Behavior of cartilage-derived microtissue and ability of cartilage formation in three-dimensional dynamic and static culture conditions / 中国组织工程研究

BACKGROUND:Compared with traditional two-dimensional culture,three-dimensional microtissue culture can show greater advantages.However,more favorable cultivation methods in three-dimensional culture still need to be further explored. OBJECTIVE:To evaluate the cell behavior of microtissue and its ability to promote cartilage formation under two three-dimensional culture methods. METHODS:Cartilage-derived microcarriers were prepared by chemical decellularization and tissue crushing.DNA quantification and nuclear staining were used to verify the success of decellularization,and histological staining was used to observe the matrix retention before and after decellularization.The microcarriers were characterized by scanning electron microscopy and CCK-8 assay.Cartilage-derived microtissues were constructed by combining cartilage-derived microcarriers with human adipose mesenchymal stem cells through three-dimensional static culture and three-dimensional dynamic culture methods.The cell viability and chondrogenic ability of the two groups of microtissues were detected by scanning electron microscopy,live and dead staining,and RT-qPCR. RESULTS AND CONCLUSION:(1)Cartilage-derived microcarriers were successfully prepared.Compared with before decellularization,the DNA content significantly decreased after decellularization(P<0.001).Scanning electron microscope observation showed that the surface of the microcarrier was surrounded by collagen,maintaining the characteristics of the natural extracellular matrix of cartilage cells.CCK-8 assay indicated that microcarriers had no cytotoxicity and could promote cell proliferation.(2)Scanning electron microscopy and live and dead staining results showed that compared with the three-dimensional static group,the three-dimensional dynamic group had a more extended morphology of microtissue cells,and extensive connections between cells and cells,between cells and matrix,and between matrix.(3)The results of RT-qPCR showed that the expressions of SOX9,proteoglycan,and type Ⅱ collagen in microtissues of both groups were increased at 7 or 14 days.The relative expression levels of each gene in the three-dimensional dynamic group were significantly higher than those in the three-dimensional static group at 14 days(P<0.05).At 21 days,the three-dimensional static group had significantly higher gene expression compared with the three-diomensional dynamic group(P<0.001).(4)The results showed that compared with three-dimensional static culture microtissue,three-dimensional dynamic culture microtissue could achieve higher expression of chondrogen-related genes in a shorter time,showing better cell viability and chondrogenic ability.

Evidence-Based Dampness-Heat ZHENG (Syndrome) in Cancer: Current Progress toward Establishing Relevant Animal Model with Pancreatic Tumor / 中国结合医学杂志

Cancer is one of the deadliest diseases affecting the health of human beings. With limited therapeutic options available, complementary and alternative medicine has been widely adopted in cancer management and is increasingly becoming accepted by both patients and healthcare workers alike. Chinese medicine characterized by its unique diagnostic and treatment system is the most widely applied complementary and alternative medicine. It emphasizes symptoms and ZHENG (syndrome)-based treatment combined with contemporary disease diagnosis and further stratifies patients into individualized medicine subgroups. As a representative cancer with the highest degree of malignancy, pancreatic cancer is traditionally classified into the "amassment and accumulation". Emerging perspectives define the core pathogenesis of pancreatic cancer as "dampness-heat" and the respective treatment "clearing heat and resolving dampness" has been demonstrated to prolong survival in pancreatic cancer patients, as has been observed in many other cancers. This clinical advantage encourages an exploration of the essence of dampness-heat ZHENG (DHZ) in cancer and investigation into underlying mechanisms of action of herbal formulations against dampness-heat. However, at present, there is a lack of understanding of the molecular characteristics of DHZ in cancer and no standardized and widely accepted animal model to study this core syndrome in vivo. The shortage of animal models limits the ability to uncover the antitumor mechanisms of herbal medicines and to assess the safety profile of the natural products derived from them. This review summarizes the current research on DHZ in cancer in terms of the clinical aspects, molecular landscape, and animal models. This study aims to provide comprehensive insight that can be used for the establishment of a future standardized ZHENG-based cancer animal model.

A real-world study of the effects of endocrine therapy on liver function in breast cancer / 中华外科杂志

Objective: To compare the effect of different endocrine therapy drugs on liver function in patients with early breast cancer. Methods: A retrospective cohort study was conducted to include 4 318 patients with early breast cancer who received adjuvant endocrine therapy in Department of Breast Surgery, Peking Union Medical College Hospital from January 1, 2013 to December 31, 2021. All the patients were female, aged (51.2±11.3) years (range: 20 to 87 years), including 1 182 patients in the anastrozole group, 592 patients in the letrozole group, 332 patients in the exemestane group, and 2 212 patients in the toremifene group. The mixed effect model was used to analyze and compare the liver function levels of patients at baseline, 6, 12, 18, 24, 36, 48, 60 months of medication, and 1 year after drug withdrawal among the three aromatase inhibitors (anastrozole, letrozole, exemestane) and toremifene. Results: ALT and AST of the 4 groups were significantly higher than the baseline level at 6 months (all P<0.01), and there were no significant differences in total bilirubin, direct bilirubin and AST levels among all groups one year after drug withdrawal (P: 0.538, 0.718, 0.061, respectively). There was no significant difference in the effect of all groups on AST levels (F=2.474, P=0.061), and in the effect of three aromatase inhibitors (anastrozole, letrozole, and exemestane) on ALT levels (anastrozole vs. letrozole, P=0.182; anastrozole vs. exemestane, P=0.535; letrozole vs. exemestane, P=0.862). Anastrozole and letrozole had significantly higher effects on ALT levels than toremifene (P<0.01, P=0.009). The proportion of abnormal liver function in each group increased significantly at 6 months compared with baseline, and then the proportion showed a decreasing trend over time. Conclusions: Three aromatase inhibitors (anastrozole, letrozole, and exemestane) and toremifene can significantly increase the level of ALT and AST in patients with breast cancer, and the levels can gradually recover to the baseline after 1 year of drug withdrawal. The effect of non-steroidal aromatase inhibitors (anastrozole, letrozole) on ALT levels is greater than toremifene.

Regulation of gluconeogenesis in liver, kidney and intestine by glucagon / 中国药理学通报

Aim To investigate the regulatory effect of glucagon on gluconeogenesis in liver, kidney and intes¬tine during different fasting periods and the underlying mechanism. Methods The 8-week-old male C57BIV 6J mice were randomly divided into six groups ( n = 6) :control group, control + glucagon group, fasting 18 h group, fasting 18 h + glucagon group, fasting 36 h group, and fasting 36 h + glucagon group. Glucose, triglyceride ( TG) and free fatty acids ( FFAs ) kits were used to detect their serum contents in mouse in-traperitoneal injection of glucagon at different fasting time points. Besides, liver/muscle glycogen assay kit and PAS staining were used to detect the glycogen con¬tents in liver tissue. RT-PCR method was used to observe the effects of glucagon on the gene expressions of peroxisome proliferators-activated receptor y coactivator la (PGC-1α), glucose-6-phosphatase (G6Pase) and phosphoenol pyruvate carboxykinase 1 (PEPCK) in liver, kidney and intestine of mice at different fasting time. Western blot was employed to detect the protein expressions of PGC-1α, G6Pase, PEPCK, phosphoryl-ase protein kinase A ( p-PKA) , protlein kinase A (PKA) , phosphorylase cAMp-response element binding protein (p-CREB) and cAMp-response element binding protein (CREB) in liver, kidney and intestine of mice were. Results (1) Glucagon increased the serum glucose level, reduced serum TG and FFAs levels, and reduced the hepatic glycogen content. (2) Glucagon promoted gluconeogenesis via upregulation of PGC-1α. On the stimulation of glucagon, PGC-1α gene and protein expressions in liver were significantly raised by glucagon when the mice were fasted 18 h and 36 h, while the gene and protein expressions of PGC-1α in kidney were obviously up-regulated by glucagon after fasting 18 h. However, PGC-1α gene and protein expressions in intestine were significantly elevated by glucagon at 36 h after fasting. (3 ) Glucagon induced gene and protein expressions of gluconeogenesis-related enzymes G6Pase and PEPCK in liver, kidney and intestine after fasting. (4 ) Glucagon upregulated p-PKA/PKA and p-CREB/CREB in liver. Conclusions Glucagon shows temporal difference in the gluconeo-genic response of liver, kidney and intestine in mice. Glucagon promotes the gene and protein expressions of key gluconeogenic enzymes G6Pase and PEPCK by increasing PGC-1α gene and protein expression, and thus increasing fasting blood glucose. Besides, glucagon promotes hepatic gluconeogenesis via PKA/CREB signaling pathway.

Pathogenesis and surgical outcomes of different types of myopic traction maculopathy / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To explore the pathogenesis and surgical outcomes of different types of myopic traction maculopathy(MTM)using optical coherence tomography(OCT).METHODS: A total of 193 patients(210 eyes)with MTM were retrospectively included, of which 74 eyes(35.2%)underwent vitrectomy combined with internal limiting membrane(ILM)peeling. The patients were categorized into three groups: foveal detachment(FD), foveoschisis(FS)and lamellar macular hole(LMH). Based on the central foveal thickness(CFT)at baseline(M0), eyes with FD were classified into two subgroups: extensive FD and limited FD. Outcomes included best-corrected visual acuity(BCVA), CFT, posterior staphyloma height(PSH), the presence of epiretinal membrane(ERM)and ILM detachment. Risk factors for BCVA at 6mo after vitrectomy(M6)were analyzed using linear regression.RESULTS: At M0, ERM was highly present in eyes with LMH(rs=0.28, P&#x003C;0.001). Eyes with FD and FS were characterized by higher incidence of ILM detachment(rs=-0.25, P&#x003C;0.001). After vitrectomy, CFT and BCVA significantly improved in all eyes(P&#x003C;0.001). Eyes with extensive FD were characterized by a thicker CFT(rs=0.56, P&#x003C;0.001), a lower incidence of ILM detachment(rs=-0.25, P=0.034)and a thicker nasal PSH(rs=0.27, P=0.024)than eyes with limited FD. Eyes with extensive FD were associated with a worse BCVA at M0(P=0.013)and M6(P=0.030)than eyes with limited FD. Extensive FD(β=-0.295, P=0.042)and BCVA at M0(β=0.669, P&#x003C;0.001)were risk factors for a worse BCVA at M6.CONCLUSION: There are several pathogenetic mechanisms in MTM. ILM detachment may exert a dominant role in the development of FD and FS, while ERM may have a role in LMH. Vitrectomy combined with ILM peeling improved functional and anatomical outcomes in MTM patients. Eyes with extensive FD may carry a poor prognosis.

Association of aggression and social support among adolescents / 中国学校卫生

Objective@#To explore the association between aggression and social support and their gender differences among Chinese adolescence, and to provide a scientific reference for preventing and reducing aggressive behaviors of adolescents.@*Methods@#Conducted a cross sectional survey of 15 623 adolescents in 5 provinces in China, namely, HeiLongjiang, Hubei, Anhui, Guangdong and Yunnan Province. And the Chinese version of the Adolescent Social Support Scale was employed to assess the aggression and social support, life events, psychological characteristics, family condition and demographic characteristics among adolescents.@*Results@#The prevalence of self reported high level of aggression was 23.5%(3 670/15 623). Males reported higher rate of high level aggression than females (24.4% vs 22.5%, χ 2=19.30, P <0.01). Significant association between aggression and social support was identified in univariate analysis ( χ 2=620.68, P <0.01). After controlling for potential confounders, aggression was also significantly negatively associated with social support ( OR =1.27-1.84), and there was dose response relationship between them( P < 0.05 ). Furthermore, the association between aggression and social support was similar among male participants and female participants ( ROR =1.02-1.10, P >0.05).@*Conclusion@#The findings indicate that aggression is associated with social support both in male and female adolescents. Improving the social support for adolescents can reduce their aggressive behaviors.

The gene knockout of ATlaR improves insulin resistance induced by high-fat diet in rats / 中国药理学通报

Aim To explore the role of angiotensin U type 1 a reeeptor ( AT 1 aR ) , an important component of HAS, in obesity-induced insulin resistance.Methods Wild type ( WT) and ATlaR gene knockout (ATlaR ) SD rats were fed with normal diet and 60% high-fat diet for 12 weeks, respectively.After 12 weeks, blood was collected from the abdominal aorta of rats to obtain serum, and the serum insulin level was measured by ELISA.The epididvmal adipose tissue was obtained, and gene expressions of peroxisome pro- liferator-activated receptor -y ( PPAR7) and sterol reg¬ulator}' element binding protein lc (SREBP-lc) in ad¬ipose tissue were detected by RT-PCR method.The protein expressions of insulin signaling pathway and protein kinase C (PKC) in adipose tissue were detec¬ted by Western blot.Results ATI aR knockout signif¬icantly reduced HOMA-IR and improved insulin resist¬ance induced by high-fat diet.In ATlaR rats fed with high-fat, the protein expressions of insulin signa¬ling pathway were much higher than those of WT rats, indicating that ATlaR gene knockout improved the in¬sulin signaling pathway in high-fat diet.In addition, the PKCa, PKCe and PKCr| expressions of ATlaR rats were significantly lower than those of WT rats.And the gene expressions of PPAR-y and SREBP-lc, which promoted adipogenic differentiation, significantly increased in ATlaR rats fed with a high-fat diet, demonstrating that ATlaR knockout promoted adipo¬genic differentiation.Conclusions ATlaR knockout significantly improves high-fat diet induced 1R by en¬hancing protein expressions of insulin signaling path¬way, inhibiting PKC expression and promoting adipo¬genic differentiation.

From the Origins of SARS-CoV-2 to the Correct Application of BLAST / 中国生物化学与分子生物学报

Basic local alignment search tool (BLAST) is one of the popular sequence similarity analysis tools. However, some students and researchers just blindly use the default parameters. Moreover, some students are confused about how to choose the right program. In a word, it is prone to be misused and researchers often draw conclusions incorrectly. In view of this, we traced back the internet hot topic in early 2020 - "MORDERATELY STRONG CONFIRMATION OF A LABORATORY ORIGIN OF COVID-19", and took it as teaching materials to guide the student to use BLAST currently through reanalyzing and reproducing the source of errors. Then we arranged an interesting experiment about fabricating dinosaur genes through modifying a chicken gene. In the experimental design to make the students grasp the BLAST tools better, one group fabricated the dinosaur gene and the other group decrypted the added bases. This instructional design could be conducive to cultivate students ' ability about distinguishing different viewpoints correctly, and we hope it can be enlightening and helpful to the teaching of BLAST tools.

Lipidomics analysis on schisandrol B-induced liver enlargement in mice / 药学学报

Schisandrol B (SolB) is one of the active constituents from a traditional Chinese medicine Schisandra chinensis or Schisandra sphenanthera. Our previous studies found that SolB exerts hepatoprotective effects against drug-induced liver injury and promotes liver regeneration. We further found that SolB significantly induces liver enlargement but the mechanisms remain unclear. The purpose of this study was to investigate the change of lipidome in liver tissues during SolB-induced hepatomegaly. The animal experiment protocol was approved by the Institutional Animal Care and Use Committee at Sun Yat-sen University. Serum and liver samples of male C57BL/6 mice were collected after intraperitoneal injection of SolB (100 mg·kg-1·d-1) for 5 days. Lipidomics analysis was performed using Q Exactive UHPLC-MS/MS system. The results showed that SolB significantly promoted liver enlargement in mice without liver injury and inflammation. Lipid accumulation was observed in the liver tissues after SolB treatment. Thirty-five lipids were identified with significant change and triglycerides (TG) were found to have the most significant increase in SolB-treated group, indicating the increase of energy production during SolB-induced hepatomegaly. This study reveals the impact of SolB on lipid metabolism and provides a potential explanation for liver enlargement induced by SolB.

Effect of low dose heparin on coagulation index and therapeutic outcomes in premature infants with sepsis / 中华全科医师杂志

Objective To investigate the effect of low dose heparin on blood coagulation and therapeutic outcomes in premature infants with sepsis.Methods Clinical data of 69 septic preterm newborns weighting less than 1 500 g treated in Beijing Obstetrics and Gynecology Hospital were retrospectively analyzed.Among them,29 infants received heparin therapy (6 U/kg,q 8 h,for 3 d,then q12 h,heparin group)and 40 infants did not receive heparin therapy (control group),the coagulation index and therapeutic outcomes were compared between two groups.Results The coagulation indexes PT,TT,APTT and D dimer in heparin group were all significantly lower than those in control group [(15.5±3.5) s vs.(19.0±3.9) s,(15.4±3.5) s vs.(18.8±3.5) s,(47.5±8.6) s vs.(58.4±18.1) s,(1.7±0.8) mg/L vs.(2.6±1.9) mg/L;t=-3.815,4.275,-3.004,-2.459,P＜0.05].The overall clinical effective rate in heparin group was significantly higher than that in control group (86.2％ vs.60.0％,x2 =4.408,P＜0.05).Conclusion Low dose heparin can significantly improve the blood coagulation function and improve the therapeutic effect of premature infants with sepsis.