A homozygous ARMC3 splicing variant causes asthenozoospermia and flagellar disorganization in a consanguineous family.

Male infertility due to asthenozoospermia is quite frequent, but its etiology is poorly understood. We recruited two infertile brothers, born to first-cousin parents from Pakistan, displaying idiopathic asthenozoospermia with mild stuttering disorder but no ciliary-related symptoms. Whole-exome sequencing identified a splicing variant (c.916+1G>A) in ARMC3, recessively co-segregating with asthenozoospermia in the family. The ARMC3 protein is evolutionarily highly conserved and is mostly expressed in the brain and testicular tissue of human. The ARMC3 splicing mutation leads to the exclusion of exon 8, resulting in a predicted truncated protein (p.Glu245_Asp305delfs*16). Quantitative real-time PCR revealed a significant decrease at mRNA level for ARMC3 and Western blot analysis did not detect ARMC3 protein in the patient's sperm. Individuals homozygous for the ARMC3 splicing variant displayed reduced sperm motility with frequent morphological abnormalities of sperm flagella. Transmission electron microscopy of the affected individual IV: 2 revealed vacuolation in sperm mitochondria at the midpiece and disrupted flagellar ultrastructure in the principal and end piece. Altogether, our results indicate that this novel homozygous ARMC3 splicing mutation destabilizes sperm flagella and leads to asthenozoospermia in our patients, providing a novel marker for genetic counseling and diagnosis of male infertility.

Based on UHPLC-Q-TOF-MS and bioinformatics strategies, the potential allergens and mechanisms of allergic reactions caused by Danshen injection were explored.

The aim is to investigate the potential allergens and mechanisms underlying allergic-like reactions induced by Danshen injection (DSI). Utilizing ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS), metabolomics, and bioinformatics, we identified the key allergens, targets, and metabolic pathways involved in DSI-induced allergic-like reactions, validating binding efficiency through molecular docking and molecular dynamics. A total of 45 compounds were identified within DSI, with 24 compounds exhibiting strong binding activity to the MrgprX2 activation site. DSI was found to cause changes in 89 endogenous metabolites, including arachidonic acid, prostaglandins, and leukotrienes, primarily affecting pathways such as phenylalanine metabolism and arachidonic acid metabolism. The key allergens identified were Cryptotanshinone, Miltipolone, Neocryptotanshinone, Salvianolic acid B, and Isosalvianolic acid C, which primarily trigger allergic-like reactions by regulating upstream signaling targets such as ALOX5, PTGS1, PPARD, and LTB4R. Validation confirmed the high binding affinity and stability between key allergens and targets. These findings indicate that the allergic components in DSI primarily induce allergic-like reactions by modulating the aforementioned signaling targets, activating the AA metabolic pathway, promoting mast cell degranulation, and releasing downstream endogenous inflammatory mediators, subsequently eliciting allergic-like reactions.

Gas Chromatography-Mass Spectrometry Metabolites and Transcriptome Profiling Reveal Molecular Mechanisms and Differences in Terpene Biosynthesis in Two Torrya grandis Cultivars during Postharvest Ripening.

Terpene aroma compounds are key quality attributes of postharvest Torreya grandis nuts, contributing to their commercial value. However, terpene biosynthesis and regulatory networks in different T. grandis cvs. are still poorly understood. Here, chief cvs. 'Xi Fei' and 'Xiangya Fei' were investigated for their differences in terpene biosynthesis and gene expression levels during postharvest ripening using headspace solid-phase microextraction (HS-SPME) coupled with gas chromatography-mass spectrometry (GC-MS) and transcriptomic datasets. A total of 28 and 22 aroma compounds were identified in 'Xi Fei' and 'Xiangya Fei', respectively. Interestingly, differences in aroma composition between the two cvs. were mostly attributed to D-limonene and α-pinene levels as key determinants in Torreya nuts' flavor. Further, transcriptome profiling, correlation analysis, and RT-qPCR annotated two novel genes, TgTPS1 in 'Xi Fei' and TgTPS2 in 'Xiangya Fei', involved in terpene biosynthesis. In addition, six transcription factors (TFs) with comparable expression patterns to TgTPS1 and four TFs to TgTPS2 were identified via correlation analysis of a volatile and transcriptome dataset to be involved in terpene biosynthesis. Our study provides novel insight into terpene biosynthesis and its regulation at the molecular level in T. grandis nut and presents a valuable reference for metabolic engineering and aroma improvement in this less explored nut.

Experimental Demonstrations of Alignment and Mode Matching in Optical Cavities with Higher-Order Hermite-Gauss Modes.

Higher-order spatial laser modes have recently been investigated as candidates for reducing test-mass thermal noise in ground-based gravitational-wave detectors such as advanced LIGO. In particular, higher-order Hermite-Gauss (HG) modes have gained attention within the community for their more robust behaviors against random test-mass surface deformations and stronger sensing and control capacities. In this Letter we offer experimental investigations on various aspects of HG mode interferometry. We have generated purified HG modes up to the twelfth order HG_{6,6} mode, with a power conversion efficiency of 38.8% and 27.7% for the HG_{3,3} and HG_{6,6} modes respectively. We demonstrate for the first time the misalignment and mode mismatch-induced power coupling loss measurements for HG modes up to the HG_{6,6}. We report an excellent agreement with the extended numerical power loss factors that in the "small power loss" region converge to 2n+1 or n^{2}+n+1 for a misaligned or mode mismatched HG_{n,n} mode. We also demonstrate the wavefront sensing (WFS) signal measurement for HG modes up to the HG_{6,6}. The measurement result is accurately in accordance with theoretical WFS gain ß_{n,n-1}sqrt[n]+ß_{n,n+1}sqrt[n+1] for an HG_{n,n} mode, with ß_{n,n-1} being the beat coefficient of the adjacent HG_{n,n} and HG_{n-1,n} modes on a split photodetector.

Efficacy and safety of budesonide combined with pulmonary surfactant in the treatment of neonatal meconium aspiration syndrome:a systematic review / 药物流行病学杂志

Objective To evaluate the efficacy and safety of budesonide combined with pulmonary surfactant(PS)in the treatment of meconium aspiration syndrome(MAS)in neonates.Methods PubMed,Cochrane Central Register of Controlled Trials(Central),Embase,Web of Science,SinoMed,VIP,WanFang Data and CNKI databases were electronically searched to collect randomized controlled trials(RCTs)of budesonide combined with PS in the treatment of neonatal MAS from inception to September 2,2023.Two researchers independently screened literature,extracted data and assessed the risk of bias of the included studies,meta-analyses were performed by using the RevMan 5.4 software.Results A total of 6 RCTs involving 544 patients were included.The results of meta-analysis showed that compared with PS group,budesonide combined with PS group had higher overall effective rate(RR=1.29,95％CI 1.17 to 1.41,P＜0.001),shorter hospital stay(MD=-6.35,95％CI-9.25 to-3.46,P＜0.001)and shorter time of oxygen inhalation(MD=-1.61,95％CI-2.23 to-0.98,P＜0.001),shorter the duration of ventilator use(MD=-26.46,95％CI-35.98 to-16.95,P＜0.001),improved the blood gas analysis indexes at each time after treatment(P＜0.05);In terms of safety,the incidence of total complications and adverse reactions in budesonide combined with PS group was significantly lower(RR=0.35,95％CI 0.25 to 0.47,P＜0.001).Subgroup analysis showed that the incidence of persistent pulmonary hypertension of the newborn(PPHN)in the budesonide combined with PS group was decreased(RR=0.38,95％CI 0.19 to 0.74,P=0.004),and the incidence of pneumorrhagia was decreased(RR=0.26,95％CI 0.10 to 0.69,P=0.007),and the difference was statistically significant;the incidence of heart failure and sepsis was not statistically significant compared with the PS group(P＞0.05).Conclusion Current evidence shows that budesonide combined with PS in the treatment of neonatal meconium aspiration syndrome can improve the symptoms and signs of MAS children,improve the blood gas analysis index,accelerate disease rehabilitation,shorten the course of the disease,can help reduce the risk of complications and PPHN,pneumorrhagia,and doesn't increase the incidence of heart failure,sepsis.Due to the limited quantity of the included studies,more high-quality and large-sample RCTs are needed to further validate the above conclusions.

Application progresses of new ultrasonic technologies for assisting diagnosis of BI-RADS 4 lesions / 中国介入影像与治疗学

The ultrasonic manifestations of benign and malignant breast imaging-reporting and data system(BI-RADS)4 lesions overlap in some degrees,is able to result in unnecessary biopsy or untimely therapy.Accurate classifying the nature of BI-RADS 4 breast lesions can provide reliable references for clinical decision-making.The progresses of application of new ultrasonic technologies,including automated breast volume scanner,superb micro-vascular imaging,elastography,contrast-enhanced ultrasound and artificial intelligence for assisting diagnosis of BI-RADS 4 lesions were reviewed in this article.

Study on the application value of combined spinal-epidural anesthesia under the assistant of ultrasound localization on patients with lower limb fracture / 中国医学装备

Objective:To explore application value of combined spinal-epidural anesthesia under the assistant of ultrasound location on lower limb fractures.Methods:A total of 80 patients with lower limb fractures who underwent surgical treatment at the 901th Hospital of the PLA Joint Service Support Force from July 2020 to July 2022 were selected,and they were divided into a control group and an observation group according to the random number table method,with 40 cases in each group.The control group received epidural anesthesia under ultrasound,and the observation group received the combined lumbar-epidural anesthesia under ultrasound.The lidocaine dosage,anesthetic block time,anesthesia onset time and dosage of additional analgesic,as well as the changes in vital signs such as diastolic blood pressure(DBP),systolic blood pressure(SBP)and heart rate(HR),between the two groups of patients were compared.In addition,the thrombelastogram,anesthetic effects and occurrence of adverse reactions also were compared between two groups.Results:The lidocaine dosage,anesthetic block time,anesthesia onset time and dosage of additional analgesic of the observation group were significantly higher than those in the control group,and the differences were statistically significant(t=8.657,23.483,12.785,16.600,P<0.05),respectively.There were no statistically significant differences in DBP,SBP,HR,comprehensive coagulation index(CI),reaction time(R),formation time of blood cell agglutination(K)and incidence of adverse reactions between two groups before anesthesia,at the 30th minute after anesthesia and after the end of anesthesia(P>0.05).Compared with α angle before anesthesia and at the 30th minute after anesthesia,the α angles of the two groups increased significantly after anesthesia(t=6.564,5.783,P<0.05),respectively.The mechanical strength(G)of the blood clot and the maximum amplitude(MA)of chromatogram of the observation group were significantly reduced after completed anesthesia,and the differences of them were statistically significant(t=8.480,4.236,P<0.05),respectively.There were no significant differences between G and MA in the control group(P>0.05).The total effective rate of the observation group was 97.50%,which was significantly higher than 80.00% of the control group,and the difference was statistically significant(x2=4.507,P<0.05).Conclusion:The combined spinal-epidural anesthesia under the assistant of ultrasound location can effectively reduce the amount of anesthetics in patients with lower limb fracture,which has fast block and effect.In addition,it has little influence on circulatory function,and it is less likely to form a hypercoagulable state.It has better clinical anesthesia effect.

Clinical comparative analysis of computer navigation-assisted versus freehanded pedicle screw placement in lumbar spondylolysis surgery / 中华创伤骨科杂志

Objective:To compare the efficacy of pedicle screw placement between computer navigation guidance and freehand assistance in the surgical treatment of isthmic spondylolysis at the lumbar vertebrae.Methods:A retrospective study was conducted to analyze the 47 patients with bilateral isthmic spondylolysis at the L 5 vertebra who had been treated at Department of Spinal Surgery, The General Hospital of Xinjiang Military Command from January 2020 to April 2023. All were male patients with an age of (24.0±4.3) years. They were divided into a study group (13 cases subjected to pedicle screw placement assisted by computer navigation guidance) and a control group (34 cases subjected to pedicle screw placement assisted freehandedly). The 2 groups were compared in terms of surgical incision length, intraoperative bleeding, screw placement time, postoperative hospital stay, total hospitalization cost, postoperative complications, rate of screw reposition, angle between pedicle screw and upper endplate, angle between bilateral pedicle screws, and placement accuracy; the visual analogue scale (VAS) for pain, Japanese Orthopaedic Association (JOA) score for lumbar spine function, and Oswestry disability index (ODI) were also compared between preoperation, 1-week postoperation, and the last follow-up. Patient satisfaction was assessed according to the modified MacNab criteria, and internal fixation failure and isthmic healing were also evaluated at the last follow-up. Results:There were no statistically significant differences in the preoperative general data between the 2 groups, showing comparability ( P>0.05). The differences were not statistically significant in surgical incision length, intraoperative bleeding, screw placement time, postoperative hospital stay, or postoperative complications ( P>0.05). However, in the study group, the total hospitalization cost was significantly higher than that in the control group, the rate of screw reposition [7.7% (2/26)] significantly lower than that in the study group [26.5% (18/68)], the angle between pedicle screw and upper endplate and the angle between bilateral pedicle screws were both significantly smaller than those in the control group, and the placement accuracy [92.3% (24/26)] was significantly greater than that [70.6% (48/68)] in the control group (all P<0.05). All patients were followed up for 7.0 (5.0, 14.0) months. Patients in both groups showed significant improvements in VAS, JOA score, and ODI at postoperative 1 week and the last follow-up compared with the preoperative values, and the improvements at the last follow-up were significantly larger than those at postoperative 1 week ( P<0.05). According to the modified MacNab criteria at the last follow-up, patient satisfaction was rated as excellent in 10 cases, as good in 2 cases and as moderate in 1 case in the study group while as excellent in 27 cases, as good in 3 cases, as moderate in 3 cases and as poor in 1 case in the control group. In the study group, there were 1 case of internal fixation failure, 1 case of spine cutting-out by titanium cable, and 12 cases of bony healing of the isthmus; in the control group, there were 2 cases of internal fixation failure, 2 cases of spine cutting-out by titanium cable, and 29 cases of bony healing of the isthmus. Conclusions:In the surgical treatment of bilateral isthmic spondylolysis at the L 5 vertebra, computer navigation-guided pedicle screw placement is safe and reliable, showing an advantage of higher accuracy over freehand placement. It deserves clinical promotion due to its satisfactory therapeutic effects.

Clinical features of maternal pulmonary thromboembolism: analysis of 16 cases / 中华围产医学杂志

Objective:To summarize the clinical features, pregnancy outcomes, and treatment strategies of pulmonary thromboembolism (PTE) in pregnant women and puerperae.Methods:Clinical data of 16 pregnant women or puerperae with PTE who were admitted to Beijing Anzhen Hospital from January 2012 to December 2022 were retrospectively collected. Descriptive statistical analysis was used to summarize the clinical features, treatment strategies, and pregnancy outcomes in these cases.Results:The average age of the 16 patients was (29.6±3.5) years (26-35 years) and the median onset time was 12 weeks (7-38 weeks) of gestation in six pregnant women and 4 d (16 h-40 d) after delivery in ten puerperae. There were two cases of high-risk type; nine cases of medium-risk type (six of medium-high risk and three of medium-low risk); and five cases of low-risk type. Definite high-risk factors were detected in four pregnant women (venous thromboembolism risk score ≤2) and nine puerperae (venous thromboembolism risk score of 2-9). None of the six pregnant women had any indications for preventive anticoagulant therapy and nine puerperae had indications but without preventive therapy. All the patients were treated with low molecular weight heparin and sequential administration of warfarin/rivaroxaban, in addition to that, two high-risk patients also received thrombolytic therapy. After therapy, all pregnant women terminated their pregnancies in time and then continued to receive anticoagulation treatment. All 16 patients survived. Among the six pregnant women, five who developed PTE in the first or second trimester underwent iatrogenic termination of pregnancy, and one who developed PTE in the third trimester gave live birth. Among the 10 puerperae, one had PTE after the termination of pregnancy in the second trimester due to intrauterine fetal death; one developed PTE after abortion in the first trimester; the other eight cases developed PTE after cesarean section in the third trimester, with all newborns surviving.Conclusions:Pregnant women and puerperae are at high risk of PTE and most have high-risk factors. Therefore, more attention should be paid to the screening of high-risk factors and the initiation of preventive anticoagulant therapy. Maternal outcomes are good after PTE treatment, but fetal outcomes depend on the time of onset.

Role of MAPK Signaling Pathway in Prevention and Treatment of Rheumatoid Arthritis and Chinese Medicine Intervention： A Review / 中国实验方剂学杂志

Rheumatoid arthritis （RA） is an autoimmune disease involving symmetrical small joints， with clinical manifestations such as small joint swelling， morning stiffness， progressive pain， and even joint deformity and loss of function. Due to the complex immune mechanism， the pathogenesis of RA remains unclear. However， studies have shown that the pathogenesis of RA is related to abnormal immune mechanism， increased synovial inflammatory response， abnormal biological behavior of RA fibroblast-like synoviocytes （RA-FLSs）， and abnormal degradation of extracellular matrix. Mitogen-activated protein kinase （MAPK） plays a key role in the regulation of cell growth， proliferation， differentiation， and apoptosis. It is involved in the abnormal release and activation of inflammatory mediators in RA， the abnormal proliferation， migration， and invasion of RA-FLSs， synovial angiogenesis， bone erosion， and cartilage destruction. The thousands of years of practical experience show that Chinese medicine can effectively mitigate the clinical symptoms such as joint swelling， morning stiffness， and pain and delay the occurrence of joint deformity in RA patients. Moreover， the Chinese medicine treatment has the advantages of overall regulation， personalized treatment， multiple pathways and targets， high safety， few adverse reactions， and stable quality. Modern studies have confirmed that Chinese medicine can play a role in the prevention and treatment of RA by interfering in the MAPK signaling pathway， reducing pro-inflammatory cytokines， inhibiting the abnormal proliferation， migration， and invasion of RA-FLSs， regulating the apoptosis of RA-FLSs， and protecting extracellular matrix. This article elaborates on the key role of MAPK signaling pathway in the development of RA and reviews the latest research results of Chinese medicine intervention in MAPK signaling pathway for the prevention and treatment RA， aiming to provide a basis for the development of new drugs and the clinical application of Chinese medicine in the prevention and treatment of RA.

Discussion on the relationship between irritable bowel syndrome and premature ejaculation from 5-HT and prediction of natural drugs / 国际中医中药杂志

Objective:To explore the relationship between irritable bowel syndrome (IBS) and premature ejaculation (PE) from 5-HT; To predict the natural drugs with therapeutic effect.Methods:Targets related to IBS and PE were screened in the GeneCards, DisGeNET, TTD, OMIM, DrugBank databases. After removing duplicates, the two disease targets were intersected and imported into STRING platform, and the protein interaction network between IBS and PE targets related to 5-HT receptor was obtained. GO enrichment analysis was carried out on the intersected targets by R language, and Coremine Medical platform was used for predicting natural drugs.Results:5-HT1A, 5-HT1B, 5-HT2A, 5-HT2C and 5-HT3A were the common targets related to 5-HT in IBS and PE. GO function enrichment yielded 250 gene function related information, mainly enriched in serotonin receptor signaling pathways, cell response to dopamine, and response to dopamine. The prediction of natural drugs obtained 14 kinds of Chinese materia medica, including Nelumbinis Semen, Nelumbinis Rhizomatis Nodus, Nelumbinis Receptaculum, Nelumbinis Stamen, Nelumbinis Folium, Nelumbinis Plumula, Ginkgo Semen, and Ginkgo Folium.Conclusions:Abnormal 5-HT levels can affect gastrointestinal motility, ejaculation latency, and glans sensitivity. Elevated central 5-HT levels are a common pathogenesis of IBS and PE. The interaction between receptors such as 5-HT1A and 5-HT3A and 5-HT can regulate gastrointestinal motility and secretion activities, intestinal nervous system, and reduce intestinal hypersensitivity; increasing the sensitivity of the 5-HT1A receptor can reduce the ejaculation threshold and promote ejaculation, while increasing the sensitivity of the 5-HT2C receptor can increase the ejaculation threshold.

Safety and efficacy of ExoSeal vascular occluder in bridging therapy for acute ischemic stroke / 介入放射学杂志

Objective To investigate the safety and efficacy of ExoSeal vascular occluder in bridging therapy for patients with acute ischemic stroke(AIS).Methods The clinical data of 142 AIS patients,who received mechanical thrombectomy in the bridge-connected vascular lumen after full dose recombinant tissue plasminogen activator(rt-PA)thrombolysis at the Weifang Municipal People's Hospital of China between June 2018 and December 2020,were retrospectively analyzed.An 8-F femoral arterial sheath was used for the performance of endovascular mechanical thrombectomy in all patients.After the interventional procedure finished,the hemostasis of femoral artery puncture point was achieved by using manual compression(MC)method in 68 patients(MC group)and by using a 7-F ExoSeal vascular occluder method in 74 patients(ExoSeal group).The success rate of puncture point hemostasis and the incidence of puncture point-related complications were compared between the two methods.Results The success rate of surgery in the ExoSeal group was 94.6％,which was obviously higher than 83.8％in the MC group(P=0.037).During the period from the time of finishing surgery and the time of discharge,11 patients(16.2％)in the MC group and 4 patients(5.4％)in the ExoSeal group developed puncture point-related complications(P=0.030),and 6 patients(8.8％)in the MC group and 2 patients(2.7％)in the ExoSeal group developed deep vein thrombosis(P=0.109).No arteriovenous fistula,pseudoaneurysm,acute ischemia of the ipsilateral lower limb,puncture point-associated major bleeding,or other complications that required vascular surgery or interventional therapy occurred in all patients.Conclusion ExoSeal vascular closure device can be safely used in AIS patients who are receiving mechanical thrombectomy in the bridge-connected vascular lumen after thrombolysis.It carries high success rate for femoral artery puncture point hemostasis,besides,it can reduce the incidence of puncture point hematoma.

Transarterial infusion chemotherapy combined with lipiodol chemoembolization for the treatment of advanced colorectal cancer / 介入放射学杂志

Objective To discuss the clinical safety,feasibility and efficacy of transcatheter arterial infusion chemotherapy(TAI)combined with lipiodol chemoembolization in the treatment of advanced colorectal cancer(CRC).Methods The clinical data of 37 patients with advanced CRC,who received TAI combined with lipiodol chemoembolization at the First Affiliated Hospital of Zhengzhou University of China between June 2016 and December 2022,were retrospectively analyzed.The clinical efficacy was evaluated,the progression-free survival(PFS)and the serious complications were recorded.Results A total of 55 times of TAI combined with lipiodol chemoembolization procedures were successfully accomplished in the 37 patients.The mean used amount of lipiodol emulsion was 2.9 mL(0.8-10 mL).No serious complications such as bleeding and intestinal perforation occurred.The median follow-up time was 24 months(range of 3-48 months).The postoperative one-month,3-month,6-month and 12-month objective remission rates(ORR)were 67.6%(25/37),67.6%(25/37),64.9%(24/37)and 56.8%(21/37)respectively,and the postoperative one-month,3-month,6-month and 12-month disease control rates(DCR)were 91.9%(34/37),91.9%(34/37),89.2%(33/37)and 81.1%(30/37)respectively.The median PFS was 16 months(range of 2-47 months).As of the last follow-up,22 patients survived and 15 patients died of terminal stage of tumor.Conclusion Preliminary results of this study indicate that TAI combined with lipiodol chemoembolization is clinically safe and effective for advanced CRC,and it provide a new therapeutic method for patients with advanced CRC.

Clinical analysis of 29 cases of postsurgical gastroparesis syndrome after laparoscopic radical resection of right-side colon cancer / 临床外科杂志

Objective To investigate the influencing factors of postoperative gastroparesis syndrome(PSG)after laparoscopic right hemicolon cancer resection.Methods A total of 1070 patients with laparoscopic right hemicolon cancer resection(complete right hemicolon mesoresection)were selected from Wuhan General Hospital of Yangtze River Shipping and Wuhan Union Hospital Cancer Department from December 2012 to June 2022.According to whether the patients got postoperative gastroparesis,were divided into the postoperative gastroparesis syndrome(PSG)group or the normal control group.Univariate and multivariate Logistic regression analysis were used to analyze the risk factors of PGS after right hemicolon resection.Results There were 29 patients in the gastroparesis group and 1041 patients in the normal control group.Univariate analysis showed that age,perioperative blood glucose level,surgical resection range,and surgical approach were related to the occurrence of PGS(P＜0.05).Multivariate Logistic analysis showed that age,high perioperative blood glucose level,caudal approach plus combined approach,and large surgical resection range were independent influencing factors of PGS(P＜0.05).Conclusions Age,high perioperative blood glucose level,caudal approach plus combined approach,and large surgical resection range are influencing factors of PGS.

The effect of Xiaoaiping combined with camrelizumab on serum VEGF and tumor markers in advanced esophageal cancer / 中国现代医生

@#Objective To explore the effects of Xiaoaiping and camrelizumab on vascular endothelial growth factor(VEGF)and tumor markers in patients with advanced esophageal cancer.Methods A total of 43 patients with advanced esophageal cancer who were treated in the First Affiliated Hospital of Guangxi Medical University and Guangxi International Zhuang Medicine Hospital Affiliated to Guangxi University of Chinese Medicine from March 2020 to March 2022 were selected and divided into control group and combined treatment group according to the random number table method.Both groups were treated with camrelizumab immunotherapy,and the patients in combined treatment group were also treated with Xiaoaiping injection until disease progression.The levels of VEGF and tumor markers in two groups were detected after the first cycle,the third cycle,the sixth cycle,the ninth cycle and the seventeenth cycle of treatment.Results The levels of VEGF,carbohydrate antigen 125(CA125),carbohydrate antigen 199(CA199)and carcinoembryonic antigen(CEA)in the first cycle and the third cycle in two groups had no significant difference before and after treatment(P>0.05);There was no significant difference in CA125,CA199 and VEGF levels between two groups in the 6th cycle(P>0.05);There was a significant difference in CEA level between two groups(P<0.05);The levels of VEGF,CA125,CA199 and CEA in combined treatment group were significantly lower than those in control group at the 9th cycle and the 17th cycle(P<0.05).Conclusion Xiaoaiping combined with camrelizumab has a good clinical effect on patients with advanced esophageal cancer,which can reduce the levels of VEGF and tumor markers in patients.

Traditional Chinese medicine monomer in the prevention and treatment of flap necrosis by regulating"autophagy" / 中国组织工程研究

BACKGROUND:In recent years,it has been found that some traditional Chinese medicine monomers can alleviate oxidative stress and apoptosis of the skin flap,promote vascular regeneration of the skin flap and prevent skin flap necrosis by activating autophagy. OBJECTIVE:To review the research progress of traditional Chinese medicine monomer regulating autophagy in preventing flap necrosis. METHODS:The Chinese and English key words were"traditional Chinese medicine(TCM),autophagy,skin flaps".The first author searched the relevant articles published in CNKI and PubMed databases from January 2010 to October 2022.A total of 196 articles were retrieved in the preliminary screening and then screened according to the inclusion and exclusion criteria.The quality assessment was conducted by reading the literature titles and abstracts.Finally,55 articles were summarized. RESULTS AND CONCLUSION:(1)The regulation of autophagy is mediated by AMPK/mTOR,PI3K/AKT and other signaling pathways.Activation of autophagy can alleviate the oxidative stress and apoptosis of the flap,promote the regeneration of blood vessels in the flap,and prevent flap necrosis.(2)Terpenoids(Betulinic acid,Andrographolide,Notoginseng Triterpenes,Catalpa),phenolic compounds(Resveratrol,Curcumin,Gastrodin),phenolic acids(Salvianolic acid B)and steroid compounds(Pseudoginsenoside F11)in traditional Chinese medicine monomers can alleviate oxidative stress and apoptosis of skin flap by regulating related signaling pathways to activate autophagy,promote skin flap angiogenesis and promote skin flap survival.(3)Studying the research progress of traditional Chinese medicine monomer to prevent flap necrosis by regulating autophagy can provide a reference and theoretical basis for traditional Chinese medicine to prevent flap necrosis and promote flap healing in the clinic.

Animal models of femoral bone defects:preparation status and characteristics / 中国组织工程研究

BACKGROUND:The repair and clinical outcome of bone defects remains a hot and difficult area of clinical research,which is a common problem that plagues clinicians.Constructing suitable,reproducible and infinitely close to clinical animal experimental models and their scientific evaluation are essential for further clinical treatment of related diseases. OBJECTIVE:To retrospectively analyze the preparation methods and characteristics of common animal models of femoral bone defects and to assess their strengths and weaknesses,thereby providing some reference for relevant researchers to select appropriate animal models of femoral bone defects. METHODS:PubMed,Web of Science,Medline,and CNKI were retrieved for relevant literature published from January 1,2000 to August 1,2022.The keywords were"bone defect,bone,bones,defect,defects,defective,animal model,animal,model,laboratory,laboratory animal,animal laboratory"in English and"bone defect,animal model,experiment"in Chinese. RESULTS AND CONCLUSION:Twenty-seven randomized controlled animal experiments involving rats,mice,New Zealand rabbits,and sheep were included,analyzed and assessed.The most common types of bone defects were cylindrical bone defects and segmental osteotomy bone defects,generally found in the middle and distal femur.These models are mostly used to evaluate the effects of bone repair materials,drugs,drug-loaded active substances and physical therapy on bone defect repair and explore defect healing mechanisms,particularly the weight-bearing bone defect repair mechanism.Different defect kinds and femoral bone defect ranges have been found in different animal experiments.Researchers can select the suitable animal model and bone defect type based on the goal of the experiment and then set an acceptable bone defect value.Current studies have shown that cylindrical and segmental osteotomy-induced bone defects,mainly in the distal and middle femur,are mostly used in the animal models of femoral bone defects and that the surgical methods and postoperative management are more mature and operable to provide mature experimental animal models.In terms of cylindrical bone defects,rats and New Zealand rabbits are more suitable,whereas segmental osteotomy has no special requirements and all types of animals can meet the experimental requirements.

In vitro evaluation of sustained release Kartogenin by gelatin methacryloyl microspheres for repairing nucleus pulposus degeneration / 中国组织工程研究

BACKGROUND:The imbalance of matrix synthesis and degradation is the main cause of nucleus pulposus degeneration.Small molecule drug Kartogenin(KGN)can restore the balance of matrix synthesis and degradation.Sustained release of KGN using an appropriate drug delivery system is essential for the long-term and effective treatment of KGN.OBJECTIVE:To prepare the injectable hydrogel microspheres by encapsulating KGN with gelatin methacryloyl(GelMA)by microfluidic technology and to investigate the biocompatibility and biological function of nucleus pulposus cells.METHODS:β-Cyclodextrins(β-CD)and KGN were mixed firstly and then mixed with 10%GelMA at a volume of 1:9.Injectable hydrogel microspheres GelMA@β-CD@KGN were prepared by microfluidic technology.The micromorphology of the microspheres was characterized using a scanning electron microscope.The drug release of hydrogel microspheres immersed in PBS within one month was measured.Nucleus pulposus cells were isolated from SD rats and passage 1 cells were cultured in three groups.In the control group,nucleus pulposus cells were cultured separately.In the other two groups,GelMA@β-CD microspheres and GelMA@β-CD@KGN microspheres were co-cultured with nucleus pulposus cells.Cell proliferation was detected by CCK-8 assay and cell survival was detected by live/dead cell staining.Cells were cultured by two complete media with and without interleukin-1β with two kinds of microspheres.mRNA expressions of matrix synthesis and decomposing proteins in nucleus pulposus cells were detected by RT-PCR.RESULTS AND CONCLUSION:(1)Under the scanning electron microscope,the GelMA@β-CD@KGN microspheres after lyophilization were regularly spherical,highly dispersed,uniform in size and full in shape.GelMA@β-CD@KGN microspheres sustained drug release in vitro,reaching 62%of the total drug release at 30 days.(2)Live/dead cell staining showed that GelMA@β-CD@KGN could maintain the activity of nucleus pulposus cells.CCK-8 assay showed that GelMA@β-CD@KGN could promote the proliferation of nucleus pulposus cells.(3)In the complete media with and without interleukin-1β,mRNA expression of aggrecan and type Ⅱ collagen was higher in the GelMA@β-CD@KGN microsphere group than that in the GelMA@β-CD microsphere group(P<0.05,P<0.01);mRNA expression of matrix metalloproteinase 13 and platelet reactive protein disintegrin metallopeptidase 5 was lower than that in the GelMA@β-CD microsphere group(P<0.01).(4)These findings indicate that GelMA@β-CD@KGN microspheres have good biocompatibility and sustained drug release ability.As a drug delivery system,it is a kind of biomaterial with broad application prospects.

Riluzole interferes with the activation of NLRP3 inflammasome in microglia of rats with spinal cord injury / 中国组织工程研究

BACKGROUND:Previous animal studies have shown that riluzole can inhibit neuroinflammatory response after spinal cord injury and promote functional recovery in injured rats,but the study on whether it can regulate the expression of nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)inflammasome in the acute stage is lacking. OBJECTIVE:To observe whether riluzole can reduce microglial pyroptosis and promote functional recovery after spinal cord injury by modulating NLRP3 inflammasome through animal experiments,histological experiments and molecular biology experiments. METHODS:Female SD rats were divided into sham operation,model and riluzole groups,with 12 rats in each group.In addition to the sham operation group,T10 spinal cord injury was conducted in rats.The model group was treated with intraperitoneal administration of riluzole with solvent cyclodextrin.The riluzole group was treated with a 4 mg/kg dose of riluzole injection.The effect of riluzole on motor function recovery was assessed using the BBB score and inclined plane test.The recovery of sensory-evoked potential and motor-evoked potential was measured by electrophysiology.Hematoxylin-eosin staining was used to evaluate spinal cord tissue repair.The regulatory effects of riluzole on NLRP3,Caspase-1 and gasdermin D protein expression in spinal cord tissues were detected by western blot assay.ELISA was utilized to detect the expression levels of inflammatory factors interleukin-1β and interleukin-18.The effects of riluzole on the expression of NLRP3,Caspase-1,gasdermin D and interleukin-1β in microglial cells of the injured spinal cord were determined by immunofluorescence staining. RESULTS AND CONCLUSION:(1)At 35 days after spinal cord injury,BBB score and inclined plane test score in the riluzole group were higher than those in the model group(P<0.05).(2)At 3 days after spinal cord injury,the protein expressions of NLRP3,cleaved Caspase-1,gasdermin D-N(N-terminal domain),interleukin-1β,and interleukin-18 in the spinal cord homogenate of the riluzole group were significantly lower than those of the model group(P<0.05).(3)At 3 days after spinal cord injury,the fluorescence intensity of NLRP3,Caspase-1,gasdermin D and interleukin-1β in the riluzole group was significantly lower than that in the model group(P<0.05).(4)At day 35 after spinal cord injury,hematoxylin-eosin staining showed that the area of spinal cord injury in the riluzole group was smaller than that in the model group.Electrophysiological tests showed that the latency periods of sensory-evoked potential and motor-evoked potential in the riluzole group were shorter than those in the model group,and the latency period of wave amplitude in the riluzole group was higher than that in the model group.(5)These results suggest that riluzole can promote the repair of injured spinal cord tissue,promote the repair of nerve conduction function,and further promote the recovery of motor function in rats with spinal cord injury,which may be achieved through the regulation of NLRP3 inflammasome and the reduction of microglial pyroptosis.

Role and mechanism of noncoding RNA in diabetic peripheral neuropathy / 中国组织工程研究

BACKGROUND:Persistent hyperglycemia has been identified as promoting neurovascular dysfunction,leading to irreversible endothelial dysfunction,increased neuronal apoptosis,oxidative stress and inflammation.These changes in combination or alone lead to microvascular and macrovascular lesions as well as progressive neuropathy.Noncoding RNAs may provide a new strategy for understanding the etiology,pathogenesis and treatment of the disease. OBJECTIVE:To review the role and mechanism of noncoding RNAs in the occurrence and development of diabetic peripheral neuropathy by reviewing relevant literature at home and abroad,in order to provide new ideas and approaches for noncoding RNAs in the prevention,diagnosis and treatment of diabetes neuropathy. METHODS:CNKI and PubMed were retrieved for relevant literature published from database inception to 2022.The key words were"noncoding RNA;lncRNA;miRNA;diabetes peripheral neuropathy;expression profile"in Chinese and English,respectively.The retrieved documents were summarized and analyzed,and 61 articles were finally selected for further review. RESULTS AND CONCLUSION:(1)Noncoding RNA plays a key role in the pathophysiological process of diabetic peripheral neuropathy.Among the most widely studied regulatory noncoding RNA species,there are long noncoding RNAs,circular RNAs and microRNAs.(2)Through the regulation of noncoding RNAs,the activation or inhibition of related cell pathways,inflammatory genes and downstream-related cytokines will inhibit cell apoptosis,improve inflammation,and thus change the expression of target genes to participate in the process of diabetic neuralgia.(3)Although many microRNAs and long noncoding RNAs have been found to participate in diabetic peripheral neuropathy,the mechanisms of many noncoding RNAs are unclear,and the same noncoding RNAs may play different roles in different modes.Therefore,it is necessary to further study their action modes in disease etiology and pathology,thereby clarifying their role in the pathogenesis of diabetic peripheral neuropathy.However,the criteria for evaluating noncoding RNA activity have not yet been established,and further research is needed on which specific noncoding RNAs play a dominant regulatory role.(4)MicroRNAs,long noncoding RNAs and their target genes can regulate progressive neuropathy,which are expected to become new targets for the clinical prevention and treatment of diabetic peripheral neuropathy and new biomarkers for the development and prognosis of diabetic peripheral neuropathy.