Chronic urticaria （CU） is a common skin disease worldwide， and its incidence is increasing year by year in various regions. Clinical manifestations such as severe itching can affect normal work， sleep， and daily life and increase the negative psychological burden caused by stress， anxiety， and depression. Mast cell activation and degranulation induced by immunoglobulin（Ig）E hypersensitivity is one of the core pathogenic mechanisms of CU， and there is no cure. Antihistamines such as cetirizine and loratadine are preferred for the clinical treatment of CU. Although they can effectively improve clinical manifestations such as itchiness， long-term application can increase the risk of adverse reactions and drug resistance. The phosphatidylinositol kinase/serine-threonine protein kinase B（PI3K/Akt） signaling pathway， as a classical signaling pathway regulated by phosphatidylinositol and tyrosine kinase receptor （RTK）， is a key target regulating the production and release of cytokines in macrophages and affecting the migration of leukocytes and the activation of mast cells and inflammation， and it can be involved in a variety of metabolic processes， such as mast cell activation and degranulation induced by IgE hypersensitivity and abnormal activation of the complement system so that the PI3K/Akt molecular pathway could be an important target for the future eradication of CU. However， the mechanism and potential role of the PI3K/Akt signaling pathway in the treatment of CU are less reported in China. Now， this paper reviewed the molecular mechanism of PI3K/Akt signaling pathway regulation in the treatment of CU and provided corroborative evidence and therapeutic strategy choices for the treatment of CU with traditional Chinese medicine （TCM） from the perspectives of molecular regulation and network pharmacology analysis.

OBJECTIVE To explore the mechanism of action of Fushao Diqin Decoction in the treatment of colorectal cancer.METHODS In vitro cell experiments were conducted using Fushao Diqin Decoction to treat colorectal cancer CT-26 cells,and the cell proliferation and migration abilities were detected.Flow cytometry was used to detect the levels of reactive oxygen species(ROS)in colorectal cancer CT-26 cells,as well as the levels of iron ions(Fe2+),malondialdehyde(MDA),and the activity of su-peroxide dismutase(SOD).PCR Array and Western blot methods were used to analyze and verify the differential gene expression of ferroptosis.Balb/c mice were randomly divided into a blank control group,a model group,an oxaliplatin group(1.5 mg·kg-1·d-1),a low-dose group of Fushao Diqin Decoction(4.49 g·kg-1·d-1),a medium dose group of Fushao Diqin Decoction(8.97 g·kg-1·d-1),and a high-dose group of Fushao Diqin Decoction(17.94 g·kg-1·d-1)for in vivo animal experi-ments.The effects of Fushao Diqin Decoction on Fe2+,ROS,MDA levels,SOD activity,and Nrf2,Keap1,SLC7A11 and GPX4 ex-pression levels in mouse tumor tissues were tested.RESULTS In vitro cell experiments showed that compared with the blank control group,Fushao Diqin Decoction significantly inhibited the proliferation and migration of colorectal cancer CT-26 cells in a dose-de-pendent manner.Fushao Diqin Decoction could increase the Fe2+content(P＜0.05)and ROS level(P＜0.01)in colorectal cancer CT-26 cells,increase the MDA level in CT-26 cells of colorectal cancer(P＜0.01)and significantly reduce SOD activity(P＜0.01).Iron death PCR array analysis found that compared with the blank control group,after intervention with Fushao Diqin Decoc-tion,the expression of genes GPX4 and SLC7A11 was significantly downregulated,while the expression of GSTA1,HMOX1,Ca9,Chac1,Keap1,Sqstm1,NOX1,FTH1,Tfr1,SAT2,Pparg,and Hamp was significantly upregulated.Western blot analysis revealed that after intervention with Fushao Diqin Decoction,the expression of Keap1 protein was upregulated(P＜0.01),while the expression of Nrf2,SLC7A11,and GPX4 proteins was downregulated(P＜0.01)in colorectal cancer CT-26 cells.The results of in vivo animal experiments showed that Fushao Diqin Decoction significantly inhibited the growth of subcutaneous transplanted tumors in mice(P＜0.05),increased the degree of tumor tissue necrosis,and levels of Fe2+,ROS,and MDA(P＜0.05,P＜0.01),decreased SOD ac-tivity(P＜0.01)and upregulated Keap1 protein expression(P＜0.01),while downregulated Nrf2,SLC7A11,and GPX4 protein ex-pression(P＜0.01).CONCLUSION Fushao Diqin Decoction has an anti-colorectal cancer effect and may promote ferroptosis in colorectal cancer cells by inhibiting the Nrf2/SLC7A11/GPX4 signaling pathway to exert its anti-colorectal cancer effect.

OBJECTIVE To investigate the effect of salidroside (Sal) on bone loss in obstructive sleep apnea syndrome(OSAS) rats by regulating the osteoprotegerin(OPG)/receptor activator of nuclear factor kappa-B ligand(RANKL) pathway. METHODS Rats were randomly divided into(12 rats/group) control group,OSAS group,Sal-L,Sal-M,and Sal-H groups(17.5,35,70 mg/kg). Except for the control group,all other groups were used to replicate the OSAS rat model through hypoxia and reoxygenation cycles. Bone density meters,three-point bending experiments,and Micro CT were applied to measure the bone density,biomechanics,and microstructural changes of the femur in rats. ELISA method was applied to detect serum levels of osteocalcin(BGP),alkaline phosphatase(ALP),and cross-linked carboxy-terminal telopeptide of type Ⅰ collagen(CTX-I). RT-PCR was applied to detect OPG and RANKL mRNA levels in the femur. Western blotting was applied to detect the expression of OPG/RANKL pathway proteins in the femur. RESULTS Compared with the control group,the bone density,maximum intensity,maximum load,trabecular bone volume fraction(Tb.BV/TV),trabecular number(Tb.N),trabecular thickness(Tb.Th),BGP,ALP,OPG mRNA and protein expression,OPG/RANKL ratio of rats in the OSAS group were decreased,the mRNA and protein expression of CTX-I and RANKL were increased(P<0.05). Compared with the OSAS group,the bone density,maximum intensity,maximum load,Tb.BV/TV,Tb.N,Tb.Th,BGP,ALP,OPG mRNA and protein expression,OPG/RANKL ratio of rats in the Sal-L,Sal-M,and Sal-H groups were increased sequentially,the mRNA and protein expression of CTX-I and RANKL were decreased sequentially,the above changes were most great in the Sal-H group(P<0.05). CONCLUSION Salidroside promotes bone formation and inhibits bone resorption by increasing OPG expression and decreasing RANKL expression,thereby reducing bone loss in OSAS rats.

S-adenosyl-l-methionine (SAM) is ubiquitous in living organisms and plays important roles in transmethylation, transsulfuration and transamination in organisms. Due to its important physiological functions, production of SAM has attracted increasing attentions. Currently, researches on SAM production mainly focus on microbial fermentation, which is more cost-effective than that of the chemical synthesis and the enzyme catalysis, thus easier to achieve commercial production. With the rapid growth in SAM demand, interests in improving SAM production by developing SAM hyper-producing microorganisms aroused. The main strategies for improving SAM productivity of microorganisms include conventional breeding and metabolic engineering. This review summarizes the recent research progress in improving microbial SAM productivity to facilitate further improving SAM productivity. The bottlenecks in SAM biosynthesis and the solutions were also addressed.
S-Adenosylmethionine/metabolism* ; Plant Breeding ; Fermentation ; Metabolic Engineering

The passing of ethical review is a necessary conditions and prerequisite for the development of life science and medical research involving humans. At present, some medical and health institutions have no or insufficient ethical review capabilities. The lack of ethical review ability has become a bottleneck restricting the development of life science and medical research involving humans. According to documents such as Opinions on Deepening the Reform of the Review and Approval System and Encouraging the Innovation of Pharmaceutical and Medical Devices, Opinions on Strengthening the Ethical Governance of Science and Technology, institutions can entrust competent institutional ethics review committees or regional ethics review committees in writing to conduct ethical review. Entrustment ethical review provides a viable solution for institutions that need to carry out life science and medical research involving humans but do not have an ethics (review) committee or the ethics (review) committee is not competent to review. To conduct the entrustment ethical review, the entrustment between the principal and the trustee is required. According to The Measures for Ethical Review of Life Sciences and Medical Research Involving Humans, if medical and health institutions and their ethical review committees do not accept the formal entrustment to provide the ethical review opinions for other institutions, the local health authorities at or above the county level will impose administrative penalties and sanctions on the relevant institutions and personnel in accordance with the law. Signing the entrustment ethical review contract, implementing legal compliance entrusted ethical review to protect the rights and interests of the trustee and the principal, and protect the research participants.

The limited coverage of soft tissue and complex biomechanical factors make resection and reconstruction of distal tibial tumors extremely challenging. Megaprosthesis can provide good mechanical strength for tumor en bloc resection, but there are many postoperative complications, and the problems of insufficient soft tissue coverage and postoperative ankle instability must be solved. The development of three-dimensional digital technology may provide a new treatment strategy for distal tibial reconstruction. Compared to ankle joint preservation endoprostheses, the rapid osseointegration effect of three dimensional-printed megaprosthesis with ankle arthrodesis provides better ankle joint stability and postoperative function. In addition, the three dimensional-printed megaprosthesis may improve complications such as insufficient soft tissue coverage and talus collapse by reducing the circumference of the prosthesis and matching it with the talus through personalized design. Of course, there are few research reports on distal tibial prostheses, and the safety of three dimensional-printed megaprosthesis with ankle arthrodesis needs to be confirmed through extensive long-term follow-up studies. The selection of proximal and distal fixation methods for prostheses needs to be explored in future research.

The limited coverage of soft tissue and complex biomechanical factors make resection and reconstruction of distal tibial tumors extremely challenging. Megaprosthesis can provide good mechanical strength for tumor en bloc resection, but there are many postoperative complications, and the problems of insufficient soft tissue coverage and postoperative ankle instability must be solved. The development of three-dimensional digital technology may provide a new treatment strategy for distal tibial reconstruction. Compared to ankle joint preservation endoprostheses, the rapid osseointegration effect of three dimensional-printed megaprosthesis with ankle arthrodesis provides better ankle joint stability and postoperative function. In addition, the three dimensional-printed megaprosthesis may improve complications such as insufficient soft tissue coverage and talus collapse by reducing the circumference of the prosthesis and matching it with the talus through personalized design. Of course, there are few research reports on distal tibial prostheses, and the safety of three dimensional-printed megaprosthesis with ankle arthrodesis needs to be confirmed through extensive long-term follow-up studies. The selection of proximal and distal fixation methods for prostheses needs to be explored in future research.

Prostate cancer (PCa) patients who progress to metastatic castration-resistant PCa (mCRPC) mostly have poor outcomes due to the lack of effective therapies. Our recent study established the orphan nuclear receptor ROR

Objective:To investigate the expression and clinical significance of Golgi phosphoprotein 3 (GOLPH3) and NOD-like receptor protein 3 (NLRP3) in gallbladder carcinoma (GBC).Methods:Surgical specimens and clinical data were collected from 63 patients with GBC who underwent radical cholecystectomy in the 904th Hospital of Joint Logistic Support Force of PLA from January 2014 to January 2019. In the GBC group, there were 21 males and 42 females, with an average age of 62.5 years. For 30 patients with mild to moderate atypical hyperplasia of gallbladder during the same period were included in the precancerous lesion group, including 9 males and 21 females, with an average age of 62.4 years. Normal gallbladder specimens from 20 patients who underwent surgical resection due to liver trauma or giant hepatic hemangioma were collected and included in the normal group, including 7 males and 13 females, with an average age of 61.9 years. The expressions of GOLPH3, NLRP3, Ki-67 were detected by immunohistochemistry. Log-rank test and Cox regression were adopted to analyze the GOLPH3 and NLRP3 expression and survival prognosis of gallbladder cancer patients.Results:Expression of GOLPH3 and NLRP3 in the tumor group, precancerous lesion group and normal group was decreased separately. In GBC tissues, the level of GOLPH3 and NLRP3 was positively correlated with the Ki-67 expression ( r=0.972 and r=0.969, both P<0.05). Multivariate analysis showed that high level of GOLPH3 ( HR=4.891, 95% CI: 1.776-13.470) and NLRP3 ( HR=3.006, 95% CI: 1.273-7.099) was an independent risk factor for predicting the postoperative survival of patients with GBC (both P<0.05). Conclusion:GOLPH3 and NLRP3 are highly expressed in GBC tissues, and high expression of GOLPH3 and NLRP3 is an independent risk factor for postoperative survival in patients with GBC.

Objective:To evaluate the association between smoking and the risk of type 2 diabetes (T2DM) incidence among Asian adults based on the prospective studies.Methods:Prospective studies conducted on Asian adults through May, 2019 were retrieved from the following databases: SinoMed, CNKI, VIP, WanFang, PubMed, Web of Science, Embase, and Cochrane Library. Then data were extracted on smoking status, smoking quantity, the number of newly-onset T2DM cases, and effect sizes.Results:A total of 31 studies were included. There were 2 159 787 investigators, 599 340 (27.75%) smokers, and 124 883 (5.78%) T2DM cases identified during the mean follow-up period of 8.3 years. Compared with non-smokers, the combined relativerisk ( RR) and 95% confidence interval ( CI) of current smokers and quitting smokers were 1.52 (1.34- -1.72) ( P<0.001) and 1.22 (1.09- -1.37) ( P=0.047), respectively. The RR and 95% CI of light smokers (<20/day), moderate smokers (20- -29/day), and heavy smokers (≥30/day) were 1.31(1.21- -1.53) ( P=0.001),1.42(1.14- -1.76)( P=0.212), and 2.17(1.50- -3.16) ( P=0.198), respectively. In males and females, the RR and 95% CI were 1.15 (1.08- -1.21) ( P<0.001) and 1.20 (1.11- -1.30) ( P=0.038), respectively. In addition, compared with non-smokers, the RR and 95% CI of current smokers were 1.57 (1.22- -2.03) ( P<0.001) and 1.47 (1.30- -1.66) ( P=0.063) during the follow-up periods of less than and more than 8.0 years, respectively, while the RR and 95% CI of quitters were 1.23 (1.06- -1.43) ( P=0.091)and 1.20 (1.07- -1.34) ( P=0.041), respectively. Conclusions:Prospective studies based on Asian adults have shown that smoking significantly increases the risk of diabetes incidence. That is, as cigarette consumption increases, the risk of diabetes increases accordingly. Moreover, compared to males, the risk for female smokers is greater. In addition, longer durations of smoking cessation are associated with a lower risk of T2DM.