Unraveling power-law scaling through exponential cell division dynamics.

A primary objective of biology is the development of universal laws that define how organic form develops and how it evolves as a function of size, both ontogenetically and across evolutionary time. Scaling theory has been essential in reaching this goal by giving a complete perspective point, particularly in illuminating the fundamental biological features produced within scaling exponents defining families of equations. Nonetheless, the theoretical basis of the allometric equation within scaling theory are inadequately explained, particularly when it comes to establishing links between micro-level processes at the cellular level and macro-level phenomena. We proposed an unlimited cell bipartition, resulting in an exponential growth in cell numbers during an individual's lifespan, to bridge this conceptual gap between cellular processes and allometric scaling. The power-law scaling between body mass and organ weight was produced by the synchronous exponential increments and the allometric exponent is rate of logarithmic cell proliferation rate. Substituting organ weight for erythrocyte weight aided in the development of a power-law scaling relationship between body mass and metabolic rate. Furthermore, it is critical to understand how cell size affects the exponent in power-law scaling. We find that a bigger exponent will result from an increase in the average weight of organ cells or a decrease in the average weight of all cells. Furthermore, cell proliferation dynamics showed a complex exponential scaling between body mass and longevity, defying the previously reported power-law scaling. We discovered a quadratic link between longevity and logarithmic body mass. Notably, all of the parameters included in these relationships are explained by indices linked to cell division and embryonic development. This research adds to our understanding of the complex interaction between cellular processes and overarching scaling phenomena in biology.

Effects of environmental feedback on species with finite population.

In an unchanging environment, natural selection always selects species with high fitness. In this study, we build a co-evolutionary system to study the interaction between stochasticity in finite populations and environmental feedback. Positive feedback between species and environment is detrimental to the invasion success, whereas negative feedback is beneficial to invasion since feedback makes population size important enough to revise natural selection's preference. In competition scenario, positive and negative feedback will benefit the initially inferior species. When selection intensity is high, negative feedback may even cause natural selection to favor the initially inferior species. All of these effects are caused by feedback that allows the initially inferior species to have greater fitness than the initially dominant species. Our results emphasize that the effects of stochasticity in evolutionary path can be reinforced by feedback with environment and then reverse the preference of natural selection.

Super-rational aspiration promotes cooperation in the asymmetric game with peer exit punishment and reward.

Super-rational aspiration induced strategy updating with exit rights has been considered in some previous studies, in which the players adjust strategies in line with their payoffs and aspirations, and they have access to exit the game. However, exit payoffs for exiting players are automatically allocated, which is clearly contrary to reality. In this study, evolutionary cooperation dynamics with super-rational aspiration and asymmetry in the Prisoner's Dilemma game is investigated, where exit payoffs are implemented by local peers. The results show that for different population structures, the asymmetry of the system is always contributive to the participation of the players. Furthermore, we show that under different exit payoffs, super-rationality and asymmetry are conductive to the evolution of cooperation.

Elusive workers are more likely to differentiate into replacement reproductives than aggressive workers in a lower termite.

One of the most intriguing questions in eusocial insects is to understand how the overt reproductive conflict in the colony appears limited when queens or kings are senescent or lost because the morphologically similar individuals in the colony are reproductively totipotent. Whether there are some individuals who preferentially differentiate into replacement reproductives or not has received little attention. The consistent individual behavioral differences (also termed "animal personality") of individuals from the colony can shape cunningly their task and consequently affect the colony fitness but have been rarely investigated in eusocial insects. Here, we used the termite Reticulitermes labralis to investigate if variations in individual personalities (elusiveness and aggressiveness) may predict which individuals will perform reproductive differentiation within colonies. We observed that when we separately reared elusive and aggressive workers, elusive workers differentiate into reproductives significantly earlier than aggressive workers. When we reared them together in the proportions 12:3, 10:5, and 8:7 (aggressive workers: elusive workers), the first reproductives mostly differentiated from the elusive workers, and the reproductives differentiated from the elusive workers significantly earlier than from aggressive workers. Furthermore, we found that the number of workers participating in reproductive differentiation was significantly lower in the groups of both types of workers than in groups containing only elusive workers. Our results demonstrate that the elusiveness trait was a strong predictor of workers' differentiation into replacement reproductives in R. labralis. Moreover, our results suggest that individual personalities within the insect society could play a key role in resolving the overt reproductive conflict.

Role of brown adipose tissue in phlegm-dampness metabolic syndrome based on infrared thermal imaging / 中国中药杂志

This study aimed to explore the infrared manifestation and role of brown adipose tissue(BAT) in phlegm-dampness me-tabolic syndrome(MS), and to provide objective basis for clinical diagnosis and treatment of phlegm-dampness MS. Subjects were selected from the department of endocrinology and ward in the South District of Guang'anmen Hospital, China Academy of Chinese Medical Sciences from August 2021 to April 2022, including 20 in healthy control group, 40 in non phlegm-dampness MS group and 40 in phlegm-dampness MS group. General information, height and weight of the subjects were collected and body mass index(BMI) was calculated. Waist circumference(WC), systolic blood pressure(SBP) and diastolic blood pressure(DBP) was measured. Triglyceride(TG), high density lipoprotein cholesterol(HDL-C), fasting blood glucose(FBG), fasting insulin(FINS), leptin(LP), adiponectin(ADP) and fibroblast growth factor-21(FGF-21) were detected. The infrared thermal image of the supraclavicular region(SCR) of the subjects before and after cold stimulation test was collected by infrared thermal imager and the changes of infrared thermal image in the three groups were observed. In addition, the differences in the average body surface temperature of SCR among the three groups were compared, and the changes of BAT in SCR were analyzed. The results showed compared with the conditions in healthy control group, the levels of WC, SBP, DBP, TG and FPG in MS groups were increased(P<0.01), and the HDL-C level was decreased(P<0.01). Compared with non phlegm-dampness MS group, phlegm-dampness MS group had higher conversion score of phlegm dampness physique(P<0.01). According to the infrared heat map, there was no difference in the average body surface temperature of SCR among the three groups before cold stimulation. while after cold stimulation, the average body surface temperature of SCR in MS groups was lower than that in healthy control group(P<0.05). After cold stimulation, the maximum temperature of SCR and its arrival time in the three groups were as follows: healthy control group(3 min)>non phlegm-dampness MS group(4 min)>phlegm-dampness MS group(5 min). The thermal deviation of SCR was increased and the average body surface temperature of left and right sides were higher(P<0.01) in healthy control group and non phlegm-dampness MS group, while the thermal deviation of SCR did not change significantly in the phlegm-dampness MS group. Compared with that in healthy control group, the elevated temperature between left and right sides was lower(P<0.01, P<0.05), and compared with that in non phlegm-dampness MS group, the elevated temperature of left side was lower(P<0.05). The changes of the average body surface temperature of SCR in the three groups were in the order of healthy control group>non phlegm-dampness MS group>phlegm-dampness MS group. Compared with the conditions in healthy control group and non phlegm-dampness MS group, FINS, BMI and FGF-21 levels were increased(P<0.01,P<0.05), while ADP level was decreased(P<0.01, P<0.05) in phlegm-dampness MS group. Moreover, the LP level in phlegm-dampness MS group was higher than that in non phlegm-dampness MS group(P<0.01). It was observed in clinical trials that after cold stimulation, the average body surface temperature of SCR in MS patients was lower than that of the healthy people; the thermal deviation of SCR did not change significantly in the phlegm-dampness MS patients, and the difference in their elevated temperature was lower than that in the other two groups. These characteristics provided objective basis for clinical diagnosis and treatment of phlegm-dampness MS. With abnormal BAT related indicators, it was inferred that the content or activity of BAT in SCR of phlegm-dampness MS patients were reduced. There was a high correlation between BAT and phlegm-dampness MS, and thus BAT might become an important potential target for the intervention in phlegm-dampness MS.

Hepatotoxicity and mechanism of Rhododendri Mollis Flos based on zebrafish model / 中国中药杂志

This study used the zebrafish model to explore the hepatotoxicity of Rhododendri Mollis Flos(RMF). The mortality was calculated according to the number of the survival of zebrafish larvae 4 days after fertilization under different concentration of RMF, and the dose-toxicity curve was fitted to preliminarily evaluate the toxicity of RMF. The liver phenotypes under the sublethal concentration of RMF in the treatment group and the blank control group were observed by hematoxylin-eosin(HE) staining and acridine orange(AO) staining. Meanwhile, the activities of alanine aminotransferase(ALT) and aspartate aminotransferase(AST) were determined to confirm the hepatotoxicity of RMF. Real-time quantitative polymerase chain reaction(real-time PCR) and Western blot were used to determine the expressions of genes and proteins in zebrafish larvae. Gas chromatography time-of-flight mass spectrometry(GC-TOF-MS) was used to conduct untargeted metabolomics testing to explore the mechanism. The results showed that the toxicity of RMF to zebrafish larvae was dose-dependent, with 1 100 μg·mL~(-1) of the absolute lethal concentration and 448 μg·mL~(-1) of sublethal concentration. The hepatocyte apoptosis and degeneration appeared in the zebrafish larvae under the sublethal concentration of RMF. The content of ALT and AST in zebrafish larvae at the end of the experiment was significantly increased in a dose-dependent manner. Under the sublethal concentration, the expressions of genes and proteins related to apoptosis in zebrafish larvae were significantly increased as compared with the blank control group. The results of untargeted metabolomics showed that the important metabolites related to the he-patotoxicity of RMF were mainly enriched in alanine, aspartic acid, glutamic acid, and other pathways. In conclusion, it is inferred that RMF has certain hepatotoxicity to zebrafish larvae, and its mechanism may be related to apoptosis.

Empirical analysis on lumbar disc herniation treated with "sinew-bone three needling technique" of Chinese medicine / 中国针灸

The paper presents professor WU Han-qing's experience in treatment of lumbar disc herniation (LDH) with "sinew-bone three needling technique" of Chinese medicine. Based on the theory of meridian sinew, the points are located by "three-pass method" in terms of the distribution of meridian sinew and syndrome/pattern differentiation. The cord-like muscles and adhesion are relieved by relaxing technique to work directly on the affected sites and alleviate the local compression to the nerve root. The needle technique is operated flexibly according to the affected regions involved, due to which, the needling sensation is increased while the safety ensured. As a result, the meridian qi is enhanced, the mind and qi circulation is regulated; and the clinical effect is improved.

Early prediction of severe COVID-19 in patients with Sjögren's syndrome / 北京大学学报(医学版)

OBJECTIVE@#To investigate the predictive value of blood cell ratios and inflammatory markers for adverse prognosis in patients with primary Sjögren's syndrome (PSS) combined with coronavirus disease 2019 (COVID-19).@*METHODS@#We retrospectively collected clinical data from 80 patients with PSS and COVID-19 who visited the Rheumatology and Immunology Department of the First Affiliated Hospital of Nanchang University from December 2022 to February 2023. Inclusion criteria were (1) meeting the American College of Rheumatology (ACR) classification criteria for Sjögren's syndrome; (2) confirmed diagnosis of COVID-19 by real-time reverse transcription polymerase chain reaction or antigen testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); (3) availability of necessary clinical data; (4) age > 18 years. According to the clinical classification criteria of the "Diagnosis and Treatment Protocol for Novel Coronavirus Pneumonia (trial the 10th Revised Edition)", the patients were divided into the mild and severe groups. Disease activity in primary Sjögren' s syndrome was assessed using the European League Against Rheumatism (EULAR) Sjögren' s syndrome disease activity index (ESSDAI). Platelet-lymphocyte ratio (PLR), C-reactive protein-lymphocyte ratio (CLR), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and other laboratory data were compared between the two groups within 24-72 hours post-infection.@*RESULTS@#The mild group consisted of 66 cases with an average age of (51. 52±13. 16) years, and the severe group consisted of 14 cases with an average age of (52.64±10.20) years. Disease activity, CRP, platelets, PLR, and CLR were significantly higher in the severe group compared with the mild group (P < 0.05). Univariate analysis using age, disease activity, CRP, platelets, PLR, and CLR as independent variables indicated that disease activity, CRP, PLR, and CLR were correlated with the severity of COVID-19 (P < 0.05). Multivariate logistic regression analysis further confirmed that PLR (OR=1.016, P < 0.05) and CLR (OR=1.504, P < 0.05) were independent risk factors for the severity of COVID-19 in the critically ill patients. Receiver operator characteristic (ROC) curve analysis showed that the area under the curve (AUC) for PLR and CLR was 0.708 (95%CI: 0.588-0.828) and 0.725 (95%CI: 0.578-0.871), respectively. The sensitivity for PLR and CLR was 0.429 and 0.803, respectively, while the highest specificity was 0.714 and 0.758, respectively. The optimal cutoff values for PLR and CLR were 166.214 and 0.870, respectively.@*CONCLUSION@#PLR and CLR, particularly the latter, may serve as simple and effective indicators for predicting the prognosis of patients with PSS and COVID-19.

Risk factors analysis and prediction model construction of submucosal deep infiltration of early colorectal tumor / 中华肿瘤杂志

Objective: To investigate the risk factors for the development of deep infiltration in early colorectal tumors (ECT) and to construct a prediction model to predict the development of deep infiltration in patients with ECT. Methods: The clinicopathological data of ECT patients who underwent endoscopic treatment or surgical treatment at the Cancer Hospital, Chinese Academy of Medical Sciences from August 2010 to December 2020 were retrospectively analyzed. The independent risk factors were analyzed by multifactorial regression analysis, and the prediction models were constructed and validated by nomogram. Results: Among the 717 ECT patients, 590 patients were divided in the within superficial infiltration 1 (SM1) group (infiltration depth within SM1) and 127 patients in the exceeding SM1 group (infiltration depth more than SM1). There were no statistically significant differences in gender, age, and lesion location between the two groups (P>0.05). The statistically significant differences were observed in tumor morphological staging, preoperative endoscopic assessment performance, vascular tumor emboli and nerve infiltration, and degree of tumor differentiation (P<0.05). Multivariate regression analysis showed that only erosion or rupture (OR=4.028, 95% CI: 1.468, 11.050, P=0.007), localized depression (OR=3.105, 95% CI: 1.584, 6.088, P=0.001), infiltrative JNET staging (OR=5.622, 95% CI: 3.029, 10.434, P<0.001), and infiltrative Pit pattern (OR=2.722, 95% CI: 1.347, 5.702, P=0.006) were independent risk factors for the development of deep submucosal infiltration in ECT. Nomogram was constructed with the included independent risk factors, and the nomogram was well distinguished and calibrated in predicting the occurrence of deep submucosal infiltration in ECT, with a C-index and area under the curve of 0.920 (95% CI: 0.811, 0.929). Conclusion: The nomogram prediction model constructed based on only erosion or rupture, local depression, infiltrative JNET typing, and infiltrative Pit pattern has a good predictive efficacy in the occurrence of deep submucosal infiltration in ECT.

Risk factors for residual cancer or lymph node metastasis after endoscopic noncurable resection of early colorectal cancer / 中华肿瘤杂志

Objective: Risk factors related to residual cancer or lymph node metastasis after endoscopic non-curative resection of early colorectal cancer were analyzed to predict the risk of residual cancer or lymph node metastasis, optimize the indications of radical surgical surgery, and avoid excessive additional surgical operations. Methods: Clinical data of 81 patients who received endoscopic treatment for early colorectal cancer in the Department of Endoscopy, Cancer Hospital, Chinese Academy of Medical Sciences from 2009 to 2019 and received additional radical surgical surgery after endoscopic resection with pathological indication of non-curative resection were collected to analyze the relationship between various factors and the risk of residual cancer or lymph node metastasis after endoscopic resection. Results: Of the 81 patients, 17 (21.0%) were positive for residual cancer or lymph node metastasis, while 64 (79.0%) were negative. Among 17 patients with residual cancer or positive lymph node metastasis, 3 patients had only residual cancer (2 patients with positive vertical cutting edge). 11 patients had only lymph node metastasis, and 3 patients had both residual cancer and lymph node metastasis. Lesion location, poorly differentiated cancer, depth of submucosal invasion ≥2 000 μm, venous invasion were associated with residual cancer or lymph node metastasis after endoscopic (P<0.05). Logistic multivariate regression analysis showed that poorly differentiated cancer (OR=5.513, 95% CI: 1.423, 21.352, P=0.013) was an independent risk factor for residual cancer or lymph node metastasis after endoscopic non-curative resection of early colorectal cancer. Conclusions: For early colorectal cancer after endoscopic non-curable resection, residual cancer or lymph node metastasis is associated with poorly differentiated cancer, depth of submucosal invasion ≥2 000 μm, venous invasion and the lesions are located in the descending colon, transverse colon, ascending colon and cecum with the postoperative mucosal pathology result. For early colorectal cancer, poorly differentiated cancer is an independent risk factor for residual cancer or lymph node metastasis after endoscopic non-curative resection, which is suggested that radical surgery should be added after endoscopic treatment.

Etiological characteristics of hand, foot and mouth disease in Xi′an from 2019 to 2021 / 中华微生物学和免疫学杂志

Objective:To analyze the etiological and epidemiological characteristics of hand, foot and mouth disease (HFMD) in Xi′an from 2019 to 2021, so as to provide evidence for the prevention and control of HFMD.Methods:Stool specimens and anal swabs were collected from patients with HFMD. Enteroviruses (EVs) including enterovirus 71 (EV71), coxsackievirus A16 (CVA16), CVA6 and CVA10 were detected by RT-PCR. Excel 2007 and SPSS18.0 software were used for data collection and statistical analysis, respectively. The epidemiological data of HFMD cases were analyzed by descriptive epidemiology method. The VP1 gene sequence of the representative strain of each CVA6 genotype was downloaded. Phylogenetic trees were constructed using MEGA X software and the genetic characteristics were analyzed.Results:A total of 1 531 HFMD cases were involved and 1 365 were positive for EVs with a positive rate of 89.16%. The detection rates of EV71, CVA16, CVA6, CVA10 and other EVs were 1.31% (20/1 531), 32.46% (497/1 531), 38.47% (589/1 531), 5.09% (78/1 531) and 11.23% (172/1 531), respectively. There were significant differences in the pathogen composition in HFMD cases of different clinical types (χ 2=46.14, P<0.01) and occupations (χ 2=34.65, P<0.01) as well as in different years (χ 2=462.86, P<0.01). The average age was greater in patients with CVA16 infection than in those with CVA6 or CVA10 infection ( F=6.00, P<0.01). In 2019, the HFMD cases were mainly caused by CVA16, while in 2020 and 2021, the main pathogen was CVA6. Enterovirus-positive cases showed a bimodal distribution with the main peak from May to July and the secondary peak from September to November. CVA16 was the predominant pathogen in spring and summer, and CVA6 was the predominant pathogen in autumn. CVA6 was the dominant pathogen in eight districts and counties of Xi′an; CVA16 was the dominant pathogen in six districts and counties; CVA6 and CVA16 co-circulated in one district. The CVA6 isolates belonged to two evolutionary branches of D3a subtype. Conclusions:CVA6 and CVA16 were the prevalent pathogens of HFMD and CVA6 subtype D3a circulated in Xi′an from 2019 to 2021. The pathogen composition of HFMD cases showed obvious differences in population, time and regional distribution.

Evaluation of neutrophil/lymphocyte ratio and the end-stage liver disease-sodium model in predicting short-term prognosis of patients with HBV-related acute-on-chronic liver failure / 中华全科医师杂志

Objective:To evaluate neutrophil/lymphocyte ratio(NLR) and the model for end-stage liver disease-sodium(MELD-Na)score in predicting short-term prognosis of patients with HBV-related acute-on-chronic liver failure(HBV-ACLF).Methods:A total of 234 consecutive HBV-ACLF patients(194 males and 40 females, aged 23-85 years)admitted to Hangzhou Xixi Hospital from January 2019 to December 2021 were enrolled. According to the 12-week clinical outcomes, patients were divided into good prognosis group( n=141)and poor prognosis group( n=93). Univariate and multivariate Logistic regression were performed to identify independent risk factors for poor prognosis of HBV-ACLF patients. Receiver operating characteristics(ROC)curve was applied to evaluate the accuracy of risk factors in predicting short-term prognosis of HBV-ACLF patients. Results:The age [(48.7±11.9) vs. (52.5±9.9) years old, t=-2.59, P=0.011], proportion of males [78.0%(110/141) vs. 90.3%(84/93), χ2=5.99, P=0.014], total bilirubin[202.9(141.2, 287.6) vs. 320.0(224.4, 400.0) μmol/L, Z=-5.14, P<0.001], creatinine [71.0(59.0, 78.0) vs. 81.0(64.0, 111.0)μmol/L, Z=-3.98, P<0.001], international normalized ratio[1.66(1.52, 1.86) vs. 1.91(1.66, 2.27), Z=-5.46, P<0.001], leukocyte count[5.16(3.99, 6.95)×10 9/L vs. 6.57(4.83, 8.30)×10 9/L, Z=-4.14, P=0.001], NLR[2.77(2.02, 3.55) vs. 5.48(3.44, 8.53), Z=-8.48, P<0.001], MELD score[22.0(20.0, 24.0) vs. 26.0(24.0, 29.0), Z=-9.22, P<0.001], MELD-Na score[22.8(20.0, 25.6) vs. 29.0(25.0, 36.0), Z=-9.16, P<0.001], liver cirrhosis[77.3%(109/141) vs. 88.2%(82/93), χ2=4.41, P=0.036], hepatorenal syndrome[4/141(2.8%) vs. 12/93(12.9%), χ2=8.91, P=0.003] and the proportion of artificial liver treatment[21/141(14.9%) vs. 24/93(25.8%), χ2=4.30, P=0.038] were significantly elevated in poor prognosis group compared with survival group. Logistic regression analysis showed that NLR( OR=3.76, 95 %CI: 2.10-6.74, P<0.001)and MELD-Na score( OR=2.24, 95 %CI: 1.17-4.29, P=0.015) were independent risk factors for poor short-term prognosis of HBV-ACLF patients. The area under the ROC curve(AUC)of NLR, and MELD-Na for the short-term prognosis of HBV-ACLF patients was 0.792 and 0.822, respectively. The AUC of the combination of NLR with MELD-Na was 0.858, which was significantly higher than that of NLR( Z=-3.04, P=0.001) or MELD-Na score( Z=-2.16, P=0.031)alone. Based on the cut-off value of the combined model, patients were classified into high combined model score (≥0.04) group and low combined model score (<0.04) group, the survival rate of the high group was significantly higher than that of the low group( χ2=67.47, P<0.001). Conclusions:NLR and MELD-Na score are independent risk factors of the short-term prognosis of HBV-ACLF patients. The combination of NLR and MELD-Na score will be beneficial to predict the short-term prognosis of HBV-ACLF patients.

Research status of artificial intelligence and bone age assessment based on deep learning / 中华实用儿科临床杂志

Bone age can objectively reflect the human body growth and accurately assess the physical development level.Bone age assessment plays an important role in the growth and development, disease diagnosis and the monitoring of therapeutic efficacy in children and adolescents.In recent years, the artificial intelligence technology has been developed continuously.Applying artificial intelligence technology is expected to realize the automatic assessment of bone age.At present, the artificial intelligence technology of bone age assessment is mainly based on the deep learning (DL) algorithm.Although there have been many research on DL and bone age assessment, most are still in the experimental stage.This study reviews the research and progress of artificial intelligence technology based on DL applied to bone age assessment, aiming to provide reference and research ideas for relevant staff.

Secondary metabolites of endophytic fungus Aspergillus sp. J218 from Anectochilus roxburhii / 药学实践杂志

Objective To isolate the secondary metabolites of endophytic fungus Aspergillus sp. J218 from Anectochilus roxburhii. Methods Different chromatographic methods, including Sephadex LH-20 and silica gel chromatography as well as HPLC, were used to isolate compounds from the EtOAc fraction of the solid fermentation of J218, and their structures were identified by spectral methods. Results Ten compounds were isolated from the fermentation of J218 and their structures were individually identified as kotanin（1）, flavasperone（2）, aurasperone B（3）, fonsecinone B（4）, fonsecinone D（5）, ensidol A（6）, fonsecinone A（7）, fonsecinone C（8）, aurasperone A（9）, and fonsecinone F（10）. Conclusion Most compounds isolated from endophytic fungus Aspergillus sp. J218 in Anectochilus roxburhii were identified as dimeric naphthopyrones. These results suggest that this strain contains rich dimerization synthase, which could provide clues for the further exploration of the rational biosynthesis pathway of dimeric naphthopyrones in this strain.

Comprehensive assessment of mismatch repair and microsatellite instability status in molecular classification of endometrial carcinoma / 中华妇产科杂志

Objective: To explore the concordance and causes of different mismatch repair (MMR) and microsatellite instability (MSI) detection results in endometrial carcinoma (EC) molecular typing. Methods: A total of 214 EC patients diagnosed from January 2021 to April 2023 were selected at the Department of Pathology, Peking University Third Hospital. The immunohistochemistry (IHC) results of MMR protein were reviewed. Tumor specific somatic mutations, MMR germline mutations, microsatellite scores and tumor mutation burden (TMB) were detected by next-generation sequencing (NGS) with multi-gene panel. Methylation-specific PCR was used to detect the methylation status of MLH1 gene promoter in cases with deficient MLH1 protein expression. In cases with discrepant results between MMR-IHC and MSI-NGS, the MSI status was detected again by PCR (MSI-PCR), and the molecular typing was determined by combining the results of TMB and MLH1 gene promoter methylation. Results: (1) In this study, there were 22 cases of POLE gene mutation subtype, 55 cases of mismatch repair deficient (MMR-d) subtype, 29 cases of p53 abnormal subtype, and 108 cases of no specific molecular profile (NSMP). The median age at diagnosis of MMR-d subtype (54 years old) and the proportion of aggressive histological types (40.0%, 22/55) were higher than those of NSMP subtype [50 years old and 12.0% (13/108) respectively; all P<0.05]. (2) Among 214 patients, MMR-IHC test showed that 153 patients were mismatch repair proficient (MMR-p), 49 patients were MMR-d, and 12 patients were difficult to evaluate directly. MSI-NGS showed that 164 patients were microsatellite stable (MSS; equal to MMR-p), 48 patients were high microsatellite instability (MSI-H; equal to MMR-d), and 2 patients had no MSI-NGS results because the effective sequencing depth did not meet the quality control. The overall concordance between MMR-IHC and MSI-NGS was 94.3% (200/212). All the 12 discrepant cases were MMR-d or subclonal loss of MMR protein by IHC, but MSS by NGS. Among them, 10 cases were loss or subclonal loss of MLH1 and (or) PMS2 protein. Three discrepant cases were classified as POLE gene mutation subtype. In the remaining 9 cases, 5 cases and 3 cases were confirmed as MSI-H and low microsatellite instability (MSI-L) respectively by MSI-PCR, 6 cases were detected as MLH1 gene promoter methylation and 7 cases demonstrated high TMB (>10 mutations/Mb). These 9 cases were classified as MMR-d EC. (3) Lynch syndrome was diagnosed in 27.3% (15/55) of all 55 MMR-d EC cases, and the TMB of EC with MSH2 and (or) MSH6 protein loss or associated with Lynch syndrome [(71.0±26.2) and (71.5±20.1) mutations/Mb respectively] were significantly higher than those of EC with MLH1 and (or) PMS2 loss or sporadic MMR-d EC [(38.2±19.1) and (41.9±24.3) mutations/Mb respectively, all P<0.01]. The top 10 most frequently mutated genes in MMR-d EC were PTEN (85.5%, 47/55), ARID1A (80.0%, 44/55), PIK3CA (69.1%, 38/55), KMT2B (60.0%, 33/55), CTCF (45.5%, 25/55), RNF43 (40.0%, 22/55), KRAS (36.4%, 20/55), CREBBP (34.5%, 19/55), LRP1B (32.7%, 18/55) and BRCA2 (32.7%, 18/55). Concurrent PTEN, ARID1A and PIK3CA gene mutations were found in 50.9% (28/55) of MMR-d EC patients. Conclusions: The concordance of MMR-IHC and MSI-NGS in EC is relatively high.The discordance in a few MMR-d EC are mostly found in cases with MLH1 and (or) PMS2 protein loss or MMR protein subclonal staining caused by MLH1 gene promoter hypermethylation. In order to provide accurate molecular typing for EC patients, MLH1 gene methylation, MSI-PCR, MMR gene germline mutation and TMB should be combined to comprehensively evaluate MMR and MSI status.

Path probability selection in nature and path integral.

Understanding of any biological evolutions, such as speciation, adaptation behavior and biodiversity pattern, is based on a fundamental concept of fitness, in which natural selection implies the improvement and progress of fitness in either direct/indirect benefit or genetic transmission to the next generation. However, this basic idea of biological evolution, which is mathematically described by Price equation or its relations, has not fully considered feedback effects from the environment or other generations. They lost the global dynamics of the evolutions consequently. Drawing on the idea of modern physics, we introduce the path integral by iterating the Price equation step by step to characterize the evolutionary path in which the stationary fitness is replaced by the path probability. The evolutionary selection therefore will depend on path probability instead of fitness advantage. In such a framework of the evolutionary path, the intermediate process of evolution is not always pointing to the fitness-maximizing equilibrium and multiple evolutionary paths could thus coexist without fitness advantage discrimination. This mechanism could potentially explain fitness evolutionary strategies with the diversified fitness (e.g., coexistence of altruism and selfishness) and thus species diversity.

Development of a highly efficient virus-free regeneration system of Salvia miltiorrhiza from Sichuan using apical meristem as explants.

BCAKGROUND: The dry root and rhizome of Salvia miltiorrhiza are used to treat cardiovascular diseases, chronic pain, and thoracic obstruction over 2000 years in Asian countries. For high quality, Sichuan Zhongjiang is regarded as the genuine producing area of S. miltiorrhiza. Given its abnormal pollen development, S. miltiorrhiza from Sichuan (S.m.-SC) relies on root reproduction and zymad accumulation; part of diseased plants present typical viral disease symptoms and seed quality degeneration. This study aim to detected unknown viruses from mosaic-diseased plants and establish a highly efficient virus-free regeneration system to recover germplasm properties. RESULTS: Tobacco mosaic virus (TMV) and cucumber mosaic virus (CMV) were detected from mosaic-diseased plants. Primary apical meristem with two phyllo podium in 0.15-0.5 mm peeled from diseased plants were achieved 73.33% virus-free rate. The results showed that the medium containing MS, 0.5 mg/L 6-BA, 0.1 mg/L NAA, 0.1 mg/L GA3, 30 g/L sucrose and 7.5 g/L agar can achieve embryonic-tissue (apical meristem, petiole and leaf callus) high efficient organogenesis. For callus induction, the optimal condition was detected on the medium containing MS, 2 mg/L TDZ, 0.1 mg/L NAA by using secondary petiole of virus-free plants under 24 h dark/d condition for 21 d. The optimal system for root induction was the nutrient solution with 1/2 MS supplemented with 1 mg/L NAA. After transplant, the detection of agronomic metric and salvianolic acid B content confirmed the great germplasm properties of S.m.-SC virus-free plants. CONCLUSIONS: A highly efficient virus-free regeneration system of S.m.-SC was established based on the detected viruses to recover superior seed quality. The proposed system laid support to control disease spread, recover good germplasm properties in S.m.-SC.

Research progress in prediction of pump thrombosis after ventricular assist device implantation / 中华胸心血管外科杂志

Pump thrombosis after ventricular assist device implantation is a major limiting factor in its long-term clinical application. Early identification and timely intervention for pump thrombosis complications are great important for the curative effect after ventricular assist device implantation. This paper summarizes the predictive factors and risk factors of pump thrombosis after ventricular assist device implantation, and discusses the monitoring of pump thrombosis.

Targeting macrophagic SHP2 for ameliorating osteoarthritis via TLR signaling

Osteoarthritis (OA), in which M1 macrophage polarization in the synovium exacerbates disease progression, is a major cause of cartilage degeneration and functional disabilities. Therapeutic strategies of OA designed to interfere with the polarization of macrophages have rarely been reported. Here, we report that SHP099, as an allosteric inhibitor of src-homology 2-containing protein tyrosine phosphatase 2 (SHP2), attenuated osteoarthritis progression by inhibiting M1 macrophage polarization. We demonstrated that M1 macrophage polarization was accompanied by the overexpression of SHP2 in the synovial tissues of OA patients and OA model mice. Compared to wild-type (WT) mice, myeloid lineage conditional Shp2 knockout (cKO) mice showed decreased M1 macrophage polarization and attenuated severity of synovitis, an elevated expression of cartilage phenotype protein collagen II (COL2), and a decreased expression of cartilage degradation markers collagen X (COL10) and matrix metalloproteinase 3 (MMP3) in OA cartilage. Further mechanistic analysis showed thatSHP099 inhibited lipopolysaccharide (LPS)-induced Toll-like receptor (TLR) signaling mediated by nuclear factor kappa B (NF-κB) and PI3K-AKT signaling. Moreover, intra-articular injection of SHP099 also significantly attenuated OA progression, including joint synovitis and cartilage damage. These results indicated that allosteric inhibition of SHP2 might be a promising therapeutic strategy for the treatment of OA.