Aim To explore the effects of Lycium berry seed oil on Nrf2/ARE pathway and oxidative damage in testis of subacute aging rats. Methods Fifty out of 60 male SD rats, aged 8 weeks, were subcutaneously injected with 125 mg • kg"D-galactosidase in the neck for 8 weeks to establish a subacute senescent rat model. The presence of senescent cells was observed using P-galactosidase ((3-gal), while testicular morphology was examined using HE staining. Serum levels of testosterone (testosterone, T), follicle-stimulating hormone ( follicle stimulating hormone, FSH ) , luteinizing hormone ( luteinizing hormone, LH ) , superoxide dis-mutase ( superoxide dismutase, SOD ) , glutathione ( glutathione, GSH) and malondialdehyde ( malondial-dehyde, MDA) were measured through ELISA, and the expressions of factors related to aging, oxidative damage, and the Nrf2/ARE pathway were assessed via immunohistochemical analysis and Western blotting. Results After successfully identifying the model, the morphology of the testis was improved and the intervention of Lycium seed oil led to a down-regulation in the expression of [3-gal and -yH2AX. The serum levels of SOD, GSH, T, and FSH increased while MDA and LH decreased (P 0. 05) . Additionally, there was an up-regulated expression of Nrf2, GCLC, NQOl, and SOD2 proteins in testicular tissue ( P 0. 05 ) and nuclear expression of Nrf2 in sertoli cells. Conclusion Lycium barbarum seed oil may reduce oxidative damage in testes of subacute senescent rats by activating the Nrf2/ARE signaling pathway.

Objective To observe the clinical efficacy and safety of Sangxing Zhike Prescription in treating postinfectious cough(PIC)of warm dryness invading the lung type.Methods A total of 66 PIC patients with warm dryness invading the lung type who were admitted to the First Affiliated Hospital of Guangzhou University of Chinese Medicine from January 2020 to June 2022 were randomly divided into a treatment group and a control group,with 33 patients in each group.The treatment group was given Sangxing Zhike Prescription combined with Compound Methoxyphenamine Capsules,and the control group was given Compound Methoxyphenamine Capsules combined with Chinese medicine placebo.The course of treatment covered 7 days.The changes in the Visual Analogue Scale(VAS)scores of the severity of cough,the scores of cough symptom,and the scores of traditional Chinese medicine(TCM)syndrome in the two groups were observed before and after the treatment.After treatment,the clinical efficacy and safety in the two groups were evaluated.Results(1)During the trial,one case fell off from the treatment group and 4 cases fell off from the control group,and eventually 61 cases completed the observation,of which 32 cases were in the treatment group and 29 cases were in the control group.(2)After 7 days of treatment,the total effective rate of the treatment group was 84.38%(27/32)and that of the control group was 58.62%(17/29),and the intergroup comparison(tested by chi-square test)showed that the therapeutic efficacy of the treatment group was significantly superior to that of the control group(P＜0.05).(3)After treatment,the VAS scores of the severity of cough,and the scores of daytime cough,nighttime cough of the Cough Symptom Score Scale as well as the overall cough scores in the two groups were significantly lower than those before treatment(P＜0.05 or P＜0.01),and the reduction of the VAS scores and the overall cough symptom scores in the treatment group was significantly superior to that in the control group(P＜0.05).(4)After treatment,obvious improvement was presented in the scores of TCM symptoms of cough,throat itching,dry throat,foreign body sensation in the throat,sore throat and pharyngeal signs as well as total TCM syndrome scores in the treatment group when compared with the pre-treatment period(P＜0.01),whereas in the control group,only the scores of cough,throat itching,dry throat,and sore throat and the total TCM syndrome scores were improved compared with the pre-treatment period(P＜0.05 or P＜0.01).The post-treatment intergroup comparison showed that the treatment group was significantly superior to the control group in improving the scores of throat itching,foreign body sensation in the throat,and pharyngeal signs as well as total TCM syndrome scores(P＜0.05 or P＜0.01).(5)During the treatment process,no significant adverse reactions occurred in both groups,or no abnormal changes were shown in the safety indexes such as blood routine test,liver and kidney functions of the patients.Conclusion Sangxing Zhike Prescription combined with Compound Methoxyphenamine Capsules exerts certain effect in treating patients with PIC of warm dryness invading the lung type,and its efficacy is significantly superior to that of Compound Methoxyphenamine Capsules treatment alone with relatively high safety profile.

To perform a comprehensive analysis of the pathogenic causes of a food poisoning case in a district of Wuhan Cit-y,we investigated the molecular epidemiological relationships among pathogenic bacteria,to aid in traceability analysis of food-borne disease outbreaks,as well as clinical diagnosis and treatment.The pathogenic bacteria in this food poisoning case were i-solated and identified according to GB789.4-2016.The isolated strains were subjected to genotyping with pulsed field gel elec-trophoresis(PFGE).Drug resistance gene analysis,multi-locus sequence typing(MLST),and genome-wide single-nucleotide polymorphism analysis(wgSNP)were conducted via whole genome sequencing(WGS).The evolutionary tree for cluster analy-sis was constructed in fasttree software.Drug susceptibility testing was conducted with the broth microdilution method.A total of 12 strains of Salmonella were detected in seven anal swab samples and two fecal samples from the case,as well as three anal swab samples from unaffected individuals.The serotype of the strains was Salmonella typhimurium.The strain exhibited severe multiple drug resistance,including resistance to amikacin,ampi-cillin,cefazolin,gentamicin,piperacillin,and tetracycline,but susceptibility to other antibiotics.The coincidence rate between drug resistance genes and drug resistance phenotypes was high.PFGE revealed that nine strains from this food poisoning case were highly homologous.WGS revealed that the MLST type was ST19,and varying numbers of SNPs(1-6)were present a-mong strains.The phylogenetic tree revealed nine isolated strains forming a distinct cluster,differing from other Salmonella strains in the database and belonging to a novel clonal branch.The single nucleotide site in the strains was highly homologous to that of GCF in Jiangxi_020221795.1.The food poisoning case was caused by Salmonella typhimurium ST19,and all nine iso-lated strains originated from the same source.The chef is closely connected to this food poisoning case.This strain of Salmo-nella typhimurium belongs to a new clonal branch and exhibits multiple drug resistance.

Objective To investigate the effect of Polyetheretherketone(PEEK)rod semi-rigid pedicle screw fixation sys-tem in lumbar spine non-fusion surgery.Methods A total of 74 patients with tow-level lumbar degenerative diseases who un-derwent surgery from March 2017 to December 2019 were divided into PEEK rod group and titanium rod group.In the PEEK rod group,there were 34 patients,including 13 males and 21 females,aged from 51 to 79 years old with an average of(62.4±6.8)years old;There were 1 patient of L1-L3 segments,7 patients of L2-L4 segments,20 patients of L3-L5 segments and 6 pa-tients of L4-S1 segments.In the titanium rod group,there were 40 patients,including 17 males and 23 females,aged from 52 to 81 years old with an average of(65.2±7.3)years old;There were 3 patient of L1-L3 segments,11 patients of L2-L4 segments,19 patients of L3-L5 segments and 7 patients of L4-S1 segments.The general conditions of operation,such as operation time,intraoperative blood loss,postoperative drainage was recorded.The visual analogue scale(VAS)for low back pain and Os-westry disability index(ODI)were compared in preoperatively and postoperatively(3 months,12 months and last follow-up)between two groups.The change of range of motion(ROM)was observed by flexion and extension x-ray of lumbar Results All patients successfully completed the operation.The follow-up time ranged from 22 to 34 months with an average of(26.8±5.6)months.The operative time(142.2±44.7)min and intraoperative blood loss(166.5±67.4)ml in PEEK group were lower than those in titanium group[(160.7±57.3)min、(212.8±85.4)ml](P＜0.05).There was no significant differences in postoperative drainage between the two groups(P＞0.05).At the final follow-up visit,in PEEK group and titanium group VAS of low back pain[(0.8±0.4)points vs(1.0±0.5)points],VAS for leg pain[(0.7±0.4)points vs(0.8±0.5)points]and ODI[(9.8±1.6)％vs(12.1±1.5)％]were compared with preoperative[(5.8±1.1)points vs(6.0±1.1)points],[(7.2±1.7)points vs(7.0±1.6)points],[(68.5±8.9)％vs(66.3±8.2)％]were significantly different(P＜0.05).There was no significant difference in VAS scores between the two groups at each postoperative time point(P＞0.05).At 3 months after surgery,there was no difference in ODI between the two groups(P＞0.05).There were significant differences in ODI between PEEK group and titanium rod group at 12 months[(15.5±2.1)％vs(18.4±2.4)％]and at the last follow-up[(9.8±1.6)％vs(12.1±1.5)％](P＜0.05).The total range of motion(ROM)of lumbar decreased in both groups after surgery.At 12 months after surgery and the last follow-up,the PEEK group compared with the titanium rod group,the total range of motion of lumbar was statistically significant(P＜0.05).The range of motion(ROM)of the fixed segments decreased in both groups after surgery.The ROM of the fixed segments in PEEK group decreased from(9.5±4.6)° to(4.1±1.9)° at the last follow-up(P＜0.05),which in the titanium rod group was de-creased from(9.8±4.3)°to(0.9±0.5)° at the last follow-up(P＜0.05).The range of motion(ROM)of upper adjacent segment increased in both groups,there was statistical significance in the ROM of upper adjacent segment between the two groups at 12 months after surgery and the last follow-up,(P＜0.05).There was no screw loosening and broken rods in both groups during the follow-up period.Conclusion The PEEK rod semi-rigid pedicle screw internal fixation system used in lumbar non-fusion surgery can retain part of the mobility of the fixed segment,showing comparable short-term clinical efficacy to titanium rod fu-sion.PEEK rod semi-rigid pedicle screw internal fixation system is a feasible choice for the treatment of lumbar spine degener-ative diseases,and its long-term efficacy needs further follow-up observation.

This study performed to determine whether OX40L overexpressed by recombinant rabies virus(LBNSE-OX40L)can enhance the innate immune response through activation of dendritic cells and thus activate early antibody production.Bone marrow dendritic cells(BMDCs)were extracted from the femur of Balb/c mice and cultured for 6 days,and the cultured BMDCs were infected with the parental virus LBNSE and the recombinant virus LBNSE-OX40L with the multiplicity of infections(MOI)=1.The effect of each virus on the maturation of BMDCs was analyzed by flow cytometry;ELISA was used to detect the expression of innate immunity-related cytokines such as interferon-α(IFN-α)and interleukin-12p40(IL-12p40)in the supernatants of the infected BMDCs.For in vivo study,Balb/c female mice were injected intramuscularly with 106 FFU of parental virus LBNSE and recombinant virus LBNSE-OX40L in both hind limbs,and the inguinal lymph nodes of mice were collected on day 6 after immunization,and the proportion of mature DCs was detected by flow cytometry.The serum was collected on day 6 after immunization,and the content of virus-neutralizing antibody(VNA)was detected by antiviral neutralizing antibody titration.Mouse serum was collected on day 6 after immunization,and virus neutralizing antibody content was measured by titration of antiviral neutralizing antibody,while IgG antibody in mouse serum was detected by ELISA.IgM antibody subclasses were detected by ELISA on days 2,4,and 6 after immunization.Compared with the parental virus LBNSE,the recombinant virus LBNSE-OX40L was able to activate more BMDCs in vitro and produce significantly higher levels of IFN-α and IL-12p40.Furthermore,the recombinant virus LBNSE-OX40L stimulated the maturation and differentiation of the DCs in vivo,which led to the rapid production of high levels of VNA and RABV-specific IgG and IgM antibodies.Taken together,LBNSE-OX40L activates dendritic cells to promote the body's innate immune response,and in turn enhances early antibody production,thus can be an early effective rabies vaccine candidate.

This review introduced the research progress of covalent modification strategies in local anesthetic drug delivery systems. As a commonly used and multimodal analgesic drug, local anesthetics have limited duration of action and potential toxicity in clinical application. In order to prolong the analgesic effect and reduce systemic toxicity, researchers are committed to the development of sustained-release local anesthetics with long-lasting dose-controlled-release functions. When it comes to the delivery of local anesthetics, the covalent modification strategy is a key approach. By covalently binding drugs to large molecule carriers, covalent modification strategies can improve drug stability, targeting and delivery efficiency. Macromolecular prodrugs can modulate the kinetic process of the drug, so that the drug is released in the form of the active ingredient and achieve better therapeutic effects. In recent years, stimulus-responsive macromolecular prodrugs have become a research hotpot for local anesthetic drug delivery systems, and the stimulus-responsive performance of macromolecular prodrugs can rapidly release drugs under internal and external stimulus conditions, and maintain low toxicity and high efficiency in blood circulation and normal tissues. These emerging research directions provide important guidance for prolonging the analgesic effect of local anesthetics and reducing systemic toxicity, and provide new idea for the development of more effective drug delivery systems in the future.

Objective To evaluate extrathyroidal extension (ETE) in papillary thyroid microcarcinoma (PTMC) with three-dimensional tomographic ultrasound imaging (3D-TUI). Methods A total of 97 thyroid nodules of 79 patients with PTMC treated in PUMC Hospital from February 2016 to January 2018 were included in this study.Two ultrasound experts performed independent blinded assessment of the relationship between thyroid nodules and thyroid capsule by two-dimensional ultrasound (2D-US) and 3D-TUI.The results of 2D-US and 3D-TUI in evaluating ETE were compared with intraoperative findings and postoperative histological and pathological results. Results Among the 97 nodules,54 (55.7%) nodules had ETE.The diagnostic sensitivity (68.5% vs.37.0%;χ²=10.737,P=0.002),accuracy (74.5% vs.56.7%;χ²=6.686,P=0.015),and area under the receiver operating characteristic curve[0.761 (95%CI=0.677-0.845) vs.0.592 (95%CI=0.504-0.680);Z=3.500,P<0.001] of 3D-TUI were higher than those of 2D-US.However,3D-TUI and 2D-US showed no significant difference in the specificity (84.1% vs.81.4%;χ²=0.081,P=0.776),negative predictive value (67.9% vs.50.7%;χ²=3.645,P=0.066),or positive predictive value (84.1% vs.71.4%;χ²=1.663,P=0.240). Conclusion Compared with 2D-US,3D-TUI demonstrates increased diagnostic efficiency for ETE of PTMC.
Humans ; Thyroid Nodule ; Thyroid Neoplasms/diagnosis* ; Carcinoma, Papillary/pathology* ; Ultrasonography/methods* ; Retrospective Studies

This study aims to investigate the therapeutic effect of alcohol extract of root and root bark of Toddalia asiatica(TAAE) on collagen-induced arthritis(CIA) in rats through phosphatidylinoinosidine-3 kinase/protein kinase B(PI3K/Akt) signaling pathway. To be specific, CIA was induced in rats, and then the rats were treated(oral, daily) with TAAE and Tripterygium Glycoside Tablets(TGT), respectively. The swelling degree of the hind leg joints was scored weekly. After 35 days of administration, the histopathological changes were observed based on hematoxylin and eosin(HE) staining. Enzyme-linked immunosorbent assay(ELISA) was employed to detect the levels of cytokines [tumor necrosis factor-α(TNF-α), interleukin(IL)-6)]. Terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL) staining was performed to detect the apoptosis of synoviocytes in rats. Western blot was used to detect the expression levels of apoptosis-related proteins B-cell lymphoma 2(Bcl-2)-associated X(Bax), Bcl-2, and caspase-3 and pathway-related proteins phosphoinositide 3-kinase(PI3K), phosphorylated(p)-PI3K, protein kinase B(Akt), and p-Akt. RT-qPCR was conducted to examine the mRNA levels of Bax, Bcl-2, caspase-3, TNF-α, IL-6, and IL-1β and pathway-related proteins PI3K, p-PI3K, Akt, and p-Akt. TAAE can alleviate the joint swelling in CIA rats, reduce serum levels of inflammatory cytokines, improve synovial histopathological changes, promote apoptosis of synoviocytes, and inhibit synovial inflammation. In addition, RT-qPCR and Western blot results showed that TAAE up-regulated the level of Bax, down-regulated the level of Bcl-2, and activated caspase-3 to promote apoptosis in synoviocytes. TAAE effectively down-regulated the protein levels of p-PI3K and p-Akt. In this study, TAAE shows therapeutic effect on CIA in rats and reduces the inflammation. The mechanism is that it suppresses PI3K/Akt signaling pathway and promotes synoviocyte apoptosis. Overall, this study provides a new clue for the research on the anti-inflammatory mechanism of TAAE and lays a theoretical basis for the better clinical application of TAAE in the treatment of inflammatory and autoimmune diseases.
Rats ; Animals ; Proto-Oncogene Proteins c-akt/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Caspase 3/genetics* ; Tumor Necrosis Factor-alpha/metabolism* ; bcl-2-Associated X Protein/metabolism* ; Plant Bark ; Anti-Inflammatory Agents/therapeutic use* ; Arthritis, Experimental/chemically induced* ; Inflammation/drug therapy* ; Cytokines/metabolism* ; Proto-Oncogene Proteins c-bcl-2 ; Apoptosis

Arrhythmia, a common and frequently occurring cardiovascular disease, causes a heavy burden on the public health of China. Approximately 20 million patients are suffering from this disease in China and treated by pharmacological and surgical therapies. However, antiarrhythmic drugs can cause arrhythmia and surgical treatment has the risks of failure and recurrence. Therefore, the clinical outcome of arrhythmia remains to be improved. According to the traditional Chinese medicine(TCM) theory, arrhythmia is a disease of palpitation induced by 7 conditions: liver depression and Qi stagnation, accumulation of turbid phlegm, fluid retention attacking the heart, fire-heat disturbing the heart, stasis obstruction of heart vessel, cold congealing in heart vessel, and the deficiency of Qi, blood, Yin, and Yang. Therefore, this study concisely proposed 7 TCM syndromes of arrhythmia, including the palpitation due to depression, phlegm, fluid retention, fire, blood stasis, cold, and deficiency. The corresponding treatment strategies were recommended as follows: Chaihu Longgu Muli Decoction for the palpitation due to depression, Wendan Decoction for the palpitation due to phlegm, Linggui Zhugan Decoction for the palpitation due to fluid retention, Sanhuang Xiexin Decoction for the palpitation due to fire, Xuefu Zhuyu Decoction for the palpitation due to blood stasis, and Mahuang Fuzi Xixin Decoction for the palpitation due to cold, and Guizhi Gancao Decoction, Guizhi Gancao Longgu Muli Decoction, Huanglian Ejiao Decoction, Zhigancao Decoction, and Guipi Decoction for the palpitation due to the deficiency of Qi, blood, Yin, and Yang. Multiple formulas should be combined if the patient presents several TCM syndromes simultaneously. According to the principles of the correspondence between formula and syndrome and the treatment with consideration to both pathogenesis and pathology and both herbal nature and pharmacology, this study proposed an integrated treatment model of "pathogenesis-pathology-nature-pharmacology" to enhance the clinical efficacy of classic herbal formulas in the treatment of arrhythmia.
Humans ; Medicine, Chinese Traditional ; Syndrome ; Drugs, Chinese Herbal/therapeutic use* ; Heart Failure/drug therapy* ; Arrhythmias, Cardiac/drug therapy* ; China

Chaihu Jia Longgu Muli Decoction was firstly recorded in Treatise on Cold Damage(ZHANG Zhong-jing, Eastern Han dynasty). According to this medical classic, it is originally used in the treatment of the Shaoyang and Yangming syndrome. Based on the modern pathophysiological mechanism, this study interpreted the classic provisions of Chaihu Jia Longgu Muli Decoction. Original records of "chest fullness" "annoyance" "shock" "difficult urination" "delirium" "heavy body and failing to turn over" all have profound pathophysiological basis, involving disorders in cardiovascular, respiratory, nervous, and mental systems. This formula is widely used, which can be applied to treat epilepsy, cerebral arteriosclerosis, cerebral infarction, and other cerebrovascular diseases, hypertension, arrhythmia, and other cardiovascular diseases, insomnia, constipation, anxiety, depression, cardiac neurosis and other acute and chronic diseases as well as diseases in psychosomatic medicine. The clinical indications include Bupleuri Radix-targeted syndrome such as fullness and discomfort in chest and hypochondrium, bitter taste mouth, dry throat, and dizziness, the insomnia, anxiety, depression, susceptibility to fright, upset, dreamfulness and other psychiatric symptoms, red tongue, thick and yellow tongue coating, and wiry hard and powerful pulse. This formula was found to be used in combination with other formulas, such as Gualou Xiebai Decoction, Wendan Decoction, Zhizhu Pills, Juzhijiang Decoction, Suanzaoren Decoction, and Banxia Baizhu Tianma Decoction.
Humans ; Sleep Initiation and Maintenance Disorders/drug therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Hypertension/drug therapy* ; Syndrome ; Arrhythmias, Cardiac/drug therapy* ; Medicine, Chinese Traditional