Purpose To explore the predictive value of nomogram model for invasive breast cancer with axillary lymph node metastasis.Materials and Methods Retrospective analysis was made on 122 patients suspected to be breast cancer in the General Hospital of Ningxia Medical University from September 2020 to March 2022.According to whether there was axillary lymph node metastasis,all subjects were divided into 57 patients in the metastasis group and 65 patients in the non-metastasis group.All lesions were pathologically confirmed by surgery.The two groups received synthesis of magnetic resonance imaging(syMRI),dynamic contrast enhancement magnetic resonance imaging(DCE-MRI)and diffusion weighted imaging(DWI)scans.The syMRI parameters[including T1,T2,proton density(PD)],DCE-MRI time signal intensity curve,apparent diffusion coefficient(ADC)value of breast lesions were measured.Compared the difference of parameters between the two groups,and screened the independent risk factors of invasive breast cancer with axillary lymph node metastasis.Results Logistic regression results showed that Ki-67(OR=2.971,95%CI 1.306-6.762,P=0.009),lesion size(OR=1.652,95%CI 1.067-2.556,P=0.024),ADCratio(OR=1.685,95%CI 1.014-2.801,P=0.044),T2ratio(OR=3.015,95%CI 1.433-6.340,P=0.003),PDratio(OR=2.782,95%CI 1.471-5.262,P=0.002)were independent risk factors for invasive breast cancer with axillary lymph node metastasis.The comparison of the five models showed that the Logistic regression model had the best performance,with the area under curve of 0.729(95%CI 0.621-0.789),the accuracy,specificity and sensitivity were 70.65%,62.79%and 77.55%,respectively.The accuracy of the nomogram model was tested,and C-index=0.844,the accuracy of the nomogram model established was good,cut-off risk was 0.468,and the cut-off score was 143.50,which means that when the total score exceeds 143.50,the risk of axillary lymph node metastasis would be higher than 46.8%.Conclusion Nomogram model has a good predictive ability for invasive breast cancer patients with axillary lymph node metastasis.

BACKGROUND:Internal heat-type acupuncture therapy is a new treatment technique that combines acupuncture therapy with hyperthermia.It has good clinical effects on steroid-induced osteonecrosis of the femoral head,but the mechanism of action is still not fully clear. OBJECTIVE:To explore the possible mechanism of internal heat-type acupuncture therapy in treating steroid-induced osteonecrosis of the femoral head in rabbits. METHODS:Thirty-two New Zealand rabbits were randomly divided into blank group,model group,internal heat-type acupuncture group and shock wave group using a random number table method,with 8 rabbits in each group.The model group,internal heat-type acupuncture group and shock wave group were modeled using methylprednisolone sodium succinate combined with Escherichia coli endotoxin.The internal heat-type acupuncture group received an internal heat-type acupuncture intervention on the buttocks of rabbits,once a week,for 20 minutes each time.The shock wave group received shock wave intervention on the buttocks of rabbits,once a week,with 2 000 beats per session.The blank group and model group were not given any treatment.After 4 weeks of intervention,blood samples and bilateral femoral head samples were collected from experimental rabbits.The levels of tumor necrosis factor-α and interleukin-6 in serum were detected by ELISA;the histomorphology of the femoral head was observed using hematoxylin-eosin staining and the rate of empty lacunae was calculated;the protein expressions of matrix metalloproteinase 2,matrix metalloproteinase 9,matrix metalloproteinase tissue inhibitor 1,and matrix metalloproteinase tissue inhibitor 2 were detected by immunohistochemistry and western blot. RESULTS AND CONCLUSION:Compared with the blank group,the model rabbits showed reduced food intake,mental fatigue,and decreased activity;compared with the model group,the above performance of the experimental rabbits was significantly improved after internal heat-type acupuncture and shock wave treatment.Compared with the blank group,the histomorphology of the femoral head in the model group deteriorated significantly and the rate of empty bone lacuna increased(P<0.001),while the histomorphology of the femoral head in the internal heat-type acupuncture group and shock wave group was significantly improved compared with the model group,and the rate of empty bone lacuna was reduced(P<0.001).The serum levels of tumor necrosis factor-α and interleukin-6 in the model group were significantly higher than those in the blank group(P<0.05),while the serum levels of tumor necrosis factor-α and interleukin-6 in the internal heat-type acupuncture group and the shock wave group were significantly lower than those in the model group(P<0.05).Compared with the blank group,the expression levels of matrix metalloproteinase 2 and matrix metalloproteinase 9 in the femoral head of the model group were significantly increased,while the expression levels of matrix metalloproteinase tissue inhibitor 1 and matrix metalloproteinase tissue inhibitor 2 were significantly decreased(P<0.001);compared with the model group,the protein expression levels of matrix metalloproteinase 2 and matrix metalloproteinase 9 were significantly decreased,while the protein expression levels of matrix metalloproteinase tissue inhibitor 1 and matrix metalloproteinase tissue inhibitor 2 were significantly increased in the internal heat-type acupuncture group and the shock wave group(P<0.001).Overall,these findings indicate that internal heat-type acupuncture may promote the repair of the necrotic femoral head by regulating the levels of matrix metalloproteinases/matrix metalloproteinase tissue inhibitors and serum inflammatory factors,thus treating early steroid-induced osteonecrosis of the femoral head.

Objective To investigate the effect of fluid flow shear stress(FFSS)on the fluid mechanic threshold of high-mobility group box 1(HMGB1)release by synovial cells and chondrocytes.Moreover,the mechanism of chondro-cyte and synovial cell damage induced by abnormal mechanical force was investigated to provide an experimental basis for exploring the pathogenesis and pathology of temporomandibular joint osteoarthritis.Methods With the approval of the Ethics Committee for Animal Experiments of the hospital,synovial tissue and cartilage tissue blocks were obtained from the knee joints of Sprague-Dawley(SD)rats,and synovial cells and chondrocytes were cultured and digested for subsequent experiments.Synovial cells and chondrocytes of 3-4 generations were acquired,and FFSS was applied to sy-novial and cartilage cells using a fluid shear mechanical device.The cells were divided according to the FFSS values of different sizes.Synovial cells were stimulated for 1 h with 1,3,5,or 10 dyn/cm2 of FFSS,and chondrocytes were stimu-lated for 1 h with 4,8,12,or 16 dyn/cm2 of FFSS.Resting cultures(0 dyn/cm2)were used as the control group.Changes in the morphology of the cells were observed.The expression and distribution of HMGB1 and interleukin-1β(IL-1β)were observed by immunohistochemistry.The expression of HMGB1 and IL-1β in the supernatant was analyzed by ELI-SA.The protein expression levels of intracellular HMGB1 and IL-1β were detected by Western blot.Results With in-creasing FFSS,the synovial cells and chondrocytes gradually swelled and ruptured,and the number of cells decreased.With increasing FFSS,the localizationof HMGB1 and IL-1β gradually shifted from the nucleus to the cytoplasm.In synovial cells,compared with those in the control group,the expression levels of HMGB1 and IL-1β were increased both in the supernatant and cells in the 1,3,5 and 10 dyn/cm2 intervention groups(P＜0.01).In chondrocytes,com-pared with those in the control group,the expression levels of HMGB1 in the supernatant were increased in the 4,12 and 16 dyn/cm2 intervention groups(P＜0.05),and the protein expression levels of HMGB1 were significantly increased(P＜0.01).The expression levels of HMGB1 in the supernatant were significantly increased in the 8 dyn/cm2 intervention groups(P＜0.01);however,the protein expression levels of HMGB1 were significantly decreased.Compared with those in the control group,the expression levels of IL-1β in the supernatant gradually increased in the 4,8,12 and 16 dyn/cm2 intervention groups(P＜0.01).With the exception of those in the 4 dyn/cm2 group,the protein expression levels of IL-1β gradually increased with increasing FFSS(P＜0.05).Conclusion With increasing FFSS,synovial cells and chondro-cytes gradually swelled and burst,and the hydromechanical thresholds of HMGB1 release were 1 dyn/cm2 and 8 dyn/cm2,respectively.Therefore,upon stimulation with a mechanical force,synovial damage was damaged before chondrocytes.

Purpose To investigate the abnormal brain development in fetuses with isolated mild to moderate ventriculomegaly(VM)during the second and third trimesters of pregnancy by using semi-quantitative fetal total maturation score(fTMS).Materials and Methods A retrospective analysis was performed on 45 normal fetuses and 78 abnormal fetuses who underwent fetal MRI in the General Hospital of Ningxia Medical University from January 2018 to October 2022.fTMS was used to score all images.Linear regression was used to assess the relationship between fTMS and gestational age between normal and abnormal fetuses and to analyze the differences between fetuses with isolated mild and moderate VM and controls.Results In the control group,fetal fTMS was significantly positively correlated with gestational age(r=0.939,P<0.05).The linear regression equation between fTMS(Y)and gestational age(X)was as follows:Y=-28.1+1.25X.In the mild and moderate isolated VM groups,fTMS was positively correlated with gestational age(r=0.945,0.906,P<0.05).The linear regression equations of fTMS(Y)and gestational age(X)were:Y=-28.46+1.24X,Y=-25.57+1.13X.The average fTMS of healthy fetus,mild VM and moderate VM were(10.55±4.25)points,(10.13+4.08)points and(9.22±3.77)points,respectively.There was no significant difference in fTMS between the 49 fetuses with mild isolated VM and the control group(t=1.651,P>0.05).There was significant difference in fTMS between the 29 fetuses with moderate isolated VM and the control group(t=2.306,P<0.05).Conclusion fTMS is suitable for routine clinical use and sensitive to differences in brain maturation between fetuses with isolated moderate VM and healthy controls.

Objective To observe the effects of AnMeiDan(AMD),a representative formula of Peiyuan Guben Tranquilisation method,on the learning memory of zebrafish model of sleep deprivation(SD),and to explore the possible mechanism and the optimal apparent dose based on the Orexin signalling pathway.Methods 120 4-month-old wild-type AB line zebrafish were randomly divided into blank group,model group,AMD low-dose group(0.009 mg·mL-1·d-1),AMD medium-dose group(0.027 mg·mL-1·d-1),AMD high-dose group(0.081 mg·mL-1·d-1),and melatonin group(0.4 mg·mL-1·d-1).Zebrafish SD model was established by LED light induction method,24 h behavioural changes of zebrafish in each group were monitored by zebrafish behavioural tracking system,differences in learning and memory ability of zebrafish in each group were detected by T-maze,the state and number of neurons in the brain of zebrafish in each group were observed by Hematoxylin-Eosin(HE)staining method,the structural changes of neurons in the brain of zebrafish in each group were observed by transmission electron microscopy,and changes in neuron structure in the brain of zebrafish in each group were detected by ELISA method.The levels of Orexin A(OXA)and Orexin B(OXB)in zebrafish were detected by enzyme-linked immunosorbent assay(ELISA),and the protein and mRNA expression levels of OXA/p38 mitogen-activated protein kinase(P38 MAPK)/extracellular regulated protein kinase(ERK1/2)were detected by protein immunoblotting and real-time fluorescence quantitative assay(RT-PCR)in zebrafish.Results Compared with the blank group,the total number of rests,duration and distance were reduced in the model group(P<0.05),and the latency to enter the target region(OR)was prolonged(P<0.01);the number of neuronal cells was reduced,the nuclei were degenerated(P<0.01),cytoplasmic hyalinosis was increased(P<0.01),and light colouring was observed,the nuclei were collapsed,the nuclear membranes were ruptured and lysed,the chromatin was solidified,and the mitochondria were swollen and deformed with internal cavities,and lamellipod-like myelin-like structure was formed;the brain tissue OXA,OXA,and ERK1/2 expression levels of the mRNAs and the mRNAs of these signaling pathways were increased(P<0.01).brain tissue OXA and OXB proteins were significantly elevated,OXA mRNA and protein were significantly up-regulated,and P38 MAPK and ERK1/2 mRNA and protein were significantly down-regulated(P<0.01).Compared with the model group,the drug intervention could prolong the total resting exercise time of SD zebrafish(P<0.05);shorten the latency of zebrafish to reach OR(P<0.05);protect the structure and morphology of neuronal cells,and alleviate the damage of brain tissues;reduce the content of OXA and OXB in the brain tissues(P<0.01);and down-regulate the expression of OXA mRNA and protein(P<0.01),and up-regulate the P38 MAPK and ERK1/2 mRNA and protein expression of P38 MAPK and ERK1/2(P<0.01);and the quantity-effect relationship was obvious,and the effect of high dose of AMD was optimal.Conclusion AMD can improve the learning and memory ability in zebrafish SD model,and its mechanism may be related to the regulation of OXA/P38 MAPK/ERK1/2 signalling pathway and alleviation of neuronal damage in the brain,and the high dose group of AMD showed the best effect.

Objective To provide pharmaceutical care for patients with hepatitis B cirrhosis by using the medication therapy management(MTM)model combined with Pharmaceutical Care Network Europe(PCNE),and to analyze the effectiveness of pharmaceutical care from clinical efficacy,safety,humanistic effect and drug-related problems(DRPs).Methods Patients with hepatitis B cirrhosis were randomly divided into the pharmaceutical care group and the control group who received only conventional treatment.Clinical pharmacists used MTM combined with PCNE to provide pharmaceutical care in the pharmaceutical care group.Economic effects,clinical indicators,safety,medication compliance and quality of life were compared between the two groups during the treatment and follow-up period.DRPs were analyzed in the pharmaceutical care group.Results The cost-utility ratio and clinical indicators in the pharmaceutical care group were better than those in the control group,and the adverse drug reactions of the former were statistically significant compared with the latter at the three months follow-up,and medication compliance and quality of life were statistically significant after intervention and during follow-up(P＜0.05).There were 52 DRPs in the pharmaceutical care group,mainly in the category of poor treatment outcome.The main reasons were poor drug selection and excessive usage and dosage.There were 46 DRPs accepted by intervention,and 45 DRPs were completely and partially solved.Conclusion The pharmaceutical care model of MTM combined with PCNE classification system for patients with hepatitis B cirrhosis played a positive role in the treatment and follow-up period.

Colorectal cancer is currently one of the most common malignant tumors in the world,and its incidence and mortality rates have gradually increased in recent years.As insidious symptoms characterize early colorectal cancer,most of the patients have already developed into late or advanced stages in the primary survey.For stage Ⅳ metastatic colorectal cancer(mCRC),surgery supplemented with chemotherapy or radiotherapy for mCRC patients has a low 5-year survival rate.With the development of immunology in recent years,PD-1/PD-L1 inhibitors have made breakthroughs in treating malignant tumors.They also have improved the therapeutic efficacy of some mCRC patients,especially those with microsatellite instability-high/mismatch repair deficient.The guidelines recommend this approach.However,patients with microsatellite stable/mismatch repair proficiency,which accounts for more than 90%,are poorly treated with PD-1/PD-L1 inhibitors.Fortunately,there are several clinical studies that reported that some of this type of mCRC can gain some benefit.In this review,we examined the anti-tumor mechanism of PD-1/PD-L1 inhibitors and the latest progress of PD-1/PD-L1 inhibitor's clinical application in patients of mCRC with different genotypes.We discussed the prospect of PD-1/PD-L1 inhibitor combination therapy to provide a reference to the benefit of this type of patients and provide information for optimizing the dosing regimen of PD-1/PD-L1 inhibitors in the treatment of mCRC.

Objective To observe the influence of the staining phenomenon after fluorescein sodium staining on eye irritation in normal rabbits.MethodsIn the experimental rabbit eye irritation test conducted with sodium chloride eye drops, Siwei Zhenceng Bingpeng eye drops, sodium hyaluronate eye drops, sodium cromoglycate eye drops, and compound aspartate eye drops (4 in each group, half male and half female), the left eyes of rabbits were administered normal saline (self-negative control) and the right eyes were administered the experimental medicine; the eyes were stained with 1% sodium fluorescein, and eye irritation was observed and scored using slit lamp microscope for 31 days. Morphological changes of corneal epithelial staining were recorded and the incidence of staining was calculated. After the observation, the eyeballs and Hasselblad glands were examined histopathologically, and the staining rate of the left eye was compared with that of the right eye which was administered the corresponding medicine.ResultsNeither eye had any irritation symptoms; the scores were 0, and the total incidences of corneal staining were 3% (left) and 1% (right), respectively. There was no significant difference between the two groups (P > 0.05). Corneal epithelial staining showed single-spot staining, scattered dot, localized, or large areas of fusion staining. No histopathological changes were found in the eyeballs or Hasselblad glands, and the results were evaluated as non-irritative.Conclusion The irregularity of corneal epithelial staining in rabbits did not influence the results of the ocular irritation test.

Sugar reduction and restriction have become one of the most urgent health demands as the number of obese people increases globally. Sugar substitutes (mainly classified into sugar alcohols, natural sweeteners, and artificial sweeteners) have been widely used in food processing as alternatives to sugar for their low energy and high sweetness. Thus, the classification, metabolism pathways, advantages, applications, and human health effects of sugar substitutes, their effects on human health were introduced, and the relationships between sugar substitutes and obesity, diabetes, intestinal microbes, hypertension, and all-cause mortality were emphatically summarized in this paper. Generally, long-term high intake of sugar substitutes is associated with adverse health outcomes such as elevated blood pressure, higher risks of diabetes, cancer, and increased all-cause mortality. Meanwhile, sugar alcohols and natural sweeteners are more likely to associate with beneficial effects on human gut microbial diversity, while artificial sweeteners associate with imbalance of gut microbiota based on available evidence. Current published research focuses on single sugar substitute exposure with varied health effects, while nearly half of commercial sugar substitute products contain two or more sugar substitutes. The effects of exposure to multiple sugar substitutes on human health are not clear yet, so further strengthening the relevant epidemiological and molecular mechanism research is necessary.

Humans ; Phosphorylation ; Serine ; Protein Serine-Threonine Kinases/metabolism* ; Spasms, Infantile