BACKGROUND:After the internal fixation of cannulated screws in femoral neck fractures,because the affected limb is often unable to bear weight in the short term and the implants with high stiffness have a stress shielding effect on the fracture end,it is easy to cause osteoporosis of the affected limb and changes in the biomechanical distribution of the proximal femur,the incidence of osteonecrosis of the femoral head is high after surgery.At present,few studies have been conducted on the biomechanical effects of osteoporosis at the proximal end of the femur occurring after femoral neck fracture surgery on femoral neck fracture treated with cannulated screws. OBJECTIVE:Using finite element analysis,to investigate the biomechanical effects of osteoporosis occurring after femoral neck fracture surgery on femoral neck fracture treated with cannulated screws and explore the role of biomechanical factors in osteonecrosis of the femoral head. METHODS:Based on the obtained CT scan data of the femur in a patient with a femoral neck fracture,a proximal femoral model for internal fixation for femoral neck fracture was established by Mimics 19.0,3-Matic,UG 11.0,Hypermesh 14.0,and Abaqus software.One finite element model of the proximal femur without osteoporosis and three finite element models of the proximal femur with osteoporosis were analyzed using Abaqus software.The stress,contact pressure,displacement peak and cloud map under different components of the four models were measured and analyzed,and the internal stress changes and distribution of the femoral head were compared and analyzed. RESULTS AND CONCLUSION:The stresses and contact pressures of the femoral head and lower anterior cannulated screws varied more with the degree of osteoporosis.The peak displacement of the four models increased slowly with the degree of osteoporosis.By one-way analysis of variance,there was no significant effect of the degree of osteoporosis on the peak stress,contact pressure,and displacement of the different components.The internal stress distribution of the femoral head changed with the degree of osteoporosis.Changes in the biomechanical environment of the proximal femur have an important impact on osteonecrosis of the femoral head.

Regarding the air quality problems,this article summarized the adverse factors such as trace harmful gases,small particulate matter,and high concentration carbon dioxide that existed in space closed environment,and compared the advantages and disadvantages of physical and chemical treatment methods to improve air quality.The focus was on exploring the improvement benefits of plants method on air quality,and summarizing the research progress in three aspects:absorption of trace harmful gases,release of negative oxygen ions,and absorption of carbon dioxide.The current research problems were pointed out,and the future research directions on using plants to improve the air quality in space closed environment were predicted.

Objective:To analyze and summarize the clinical manifestations, pathological characteristics, treatment, and outcomes of primary malignant melanoma of the esophagus(PMME)in elderly Chinese patients.Methods:A case study of an elderly patient with PMME was conducted at the Department of Gastroenterology in the China-Japan Friendship Hospital.Additionally, literature and case data on elderly PMME cases reported in China up to July 2023 were gathered and analyzed to summarize the epidemiological characteristics, endoscopic manifestations, clinical presentations, diagnosis, treatment, and prognosis of the disease.Results:A comprehensive review of the literature up to July 2023 documented a total of 114 cases of elderly patients with PMME in China, which also included cases from our hospital.Among these cases, there were 68 male patients(59.6%)and 46 female patients(40.4%), ranging in age from 60 to 81 years, with a median age of 65 years.The predominant clinical manifestations observed were dysphagia and choking while eating, followed by chest pain and retrosternal burning sensation.The majority of the lesions were found in the middle and lower segments of the esophagus, predominantly protruding into the lumen, with only 2 cases(1.8%)displaying esophageal mucosal pigmentation.Immunohistochemical analysis revealed that HMB45 was positive in 74 cases(64.9%)and negative in 3 cases(2.6%), while S-100 was positive in 66 cases(57.9%)and negative in 2 cases(1.8%), although data for some patients were not available.Lymph node or distant metastases were present in 45 cases(39.5%), while 38 patients(33.3%)had tumors confined to the esophagus without metastases.Of the 114 patients, 61(53.5%)had a follow-up period ranging from 0.3 to 39 months, with a median follow-up time of 6.75 months.Among the patients who survived during the follow-up period, there were 30 cases(26.3%), with a follow-up time of 1 to 39 months and a median follow-up time of 7.5 months.For the deceased patients, the time from consultation to death ranged from 0.3 to 31 months.Conclusions:Elderly individuals with PMME in China typically present with a gradual onset, nonspecific symptoms, frequent metastasis upon diagnosis, aggressive behavior, and unfavorable outcomes.

Objective To provide a reliable and stable animal model for investigating the molecular pathogenesis of radiation-induced liver disease (RILD). Methods Ninety C57BL/6J mice were divided into control, 20 Gy, 25 Gy, 30 Gy and 35 Gy radiation groups. The mice were executed at 4 weeks after radiation and the levels of alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase in the liver serum were measured. HE staining was performed on the pathological liver tissues. Masson staining was performed at 36 weeks after radiation. Results Compared with the control group, the fatality rate was higher in the 30 and 35 Gy radiation groups, and the body weight significantly decreased in the 20 and 25 Gy radiation groups. Compared with the control group, alanine aminotransferase significantly increased in mice exposed to 20 Gy, while aspartate aminotransferase and alanine aminotransferase increased in mice exposed to 25 Gy. No significant changes were observed in the livers of the mice in the 20 and 25 Gy radiation groups, but pathological examination showed liver damage induced by both 20 and 25 Gy radiation. Conclusion A stable and reliable mouse model of RILD was constructed for treatment with linear accelerator. The mouse model of RILD constructed for stereotactic body radiation therapy using linear accelerator has significant research implications for the exploration of RILD.

Objective:To investigate the effect of visceral obesity on the short-term curative effect of Da Vinci robotic-assisted radical resec-tion for rectal cancers.Methods:Clinical and pathological data of patients with rectal cancer undergoing Da Vinci robotic-assisted surgery,admitted to People's Hospital of Zhengzhou University and Cancer Hospital of Zhengzhou University from November 2019 to June 2022 were retrospectively analyzed.Visceral fat area(VFA)≥100 cm2 was used as the standard to define visceral obesity.Patients were categorized in-to visceral and non-visceral obesity groups.The short-term efficacy of the two groups was evaluated,and the influencing factors of post-operative complications were analyzed using univariate and multivariate Logistic regression.Results:Among a total of 169 patients,93 were included in the visceral obesity group and 76 in the non-visceral obesity group.There was no significant difference in the baseline data between the two groups(P>0.05).There was no conversion to laparotomy in the non-visceral obesity group,and the conversion rate was 1.1%(1/93)in the visceral obesity group.The second operation rate was 2.2%(2/93)in the visceral obesity group and 1.3%(1/76)in the non-visceral obesity group with no statistical difference between the two groups.There were no significant differences in the operation dur-ation,intraoperative blood loss,number of lymph node dissections,and total postoperative complication rate between the two groups(P>0.05).Multivariate Logistic regression analysis revealed that an NRS≥3 independently contributed as a risk factor for postoperative com-plications(OR=3.190,95%CI:1.240-8.210,P=0.016).Conclusions:An NRS≥3 is an independent risk factor for complications post-robotic rad-ical rectal cancer surgery.The robotic surgical platform can overcome obesity-related limitations and is equally safe and effective for pa-tients with visceral obesity presenting with rectal cancer.

Objective:To investigate the diagnostic and prognostic value of 68Ga-fibroblast activation protein inhibitor (FAPI) PET for hepatobiliary malignancies. Methods:From July 2020 to February 2023, 33 patients (23 males, 10 females; age (55.4±13.5) years) with suspected or confirmed liver or biliary tract malignancies who underwent 68Ga-FAPI PET in Union Hospital, Tongji Medical College, Huazhong University of Science and Technology were retrospectively analyzed. PET images were evaluated by 3 experienced nuclear medicine physicians, and the results of biopsy or postoperative pathology, clinical and imaging follow-up were used as the gold standard. One-way analysis of variance and least significant difference t test were used to compare the differences among groups. Survival analysis was performed using Kaplan-Meier curves and the log-rank test. Results:Of 33 patients, 14 performed PET for initial diagnosis and staging, and 19 for restaging. There were 14 patients with hepatocellular carcinoma (HCC), 13 patients with cholangiocarcinoma (CCA), and 6 patients with gallbladder carcinoma (GBC). The primary tumor of HCC, CCA and GBC all showed significant 68Ga-FAPI uptake, with no statistically significant difference in SUV max among groups ( F=1.58, P=0.250). The sensitivities of 68Ga-FAPI PET for initial diagnosis and restaging of hepatobiliary malignancies were 14/14 and 15/15, respectively. Compared with conventional imaging, 68Ga-FAPI PET changed the diagnosis and staging in 29.2%(7/24) patients. The treatment strategy was changed in 30.3%(10/33) patients with malignant tumors due to 68Ga-FAPI PET findings. Follow-up showed 22 cases survived and 11 cases died, with the overall survival of 355.56(80.00, 516.97) d, and 1- and 2-year survival rates were 68.2% and 57.9%, respectively. Semi-quantitative 68Ga-FAPI PET parameters such as SUV max, target-liver ratio (TLR), and target-blood ratio (TBR) had no significant prognostic value, but the prognosis of the group without distant metastases diagnosed by 68Ga-FAPI PET was significantly better than that of the group with distant metastasis ( P=0.032). Conclusion:68Ga-FAPI PET has high sensitivity for the diagnosis of hepatobiliary malignancies, which can help guide treatment decisions and prognosis evaluation.

Objective:To explore the feasibility of pretargeting technique for immunoPET with epidermal growth factor receptor (EGFR) monoclonal antibody in EGFR positive/negative tumor bearing mice.Methods:Cetuximab- Trans-cyclooctene (TCO)was obtained by modifying Cetuximab with TCO- N-hydroxysuccinimide (NHS). 2, 2′-((6-amino-1-(4, 7-bis-(carboxymethyl)-1, 4, 7-triazonan-1-yl)hexan-2-yl)azanediyl)-diacetic acid (L-NETA)was used as a chelating agent to prepare the radioligand 68Ga-L-NETA-tetrazine (Tz), then the labeling rate and in vitro stability of the product were determined. Human basal breast cancer cells MDA-MB-468 (EGFR+ ) and MDA-MB-231 (EGFR-) were cultured in vitro. In vitro experiments were performed to explore the specificity of the probe and the feasibility of pretargeting technique. Nude mice (Balb/c-nu) bearing xenografts of the above two cell lines were established. Cetuximab-TCO (50 μg) was injected into the tumor-bearing mice in advance, then 68Ga-L-NETA-Tz was injected at different time points (48, 36, 24 and 12 h), and pretargeting was realized through " click chemistry" . Small-animal PET imaging and biodistribution were performed to evaluate pharmacokinetic properties and specificity of the probe. The one-way analysis of variance was used to compare the data. Results:The 68Ga-L-NETA-Tz molecular probe was successfully prepared with the labeling yield >95%, and the radiochemical purity was >95% after 2 h. Cetuximab-TCO and 68Ga-L-NETA-Tz were added to MDA-MB-468 cells successively, and the cell uptake rate reached (0.69±0.04)% at 1 h, which demonstrated the feasibility of the pretargeting technique. PET imaging and biodistribution results showed that the best imaging results were obtained in 36 h pre-injection group, in which the tumor uptake was the highest ((0.77±0.05) percentage activity of injection dose per gram of tissue (%ID/g), 1 h) and the tumor/muscle ratio was optimal (4.67±0.46); the tumor uptake in the blocking group, the group without injecting Cetuximab-TCO, and the MDA-MB-231 group were significantly lower ((0.35±0.01), (0.39±0.05), (0.45±0.10) %ID/g; F=15.50, P=0.002). Conclusions:EGFR targeted immunoPET imaging is successfully performed in mouse models of breast cancer by injecting Cetuximab-TCO and 68Ga-L-NETA-Tz successively. It provides an effective method for immunoPET imaging of monoclonal antibodies.

Alternative polyadenylation(APA)is a crucial step in post-transcriptional regulation.Previous bioinformatic studies have mainly focused on the recognition of polyadenylation sites(PASs)in a given genomic sequence,which is a binary classification problem.Recently,computa-tional methods for predicting the usage level of alternative PASs in the same gene have been pro-posed.However,all of them cast the problem as a non-quantitative pairwise comparison task and do not take the competition among multiple PASs into account.To address this,here we propose a deep learning architecture,Deep Regulatory Code and Tools for Alternative Polyadenylation(DeeReCT-APA),to quantitatively predict the usage of all alternative PASs of a given gene.To accommodate different genes with potentially different numbers of PASs,DeeReCT-APA treats the problem as a regression task with a variable-length target.Based on a convolutional neural network-long short-term memory(CNN-LSTM)architecture,DeeReCT-APA extracts sequence features with CNN layers,uses bidirectional LSTM to explicitly model the interactions among com-peting PASs,and outputs percentage scores representing the usage levels of all PASs of a gene.In addition to the fact that only our method can quantitatively predict the usage of all the PASs within a gene,we show that our method consistently outperforms other existing methods on three different tasks for which they are trained:pairwise comparison task,highest usage prediction task,and rank-ing task.Finally,we demonstrate that our method can be used to predict the effect of genetic variations on APA patterns and sheds light on future mechanistic understanding in APA regulation.

The accurate annotation of transcription start sites(TSSs)and their usage are critical for the mechanistic understanding of gene regulation in different biological contexts.To fulfill this,specific high-throughput experimental technologies have been developed to capture TSSs in a genome-wide manner,and various computational tools have also been developed for in silico pre-diction of TSSs solely based on genomic sequences.Most of these computational tools cast the problem as a binary classification task on a balanced dataset,thus resulting in drastic false positive predictions when applied on the genome scale.Here,we present DeeReCT-TSS,a deep learning-based method that is capable of identifying TSSs across the whole genome based on both DNA sequence and conventional RNA sequencing data.We show that by effectively incorporating these two sources of information,DeeReCT-TSS significantly outperforms other solely sequence-based methods on the precise annotation of TSSs used in different cell types.Furthermore,we develop a meta-learning-based extension for simultaneous TSS annotations on 10 cell types,which enables the identification of cell type-specific TSSs.Finally,we demonstrate the high precision of DeeReCT-TSS on two independent datasets by correlating our predicted TSSs with experimentally defined TSS chromatin states.The source code for DeeReCT-TSS is available at https://github.-com/JoshuaChou2018/DeeReCT-TSS_release and https://ngdc.cncb.ac.cn/biocode/tools/BT007316.

Objective:To investigate the effect of low molecular weight heparin (LMWH) on the inflammatory response of PC12 cells induced by oxygen glucose deprivation (OGD) and its related mechanism.Methods:The PC12 cells were cultured in vitro were randomly divided into sham(control) group, OGD group, LMWH group and blocking agent group. The latter group was divided into six groups: Eritoran+ OGD group, LMWH+ Eritoran+ OGD group, ST2825+ OGD group, LMWH+ ST2825+ OGD group, pyrrolidinedithiocarbamate (PDTC)+ OGD group and LMWH+ PDTC+ OGD group. OGD cell model was established. Cell counting kit-8 (CCK-8) assay was used to detect cell activity. The expressions of toll-like receptor 4 (TLR4), MyD88 and nuclear factor κB (NF-κB) mRNA and protein were detected by real time polymerase chain reaction (qRT-PCR) and Western blot. The concentration of interleukin (IL)-1β, IL-6, tumor necrosis factor-α(TNF-α) and S100β were determined by enzyme linked immunosorbent assay (ELISA). Results:The cell activity of OGD group was significantly lower than that of control group on the first, second, third day ( P<0.05). Compared with OGD group, the activity of LMWH group was increased on the second, third day ( P<0.05), but lower than that of control group ( P<0.01). The mRNA expression of TLR4, MyD88 and NF-κB was significantly increased in OGD group compared with the control group ( F=144.9, F=710.5, 79.51, P<0.01). Compared with OGD group, the mRNA expression of TLR4, MyD88 and NF-κB were significantly decreased after treatment with LMWH ( P<0.01), and the specific inhibitor of TLR4, MyD88 and NF-κB enhanced the anti-inflammatory effect of LMWH. The protein expression of this pathway was consistent with that of the gene. The concentration of IL-1β, IL-6, TNF-α and S100β in OGD group was significantly higher than control group ( P<0.05). After treatment with LMWH, the concentrations of inflammatory factors and S100β were significantly decreased compared with OGD group ( P<0.01). When hinder TLR4, MyD88 and NF-κB respectively by Eritoran, ST2825 and PDTC, the concentrations of inflammatory factors and S100β were significantly decreased, but it was still higher than control group ( P<0.05). Conclusions:OGD can cause pathological damage of PC12 cells, including high expression level of S100β and aggravation of inflammatory reaction. LMWH can improve cell activity, down-regulate inflammatory reaction degree and protect the cells. Using inhibitors of TLR4/MyD88/NF-κB pathway to inhibit the corresponding target, the up-regulation of inflammatory factors by OGD can be inhibited in varying degrees. These suggested that LMWH may regulate inflammatory reaction of PC12 cells induced by OGD through TLR4/MyD88/NF-κB pathway.