ObjectiveThis study aims to explore the mechanism of action of Huangqi Guizhi Wuwutang in treating rheumatoid arthritis （RA）-associated sarcopenia by regulating autophagy and improving skeletal muscle homeostasis based on network pharmacology，bioinformatics，machine learning，and animal experiments. MethodsActive ingredients and targets of Huangqi Guizhi Wuwutang were screened using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP），PubChem，and SwissTargetPrediction databases. RA-related datasets were retrieved from the GEO database，and differential genes were screened. Sarcopenia-related targets were searched through GeneCards and the Comparative Toxicology Database （CTD），and autophagy-related gene sets were downloaded from the Human Autophagy Database （HADb）. Their intersection was analyzed to identify autophagy-related therapeutic targets，followed by enrichment analysis. A protein-protein interaction （PPI） network was constructed using the STRING database，and key targets were selected using multiple methods. Machine learning was applied to predict models based on the expression profiles of intersecting targets，and nomogram models were constructed based on key targets. Molecular docking of the top four active ingredients with key targets was performed using AutoDockVina. A collagen-induced arthritis （CIA） rat model was established using bovine type Ⅱ collagen，with SD rats divided into groups including a blank group，a model group，and low-，medium-，and high-dose groups of Huangqi Guizhi Wuwutang （2.44，4.88，and 9.76 g·kg^-1） and administered for five consecutive weeks. Joint scores and gastrocnemius muscle mass were recorded and analyzed after modeling. Hematoxylin and eosin （HE） staining and Masson's staining were used to observe pathological changes in muscle tissue. Immunofluorescence staining was applied to observe the protein expression levels of myosin heavy chain （MYHC） and insulin-like growth factor-1 （IGF-1） in skeletal muscle. Western blot was used to detect the protein expression levels of autophagy-related proteins ATG5，Beclin1，LC3B，muscle-specific proteins （MuRF1），MaFbx，and MYHC. Real-time quantitative reverse transcription PCR （Real-time PCR） was performed to measure the mRNA expression levels of ATG5，Beclin1，LC3B，MuRF1，MaFbx，and MYHC in muscle tissue. ResultsNetwork pharmacology revealed that Huangqi Guizhi Wuwutang shared 25 common targets with autophagy genes related to RA-associated sarcopenia. The PPI network and machine learning identified six key targets，which were primarily involved in autophagy and inflammatory pathways. Animal experiments showed that compared to the blank group，the model group had significantly higher joint scores （P<0.01） and lower gastrocnemius muscle index （P<0.01）. HE staining indicated a significant reduction in the cross-sectional area of gastrocnemius muscle fibers，with notable inflammatory cell infiltration and muscle atrophy in the model group. Masson's staining revealed obvious collagen fiber proliferation and deposition，with significant muscle fibrosis in the model group. The protein and mRNA expression levels of ATG5，Beclin1，LC3B，MuRF1，and MaFbx were significantly increased （P<0.01），while the protein expression of MYHC and IGF1 was significantly downregulated （P<0.01）. Compared with the model group，the high-dose group of Huangqi Guizhi Wuwutang showed significantly reduced protein and mRNA expression levels of ATG5，Beclin1，LC3B，MuRF1，and MaFbx （P<0.01） and increased protein expression levels of MYHC and IGF1 （P<0.01）. The cross-sectional area of muscle fibers increased，and the muscle cell morphology approached normal. Moreover，pathological abnormalities in the gastrocnemius muscle were significantly improved，with reduced collagen fiber proliferation （P<0.01）. ConclusionHuangqi Guizhi Wuwutang can mediate autophagy by regulating the expression of ATG5，Beclin1，LC3B，and IGF1，thereby reducing skeletal muscle catabolism and improving skeletal muscle homeostasis，which contributes to the treatment of RA-associated sarcopenia. The findings provide insight into the mechanisms underlying the effects of Huangqi Guizhi Wuwutang in the treatment of RA-related sarcopenia and offer a reference for its enhanced clinical application.

Objective Explore differences in the cognitive abilities of socially different Labradors.Methods The dog mentality assessment(DMA)test created by the Swedish Working Dog Association was modified to employ 12 behavioral variables from five subtests of the DMA test,social contact,play Ⅰ,distance-play,ghosts and play Ⅱ,to assess sociability of the dogs.In accordance with the scoring criteria,49 labradors provided by the China Guide Dog Training Centre in Dalian were scored on the social behavioral variables and classified into high(n=15)and low(n=34)sociability groups by cluster analysis.A new system to test canine cognitive ability was developed using the dog cognitive development battery,which tests various domains of cognitive ability such as social cue use,unsolvable task,inhibitory control,cognitive flexibility,working memory,and multistep problem solving task.The dogs'behavioral performance and duration of the test were also recorded.Statistical analysis was performed to determine assess differences in the cognitive abilities of socially diverse dogs.Results Dogs in the high and low social subgroups differed significantly in behavioral variables of the unsolvable task,inhibitory control test,and multistep problem solving task.In the unsolvable task,dogs in the high social group looked at people for significantly longer than dogs in the low social grouping(P=0.008)and looked at people with significantly less latency time than dogs in the low social group(P=0.0001).In the inhibitory control,dogs in the high social group chose significantly more correctly than dogs in the low social group(P=0.034)and chose for significantly less time than dogs in the low social group(P=0.039).In the multistep problem solving task,for dogs in the high social group.successfully completed number of stakes was significantly higher than for dogs in the low social group(P=0.044).The percentage of operation pale time was significantly lower than for dogs in the low social group(P=0.05).The average latency time to solve the bone task was significantly higher than for dogs in the low social group(P=0.037).Moreover,the percentage of operation bone time was significantly lower than for dogs in the low social group(P=0.038).In tests involving a manipulable apparatus,dogs in the high social group spent more time looking at people than dogs in the low social group and less time manipulating the apparatus than dogs in the low subgroup,but no statistically significant differences were observed(P＞0.05).Conclusions Highly sociable labradors have a greater cognitive ability,they are more able to suppress impulses during tests,more able to complete the multistep problem solving task,and more inclined to change strategies to seek new cues from people rather than obsessing over manipulating the apparatus when they are unable to solve a problem.

Objective:To explore the clinical characteristics and genetics of a pedigree with Stargardt disease, and investigate the pathogenicity of ABCA4 (ATP binding cassette subfamily A member 4) gene mutations in Stargardt disease.Methods:The proband was admitted to the Second People′s Hospital of Jinan in May 2021 due to diminution of vision. The proband was diagnosed with Stargardt disease according to the clinical diagnostic criteria of Stargardt disease. Detailed ophthalmological examinations was also performed on family members of the proband. Genomic DNA were extracted from the proband and the family members, and the whole exon sequencing was performed to find pathogenic gene mutations. The hazard of mutations was analyzed by polyphen-2, SIFT and MutationTaster websites. Sanger sequencing was used to verify the mutations. Conserved analysis of homologous species and 3-dimensional (3D) molecular model of the protein were used to analyze the pathogenicity.Results:Ophthalmological examinations showed reduced binocular vision, macular atrophy and "bull′s eye sign" in the proband and there was no abnormal signs and symptoms among the family members. Through whole exon sequencing analysis and Sanger sequencing verification, the compound heterozygous mutations (c.215G>A and c.6563T>C) of ABCA4 gene were co-segregated with this disease in this family. SIFT, Polyphen-2 and MutationTaster predicted that these two mutations were pathogenic. Conservative analysis and 3D molecular model of protein showed that mutations could cause changes in protein structure and affect protein function.Conclusion:The compound heterozygous mutations (C.215G>A and C.6563T>C) of ABCA4 gene are the pathogenic mutations of Stargardt disease in this pedigree.

The era of bioeconomy has ushered in a new wave of technological and industrial revolution for mankind. The strategic deployment for the bioindustry in China has achieved remarkable results. However, there are still problems such as unbalanced regional development in the process of bioindustry development. In order to comprehensively assess the current situation of the competitiveness of the bioindustry in various regions of China, the assessment indicator system of the overall competitiveness of the bioindustry is constructed from the perspective of the four sub-industries of biomedicine, bioenergy, bioagriculture and bio-based industry. The weight of each assessment indicator is determined by the analytic hierarchy process. According to geographical administrative division and regional economic relations, an empirical analysis of the comprehensive competitiveness score of the bioindustry in seven regions of China is carried out. The assessment results show that the competition of bioindustry in various regions of China presents a gradient distribution in space. In view of this, relevant policy recommendations are put forward from four aspects: (1) implementing the strategy of rural revitalization, (2) implementing the strategy of regional coordinated development, (3) deepening the supply-side structural reform for the bioindustry, and (4) establishing regional unified information collaboration network system.
Biotechnology/statistics & numerical data* ; China ; Industry

The advent of the bioeconomy era is triggers a new wave of technology and industrial revolution. Bioeconomy has become the commanding heights that major developed countries and emerging economies try to seize. This paper analyzes the spatiotemporal characteristics of global bioindustry development from four perspectives: biomedical industry, genetically modified crop planting industry, bioenergy industry, and bio-based chemical industry. Then it summarizes the main characteristics of the development of the global bioindustry, and further put forward policy recommendations for the bottleneck problems in the development of China's bioindustry, which can guide the future development of China's bioeconomy.

OBJECTIVETo study the risk factor of perioperative complication in gastric cancer patients with radical therapy and its influence on prognosis.

METHODSClinical, pathological and follow-up data of 1 148 gastric cancer patients undergoing radical gastrectomy at Tianjin Medical University Affiliated Tumor Hospital between January 2009 and August 2011 were retrospectively collected. Pearson 2 test and Logistic regression analysis were used to analyze the risk factor of perioperative complication. Cox regression analysis was used to evaluate the influence of perioperative complications on the prognosis in patients after radical gastrectomy. Kaplan-Meier survival curve was applied to calculate the survival.

RESULTSOf 1 148 patients, 851 were male, 297 were female, age ranged from 19 to 89 (average 59.9) years. Perioperative complication occurred in 312 cases (27.2%), including 140 cases of pulmonary infection and 53 cases of abdominal infection. Multivariate Logistic regression analysis showed that ≥65 years old (OR:0.736, 95%CI: 0.558 to 0.971, P=0.030), serum albumin less than 35 g/L(OR:2.626, 95%CI: 1.479 to 4.665, P=0.001), Borrmann type IIII((OR: 0.748, 95%CI: 0.610 to 0.917, P=0.005), tumor site at upper 1/3 of stomach (OR:1.326, 95%CI:1.167 to 1.506, P=0.000), combined organ resection(OR:0.624, 95%CI:0.428 to 0.909, P=0.014) were independent risk factors of perioperative complication. Tumor site at upper 1/3 of stomach (OR:1.649, 95%CI: 1.368 to 1.988, P=0.000), ≥65 years old (OR:0.548, 95%CI:0.379 to 0.792, P=0.001), without intraoperative chemotherapy (OR:1.671, 95%CI:1.146 to 2.437, P=0.008) were independent risk factors of perioperative pulmonary infection; Borrmann type IIII((OR:0.576, 95%CI:0.369 to 0.900, P=0.015), with intraoperative chemotherapy (OR:0.431, 95%CI:0.230 to 0.810, P=0.009), intraoperative blood loss ≥400 ml(OR:0.411, 95%CI:0.176 to 0.959, P=0.040) and combined organ resection (OR:0.412, 95%CI:0.215 to 0.789, P=0.008) were independent risk factors of perioperative intraperitoneal infection. Cox regression analysis revealed that without intraoperative chemotherapy, proximal subtotal or total gastrectomy, TNM stage III(, N3 stage lymph node metastasis, positive soft tissue outside lymph node, combined organ resection and organ failure were independent risk factors affecting the prognosis of gastric cancer patients after radical resection (all P<0.05), however the perioperative complication was not independent risk factor affecting the prognosis (P=0.259). The median survival time was 35 months, and 5-year survival rate was around 38.7%. The median survival time of gastric cancer patients with operative complications and without complications were 28.0 and 36.5 months, and the 5-year survival rates were 37.2% and 39.3%, whose difference was not statistically significant (P=0.259).

CONCLUSIONThere is a higher risk of perioperative complication in those gastric cancer patients with old age, preoperative low serum albumin level, tumor site at upper 1/3 of stomach, Borrmann type IIII(, intraoperative combined organ resection, while the perioperative complication has no significant effects on the long-term survival.

Objective To investigate the Mycobacterium tuberculosis infections in 2014 among Beijing army recruits, and evaluate a new method for screening latent tuberculosis infections.Methods A total of 194 army recruits were subjected to chest X-ray examination purified protein derivative(PPD) skin test, antibody detection, and interferon gamma release assay(IGRA) by ELISA combined with recombinant protein CFP10-ESAT6 and latent infection protein Rv2628.Results The positive rates of PPD skin test and antibody test were 49.7% and 15.5%, respectively.The latent infection rate of IGRA test was 22.2% in 194 cases after CFP10-ESAT6 stimulation.After stimulation of latent tuberculosis infection(LTBI) with Rv2628, IFN-γ level was significantly higher than that in healthy control group (P<0.05).The weak positive group of TST (5 mm≤diameter<15 mm) had a significantly higher level of IFN-γ than the strong positive group(diameter≥15 mm)(P<0.05),but after stimulation with CFP10-ESAT6,IFN-γ levels were not significantly different between the two groups(P>0.05).There was no significant difference between antibody negative and positive groups after stimulation by CFP10-ESAT6 and Rv2628 (P>0.05).The area under the ROC curve of Rv2628 diagnosis of tuberculosis infection was 0.84.When Youden index was 0.621,the specificity was 94.7% and sensitivity was 67.4%.ConclusionCombined detection of antigens Rv2628 and CFP10-ESAT6 specific IFN-γ values can be potentially used for differential diagnosis of active or latent tuberculosis infections.

Objective To investigate the inhibitory effect of hydroxy safflor yellow A ( HSYA ) on angiogenesis of H22 tumor-bearing mice and it's effects on the protein expression of MMP-3 .Methods After establishing the hep-atoma model for 24 h, the mice were randomly divided into control group , sorafenib group and HSYA group , the dose HSYA group received intraperitoneal injection at different dosages (1.125 and 2.25 mg/kg).The pathologi-cal changes were examined with HE staining , immunohistochemical staining and Western blot were applied to meas-ure the expression of angiogenesis related factor ( MMP-3 ) and we also detected the microvessel density with CD 34 . Results Compared with control group , the tumor cells proliferation and the new angiogenesis in HSYA group were suppressed .The expression of MMP-3 in HSYA group was significant reduced .Especially the dose of 2.25 mg/kg HSYA group ( P<0.01 ) , and tumor MVD-CD34 was also significantly reduced ( P<0.01 ) .But the effect is not better than sorafenib group .Conclusions HSYA may inhibit angiogenesis of tumor tissue in a certain concentration range and the anti-angiogenesis effect of HSYA may be related to inhibition of the protein expression of matrix met-alloproteinase-3 .

Objective Research on the correlation of dyslipidemia of civil aviation pilots and the TCM constitution aimed to explore that how professional environmental affects the lipid metabolism and the constitution.MethodsMeasure the lipid statusand TCM constitution of 656 pilots, and 496 of them with dyslipidemia were studied. The sample were stratified according to the age and the types of dyslipidemia, including young and middle-aged groups, only abnormal total cholesterol metabolism (TC), only abnormal triglyceride metabolism (TG), and both abnormal cholesterol and triglycerides metabolism groups and then the differences in prevalence of traditional Chinese medicine in different groups were analyzed and discussed. ResultsThe prevalence of abnormal lipid metabolism was 75.61% in 656 pilots. The top three TCM constitutions among the pilot with dyslipidemia were phlegm dampness constitution (35.89%), dampness heat constitution (33.06%) and deficiency of Yang(20.97%). If age was not considered, the prevalence of TCM constitutions were not significantly different between the groups of only abnormal TC and TG (P>0.05), while the prevalence of Yang deficiency and dampness heat constitutions of only either TC or TG abnormal group were significantly higher than those of the group of both abnormal TC, TG (χ2 values were 6.793, 5.077, P<0.05). Take age as considered, TC metabolic abnormalities in youth group, the prevalence of damp heat constitution of the only TC abnormal group was higher than both TC, TG abnormal group (χ2=7.637,P<0.01); and the prevalence of Qi deficiency and Yang deficiency constitution of the only TG abnormal group were higher than both TC, TG abnormal group (χ2values were 6.139, 7.525,P<0.05). In the middle-aged group, the prevalences of Yang deficiency and Qi stagnation constitution of only TC abnormal group were higher than only TG abnormal group (χ2 values were 9.750, 3.922,P<0.05), and the prevalence of Yang deficiency of only TC abnormal group was higher than both TC, TG abnormal group (χ2=5.208,P<0.05). The prevalence of Yang deficiency of both TC, TG abnormal group was higher than only TG abnormal group (χ2= 4.489,P<0.05). Conclusions The result showed high prevalence of dyslipidemia in the population of civil aviation pilots. Age and lipid metabolism status could affect the types of TCM constitution. Damp-heat constitution was the common type of TCM constitution in the population of the young pilot, and Yang deficiency and Qi stagnation constitution were the common types in the population of middle-aged people whose lipid metabolism were disorder. The group of only abnormal TC influence on TCM constitution more than both abnormal TC and TG.

[Summary] A total of 128 individuals with type 2 diabetes underwent continuous glucose monitoring for 3 consecutive days.The dawn phenomenon was defined by three different parameters according to the previous research:(1)the absolute increase of glucose level from nocturnal nadir to prebreakfast value(?G) above 20 mg/dl;(2)?G above 10 mg/dl;( 3 ) insulin requirement increased at least 20%.The participants were secondarily separated by presence/absence of a dawn phenomenon based on the definitions above.The impact on blood glucose fluctuation of different groups was assessed according to the standard deviation of blood glucose( SDBG) , the area under curve above 10 mmol/L ( AUC ) , and the mean amplitude of glycemic excursions ( MAGE ) , etc.The frequencies of dawn phenomenon were 64.8%(?G≥20mg/dl), 85.2%(?G≥10 mg/dl), and 59.4%(rise in insulin requirement≥20%)respectively.The impacts on SDBG, AUC, MAGE, and MODD were without statistical difference(P>0.05) between the presence and absence of the dawn phenomenon patients when?G≥10 mg/dl.However, the differences reached statistical significance(P<0.05) when ?G≥20 mg/dl and the increase in insulin requirement≥20%. Besides, the incidence of dawn phenomenon was positively correlated with HOMA-IR, HbA1C , and free C-peptide.Dawn phenomenon is a very frequent event in type 2 diabetes and not only impacts the overall glycemic control but also exaggerates glucose fluctuation.To be clinically relevant, ?G≥20mg/dl should be taken as the quantitative criterion of the dawn phenomenon.