid decreased from 14.9% (90/605) at the 49th week to 1.9% (11/572) at the 52nd week, with a statistically significant difference ( χ2=62.88, P<0.001). The influenza epidemic in Jiangsu Province from 2020 to 2022 had obvious seasonal characteristics, and the distribution differences of influenza virus-positive cases in each month were statistically significant ( χ2=858.00, P<0.001), with two epidemic peaks each year: winter, spring (December to March of the following year), and summer, and autumn (July to November). The epidemic strains were the B-V strain and seasonal H3 strain, respectively. There was a statistically significant difference in the positive detection rate of influenza cases detected in different age groups ( χ2=60.00, P<0.001). The age group between 5 and 14 years old had the highest influenza-positive detection rate (10.4%), while the age group≥60 years old had a relatively low influenza-positive detection rate (5.1%). The positive detection rate decreased with the increase in the age group ( Z trend=12.82, P<0.001).

By analyzing the epidemic characteristics of influenza during the COVID-19 epidemic in Jiangsu Province from 2020 to 2022, it found that 90 721 influenza-like case samples were collected in Jiangsu Province from 2020 to 2022, of which 6 732 were nucleic acid-positive samples, with an average positive detection rate of 7.4% in three years. The annual positive detection rate presented a U-shaped distribution, with positive detection rates of 4.4%, 3.2% and 14.7%, respectively, with statistically significant differences ( χ2=12 126.00, P<0.001). During the seasonal peak period of influenza from 2020 to 2022, there was a significant decrease in the intensity of the two influenza activity peaks that occurred before the virus became fully prevalent in the population. The first peak occurred from January to February 2020, and the positive detection rate of influenza nucleic acid decreased from 54.4% (317/583) in the third week to 2.1% (12/584) in the eighth week, with a statistically significant difference ( χ2=394.49 , P<0.001) . The second occurred in December 2022, and the positive detection rate of influenza nucleic acid decreased from 14.9% (90/605) at the 49th week to 1.9% (11/572) at the 52nd week, with a statistically significant difference ( χ2=62.88, P<0.001). The influenza epidemic in Jiangsu Province from 2020 to 2022 had obvious seasonal characteristics, and the distribution differences of influenza virus-positive cases in each month were statistically significant ( χ2=858.00, P<0.001), with two epidemic peaks each year: winter, spring (December to March of the following year), and summer, and autumn (July to November). The epidemic strains were the B-V strain and seasonal H3 strain, respectively. There was a statistically significant difference in the positive detection rate of influenza cases detected in different age groups ( χ2=60.00, P<0.001). The age group between 5 and 14 years old had the highest influenza-positive detection rate (10.4%), while the age group≥60 years old had a relatively low influenza-positive detection rate (5.1%). The positive detection rate decreased with the increase in the age group ( Z trend=12.82, P<0.001).

OBJECTIVE: To explore the genetic etiology of a child suspected for β-ketothiolase deficiency by neonatal screening. METHODS: All coding exons and flanking sequences of the ACAT1 gene were subjected to targeted capture and high-throughput sequencing. Suspected variants were verified by Sanger sequencing and bioinformatic analysis. RESULTS: The child was found to harbor compound heterozygous variants of the ACAT1 gene, namely c.121-3C>G and c.275G>A (p. Gly92Asp). The c.121-3C>G variant was also detected in his father and two sisters, while the c.275G>A (p. Gly92Asp) was a de novo variant. A c.334+ 172C>G (rs12226047) polymorphism was also detected in his mother and two sisters. Sanger sequencing has verified that the c.275G>A (p. Gly92Asp) and c.334+172C>G (rs12226047) variants are located on the same chromosome. Bioinformatics analysis suggested both c.121-3C>G and c.275G>A (p.G92D) variants to be damaging. Based on the American College of Medical Genetics and Genomics standards and guidelines, the c.275G>A variant of the ACAT1 gene was predicted to be pathogenic (PS2+ PM2+ PM3+ PP3+PP4), the c.121-3C>G variant to be likely pathogenic (PM2+ PM3+ PP3+PP4). CONCLUSION The c.121-3C>G and c.275G>A variants of the ACAT1 gene probably underlay the pathogenesis of the child. Above finding has enriched the variant spectrum of the ACAT1 gene.
Acetyl-CoA C-Acetyltransferase/genetics* ; Acetyl-CoA C-Acyltransferase/genetics* ; Amino Acid Metabolism, Inborn Errors/genetics* ; Female ; High-Throughput Nucleotide Sequencing ; Humans ; Infant, Newborn ; Male ; Mutation

Objective To investigate the portal vein embolization (PVE) and portal vein ligation (PVL) in liver regeneration of rats with hepatic fibrosis.Methods Fifty rats with liver fibrosis were prepared,including 10 rats were randomly chosen as pre-operative control group.The other 40 rats were divided into two groups:PVE group (A1,n =20) and PVL group (A2,n =20).We chose to embolize and ligate the right portal vein,respectively.The blood samples were obtained at different end points for measuring ALT and AST levels.Each liver lobes and whole liver were weighed,and non-embolized liver lobe/whole liver weight ratio,non-ligated liver lobe/whole liver weight were caculated at different end points.The samples from liver with/without embolization or ligation were were stained with hematoxylin-eosin,and the changes of microstructure of liver were observed.Immunostained for PCNA and Ki-67 were performed.Results Transient elevation of postoperative ALT and AST levels were noted in each group.Serum ALT and AST reached the peak on the first day in both of PVE and PVL groups [ALT,A1 (66.5 ±6.3) U/L vs(491.5 ± 48.0) U/L,A2 group(62.8 ±5.7) U/L vs(433.7 ±41.0) U/L;AST,A1group (113.4 ± 12.5) U/L vs (685.2 ±65.7) U/L,A2 group (110.4 ± 11.1) U/L vs(623.9 ±75.2) U/L,P＜0.05),and started to decrease on the third day,recovered to the pre-operative level on the fourteenth day (P ＞ 0.05).The weight percentage of non-embolized and non-ligated liver lobes/whole liver after PVE and PVL increased.There was no significant difference between the first day and pre-operative levels (P ＞ 0.05).Nevertheless,there were significant differences observed from the third,seventh,fourteenth days (A1 group,50.2 ± 5.0,57.7 ±5.7,61.8 ±6.6;A2group,49.6 ±3.5,55.7 ±6.9,63.0±5.1,respectively)compared with preoperative groups (A1 group,34.4 ± 4.0;A2 group,34.4 ± 4.0) (P ＜ 0.05).There was no significant difference between group A1 and A2 in each time point (P ＞0.05).The PCNA and Ki-67 were positive in hepatocytes and increased after operation,reached the peak in the third day (P ＜ 0.05),decreased slowly and restored to the normal level in the fourteenth day after operation,meanwhile,there was no significant difference between group A1 and A2 (P ＞ 0.05).Conclusions Fibrosis rats had the ability of regeneration in the contralateral part of the liver after selective PVE and PVL and there was no significant difference on the proliferative degree.Therefore,the safety and reliability of PVE and PVL in inducing liver regeneration in rats with liver fibrosis were confirmed.

Objective To evaluate the postoperative effects of mixed baggy eyelid plasty with a new myocutaneous flap method combined with middle face lifting.Methods It was a retrospective study of old patients with skin and/or orbicular muscle relaxation eyelid bulging.28 patients were the control group with mixed baggy eyelid plasty with a new myocutaneous flap method only,and 32 cases were the observation group with combined middle face lift method.After six months,the condition of postoperative recovery,degree of satisfaction and complications were compared between two groups with a detailed statistical analysis.Results After six months,the total effective rate of the observation group was 96.88％,higher than the control group (92.85％).The total incidence of complications of the observation group was 3.13％,lower than the other group (7.14％).The total satisfactory rate of the observation group was 93.75％,higher than the control group (89.29％).The differences of two groups were all statistically significant (P＜0.05).Conclusions The advantages of mixed baggy eyelid plasty with a new myocutaneous flap combined middle face lifting method are more effectively facial aging improved and higher satisfaction than others.

OBJECTIVE:To observe the clinical efficacy and sequela of Salvia miltiorrhiza treatment for severe craniocere-bral injury patients after operation. METHODS:60 severe craniocerebral injury patients were randomly divided into control group and treatment group with 30 cases in each group. Control group was given routine and symptomatic treatment after clearance of hematoma by craniotomy or decompressive craniectomy according to the patient’s condition;treatment group was additionally giv-en intravenous injection of Danshen injection 20 ml/d for 7-10 days 3-5 days after operation without hemorrhagic tendency,on the basis of control group,and then given Compound danshen dropping pills instead (10 pills/time,3 times/d) for one month. GCS score,GOS score,intracranial pressure and brain CT,the levels of ET and CRP were compared between 2 groups after op-eration. The occurrence of sequelae were evaluated 3 months after operation. RESULTS:After the operation,S. miltiorrhiza treat-ment could increase GCS score and GOS score,reduced intracranial pressure and brain edema of craniocerebral injury patients, and the improvement of clinical symptoms in treatment group was significantly faster than in control group,with statistical signifi-cance(P<0.05 or P<0.01). The postoperative S. miltiorrhiza treatment could decrease the levels of ET and CRP in patients with craniocerebral injury in the time-dependent manner,the decreased of treatment group was significantly faster than that of control group,with statistical significance (P<0.05 or P<0.01). The effective of postoperative sequelae improvement was 93.3% in treatment group,which was significantly higher than that of control group(76.7%),with statistical significance(P<0.05). CON-CLUSIONS:Postoperative S. miltiorrhiza treatment can improve the clinical symptoms of severe craniocerebral injury patients,re-duce the incidence of complication and improve the prognosis. The effect may be related to the decrease of plasma ET and CRP levels.