Objective To explore the value of multiparameter MRI for follow-up observation on changes of spinal cord microstructures in patients with hereditary spastic paraplegias type 5.Methods Eleven patients with SPG5 who underwent cervico-thoracic spinal cord MR examination and spastic paraplegia rating scale(SPRS)were prospectively enrolled.The second MR examination and SPRS were completed after 1 year follow-up,and the changes of SPRS score,the overall structures and microstructures of spinal cord were compared.Results No significant difference of SPRS scores was found(P＞0.05).Compared to the first cervico-thoracic spinal cord MR examination,atrophy of spinal cord aggravated in the second time MRI.Significant difference of axial diffusivity of C4 right corticospinal tract(CST)was found(t=3.987,P＜0.01),but not of the other parameters of C4(all P＞0.05)between the first and the second time MRI.No significant difference of fractional anisotropy(FA),mean diffusivity(MD),AD,radial diffusivity(RD)nor T1 value of the other centrums'white matter,posterior funiculus or bilateral CST in spinal cord was found between the first and the second time MRI(all P＞0.05).Meanwhile,no significant difference of CSA,left and right diameter nor anteroposterior diameter of C1-T9 was found between the first and second time MRI(all P＞0.05).FA value of white matter,posterior funiculus and bilateral corticospinal tract in cervical spinal cord were all lower,whereas RD value at the above position were all higher in the second time MRI than those in the first time MRI(all P＞0.05).Conclusion Multiparameter MRI could be used for follow-up observation on changes of microstructure spinal cord in patients with hereditary spastic paraplegias type 5.

Objective:To explore whether the food additive sodium benzoate(NAB) induces pancreatic inflammation and β cell apoptosis through the benzoylation(Kbz) modification pathway.Methods:In vivo experiments: C57BL/6J male mice(8 weeks old, 18-20 g) were randomly divided into normal control group(double distilled water feeding) and NAB feeding group(1 g/kg NAB feeding). Blood glucose were measured. After 20 weeks, fasting serum insulin, interleukin(IL)-18, IL-1β, and benzoyl-CoA levels were detected by ELISA method. Bax, IL-18, Pan-Kbz and Pan-Kac were detected by immunohistochemistry staining. In vitro experiments: β-TC-6 cells were cultured with NAB(6 mmol/L) or benzoyl-CoA(100 μmol/L) as stimulator and acyltransferase P300 inhibitor A485(10 μmol/L) as intervention factor. 24 hours later, inflammation, apoptosis, insulin secretion and Pan-Kbz level were detected by qRT-PCR, ELISA and Western blotting.Results:In the in vivo experiments, compared to the NC group, mice in the NAB group exhibited impaired glucose tolerance, decreased fasting insulin levels, significantly increased serum benzoyl coenzyme A concentrations, relatively elevated pancreatic IL-1β, IL-18, and Bax protein expressions, increased levels of Pan-Kbz, while Pan-Kac levels were downregulated(all P<0.05); In vitro experiments, NAB dose-dependently inhibited insulin secretion, promoted the release of Pan-Kbz and inflammatory factors IL-18 and TNF- α, inhibited Bcl-2 expression and up-regulated Bax expression, A485 reversed NAB-induced Pan-Kbz modification, improved NAB-induced inflammation and apoptosis, and promoted insulin secretion(all P<0.05). Conclusion:NAB may induce pancreatic inflammation, β-cell apoptosis, and impair insulin secretion through Kbz modification pathway.

Objective:To compare the clinical efficacy and pharmacoeconomic evaluation of bevacizumab or cetuximab combined with chemotherapy in the treatment of advanced colorectal cancer.Methods:The clinical data of 68 patients with advanced colorectal cancer from January 2018 to December 2020 in Baotou Tumor Hospital were retrospectively analyzed. Among them, 40 patients with treated with bevacizumab combined with chemotherapy (bevacizumab group), 28 patients were treated with cetuximab combined with chemotherapy (cetuximab group), and the chemotherapy of two group was FOLFOX/FOLFIRI program. The short-term clinical efficacy, adverse reactions and pharmacoeconomic evaluation result were compared between two groups.Results:There were no statistical differences in effective rate and disease control rate between bevacizumab group and cetuximab group: 30.00% (12/40) vs. 28.57% (8/28) and 67.5% (27/40) vs. 60.71% (17/28), P>0.05. The incidence of Ⅲ to Ⅳ grade erythra in bevacizumab group was significantly lower than that in cetuximab group: 2.50% (1/40) vs. 71.43% (20/28), and there was statistical difference ( P<0.01); there were no statistical differences in the incidences of Ⅲ to Ⅳ grade bone marrow suppression, nausea vomiting, hepatic functional lesion and diarrhea between two groups ( P>0.05). The pharmacoeconomic evaluation result showed that the cost of monoclonal antibody and total cost in bevacizumab group were significantly lower than those in cetuximab group: (9 009 ± 1 500) yuan vs. (27 840 ± 2 202) yuan and (11 242 ± 1 731) yuan vs. (29 867 ± 3 002) yuan, and there were statistical differences ( P<0.01); the cost-effectiveness ratio in bevacizumab group was 37 473.3, and it in cetuximab group was 104 430.1, the incremental cost-effectiveness ratio of two programs was 11 640.6. Conclusions:In the treatment of advanced colorectal cancer, the efficacy of bevacizumab combined with chemotherapy is similar to that of cetuximab combined with chemotherapy, but bevacizumab combined with chemotherapy has lower costs and fewer adverse reactions, so bevacizumab is more economical and applicable.

Placental and maternal-fetal circulation Doppler ultrasound are the main noninvasive means for maternal-fetal monitoring. However, Doppler studies on placental abnormalities are not well studied yet. Doppler monitoring of the maternal-fetal circulation, involving uterine arteries, umbilical arteries, and fetal vessels, is still used to screen diseases related to placental dysfunction (such as preeclampsia and fetal growth restriction) and to guide clinical management. This article reviews the advances in the clinical application of placental and maternal-fetal circulation Doppler in obstetrics to optimize the clinical management of disorders associated with abnormal placental structure and function.

Objective:To explore the effects of self-made Huoxue Xiaozhong Xunxi Decoction combined with functional exercise on postoperative swelling of affected limbs, bone metabolism and recovery of knee function in patients with traumatic fracture of tibial plateau (FTP).Methods:Randomized controlled trial. totally 80 patients after FTP surgery in the Qidong Hospital of Traditional Chinese Medicine were enrolled and divided into two groups by random number table method from January 2018 to January 2022, with 40 cases in each group. After surgery, control group was treated with functional exercise, while observation group was additionally treated with self-made Huoxue Xiaozhong Xunxi Decoction. All were treated continuously for 8 weeks. The perioperative indexes (operation time, incision length, intraoperative blood loss, postoperative drainage volume, leaving bed time) in the two groups were recorded. The postoperative swelling and pain of affected limbs were observed, and detumescence time, pain relief time, fracture healing time and complete weight-bearing time were recorded. The knee function was evaluated by Hospital for Special Surgery (HSS). The level of serum bone morphogenetic protein-2 (BMP-2) was detected by ELISA, and total n-terminal propeptide of typeⅠprecollagen (t-PINP) and β-crossLaps (β-CTX) were detected by full-automatic immunoluminescence analyzer. The occurrence of postoperative complications in the two groups was recorded.Results:There was no significant difference in operation time, incision length, intraoperative blood loss, postoperative drainage volume or leaving bed time between the two groups ( P>0.05). The total effective rate of the observation group was 97.5% (39/40), while the control group was 80.0% (32/40), with statistical significance ( χ2=6.14, P=0.013). The detumescence time, pain relief time, fracture healing time and complete weight-bearing time were earlier in the observation group than control group ( P<0.01). After 10 d of treatment, VAS score and swelling degree in observation group were lower than those in the control group ( t=7.05, 3.81, P<0.01). After 8 weeks of treatment, levels of serum BMP-2 [(625.16±67.43) μg/L vs. (542.35±53.27) μg/L, t=6.10], t-PINP [(54.16±7.29) μg/L vs. (50.34±6.12) μg/L, t=2.54] and β-CTX [(1.26±0.38) μg/L vs. (1.04±0.23) μg/L, t=3.13] in observation group were higher than those in the control group ( P<0.05). During treatment, the incidence of complications in the observation group was 2.5% (1/40) and the control group was 7.5% (3/40), without statistical significance ( χ2=1.05, P=0.305). Conclusion:Self-made Huoxue Xiaozhong Xunxi Decoction combined with functional exercise is beneficial to improve pain and swelling of affected limbs and bone metabolism, and promote the recovery of knee function in patients after FTP surgery.

This paper summarized professor ZHANG Lei′s experience in treating scleroderma from “extraordinary pathogens entering collaterals”. The basic pathogenesis of scleroderma is “extraordinary pathogens entering the collaterals”， and extraordinary pathogens can be divided into external and internal categories. External extraordinary pathogens are mostly exogenous wind， cold and damp pathogens， and the pathogenesis is wind， cold and damp invading skin stria and retaining collaterals. Most of the endogenous extraordinary pathogens are turbid phlegm and blood stasis， and the pathogenesis is endogenous phlegm and stasis leaving the channels and overflowing the collaterals， and blocking the collaterals. Blocked by extraordinary pathogens for a long time， the long illness will lead to deficiency and develop into a syndrome of collaterals excess and channels deficiency. Therefore， professor ZHANG creats Tengluo Beverage （藤络饮） as the basic formula to unblock collaterals and dispel pathogens， and recommends to add or subtract it according to the different syndrome and pathogenic characteristics of the edema stage， sclerosis stage， and atrophy stage. In the edema stage， it is advised to expel wind， remove dampness and unblock the collaterals， while in the sclerosis stage， the method of dissolving phlegm， expelling stasis and unblocking collaterals should be used； in the atrophic stage， it is suggested to differentiate the deficiency of qi， blood， yin and yang， and eliminate extraordinary pathogens on the basis of reinforcing healthy qi .

Objective : The purpose of this study was to investigate the effect of different exposure sequence and interval on the post-antibiotic effect(PAE) and 24-hour time-kill produced by linezolid and fosfomycin in combination againstStaphylococcus aureus(S.aureus). Methods: PAEs were evaluated by exposingS.aureusto linezolid and fosfomycin individually and simultaneously for 1 h.Further assess of PAEs with the organism exposed first to linezolid for 1 h, followed by a second 1 h fosfomycin exposure at the beginning(Tb),middle(Tm)and end(Te) of the PAE phase induced by linezolid.The next study was similar to the above, but with the sequence of the two antibiotics reversed, i.e.fosfomycin then linezolid.The 24-hour time-kill studies were performed with three exposure regimens: simultaneous exposure of the two antibiotics; first exposure to linezolid for 1 h and then combined with fosfomycin, and first exposure to fosfomycin for 1 h and then combined with linezolid to draw the sterilized curve. Results: Compared with the PAE of individual antibiotics [ linezolid(1.2±0.1) h, fosfomycin(1.6±0.1) h],the PAE produced by simultaneous exposure of the combination(2.9±0.1) h presented additive interaction.However, the PAE of fosfomycin decreased or even disappeared(-0.3 h for Tb, 0 h for Tm and 0.9 h for Te) during the PAE phase of linezolid, and with a stronger antagonism at the beginning.Differently, an additive interaction was observed again when the test organism was exposed to fosfomycin first.In the 24-hour time-kill assays, the antibacterial effect of the first exposure to fosfomycin regimens was significantly stronger(difference of 1 log10)than that of the simultaneous exposure and the first exposure to linezolid, while the latter two were similar. Conclusion The pharmacodynamic behaviour of linezolid combined with fosfomycin againstS.aureuswas influenced by exposure regimen.The first exposure to fosfomycin regimens rather than simultaneous exposure may exert the optimal antibacterial activity.Therefore, the exposure regimen is one of the important factors to be considered for the clinical application of this combination.

The CRISPR-Cas (clustered regularly interspaced short palindromic repeats and CRISPR-associated) system is an "adaptive immune system" found in the genomes of bacteria and archaea which is mediated by RNA and resists foreign nucleic acid invasion.Take advantage of specific recognition of target nucleic acid, CRISPR-Cas system can efficiently edit their target site or accurately regulate gene expression, and now have been developed into a powerful tool for gene editing.According to the different compositions of the effector complex, the system has been divided into two categories: class 1 (type I, type IV, and type III) and class 2 (type II, type V, and type VI).Class 2 system, like the CRISPR-Cas9, is widely used in basic research due to the earliest discovery and best research.However, class 1 has not been maturely developed and utilized though it makes up 90% of the entire CRISPR-Cas system.In this essay, the classification of subtype, the assembly of Cascade complex, the cleavage and degradation mechanism of Cas3, and the application in gene editing of class 1 type I CRISPR-Cas system will be discussed and summarized to provide new ideas and methods for further mechanism studying and application of this category.

Placenta-mediated pregnancy complication (PMPC), including preeclampsia, fetal growth restriction and recurrent pregnancy loss, is caused by inadequate trophoblast invasion and abnormal remodeling of maternal spiral arteries in early pregnancy, resulting in adverse perinatal outcomes and affecting the long-term maternal and child health. However, the molecular mechanisms of PMPC remain unclear. Endocrine gland-derived vascular endothelial growth factor (EG-VEGF) is highly expressed in human placenta and plays an important role in the development of a normal placenta through promoting placental angiogenesis and inhibiting trophoblast migration and invasion. EG-VEGF dysregulation is closely related to the pathogenesis of PMPC. This review described recent advances in EG-VEGF for better understanding of the underlying mechanism of PMPC and providing a potential biomarker for early diagnosis of PMPC.

Objective To investigate the clinical effect of perioperative electroacupuncture intervention on postoperative delirium (POD) in hip replacement surgery patients.Method One hundred and twenty-eight patients who would undergo hip replacement surgery were randomly allocated to treatment and control groups, 64 cases each. The treatment group received perioperative electroacupuncture and the control group, routine preoperative preparation and postoperative treatment. Serum S100β protein concentration was measured in the two groups of patients at one day before, the end of and one day after surgery. The incidences of POD were compared between the two groups at one, two and three days after surgery.Result There was a statistically significant difference in the incidence of POD between at one day after surgery and recovery from anesthesia in the two groups (P<0.01). In the treatment group, the incidence of POD was significantly lower at two and three days than at one day after surgery (bothP<0.05) and at three days than at two days after surgery (bothP<0.05). There was a statistically significant difference in the incidence of POD between the treatment and control groups at different time points (recovery from anesthesia, and one, two and three days after surgery) (P<0.01). In the treatment group, there was a statistically significant difference in S100β protein concentration between at one day after and the end of surgery (P<0.05). There was a statistically significant difference in S100β protein concentration between the treatment and control groups at the end of and one day after surgery (P<0.05).Conclusions Perioperative electroacupuncture treatment can effectively decrease postoperative incidence of delirium and its duration in hip replacement surgery patients.