BACKGROUND:The authors found that when the bilateral percutaneous vertebral augmentation is used to treat osteoporotic vertebral compression fractures with a total bone cement injection of 4 mL or more,different distribution patterns were usually presented on the X-rays;however,there were few reports addressing the effects of these patterns of bone cement distribution on the biomechanical properties of fractural vertebrae. OBJECTIVE:To further explore the biomechanical effects of different bone cement filling doses and distribution patterns on biomechanics of the fractural vertebrae using the finite element method. METHODS:The L1-L3 finite element models of osteoporosis were established,and the vertebral compression fractures were simulated in L2.Four distribution patterns bilateral partial fusion(FH type),full fusion(FO type),symmetrical separation(SA type),and asymmetric segregation(SN type)were simulated in 4 and 6 mL injections in the osteoporotic vertebral compression fracture models,respectively,and a total of nine sets of models were obtained.These models were solved under the same boundary conditions and compared with the stress and displacement of the L2 fractural vertebra. RESULTS AND CONCLUSION:(1)The maximum stresses of the nine groups of models were concentrated in the L2 fractural area,and the maximum stress and maximum displacement of each filling model were lower than in the osteoporotic vertebral compression fracture model,indicating the effectiveness of bone cement filling in the treatment of osteoporotic vertebral compression fracture.(2)Compared with 4 mL bone cement filling,6 mL bone cement filling could significantly reduce the stress of fractured vertebrae and enhance the strength of fractured vertebrae while improving the stability of fractured vertebrae.(3)In the same state of movement,the FH type stress was the least,followed by the SA type,both of which were close.FO type stress was the largest,especially in the lateral bend,which might be associated with its cluster shape resulting in the concentration of lateral stress.In the aspect of displacement,FH type was the least and FO type was the largest.(4)The results show that increased dose of bone cement injection reduces fractural vertebral stress and improves stability,but increases the risk of leakage.Bilateral symmetrical dispersed bone cement(FH type,SA type)is superior in restoring vertebral strength and stability than full fusion(FO type),asymmetric separated(SN type)bone cement.Therefore,when clinically performing bilateral percutaneous vertebral augmentation treatment of osteoporotic vertebral compression fractures,the bilateral symmetric dispersions of the distribution are first guaranteed;priority is recommended for FH type distribution,for appropriate stress stimulation and best stability.

OBJECTIVE To investigate the ameliorative effect and potential mechanism of imperatorin （IMP） on doxorubicin （DOX） resistance in breast cancer. METHODS The effects of maximum non-toxic concentration （100 μg/mL） of IMP combined with different concentrations of DOX （12.5， 25， 50， 75， 100 μg/mL） on the proliferation of MCF-7/DOX cells were determined by MTT method. MCF-7/DOX cells were divided into blank control group （1‰ dimethyl sulfoxide）， DOX group （50 μg/mL）， IMP+DOX group （100 μg/mL IMP+50 μg/mL DOX） and IMP group （100 μg/mL）. mRNA and protein expressions of multidrug resistance protein 1 （MDR1） and multidrug resistance-associated protein 1 in each group were measured. The relevant pathways and targets involved in the improvement of DOX resistance in breast cancer cells by IMP were screened and validated by using transcriptome sequencing technology， along with gene ontology （GO） enrichment analyses and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analyses. RESULTS Compared with DOX alone， the combination of IMP and DOX reduced the half inhibitory concentration of DOX on MCF-7/DOX cells from 81.965 μg/mL to 43.170 μg/mL， the reverse fold was 1.90， and the mRNA expression of MDR1 was significantly down-regulated （P＜0.05）. The results of GO enrichment analyses and KEGG pathway enrichment analyses indicated that the reversal of DOX resistance in breast cancer by IMP was mainly associated with the regulation of biological processes such as detoxification， multiple biological processes， and cell killing. The main pathway involved was the p53 signaling pathway， and the key targets mainly included constitutively photomorphogenic protein 1 （COP1）， cyclin E1 （CCNE1）， growth arrest and DNA damage-inducible protein 45A E-mail：tangxilan1983@163.com （GADD45A） and GADD45B. The results of the verification experiments showed that compared with DOX group， there was a trend of up-regulation of COP1 mRNA， and significant down- regulation of CCNE1， GADD45A， and GADD45B mRNA expression in IMP+DOX group （P＜0.05）. CONCLUSIONS The effect of IMP in ameliorating DOX resistance in breast cancer is related to its regulation of COP1， CCNE1， GADD45A and GADD45B targets in the p53 signaling pathway.

Objective To explore the application of the Autoregressive Integrated Moving Average (ARIMA) model in predicting the number of reported hepatitis E cases in Yunnan Province，to use this model to predict the incidence trend of hepatitis E, and to provide reference for the scientific prevention and control of hepatitis E. Methods Monthly reported cases of hepatitis E in Yunnan Province from 2012 to 2021 were collected. The ARIMA model was established using SPSS 27.0, and the model was validated and parameters were optimized with data from January 2022 to December 2022. The optimal fitting model was used to predict the incidence of hepatitis E in 2023. Results Hepatitis E incidence in Yunnan Province showed a certain seasonal distribution, with most cases concentrated from March to August. All parameters of ARIMA(3,1,4)(1,1,1)₁₂ passed statistical tests. The Ljung-Box test showed statistic Q =10.050, P = 0.346, residual sequence was a white noise sequence, and goodness-of-fit index stationary R² was 0.591. The model extrapolation effect was verified with 2022 data, and MAPE was 14.747, indicating that the model extrapolation effect was effective. The number of hepatitis E cases in Yunnan Province in 2023 was expected to be 1,086. Conclusion The ARIMA (3,1,4)(1,1,1)₁₂ model shows good fitting performance for hepatitis E cases in Yunnan Province and can effectively predict short-term disease trends, providing a theoretical basis for formulating prevention and control measures for hepatitis E.

Medical institutions, with their clinical practice foundation and abundant human use experience data, have become important carriers for the inheritance and innovation of traditional Chinese medicine(TCM) and the "cradles" of the preparation of new TCM. To effectively promote the transformation of new TCM originating from the TCM clinical practice in medical institutions and establish an effective evaluation index system for the transformation of new TCM conforming to the characteristics of TCM, consensus experts adopted the literature research, questionnaire survey, Delphi method, etc. By focusing on the policy and technical evaluation of new TCM originating from the TCM clinical practice in medical institutions, a comprehensive evaluation from the dimensions of drug safety, efficacy, feasibility, and characteristic advantages was conducted, thus forming a comprehensive evaluation system with four primary indicators and 37 secondary indicators. The expert consensus reached aims to encourage medical institutions at all levels to continuously improve the high-quality research and development and transformation of new TCM originating from the TCM clinical practice in medical institutions and targeted at clinical needs, so as to provide a decision-making basis for the preparation, selection, cultivation, and transformation of new TCM for medical institutions, improve the development efficiency of new TCM, and precisely respond to the public medication needs.
Medicine, Chinese Traditional/standards* ; Humans ; Consensus ; Drugs, Chinese Herbal/therapeutic use* ; Surveys and Questionnaires

PURPOSE: To investigate the pathological changes of the synovium in mice with post-traumatic osteoarthritis (PTOA) treated with 4-octyl itaconate (4-OI) and evaluate the therapeutic effects of 4-OI. METHODS: In the phenotypic validation experiment, the mice were randomly divided into 3 groups: wild-type (WT) group, sham group, and destabilization of the medial meniscus (DMM) group. Through MRI, micro-CT, and histological analysis, it was determined that the DMM surgery induced a mouse PTOA model with significant signs of synovitis. At 12 weeks post-DMM surgery, synovial tissues from the DMM group and WT group mice were collected for ribonucleic acid sequencing analysis. In the 4-OI treatment experiment, mice were randomly divided into the sham group, DMM group, DMM + 4-OI (50 mg/kg) group, and DMM + 4-OI (100 mg/kg) group. Von Frey tests and open field tests were conducted at intervals during the 12 weeks following the DMM surgery. After 12 weeks of surgery, the efficacy of 4-OI treatment on PTOA in mice was evaluated using MRI, micro-CT, histological analysis, and quantitative real-time polymerase chain reaction. Finally, we utilized network pharmacology analysis to predict the mechanism of 4-OI in treating PTOA synovitis and conducted preliminary validation. Statistical analysis was performed using one-way ANOVA and the Kruskal-Wallis test. Difference was considered statistically significant at p < 0.05. RESULTS: The DMM surgery effectively induced a PTOA mouse model, which displayed significant symptoms of synovitis. These symptoms included a notable increase in both the number of calcified tissues and osteophytes (p < 0.001), an enlargement of the calcified meniscus and synovial tissue volume (p < 0.001), and thickening of the synovial lining layer attributable to M1 macrophage accumulation (p = 0.035). Additionally, we observed elevated histological scores for synovitis (p < 0.001). Treatment with 4-OI inhibited the thickening of M1 macrophages in the synovial lining layer of PTOA mice (p < 0.001) and reduced fibrosis in the synovial stroma (p = 0.004). Furthermore, it reduced the histological scores of knee synovitis in PTOA mice (p = 0.006) and improved the inflammatory microenvironment associated with synovitis. Consequently, this treatment alleviated pain in PTOA mice (p < 0.001) and reduced spontaneous activity (p = 0.003). Bioinformatics and network pharmacology analyses indicated that 4-OI may exert its therapeutic effects by inhibiting the differentiation of synovial Th17 cells. Specifically, compared to the lipopolysaccharide stimulation group, 4-OI reduced the levels of positive regulatory factors of Th17 cell differentiation (IL-1: p < 0.001, IL-6: p < 0.001), key effector molecules (IL-17A: p < 0.001, IL-17F: p = 0.004), and downstream effector molecules in the IL-17 signaling pathway (CCL2: p < 0.001, MMP13: p < 0.001). CONCLUSION 4-OI is effective in inhibiting synovitis in PTOA, thereby alleviating the associated painful symptoms.
Animals ; Synovitis/etiology* ; Mice ; Osteoarthritis/etiology* ; Disease Models, Animal ; Male ; Succinates/pharmacology* ; Mice, Inbred C57BL ; X-Ray Microtomography

The genome tagging project (GTP) plays a pivotal role in addressing a critical gap in the understanding of protein functions. Within this framework, we successfully generated a human influenza hemagglutinin-tagged sperm-specific protein 411 (HA-tagged Ssp411) mouse model. This model is instrumental in probing the expression and function of Ssp411. Our research revealed that Ssp411 is expressed in the round spermatids, elongating spermatids, elongated spermatids, and epididymal spermatozoa. The comprehensive examination of the distribution of Ssp411 in these germ cells offers new perspectives on its involvement in spermiogenesis. Nevertheless, rigorous further inquiry is imperative to elucidate the precise mechanistic underpinnings of these functions. Ssp411 is not detectable in metaphase II (MII) oocytes, zygotes, or 2-cell stage embryos, highlighting its intricate role in early embryonic development. These findings not only advance our understanding of the role of Ssp411 in reproductive physiology but also significantly contribute to the overarching goals of the GTP, fostering groundbreaking advancements in the fields of spermiogenesis and reproductive biology.
Animals ; Female ; Humans ; Male ; Mice ; Spermatids/metabolism* ; Spermatogenesis/physiology* ; Spermatozoa/metabolism* ; Thioredoxins/genetics*

OBJECTIVES: To analyze the differences in the prognosis of gastric signet ring cell carcinoma (SRCC) among different races using the US Surveillance Epidemiology and End Results (SEER) database and The Cancer Genome Atlas (TCGA) database. METHODS: We analyzed the data of patients with gastric SRCC from the SEER database from 2000 to 2020, and divided the patients into cohorts of whites, blacks, Asians or Pacific Islanders, American Indians/Alaska Natives according to their race. The prognosis and treatment of the cohorts were evaluated using baseline demographic analysis, Kamplan-Meier survival curve, and nomogram analysis. RESULTS: We analyzed the data of a total of 2058 patients, including 8.6% blacks, 72.4% whites, 16.6% Asians or Pacific Islanders, 1.0% American Indians/Alaska Natives, and 1.4% other races. The tumor grade varied among different races, and the prevalence and survival rates of patients differed significantly across races. The differences in the white cohort were the most prominent, and all the differences were statistically significant (P<0.05). Racial differences were also noted in patient management and prognosis. CONCLUSIONS There are racial differences in tumor grades and prognosis of gastric SRCC, and these differences provide evidence for optimizing clinical diagnosis and treatment strategies for this malignancy.
Aged ; Female ; Humans ; Male ; Middle Aged ; Carcinoma, Signet Ring Cell/therapy* ; Databases, Factual ; Prognosis ; Racial Groups ; SEER Program ; Stomach Neoplasms/therapy* ; Survival Rate ; United States/epidemiology* ; White ; Asian American Native Hawaiian and Pacific Islander ; American Indian or Alaska Native ; Black or African American

Objective:To compare the safety and efficacy of two different minimally invasive approaches to implant pedicle screw for the treatment of single-segment thoracolumbar spine fractures without nerve injury.Methods:This was a retrospective study. Eighty patients with mono-segmental thoracolumbar fractures treated with minimally invasive pedicle screw fixation at Beijing Friendship Hospital, Capital Medical University from January 2020 to June 2022 were included. There were 46 males and 36 females, the age was (45.93±7.91) years old, and ranged from 27 to 60 years old. They were divided into two groups according to different surgical techniques: percutaneous pedicle screw fixation group ( n=44) and Wiltse approach group ( n=36). The operative time, operative visible blood loss, hidden blood loss, total blood loss, fluoroscopy times, incision length, hospital time after surgery and ambulation time were compared. Visual analogue scale (VAS), Oswestry disability index (ODI), ratio of the vertebral anterior height, angle of injured vertebral endplate were recorded and compared between two groups before surgery and at 3 days, 6 months and 1 year after surgery. The accuracy of pedicle screw position and the facet joint violation rate were evaluated by using the postoperative CT scan. Perioperative related complications were investigated. Normally distributed numerical data were presented as mean ± standard deviation, and differences between the groups were compared using t-test. The counting data were expressed as percentages or rates and compared using χ2 test. Results:All patients were followed for a minimum of 12 months. There is no significant difference between the two groups in intraoperative visible blood loss, hospital time after surgery, ambulation time, postoperative VAS and ODI, ratio of vertebral anterior height and angle of injured vertebral endplate at 3 days after surgery, pedicle screw position accuracy and perioperative complications ( P>0.05). The operative time, hidden blood loss, total blood loss, intraoperative fluoroscopy times, facet joint violation rate in the percutaneous pedicle screw fixation group were remarkably higher than in the Wiltse approach group ( P<0.05). The ratio of vertebral anterior height in the percutaneous pedicle screw fixation group was dramatically lower than in the Wiltse approach group at 6 months and 1 year after surgery ( P<0.05). The postoperative injured vertebral endplate angle was higher in the percutaneous pedicle screw fixation group than that in the Wiltse approach group at 6 months and 1 year ( P<0.05). Conclusions:Both percutaneous pedicle screw fixation and Wiltse approach were safe and effective minimally invasive surgical procedures for the treatment of thoracolumbar fractures without neurological injury. The Wiltse approach can reduce fluoroscopy times and perioperative hidden blood loss, reduce the risk of facet joint violation, and maintain a better reduction than percutaneous pedicle screw fixation.

Objective To investigate the clinical effect of transhepatic arterial chemoembolization(TACE)combined with tyrosine kinase inhibitors(TKIs)and programmed death receptors-1(PD-1)inhibitors(TACE+TKIs+PD-1 antibody)in the treatment of moderate advanced unresectable hepatocellular carcinoma(HCC).Methods The clinical data of 65 patients with moderate advanced unresectable hepatocellular carcinoma admitted to the Affiliated Hospital of North Sichuan Medical College from January 2020 to January 2022 were analyzed retrospectively.65 patients were treated with TACE+TKIs+PD-1 antibody.The observation indexes were tumor response,objective response rate(ORR),disease control rate(DCR),total survival time,progression free survival time,conversion operation rate and adverse drug reaction.Results The ORR of 65 p-atients with hepatocellular carcinoma was 49.2％(32/65),and the DCR was 89.2％(58/65).Among them,there were 2 patients with complete remission(CR),30 patients with partial remission(PR),26 patients with stable disease(SD),and 7 patients with progression disease(PD).Among 65 patients with hepatocellular carcinoma,18 patients were transformed into resectable hepatocell-ular carcinoma and underwent RO surgery.The conversion rate was 27.6％(18/65).65 patients were followed up for 3 to 22.4 months,The median follow-up time was 16.5 months.The median overall survival time and median disease progression free survival time of 65 patients were 14.5 months(95％CI:12.3～16.6 months)and 8.8 months(95％CI:6.9～10.6 months),respectively.After treatment,65 patients all had post embolism syndrome(abdominal pain,fever,nausea,vomiting and other symptoms),and some patients had transient abnormal liver function.Adverse drug reactions below grade 3 recovered within a few days.Some patients were associated with multiple adverse drug reactions.1 patient(1.5％)stopped using TACE because of stubborn vomiting,and 5 patients(7.6％)stopped using Lenvatinib because of severe liver function damage during treatment,2 patients(3％)stopped using Camrelizumab because of severe reactive capillary hyperplasia,one patient(1.5％)stopped using Tislelizumab because of severe hypothyroidism,one patient(1.5％)stopped the treatment of Lenvatinib and Sintilimab due to severe gastrointestinal bleeding.The adverse drug reactions of grade 3～4 occurred in other patients were alleviated after drug reduction,symptomatic treatment and hormone treatment.Conclusion TACE+TKIs+PD-1 antibody can obtain reliable clinical efficacy and anti-tumor activity in the treatment of moderate advanced unresectable hepatocellular carcinoma.