ObjectiveTo investigate the mechanism by which Liuwei Dihuang Erzhiwan combination inhibit the lung metastasis of spontaneous breast cancer in mice by regulating the recruitment of myeloid-derived suppressor cells （MDSCs）. MethodThree hundred and eighty SPF-grade 10-month-old female breeders of Kunming mouse were palpated at the mammary gland site once every 3 days. Mice that have not had a lump touched after being raised for 6 months are used as control group. After tumor development， the mice were randomized into model， positive control （paclitaxel， intraperitoneal injection at 0.01 g·kg^-1 every other day for 22 d）， Liuwei Dihuangwan （0.65 g·kg^-1·d^-1 by gavage）， Erzhiwan （5.41 g·kg^-1·d^-1 by gavage）， and Liuwei Dihuang Erzhiwan combination （6.05 g·kg^-1·d^-1 by gavage） groups. The mice were euthanised when the tumor reached a diameter of about 15 mm， and the tumor and lung tissues were collected. The survival time， tumor mass， and lung metastasis rate of tumor-bearing mice were recorded. Hematoxylin-eosin （HE） staining was used to observe the histopathological and morphological changes of mouse tumor and lung tissues. Immunofluorescence （IF） was used to detect the distribution of MDSCs in tissues of mice in each group by double-staining of MDSCs cells with lymphocyte antigen 6 complex site G6D （Ly6G） and CD11 antigen-like family member B （CD11b）. Western blot was employed to determine the protein levels of matrix metalloproteinase-9 （MMP-9）， transforming growth factor-β （TGF-β）， zinc finger transcription factor 1 （Snail1）， and E-cadherin in the tumor tissue and CC motif chemokine 9 （CCL9） and CC motif chemokine receptor 1 （CCR1） in the lung tissue. ResultDuring the modelling period， the paclitaxel group and Chinese medicine intervention groups had longer median number of days of survival and lower tumor weight， lung metastasis rate， and lung nodule than the model group （P<0.05， P<0.01）. HE staining showed an increase in tumor cell necrosis in the paclitaxel group and the Liuwei Dihuang Erzhiwan combination group. The paclitaxel group and Chinese medicine intervention groups had lower fluorescence intensity of MDSCs in the tumor tissue than the model group （P<0.05， P<0.01）. Compared with the normal control group， the model group showed increased fluorescence intensity of MDSCs in the metastatic lung tissue （P<0.01）， which， however， was decreased in the paclitaxel group and Chinese medicine intervention groups （P<0.01）. The model group showed higher protein levels of MMP-9， TGF-β， and Snail1 and lower protein level of E-cadherin in the tumor tissue than in the normal control group （P<0.01）. Compared with model group， paclitaxel and Chinese medicine interventions downregulated the protein levels of MMP-9， TGF-β， and Snail1 （P<0.05， P<0.01） and upregulated the protein level of E-cadherin in the tumor tissue （P<0.01）. Moreover， the Liuwei Dihuang Erzhiwan combination group had lower protein levels of TGF-β and Snail1 than the Liuwei Dihuangwan group and Erzhiwan group （P<0.05）. In the metastatic lung tissue， the expression of CCL9 and CCR1 was higher in the model group than in the normal control group， paclitaxel group， and Chinese medicine intervention groups （P<0.05， P<0.01）. ConclusionLiuwei Dihuang Erzhiwan combination inhibit tumor growth， prolong survival time， and reduce the occurrence of lung metastasis in the mouse model of spontaneous breast cancer by reducing the recruitment of MDSCs in the tumor and lung tissues and modulating the phenotypes of epithelial-mesenchymal transition （EMT）-related molecules and the expression of CCL9/CCR1.

Objective To explore the application effect of multimodal MRI in the diagnosis of lumbar intervertebral disc degeneration.Methods A total of 78 patients with lumbar intervertebral disc degeneration treated conservatively were retrospectively selected.The patients underwent sagittal T2WI,axial T2WI sequence and sagittal synthetic MRI scanning and post-processing to generate T1,T2 and proton density(PD)mapping quantitative sequences by GE Signa Pioneer 3.0T MR machine.The T1,T2 and PD values of the anterior and posterior annulus fibrosus and nucleus pulposus of L1-L2 to L5-S1 lumbar intervertebral disc were measured.The Pfirrmann grade,visual analogue scale(VAS)and Oswestry disability index(ODI)scale of each intervertebral disc were evaluated.The T1,T2,PD,VAS and ODI of patients with different Pfirrmann grades were compared.Pearson linear analysis was used to analyze the relationship between T1,T2,PD and VAS,ODI.Spearman rank correlation method was used to analyze the relationship between T1,T2,PD and Pfirrmann.Logistic regression analysis was used to analyze the evaluation value of T1,T2 and PD in Pfirrmann.Results With the increase of Pfirrmann grade,the T1,T2 and PD values of patients decreased,while the VAS score and ODI increased(P<0.05).The T1,T2 and PD values were negatively correlated with VAS score,ODI and Pfirrmann grade(P<0.05).Logistic regression analysis showed that T1,T2 and PD values had good evaluation values for Pfirrmann grade(P<0.05).Conclusion Multimodal MRI can effectively evaluate the Pfirrmann grade,pain and lumbar function of lumbar intervertebral disc degeneration,which can be used to help determine the diagnosis.

BACKGROUND:Superior lower limb mobility is regarded as one of the prerequisites for winning competitions.Wearable resistance training can effectively overcome the deficiency in the transfer efficiency of traditional strength training in enhancing lower limb mobility.Considering that the impact of wearable resistance training based on different body parts on lower limb mobility may have significant differentiated characteristics,it is particularly important to review and summarize the specific application strategies and acute and chronic intervention effects. OBJECTIVE:To comb and analyze acute and chronic intervention effects of wearable resistance training based on different body parts on lower limb mobility,in order to provide insightful and methodological references for optimizing application strategies for lower limb movement ability. METHODS:A literature search was conducted in CNKI,Wanfang,VIP,Web of Science,Medline,SPORTDiscus,and PubMed databases for publications up to October 2023.Chinese and English search terms were"arm,forearm,limb,leg,lower extremity,vest,trunk,resist,weight,load,sprint,agility,change of direction".A total of 60 articles were ultimately included for review after screening the retrieval results. RESULTS AND CONCLUSION:(1)Trunk loading of 6-20%of body mass is suitable for optimizing acceleration in sprinting,while trunk loading of≤6%body mass is suitable for optimizing high-speed running.A trunk load of 5%body mass is applicable for optimizing change-of-direction movement;forearm,calf,or thigh loading often uses 1%or 2%body mass.(2)Trunk loading optimizes the functional performance of the lower limb stretch-shortening cycle by increasing vertical load.This enhances the efficiency of ground reaction force utilization and strengthens the coordinated stability control of the whole body musculature.Forearm loading effectively enhances the driving force of the upper limb swing,improves the propulsive force of the lower limb sprint,and optimizes the efficiency of inter-limb coordination.Calf loading can impose restrictions on the function of the hip joint,thereby leading to localized load stimulation and compensatory functional enhancement in the knee or ankle joint.Thigh loading partially restricts the peak extension angle and speed of the knee joint,creates specific load stimulation at the hip joint,and significantly improves its rotational kinetic energy output.(3)During larger-angle change-of-direction movements,the impact of calf loading is more significant than thigh loading.Thigh loading stimulation helps to enhance power output,while calf loading stimulation aids in improving stability control and directional change.(4)Currently,wearable resistance training has been proven to be an effective way to improve sprint and change-of-direction performance.The methodological strategies to improve sprint performance are relatively mature,but the optimal application scheme to improve change-of-direction performance needs to be further refined and optimized.Further research is recommended to supplement this area.

Objective:To evaluate the reliability and validity of the Chinese version of HEMO-FISS-QoL(HF-QoL) questionnaire (HF-QoL-C) in the Chinese population with hemorrhoids.Methods:From November 2021 to November 2022, a self-constructed general information questionnaire, HF-QoL-C, and the 36-item short form health survey (SF-36), Goligher classification, and Giordano severity of hemorrhoid symptom questionnaire (GSQ) were used to conduct a questionnaire survey on 760 hemorrhoid patients in the anorectal department of six hospitals. The data was analyzed for reliability and validity using SPSS 21.0 and AMOS 26.0 software.Results:The Cronbach's α coefficient of HF-QoL-C and its dimension ranged from 0.831 to 0.960, and the split coefficient was 0.832-0.915. Four common factors were extracted through principal component exploratory factor analysis. Confirmatory factor analysis indicated acceptable structural validity( χ2/ df=8.152, RSMEA=0.097, CFI=0.881, IFI=0.881, NFI=0.867). HF-QoL-C was correlated with SF36 and GSQ( r=-0.694, 0.501, both P<0.01). There were differences in the total score and dimensional scores of HF-QoL-C between surgical and drug treated patients, different grades of Goligher classification for hemorrhoidal disease, and different ranges of hemorrhoid prolapse (all P<0.001). No ceiling effect was found in the total score and the scores of each dimension(0.3%-2.0%). There was a floor effect in both psychological function and sexual activity dimensions (16.7%, 35.1%). Conclusion:HF-QoL-C has good reliability and validity, which can be used to measure the quality of life of Chinese hemorrhoid patients.

The amygdala is an important hub for regulating emotions and is involved in the pathophysiology of many mental diseases, such as depression and anxiety. Meanwhile, the endocannabinoid system plays a crucial role in regulating emotions and mainly functions through the cannabinoid type-1 receptor (CB₁R), which is strongly expressed in the amygdala of non-human primates (NHPs). However, it remains largely unknown how the CB₁Rs in the amygdala of NHPs regulate mental diseases. Here, we investigated the role of CB₁R by knocking down the cannabinoid receptor 1 (CNR1) gene encoding CB₁R in the amygdala of adult marmosets through regional delivery of AAV-SaCas9-gRNA. We found that CB₁R knockdown in the amygdala induced anxiety-like behaviors, including disrupted night sleep, agitated psychomotor activity in new environments, and reduced social desire. Moreover, marmosets with CB₁R-knockdown had up-regulated plasma cortisol levels. These results indicate that the knockdown of CB₁Rs in the amygdala induces anxiety-like behaviors in marmosets, and this may be the mechanism underlying the regulation of anxiety by CB₁Rs in the amygdala of NHPs.
Animals ; Callithrix ; Receptors, Cannabinoid ; Anxiety ; Amygdala ; Cannabinoids ; Phenotype

ObjectiveTo observe the effects of Wendantang on the expression of inflammatory cytokines， autophagy markers， and key molecules of phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin （PI3K/Akt/mTOR） signaling pathway in the adipocytes of the rat model of obesity （syndrome of phlegm-dampness） and to explore the material basis of inflammation in obesity （syndrome of phlegm-dampness） and the underlying mechanism of Wendantang intervention. MethodA total of 126 SD rats were randomized into 2 groups： 16 rats in the blank group and 110 rats in the modeling group. The blank group was fed with a basic diet while the modeling group with a high-fat diet to establish the animal model of obesity （syndrome of phlegm-dampness） for 8 weeks. After successful modeling， 48 obese rats were selected according to their body mass and randomized into a model control group， an orlistat （ORLI， 32.40 mg·kg^-1） group， a rapamycin （RAPA， 2 mg·kg^-1） group， and low-， medium-， and high-dose （4.45， 8.90， 17.80 g·kg^-1， respectively） Wendantang groups， with 8 rats in each group. In addition， 8 rats were randomly selected from the blank group to be set as the normal control group. The corresponding agents in each group were administrated by gavage and the model and control groups were administrated with equal amounts of distilled water once daily for 6 weeks. The body mass， Lee's index， body fat ratio， and obesity rate were measured or calculated. The expression of UNC51-like kinase-1 （ULK1）， Beclin1， human autophagy-related protein 5 （Atg5）， p62， and microtubule-associated protein 1 light chain 3 （LC3） Ⅰ/Ⅱ （markers of autophagy in adipocytes） was detected by the immunohistochemical two-step method. Enzyme-linked immunosorbent assay （ELISA） was employed to determine the expression of tumor necrosis factor （TNF）-α， interleukin-6 （IL-6）， IL-1β， monocyte chemotactic protein-1 （MCP-1）， IL-4， IL-10， IL-13， and transforming growth factor （TGF）-β in adipocytes. Western blot was employed to measure the protein levels of classⅠ-PI3K， phosphatidylinositol triphosphate （PIP3）， Akt， mTORC1， ULK1， TSC1， and TSC2 in adipocytes. ResultCompared with the blank group， the modeling group showed increased body mass and Lee's index （P<0.01）， the obesity rate >20%， and phlegm-dampness syndrome manifestations such as physical obesity， decreased mobility， decreased appetite， lusterless and tight fur， loose stools， decreased responsiveness to the outside world， and decreased water intake. Compared with the normal control group， the model control group showed increased body mass， Lee's index， body fat ratio， adipocyte autophagy marker expression， pro- and anti-inflammatory cytokine levels （P<0.05， P<0.01）， down-regulated protein levels of classⅠ-PI3K， PIP3， Akt， mTORC1， TSC1， and TSC2 （P<0.01）， and up-regulated protein level of ULK1 （P<0.01）. The intervention groups showed lower body mass， body fat ratio， adipocyte autophagy marker protein expression， and protein levels of TNF-α， IL-6， IL-1β， MCP-1， IL-4， and IL-13 than the model control group （P<0.05， P<0.01）. Moreover， the RAPA and Wendantang （medium and high dose） groups showed lowered levels of IL-10 and TGF-β （P<0.01）， and the ORLI group showed down-regulated expression of TGF-β （P<0.01）. The expression of key molecules of the signaling pathway was up-regulated （P<0.05， P<0.01） while that of ULK1 was down-regulated （P<0.01） in all the intervention groups. Compared with the RAPA group， the Wendantang groups showed up-regulated expression of all autophagy marker proteins in adipocytes （P<0.01）. In addition， the low-dose Wendantang group showed elevated levels of inflammatory cytokines （except TNF-α） （P<0.05， P<0.01） and down-regulated expression of all key molecules of the signaling pathway （P<0.05， P<0.01）. The levels of inflammatory cytokines （except IL-16， MCP-1， and IL-10） were elevated in the medium-dose Wendantang group （P<0.05， P<0.01）. The expression of key molecules except PI3K of the signaling pathway was down-regulated in the medium- and high-dose Wendantang groups （P<0.05， P<0.01）. Compared with the ORLI group， low- and medium-dose Wendantang groups showed up-regulated expression of autophagy markers in adipocytes （P<0.01）， and the low-dose group showed elevated levels of inflammatory cytokines （IL-6， IL-4， and TGF-β） （P<0.01） and down-regulated expression of all key molecules of the signaling pathway （P<0.01）. The medium-dose Wendantang group showed up-regulated expression of IL-4 （P<0.01） and down-regulated expression of key molecules except PI3K of the signaling pathway （P<0.05， P<0.01）. The high-dose Wendantang group showed increased body mass， up-regulated expression levels of autophagy markers （ULK1， LC3 Ⅰ/Ⅱ） （P<0.05， P<0.01）， down-regulated expression of PIP3， mTORC1， and TSC1 （P<0.05， P<0.01）， and lowered levels of Beclin1， Atg5， TNF-α， and IL-13 （P<0.05， P<0.01）. ConclusionThe inflammation in obesity （syndrome of phlegm-dampness） is closely associated with the PI3K/Akt/mTOR pathway-mediated adipocyte autophagy. Wendantang can treat the chronic inflammation in obese rats with the syndrome of phlegm-dampness by regulating this signaling pathway and thus improve adipocyte autophagy.

Oral squamous cell carcinoma(OSCC),a common malignancy of the head and neck,ranks sixth worldwide in terms of cancers with the most negative impact,owing to tumor relapse rates,cervical lymphnode metastasis,and the lack of an efficacious systemic therapy.Its prognosis is poor,and its mortality rate is high.Octamer-binding transcription factor 4(OCT4)is a member of the Pit-Oct-Unc(POU)family and is a key reprogramming factor that produces a marked effect in preserving the pluripotency and self-renewal state of embryonic stem cells(ESCs).According to recent studies,OCT4 participates in retaining the survival of OSCC cancer stem cells(CSCs),which has far-reaching implications for the occurrence,recurrence,metastasis,and prognosis of oral carcinogenesis.Therefore,we summarize the structure,subtypes,and function of OCT4 as well as its role in the occurrence,progression,and prognosis of OSCC.

Objective    To explore the clinical applications of 3D-CT reconstruction combined with 3D printing in the analysis of anatomical types and variations of bilateral pulmonary arteries. Methods    From January 2019 to February 2022, the clinical data of 547 patients who underwent anatomical lung lesion resection in our hospital were retrospectively collected. They were divided into a 3D-CT reconstruction plus printing technology group (n=298, 87 males and 211 females aged 53.84±12.94 years), a 3D-CT reconstruction group (n=148, 55 males and 93 females aged 54.21±11.39 years), and a non-3D group (n=101, 28 males and 73 females aged 53.17±10.60 years). Results    In the 3D-CT reconstruction plus printing technology group, the operation time of patients (right: 125.61±20.99 min, left: 119.26±28.44 min) was shorter than that in the 3D-CT reconstruction group (right: 130.48±11.28 min, left: 125.51±10.59 min) and non-3D group (right: 134.45±10.20 min, left: 130.44±9.53 min), which was not associated with the site of surgery; intraoperative blood loss (right: 20.92±8.22 mL, left: 16.85±10.43 mL) was not statistically different compared with the 3D-CT reconstruction group (right: 21.13±8.97 mL, left: 19.09±7.01 mL), but was less than that of the non-3D group (right: 24.44±10.72 mL, left: 23.72±11.45 mL). Variation was found in the right pulmonary artery of 7 (3.91%) patients and in the left pulmonary artery of 21 (17.65%) patients. We first found four-branched lingual pulmonary artery in 2 patients. Conclusion    Preoperative CT image computer-assisted 3D reconstruction combined with 3D printing technology can help surgeons to formulate accurate surgical plans, shorten operation time and reduce intraoperative blood loss.

OBJECTIVE: To analyze the clinical features and genetic basis for a Chinese pedigree affected with hereditary dyschromatosis symmetrica hereditaria (DSH). METHODS: Peripheral blood samples of the proband and his mother were collected and subjected to PCR and Sanger sequencing. RESULTS: The patient has conformed to the typical pattern of DSH and manifested with hyperpigmentation, hypo- and hyperpigmentation spots on the back of hands, feet and face. Sanger sequencing confirmed that the proband and his mother have both harbored heterozygous splicing variant c.2762+1G>T in exon 9 of the ADAR gene, which was unreported previously. The same variant was not detected among 100 healthy controls. According to the guidelines of the American College of Medical Genetics and Genomics, the variant was predicted to be pathogenic (PVS1+PM2+PP4). CONCLUSION The c.2762+1G>T variant of the ADAR gene probably underlay the DSH in this pedigree. Above finding has enriched the spectrum of ADAR gene mutations.
Adenosine Deaminase/genetics* ; China ; Humans ; Mutation ; Pedigree ; Pigmentation Disorders/congenital* ; RNA-Binding Proteins/genetics*

Background/Aims: This study aimed to explore the effect of gut microbiota-regulated Kupffer cells (KCs) on colorectal cancer (CRC) liver metastasis. Methods: A series of in vivo and in vitro researches were showed to demonstrate the gut microbiota and its possible mechanism in CRC liver metastasis. Results: Fewer liver metastases were identified in the ampicillin-streptomycin-colistin and colistin groups. Increased proportions of Parabacteroides goldsteinii, Bacteroides vulgatus, Bacteroides thetaiotaomicron, and Bacteroides uniforms were observed in the colistin group. The significant expansion of KCs was identified in the ampicillin-streptomycin-colistin and colistin groups. B.vulgatus levels were positively correlated with KC levels. More liver metastases were observed in the vancomycin group. An increased abundance of Parabacteroides distasonis and Proteus mirabilis and an obvious reduction of KCs were noted in the vancomycin group. P. mirabilis levels were negatively related to KC levels. The number of liver metastatic nodules was increased in the P. mirabilis group and decreased in the B. vulgatus group. The number of KCs decreased in the P. mirabilis group and increased in the B. vulgatus group. In vitro, as P. mirabilis or B. vulgatus doses increased, there was an opposite effect on KC proliferation in dose- and time-dependent manners. P. mirabilis induced CT26 cell migration by controlling KC proliferation, whereas B. vulgatus prevented this migration. Conclusions An increased abundance of P. mirabilis and decreased amount of B. vulgatus play key roles in CRC liver metastasis, which might be related to KC reductions in the liver.