Electromagnetic fields can regulate the fundamental biological processes involved in bone remodeling. As a non-invasive physical therapy, electromagnetic fields with specific parameters have demonstrated therapeutic effects on bone remodeling diseases, such as fractures and osteoporosis. Electromagnetic fields can be generated by the movement of charged particles or induced by varying currents. Based on whether the strength and direction of the electric field change over time, electromagnetic fields can be classified into static and time-varying fields. The treatment of bone remodeling diseases with static magnetic fields primarily focuses on fractures, often using magnetic splints to immobilize the fracture site while studying the effects of static magnetic fields on bone healing. However, there has been relatively little research on the prevention and treatment of osteoporosis using static magnetic fields. Pulsed electromagnetic fields, a type of time-varying field, have been widely used in clinical studies for treating fractures, osteoporosis, and non-union. However, current clinical applications are limited to low-frequency, and research on the relationship between frequency and biological effects remains insufficient. We believe that different types of electromagnetic fields acting on bone can induce various “secondary physical quantities”, such as magnetism, force, electricity, acoustics, and thermal energy, which can stimulate bone cells either individually or simultaneously. Bone cells possess specific electromagnetic properties, and in a static magnetic field, the presence of a magnetic field gradient can exert a certain magnetism on the bone tissue, leading to observable effects. In a time-varying magnetic field, the charged particles within the bone experience varying Lorentz forces, causing vibrations and generating acoustic effects. Additionally, as the frequency of the time-varying field increases, induced currents or potentials can be generated within the bone, leading to electrical effects. When the frequency and power exceed a certain threshold, electromagnetic energy can be converted into thermal energy, producing thermal effects. In summary, external electromagnetic fields with different characteristics can generate multiple physical quantities within biological tissues, such as magnetic, electric, mechanical, acoustic, and thermal effects. These physical quantities may also interact and couple with each other, stimulating the biological tissues in a combined or composite manner, thereby producing biological effects. This understanding is key to elucidating the electromagnetic mechanisms of how electromagnetic fields influence biological tissues. In the study of electromagnetic fields for bone remodeling diseases, attention should be paid to the biological effects of bone remodeling under different electromagnetic wave characteristics. This includes exploring innovative electromagnetic source technologies applicable to bone remodeling, identifying safe and effective electromagnetic field parameters, and combining basic research with technological invention to develop scientifically grounded, advanced key technologies for innovative electromagnetic treatment devices targeting bone remodeling diseases. In conclusion, electromagnetic fields and multiple physical factors have the potential to prevent and treat bone remodeling diseases, and have significant application prospects.

Objective To study the brain functional connectivity(FC)changes in patients with normal tension glau-coma(NTG)and healthy volunteers using FC technique of resting-state functional magnetic resonance imaging(rs-fMRI)based on V1 region seed point(ROI),so as to explore the pathogenesis and early diagnosis of NTG.Methods Fourteen NTG patients(NTG group)who met the inclusion criteria and 14 healthy controls(HCs group)were enrolled.The clinical data of all subjects were collected,and rs-fMRI was performed in both groups.The magnetic resonance data was pre-pro-cessed by software,and bilateral A1 regions were taken as the ROI to analyze their correction with the whole brain voxel time series and obtain the FC value between the ROI and the whole brain by comparison of FC values in resting state be-tween the groups.Pearson correlation analysis was used to explore the relationship between FC value in the brain regions with significant differences with the ROI and clinical variables in the NTG group.Results Compared with the subjects in the HCs group,there were no statistically significant differences in age,gender,body weight,cup-disc ratio and 24 h mean intraocular pressure of patients in the NTG group(all P＞0.05),and there were statistically significant differences in the best corrected visual acuity(BCVA)of both eyes and peripapillary retinal nerve fiber layer thickness(RNFLT)(all P＜0.05).The Pearson correlation analysis showed that FC value of the brain regions with abnormal FC to V1 region were cor-related with RNFLT in the NTG group(P＜0.05).ROI1-left superior frontal gyrus,ROI1-right superior frontal gyrus,ROI2-left cingulate gyrus and ROI2-right middle frontal gyrus were significantly positively correlated with RNFLT(all P＜0.05).Compared with the HCs group,the brain regions with reduced FC to the right ROI in the NTG group were the left superior frontal gyrus and right superior frontal gyrus;the brain regions with reduced FC to the left ROI were the left cingulate gyrus and right middle frontal gyrus.Conclusion Compared to healthy individuals,NTG patients have significant changes in the functional connections between certain specific brain regions and V1 region,including bilateral superior frontal gyrus,left cingulate gyrus,and middle frontal gyrus.The changes in brain functional activity may be caused by visual dysfunction caused by NTG,leading to functional impairment of the visual and cognitive emotion processing brain regions,which may be one of the potential neuropathological mechanisms in NTG patients.

Objective To investigate the effects of microsurgical varicocelectomy on testicular function and sexual function in patients with varicocele.Methods The clinical data of 90 patients with varicocele admitted to our hospital were retrospectively analyzed,and the patients were divided into the laparoscopic group(received laparoscopic varicocelectomy)and the microscopic group(received microsurgical varicocelectomy)according to different surgical methods,with 45 cases in each group.The testicular function and sexual function related indexes including sperm density,normal sperm ratio,rate of sperm motility(grades a+b),forward motility sperm rate,international index of erectile function-5(IIEF-5)score,and the levels of testosterone,follicle-stimulating hormone,luteinizing hormone,and androgen levels before and 6 months after surgery in the two groups were compared.The incidence of complications and recurrence 6 months after surgery in the two groups were counted.Results Compared with those before surgery,the sperm density,forward motility sperm rate,rate of sperm motility(grades a+b),normal sperm ratio,IIEF-5 score,testosterone level,and androgen level 6 months after surgery of patients in the two groups were significantly increased(P<0.05),and the levels of luteinizing hormone and follicle-stimulating hormone were decreased(P<0.05).Compared with the laparoscopic group,the levels of follicle-stimulating hormone and luteinizing hormone,and incidence of complications 6 months after surgery of patients in the microscopic group were decreased(P<0.05),and the levels of testosterone and androgens,and IIEF-5 score 6 months after surgery were increased(P<0.05).There was no significant difference in the recurrence rate between the two groups(P>0.05).Conclusion Microsurgical varicocelectomy can improve the testicular function and sexual function of patients with varicocele,with a low incidence of complications.

Endocrine therapy is the most important adjuvant treatment for early estrogen receptor(ER)-positive breast cancer.ER-low-positive(immunohistochemistry staining 1%-10%)breast cancer has drawn widespread attention in recent years.This group accounts for 3%-9%of overall breast cancer patients.The efficacy of endocrine adjuvant therapy is relatively limited in patients with ER-low-positive breast cancer.Although the proportion of patients with low ER expression in breast cancer population is relatively low,the clinical needs of this population can not be ignored because of the large number of breast cancer patients.A number of studies have suggested that ER-low-positive breast cancer is different from ER-positive breast cancer,and is similar to ER-negative breast cancer in terms of molecular and biological characteristics,clinical features and prognosis.There are still controversies on the benefit and duration of endocrine therapy for early ER-low-positive breast cancer,and there is a lack of evidence from large-scale prospective studies.Multiple retrospective studies and meta-analyses have suggested that ER-low-positive breast cancer may have limited benefit from adjuvant endocrine therapy,and therefore endocrine therapy should be considered with caution in this population.The benefit of adjuvant therapy combined with cyclin-dependent kinase(CDK)4/6 inhibitors is yet to be supported by future data.Some patients with ER-low-positive breast cancer may try adjuvant chemotherapy in consideration of other risk factors.Additionally,clinical trials that test antibody-drug conjugates(such as sacituzumab govitecan and Dato-DXd),poly(ADP-ribose)polymerase(PARP)inhibitors,and immunotherapies for the treatment of early ER-low-positive breast cancer are still ongoing,including the phase Ⅲ ASCENT-05 study evaluating the adjuvant therapy of sacituzumab govitecan combined with pembrolizumab in high-risk human epidermal growth factor receptor 2(HER2)-negative,ER and progesterone receptor(PR)＜10%patients after surgery,the phase Ⅲ SASCIA study evaluating the adjuvant therapy of sacituzumab govitecan in high-risk HER2-negative patients after surgery,and the phase Ⅲ TROPION-Breast 04 study evaluating the neoadjuvant therapy of Dato-DXd combined with durvalumab.In addition,a neoadjuvant treatment for triple-negative breast cancer(TNBC)and ER-low expression breast cancer with olaparib and durvalumab(NCT03594396)is being explored,and the results are worth expecting.This article aimed to introduce the definition,clinical and pathological characteristics,and prognosis of ER-low breast cancer,and expound on the current treatment status and potential therapeutic strategies for HER2-negative,ER-low-positive early breast cancer in the future.

Objective:This study aimed to develop a new delivery strategy that utilized metal organic framework (MOF) loaded with small-interfering RNA (siRNA) targeting ITGAV to overcome tumor matrix barrier, and thus enhance drug penetration and immune accessibility in breast cancer.Methods:MOF@siITGAV particles were constructed and characterized. The uptake of MOF@siITGAV in breast cancer cell line 4T1 was observed by the cellular uptake assay. The toxicity of MOF@siITGAV was detected by cell counting kit 8 (CCK-8). The blank control group, naked siITGAV group and MOF@siITGAV group were set. Real-time fluorescent quantitative polymerase chain reaction (RT-qPCR) and Western blot were used to detect the expressions of ITGAV. The level of transforming growth factor β1 (TGF-β1) in the cell culture medium was detected by enzyme-linked immunosorbent assay (ELISA). The penetration of MOF@siITGAV in 4T1 cells was tested by constructing 3D spheroids. Mouse models of triple negative breast cancer were established. The effect of MOF@siITGAV on the growth of transplanted tumors and main organs was verified. Imminohistochemical (IHC) was used to test the expression of collagen and CD8.Results:MOF@siITGAV particles were constructed with sizes of (198.0±3.3) nm and zeta potential of -(20.2±0.4) mV. MOF@siITGAV could be engulfed by 4T1 cells and triggered to release siRNA. Compared to the blank control group, the expression of ITGAV in the MOF@siITGAV group [(46.5±11.3)%] and the naked siITGAV group [(109.9±19.0)%] was lower. TGF-β1 in the cell culture medium of the blank control group, naked siITGAV group, and MOF@siITGAV group was (474.5±34.4) pg/ml, (437.2±16.5) pg/ml, and (388.4±14.4) pg/ml, respectively. MOF@siITGAV could better penetrate into 4T1 spheroids and exhibit no obvious toxicity. The cell viability was (99.7±3.5)%, (98.2±5.2)%, (97.3±6.6)%, (92.1±8.1)%, and (92.4±4.1)%, respectively, after MOF@siITGAV treatment with the concentration of 0, 10, 20, 40, 80, and 160 μg/ml, respectively, for 24 h. The tumor growth in the MOF@siITGAV group was suppressed significantly. After 15-day treatment, the tumor volume of the MOF@siITGAV group was (135.3±41.9) mm 3, smaller than that of the blank control group [(691.1±193.0) mm 3] ( P=0.025). The expression of collagen and the number of CD8 positive cells of the MOF@siITGAV group were lower than those of the other two groups. No significant abnormalities were observed in the main organs of mice. Conclusions:Targeting the integrinαv on the surface of cancer cells could destroy extracellular matrix, improve drug delivery, and increase immune infiltration.

Objective:This study aimed to develop a new delivery strategy that utilized metal organic framework (MOF) loaded with small-interfering RNA (siRNA) targeting ITGAV to overcome tumor matrix barrier, and thus enhance drug penetration and immune accessibility in breast cancer.Methods:MOF@siITGAV particles were constructed and characterized. The uptake of MOF@siITGAV in breast cancer cell line 4T1 was observed by the cellular uptake assay. The toxicity of MOF@siITGAV was detected by cell counting kit 8 (CCK-8). The blank control group, naked siITGAV group and MOF@siITGAV group were set. Real-time fluorescent quantitative polymerase chain reaction (RT-qPCR) and Western blot were used to detect the expressions of ITGAV. The level of transforming growth factor β1 (TGF-β1) in the cell culture medium was detected by enzyme-linked immunosorbent assay (ELISA). The penetration of MOF@siITGAV in 4T1 cells was tested by constructing 3D spheroids. Mouse models of triple negative breast cancer were established. The effect of MOF@siITGAV on the growth of transplanted tumors and main organs was verified. Imminohistochemical (IHC) was used to test the expression of collagen and CD8.Results:MOF@siITGAV particles were constructed with sizes of (198.0±3.3) nm and zeta potential of -(20.2±0.4) mV. MOF@siITGAV could be engulfed by 4T1 cells and triggered to release siRNA. Compared to the blank control group, the expression of ITGAV in the MOF@siITGAV group [(46.5±11.3)%] and the naked siITGAV group [(109.9±19.0)%] was lower. TGF-β1 in the cell culture medium of the blank control group, naked siITGAV group, and MOF@siITGAV group was (474.5±34.4) pg/ml, (437.2±16.5) pg/ml, and (388.4±14.4) pg/ml, respectively. MOF@siITGAV could better penetrate into 4T1 spheroids and exhibit no obvious toxicity. The cell viability was (99.7±3.5)%, (98.2±5.2)%, (97.3±6.6)%, (92.1±8.1)%, and (92.4±4.1)%, respectively, after MOF@siITGAV treatment with the concentration of 0, 10, 20, 40, 80, and 160 μg/ml, respectively, for 24 h. The tumor growth in the MOF@siITGAV group was suppressed significantly. After 15-day treatment, the tumor volume of the MOF@siITGAV group was (135.3±41.9) mm 3, smaller than that of the blank control group [(691.1±193.0) mm 3] ( P=0.025). The expression of collagen and the number of CD8 positive cells of the MOF@siITGAV group were lower than those of the other two groups. No significant abnormalities were observed in the main organs of mice. Conclusions:Targeting the integrinαv on the surface of cancer cells could destroy extracellular matrix, improve drug delivery, and increase immune infiltration.

Humans ; Female ; Deep Learning ; Ovarian Neoplasms/genetics* ; Carcinoma, Ovarian Epithelial/genetics* ; Neural Networks, Computer ; RNA

Humans ; Consensus ; Hypersensitivity ; Desensitization, Immunologic/adverse effects* ; Immunotherapy/adverse effects* ; Injections, Subcutaneous ; Allergens

Objective:To investigate the clinical characteristics of patients with rheumatic diseases and abnormal liver function, as well as determine the proportion and severity of liver function abnormalities.Methods:Cross-sectional study. Data were collected from patients registered in the Chinese Rheumatism Date Center from 2011 to 2021. The rheumatic diseases analyzed in this study were rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Sjogren syndrome (SS), ankylosing spondylitis (AS), and gout. Patient data, including demographic characteristics [ such as age, sex, body mass index,(BMI), and smoking history], liver function test results [including alanine aminotransferase (ALT), aspartate aminotransferase, alkaline phosphatase(ALP), and total bilirubin], and use of anti-rheumatic immune drugs and liver-protective drugs, were collected and compared between groups with normal and abnormal liver functions. In addition, the proportions of abnormal liver function were compared between sex and age groups.Results:A total of 116 308 patients were included in this study, including 49 659 with RA, 17 597 with SLE, 9 039 with SS, 11 321 with AS, and 28 692 with gout. The lowest proportion of liver function abnormalities was observed in patients with RA[11.02% (5 470/49 659)], followed by those with SS[17.97% (1 624/9 039)] and AS [18.22% (2 063/11 321) ], whereas patients with SLE [21.14% (3 720/17 597) ] and gout [28.73% (8 242/28 692)] exhibited the highest proportion of these abnormalities. Elevated ALT, mostly classified as grade 1, was the most commonly noted liver function abnormality, whereas elevated ALP was the least common. Some patients who took liver-protective drugs had normal liver function, with the lowest percentage observed in patients with gout [7.45% (36/483) ] and ranging from 21.7% to 30.34% in patients with RA, SLE, SS, and AS. The proportion of liver function abnormalities was higher in males than in females for all disease types [RA: 13.8%(1 368/9 906) vs. 10.3%(4 102/39 753); SLE: 33.6% (479/1 424) vs. 20.0% (3 241/16 173); SS: 25.4%(111/437) vs. 17.6%(1 513/8 602); AS: 20.1%(1 629/8 119) vs. 13.6% (434/3 202); and gout: 29.3% (8 033/27 394) vs. 16.1% (209/1 298)]. In RA, SLE, and AS, the proportions of liver function abnormalities were similar across all age groups. In SS, the proportion of liver function abnormalities increased with age [<40 years: 14.9%(294/1 979); 40-59 years: 18.1%(858/4 741); ≥60 years: 20.4%(472/2 319)], whereas a reversal of this trend was observed in gout [<40 years: 34.9%(4 294/12 320); 40-59 years: 25.5%(2 905/11 398);≥60 years: 21.0%(1 042/4 971)].Conclusions:The proportions of combined liver function abnormalities in patients with rheumatologic diseases were high, and the utilization rates of liver-protective drugs were low. It is necessary to pay more attention to monitoring patients′ liver function, timely administer liver-protective drugs, and optimize liver-protective regimens during the treatment of rheumatic diseases.

Objective:To explore the current status of surgery for portal hypertension to grasp current status and future development of surgery in China.Methods:This study is jointly sponsored by China Hepatobiliary & Pancreatic Specialist Alliance & Portal Hypertension Alliance in China (CHESS).Comprehensive surveying is conducted for basic domestic situations of surgery for portal hypertension, including case load, surgical approaches, management of postoperative complications, primary effects, existing confusion and obstacles, liver transplantation(LT), laparoscopic procedures and transjugular intrahepatic portosystemic shunt(TIPS), etc.Results:A total of 8 512 cases of portal hypertension surgery are performed at 378 hospitals nationwide in 2021.Splenectomy plus devascularization predominated(53.0%)and laparoscopy accounted for 76.1%.Primary goal is preventing rebleeding(67.0%) and 72.8% of hospitals used preventive anticoagulants after conventional surgery.And 80.7% of teams believe that the formation of postoperative portal vein thrombosis is a surgical dilemma and 65.3% of hospitals practiced both laparoscopy and TIPS.The major reasons for patients with portal hypertension not receiving LT are due to a lack of qualifications for LT(69.3%)and economic factors(69.0%).Conclusions:Surgery is an integral part of management of portal hypertension in China.However, it is imperative to further standardize the grasp of surgical indications, the handling of surgical operation and the management of postoperative complications.Moreover, prospective, multi-center randomized controlled clinical studies should be performed.