A new method for simultaneous determination of 23 kinds of per-and polyfluoroalkyl substances(PFASs)(13 kinds of perfluoro carboxylic acids,4 kinds of perfluoro sulfonic acids,and 6 kinds of new substitutes)in plant leaf tissue by ultra-high performance liquid chromatography-tandem mass spectrometry(UHPLC-MS/MS)using automatic online solid phase extraction(SPE)to remove the matrix interference components in plant crude extracts was developed.The plant leaf samples were extracted twice with 1%formic acid-methanol solution,then evaporated to dry,redissolved with 70%methanol solution,and directly injected for analysis.After 23 kinds of target PFASs were purified automatically by online SPE with a WAX column,the six-way valve was switched to rinse PFASs onto an alkaline mobile phase system-compatible C18 analytical column.Then,the 23 kinds of target PFASs were separated within 16 min by gradient elution using a binary mobile phase system of methanol/water(Containing 0.4%ammonium hydroxide).Tandem mass spectrometry was performed in multiple reaction monitoring(MRM)mode for online detection of various PFASs,and quantification was carried out by internal standard method.The results of the method validation showed that satisfactory average recoveries of 23 kinds of PFASs in plant leaf samples(64.2%-125.5%),precision(relative standard deviations(RSDs)of 0.7%-12.8%),linearity(R2＞0.990),and sensitivity(the detection limits(S/N=3)were in the range of 0.02-0.50 μg/kg)were achieved.Finally,this method was used to detect PFASs in the marine green tide algae(Enteromorpha prolifera)and several tree leaves,and a total of 6 kinds of PFASs were detected,in which PFBA was the main contaminant.Compared with the reported offline SPE methods,the proposed online SPE technique significantly simplified the sample pretreatment process and provided an automatic,simple,and environment-friendly method for the routine monitoring of legacy and emerging PFASs in plant tissues.

AIM To establish a quantitative analysis of multi-components by single-marker(QAMS)method for the simultaneous content determination of gastrodin,parishin E,syringin,parishin B,parishin C,ferulic acid,parishin A,buddleoside,harpagoside and cinnamic acid in Tianma Toufengling Capsules.METHODS The analysis was performed on a 30℃thermostatic GL Science InertsilTM ODS-3 column(150 mm×4.6 mm,5 μm),with the mobile phase comprising of acetonitrile-0.1%phosphoric acid flowing at 1.0 mL/min in a gradient elution manner,and the detection wavelengths were set at 220,280 nm.Syringin was used as an internal standard to calculate the relative correction factors of the other nine constituents,after which the content determination was made.RESULTS Ten constituents showed good linear relationships within their own ranges(r≥0.999 7),whose average recoveries were 98.53%-102.22%with the RSDs of 1.26%-2.68%.The result obtained by QAMS approximated those obtained by external standard method.CONCLUSION This accurate and specific method can be used for the quality control of Tianma Toufengling Capsules.

mRNA vaccines and drugs enter host cells through delivery vectors and produce target proteins using the protein synthesis mechanism of cells. mRNA and target proteins can induce the body to produce innate immunity and adaptive immunity, and the target protein itself can also play a corresponding role. Tumor cells are inhibited and cleared under the above immune effects and target proteins. This article reviews the immunogenicity of mRNA, that is, the specific mechanism of stimulating the body to produce an immune response.At the same time, the main types of cells transfected by mRNA vaccine were briefly introduced. (1) Muscle cells, epidermal cells, dendritic cells and macrophages at the injection site; (2) immune cells in peripheral lymphoid organs;(3) liver cells and spleen cells, etc. Although transfected with a variety of cells, it is mainly enriched in immune cells and liver cells because immune cells express toll-like receptors and liver cells express low-density lipoprotein receptors. mRNA vaccines and drugs are mainly divided into non-replicating mRNA (nrmRNA),self-amplifying RNA (saRNA), trans-amplifying RNA (taRNA) and circular RNA (circRNA).This article reviews how these 4 types of vaccines and drugs work, and compares their advantages and disadvantages. Due to its inherent immunogenicity, instability, and low delivery efficiency in vivo, mRNA vaccines and drugs have been unable to enter the clinic. This article describes in detail how to reformation and modify the 5'cap, 5'UTR, 3'UTR, ORF, 3'Poly(A) and some nucleotides of mRNA to eliminate its immunogenicity and instability. Due to the low efficiency of the delivery carrier, the researchers optimized it. This article briefly introduces the application of non-viral vectors and their targeting, specifically involving the mechanism of action of various types of delivery vectors and their advantages and disadvantages, and summarizes some of the current targeting vectors. Targeted carriers can improve the delivery efficiency of mRNA to specific tissues and prevent side effects of systemic exposure, such as liver injury. The specific methods of using mRNA vaccines and drugs to treat cancer are as follows: mRNA can be used to encode and transcribe tumor-associated antigens, tumor-specific antigens (TSAs), therapeutic antibodies, cytokines, tumor suppressors, oncolytic viruses, CRISPR-Cas9, CARs and TCRs, so as to play an anti-tumor role. In this paper, the specific mechanism of the above methods and the current research and development of corresponding mRNA vaccines and drugs are briefly reviewed. The successful development of the COVID-19 mRNA vaccine has brought mRNA technology to the attention of the world and brought new and effective means for the prevention and treatment of cancer. mRNA vaccines and drugs have the advantages of short development cycle, dual immune mechanism, safety, high efficiency and large-scale production. At the same time, there are also many areas that need further improvement, such as the development of ideal target TSAs, the in-depth development of saRNA, taRNA and circRNA, the development of targeted nano-delivery for different tissues and organs, the expansion of mRNA administration routes, and the development of mRNA that can be stably stored at room temperature or even high temperature. These problems need to be further studied and solved. In addition to cancer therapy, mRNA vaccines and drugs can also be used in the treatment of infectious diseases, genetic diseases, regenerative medicine and anti-aging. mRNA vaccines and drugs are a very promising platform, and we believe that they will benefit cancer patients in the near future.

Cordycepin (Cpn), a natural active compound derived from the traditional Chinese medicine Cordyceps sinensis, has antifibrotic, antioxidant, and anti-inflammatory effects, but the impact of Cpn on pulmonary fibrosis and the downstream molecular mechanism remain unclear. In this study, A549 cells were induced by transforming growth factor β1 (TGFβ1) in vitro, the viability of A549 cells was evaluated by CCK-8 assay; and migration of A549 cells were detected by wound healing assay, invasion of A549 cells were detected by transwell assay. Molecular docking and molecular dynamics simulations were used to predict the interaction of histone deacetylase 7 (HDAC7) with vimentin and the association of Cpn with HDAC7. The pulmonary fibrosis model of mice was established by bleomycin in vivo to investigate the effect of Cpn on pathological changes of lung tissue. The impact of Cpn and molecular mechanism on pulmonary fibrosis were studied by Western blot assay, cell transfection assay, immunoprecipitation assay, immunofluorescence assay, immunohistochemistry and real-time quantitative PCR (RT-qPCR). All animal experiments were approved by the Shanghai Children's Medical Center Experimental Animal Ethics Committee (grant No. SCMC-LAWEC-2022-017). Results showed that Cpn had no toxic effect on A549 cells even at the concentration of 100 μmol·L^-1. Cpn inhibited migration and invasion of A549 cells and reduced deposition of collagen, the degree of lung inflammation and fibrosis in mice; in vivo and in vitro models, Cpn significantly reversed mRNA and protein expressions of epithelial-mesenchymal transition (EMT) and lung fibrosis markers collagen I, α-smooth muscle actin (α-SMA), N-cadherin, vimentin and E-cadherin and HDAC7. Deficiency of HDAC7 suppressed TGFβ1-induced EMT and expression of collagen I; vimentin interacted with HDAC7; and molecular docking experiment revealed that Cpn was interrelated with HDAC7. In conclusion, Cpn can target HDAC7 to mediate EMT and exert its anti-fibrotic effect, the inhibition of EMT and the improvement of pulmonary fibrosis provide a new idea and choice for the development of anti-pulmonary fibrosis drug.

Objective To propose a Q factor-based fatigue vibration evaluation method of the ultrasonic knife tip.Methods Firstly,an ultrasonic cutter fatigue testing table was established to realize repeated cutting,which was composed of a power supply module,a three-axis moving module,an ultrasonic cutter clamping module and a control module.Secondly,10 ultrasonic knives of some brand underwent fatigue testing with the table,during which non-contact measurement of the ultrasonic knife tip vibration was carried out and the Q factors were calculated at the five periods of the fatigue test,including the periods before cutting,after 500 times of cutting,after 1 000 times of cutting,after 2 000 times of cutting and after 3 000 times of cutting.Finally,the average cutting speed and burst pressure for coagulated vessels were computed at each period to validata the effectiveness of the method proposed.Results It's indicated that Q factor could effectively reflect the fatigue degradation of the ultrasonic knife tip,while the average cutting speed and burst pressure for coagulated vessels were difficult to efficiently evaluate the fatigue degradation level of the ultrasonic knife tip due to the uncertainty factors in the measurement process.Conclusion The proposed Q factor-based evaluation method can directly evaluate fatigue vibration of the ultrasonic knife tip in an accurate and quantitative manner.[Chinese Medical Equipment Journal,2024,45(6):17-22]

Objective To carry out accurate quantative evaluation of MRI scanning noise based on laser vibrometry technology.Methods Skull and spine MRI was performed with mute and conventional sequences.A laser vibrometry device was used to sample the surface vibration noise at the outer edge of the inspection hole of MRI system according to GB/T 16539-1996 Acoustics—Determination of sound power levels of noise sources using vibration velocity—Measurement for seal machinery,and the indicators of sound power level,sound pressure level and perceived noise level obtained by the three calculation methods(LPN1,LPN2 and LPN3)were analyzed with some dedicated MRI noise analysis software.Results The peak sound pressure levels for conventional and mute sequences of skull scanning were 81 and 63 dB(A),respectively,and mute sequence reduced the noise level significantly;the peak sound pressure levels for conventional and mute sequences of spine scanning were 79 and 75 dB(A),respectively,and the noise reduction level was significantly lower than that of skull scanning.Significant differences in noise reduction were not found in spine scanning sequences,while were found in skull scanning sequences.During spine and skull scanning LPN1,LPN2 and LPN3 obtained by the three calculation methods of conventional and mute sequences were all higher than the overall sound power and overall pressure levels obviously.Conclusion Mute sequence can not realize linear noise reduction for the whole frequency band,the perceived noise of the human ear during MRI scanning is related directly to the scanning sequence,and there may be some bias when only one physical indicator is involved in the noise evaluation of MRI system.[Chinese Medical Equipment Journal,2024,45(10):20-24]

Objective To observe the clinical efficacy of Bazhen Decoction combined with traumatic medicated gauze(prepared mainly with the herbs of Scutellariae Radix,Phellodendri Chinensis Cortex and Sanguisorbae Radix)in the treatment of patients with diabetic foot ulcer(DFU)of qi-blood deficiency syndrome.Methods A total of 42 cases of DFU patients with qi-blood deficiency syndrome were randomly divided into a control group and an observation group,with 21 cases in each group.The control group was given basic western medicine treatment combined with external application of traumatic medicated gauze on wound surface,while the observation group was treated with Bazhen Decoction orally on the basis of treatment for the control group,and the treatment course of both groups covered four weeks.The changes of wound area,traditional Chinese medicine(TCM)syndrome scores,ankle-brachial index(ABI),and serum levels of fibrinogen(FIB),C-reactive protein(CRP),tumor necrosis factor α(TNF-α)in the two groups were observed before and after treatment.After treatment,the clinical efficacy and safety in the two groups were compared.Results(1)After four weeks of treatment,the total effective rate in the observation group was 95.24%(20/21)and that in the control group was 85.71%(18/21),and the intergroup comparison(by rank sum test)showed that the clinical efficacy in the observation group was significantly superior to that in the control group(P＜0.05).(2)After treatment,the wound area and TCM syndrome scores in the two groups were significantly improved compared with those before treatment(P＜0.05),and the improvement of the wound area and TCM syndrome score in the observation group was significantly superior to that in the control group(P＜0.05).(3)After treatment,ABI in the two groups was increased when compared with that before treatment(P＜0.05),and the improvement of ABI in the observation group was significantly superior to that in the control group(P＜0.05).(4)After treatment,the levels of serum CRP,TNF-α and FIB in the two groups were all decreased compared with those before treatment(P＜0.05),and the improvement of the serum levels in the observation group was significantly superior to that in the control group(P＜0.05).(5)During the treatment,there were no significant adverse reactions occurring in the two groups,with high safety.Conclusion Bazhen Decoction combined with traumatic medicated gauze exerts certain effect in the treatment of DFU patients with qi-blood deficiency syndrome.The combined therapy is effective on improving the coagulation function and lower limb ischemia,reducing the levels of inflammatory factors,and relieving the inflammatory reaction,without obvious adverse reactions.

Objective To explore the current application of high-throughput drug sensitivity(HDS)testing in children with relapsed and refractory acute leukemia(RR-AL)and analyze the feasibility of salvage treatment plans.Methods A retrospective collection of clinical data from children with RR-AL who underwent HDS testing at the Department of Children's Hematology and Oncology of the First Affiliated Hospital of Zhengzhou University from November 2021 to October 2023 was conducted,followed by an analysis of drug sensitivity results and treatment outcomes.Results A total of 17 children with RR-AL underwent HDS testing,including 7 cases of relapsed refractory acute myeloid leukemia and 10 cases of relapsed refractory acute lymphoblastic leukemia.The detection rate of highly sensitive chemotherapy drugs/regimens was 53%(9/17),while the detection rate of moderately sensitive chemotherapy drugs/regimens was 100%(17/17).Among the 17 RR-AL patients with highly and moderately sensitive chemotherapy drugs and regimens,the MOACD regimen(mitoxantrone+vincristine+cytarabine+cyclophosphamide+dexamethasone)accounted for 100%,with the highest inhibition rate for single-agent mitoxantrone(94%,16/17),and the highest inhibition rate for targeted therapy being bortezomib(94%,16/17).Nine patients adjusted their chemotherapy based on HDS testing results,with 4 undergoing hematopoietic stem cell transplantation.Four patients achieved disease-free survival,while 5 died.Eight patients received empirical chemotherapy,with 2 undergoing hematopoietic stem cell transplantation;4 achieved disease-free survival,while 4 died.Conclusions HDS testing can identify highly sensitive drugs/regimens for children with RR-AL,improving the rate of re-remission and creating conditions for subsequent hematopoietic stem cell transplantation.

Objective:To evaluate the safety and efficacy of 3D printing-assisted pre-fenestration and branch stent endovascular repair (F/b EVAR) in the treatment of thoracoabdominal aortic aneurysms.Methods:The clinical data of 26 patients treated with 3D printing-assisted F/b EVAR for complicated thoracic and abdominal aortic diseases at the Department of Vascular Surgery, the Ninth People's Hospital,Shanghai Jiaotong University School of Medicine from May 2019 to Sep 2022 were retrospectively analyzed.Results:The success rate in these 26 cases of TAAA with 3D printing combined with F/b EVAR was 97.89%, and the mean follow-up time was (8.03±4.15) months. Four cases had Ⅲc internal leakage and disappeared during the follow-up. One case of type Ⅲ leakage were narrowed during follow-up. Ic type internal leakage occurred in 1 patient and disappeared after the addition of a stent at the distal end. During the follow-up period, aortic CTA indicated that 1 patient had renal artery stent occlusion and smooth blood in other visceral branches. No complications such as organ ischemia, lower limb ischemia and all-cause death occurred during follow-up.Conclusion:3D printing-assisted F/b EVAR minimally invasive repair of TAAA is a feasible, effective and safe technique, with high success rate and low complication rate of visceral branch artery reconstruction.

On the basis of establishing the prescription of Xinjianqu and clarifying the increase of the lipid-lowering active ingredients of Xinjianqu by fermentation, this paper further compared the differences in the lipid-lowering effects of Xinjianqu before and after fermentation, and studied the mechanism of Xinjianqu in the treatment of hyperlipidemia. Seventy SD rats were randomly divided into seven groups, including normal group, model group, positive drug simvastatin group(0.02 g·kg~(-1)), and low-dose and high-dose Xinjianqu groups before and after fermentation(1.6 g·kg~(-1) and 8 g·kg~(-1)), with ten rats in each group. Rats in each group were given high-fat diet continuously for six weeks to establish the model of hyperlipidemia(HLP). After successful modeling, the rats were given high-fat diet and gavaged by the corresponding drugs for six weeks, once a day, to compare the effects of Xinjianqu on the body mass, liver coefficient, and small intestine propulsion rate of rats with HLP before and after fermentation. The effects of Xinjianqu before and after fermentation on total cholesterol(TC), triacylglyceride(TG), high-density lipoprotein cholesterol(HDL-C), low-density lipoprotein cholesterol(LDL-C), alanine aminotransferase(ALT), aspartate aminotransferase(AST), blood urea nitrogen(BUN), creatinine(Cr), motilin(MTL), gastrin(GAS), and the Na~+-K~+-ATPase levels were determined by enzyme-linked immunosorbent assay(ELISA). The effects of Xinjianqu on liver morphology of rats with HLP were investigated by hematoxylin-eosin(HE) staining and oil red O fat staining. The effects of Xinjianqu on the protein expression of adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK), phosphorylated AMPK(p-AMPK), liver kinase B1(LKB1), and 3-hydroxy-3-methylglutarate monoacyl coenzyme A reductase(HMGCR) in liver tissues were investigated by immunohistochemistry. The effects of Xinjianqu on the regulation of intestinal flora structure of rats with HLP were studied based on 16S rDNA high-throughput sequencing technology. The results showed that compared with those in the normal group, rats in the model group had significantly higher body mass and liver coefficient(P<0.01), significantly lower small intestine propulsion rate(P<0.01), significantly higher serum levels of TC, TG, LDL-C, ALT, AST, BUN, Cr, and AQP2(P<0.01), and significantly lower serum levels of HDL-C, MTL, GAS, Na~+-K~+-ATP levels(P<0.01). The protein expression of AMPK, p-AMPK, and LKB1 in the livers of rats in the model group was significantly decreased(P<0.01), and that of HMGCR was significantly increased(P<0.01). In addition, the observed＿otus, Shannon, and Chao1 indices were significantly decreased(P<0.05 or P<0.01) in rat fecal flora in the model group. Besides, in the model group, the relative abundance of Firmicutes was reduced, while that of Verrucomicrobia and Proteobacteria was increased, and the relative abundance of beneficial genera such as Ligilactobacillus and Lachnospiraceae＿NK4A136＿group was reduced. Compared with the model group, all Xinjianqu groups regulated the body mass, liver coefficient, and small intestine index of rats with HLP(P<0.05 or P<0.01), reduced the serum levels of TC, TG, LDL-C, ALT, AST, BUN, Cr, and AQP2, increased the serum levels of HDL-C, MTL, GAS, and Na~+-K~+-ATP, improved the liver morphology, and increased the protein expression gray value of AMPK, p-AMPK, and LKB1 in the liver of rats with HLP and decreased that of LKB1. Xinjianqu groups could regulate the intestinal flora structure of rats with HLP, increased observed＿otus, Shannon, Chao1 indices, and increased the relative abundance of Firmicutes, Ligilactobacillus(genus), Lachnospiraceae＿NK4A136＿group(genus). Besides, the high-dose Xinjianqu-fermented group had significant effects on body mass, liver coefficient, small intestine propulsion rate, and serum index levels of rats with HLP(P<0.01), and the effects were better than those of Xinjianqu groups before fermentation. The above results show that Xinjianqu can improve the blood lipid level, liver and kidney function, and gastrointestinal motility of rats with HLP, and the improvement effect of Xinjianqu on hyperlipidemia is significantly enhanced by fermentation. The mechanism may be related to AMPK, p-AMPK, LKB1, and HMGCR protein in the LKB1-AMPK pathway and the regulation of intestinal flora structure.
Rats ; Animals ; AMP-Activated Protein Kinases/metabolism* ; Rats, Sprague-Dawley ; Cholesterol, LDL ; Fermentation ; Aquaporin 2/metabolism* ; Lipid Metabolism ; Liver ; Lipids ; Hyperlipidemias/genetics* ; Adenosine Triphosphate/pharmacology* ; Diet, High-Fat/adverse effects*