Background: s/Aims: Sarcomatoid hepatocellular carcinoma (HCC) is a rare histological subtype of HCC characterized by extremely poor prognosis; however, its molecular characterization has not been elucidated. Methods: In this study, we conducted an integrated multiomics study of whole-exome sequencing, RNA-seq, spatial transcriptome, and immunohistochemical analyses of 28 paired sarcomatoid tumor components and conventional HCC components from 10 patients with sarcomatoid HCC, in order to identify frequently altered genes, infer the tumor subclonal architectures, track the genomic evolution, and delineate the transcriptional characteristics of sarcomatoid HCCs. Results: Our results showed that the sarcomatoid HCCs had poor prognosis. The sarcomatoid tumor components and the conventional HCC components were derived from common ancestors, mostly accessing similar mutational processes. Clonal phylogenies demonstrated branched tumor evolution during sarcomatoid HCC development and progression. TP53 mutation commonly occurred at tumor initiation, whereas ARID2 mutation often occurred later. Transcriptome analyses revealed the epithelial–mesenchymal transition (EMT) and hypoxic phenotype in sarcomatoid tumor components, which were confirmed by immunohistochemical staining. Moreover, we identified ARID2 mutations in 70% (7/10) of patients with sarcomatoid HCC but only 1–5% of patients with non-sarcomatoid HCC. Biofunctional investigations revealed that inactivating mutation of ARID2 contributes to HCC growth and metastasis and induces EMT in a hypoxic microenvironment. Conclusions We offer a comprehensive description of the molecular basis for sarcomatoid HCC, and identify genomic alteration (ARID2 mutation) together with the tumor microenvironment (hypoxic microenvironment), that may contribute to the formation of the sarcomatoid tumor component through EMT, leading to sarcomatoid HCC development and progression.

With the widespread use of antibiotics, drug-resistant bacterial infections have become a significant threat to human health. Finding new antibacterial strategies that can effectively control drug-resistant bacterial infections has become an urgent task. Unlike small molecule drugs that target bacterial proteins, antisense oligonucleotide (ASO) can target genes related to bacterial resistance, pathogenesis, growth, reproduction and biofilm formation. By regulating the expression of these genes, ASO can inhibit or kill bacteria, providing a novel approach for the development of antibacterial drugs. To overcome the challenge of delivering antisense oligonucleotide into bacterial cells, various drug delivery systems have been applied in this field, including cell-penetrating peptides, lipid nanoparticles and inorganic nanoparticles, which have injected new momentum into the development of antisense oligonucleotide in the antibacterial realm. This review summarizes the current development of small nucleic acid drugs, the antibacterial mechanisms, targets, sequences and delivery vectors of antisense oligonucleotide, providing a reference for the research and development of antisense oligonucleotide in the treatment of bacterial infections.

Background: s/Aims: Sarcomatoid hepatocellular carcinoma (HCC) is a rare histological subtype of HCC characterized by extremely poor prognosis; however, its molecular characterization has not been elucidated. Methods: In this study, we conducted an integrated multiomics study of whole-exome sequencing, RNA-seq, spatial transcriptome, and immunohistochemical analyses of 28 paired sarcomatoid tumor components and conventional HCC components from 10 patients with sarcomatoid HCC, in order to identify frequently altered genes, infer the tumor subclonal architectures, track the genomic evolution, and delineate the transcriptional characteristics of sarcomatoid HCCs. Results: Our results showed that the sarcomatoid HCCs had poor prognosis. The sarcomatoid tumor components and the conventional HCC components were derived from common ancestors, mostly accessing similar mutational processes. Clonal phylogenies demonstrated branched tumor evolution during sarcomatoid HCC development and progression. TP53 mutation commonly occurred at tumor initiation, whereas ARID2 mutation often occurred later. Transcriptome analyses revealed the epithelial–mesenchymal transition (EMT) and hypoxic phenotype in sarcomatoid tumor components, which were confirmed by immunohistochemical staining. Moreover, we identified ARID2 mutations in 70% (7/10) of patients with sarcomatoid HCC but only 1–5% of patients with non-sarcomatoid HCC. Biofunctional investigations revealed that inactivating mutation of ARID2 contributes to HCC growth and metastasis and induces EMT in a hypoxic microenvironment. Conclusions We offer a comprehensive description of the molecular basis for sarcomatoid HCC, and identify genomic alteration (ARID2 mutation) together with the tumor microenvironment (hypoxic microenvironment), that may contribute to the formation of the sarcomatoid tumor component through EMT, leading to sarcomatoid HCC development and progression.

Background: s/Aims: Sarcomatoid hepatocellular carcinoma (HCC) is a rare histological subtype of HCC characterized by extremely poor prognosis; however, its molecular characterization has not been elucidated. Methods: In this study, we conducted an integrated multiomics study of whole-exome sequencing, RNA-seq, spatial transcriptome, and immunohistochemical analyses of 28 paired sarcomatoid tumor components and conventional HCC components from 10 patients with sarcomatoid HCC, in order to identify frequently altered genes, infer the tumor subclonal architectures, track the genomic evolution, and delineate the transcriptional characteristics of sarcomatoid HCCs. Results: Our results showed that the sarcomatoid HCCs had poor prognosis. The sarcomatoid tumor components and the conventional HCC components were derived from common ancestors, mostly accessing similar mutational processes. Clonal phylogenies demonstrated branched tumor evolution during sarcomatoid HCC development and progression. TP53 mutation commonly occurred at tumor initiation, whereas ARID2 mutation often occurred later. Transcriptome analyses revealed the epithelial–mesenchymal transition (EMT) and hypoxic phenotype in sarcomatoid tumor components, which were confirmed by immunohistochemical staining. Moreover, we identified ARID2 mutations in 70% (7/10) of patients with sarcomatoid HCC but only 1–5% of patients with non-sarcomatoid HCC. Biofunctional investigations revealed that inactivating mutation of ARID2 contributes to HCC growth and metastasis and induces EMT in a hypoxic microenvironment. Conclusions We offer a comprehensive description of the molecular basis for sarcomatoid HCC, and identify genomic alteration (ARID2 mutation) together with the tumor microenvironment (hypoxic microenvironment), that may contribute to the formation of the sarcomatoid tumor component through EMT, leading to sarcomatoid HCC development and progression.

Under the background of carbon peaking and carbon neutrality goals, the Ministry of Ecology and Environment, together with 15 national ministries and commissions, has formulated the Implementation Plan on Establishing a Carbon Footprint Management System, and it is urgent for traditional Chinese medicine(TCM) pharmaceutical enterprises to carry out research on carbon footprint accounting methods of related products. Based on the life cycle assessment(LCA) theory, taking mulberry leaf extract produced by a certain enterprise as an example, this study analyzed the carbon footprint of TCM extracts during the life cycle. The results show that for every 1 kg of product produced, the carbon emissions from the stages of raw material acquisition, transportation, and extract production are-20.569, 1.205, and 173.577 kgCO_2eq(CO_2 equivalent), respectively. The carbon footprint of the product is 154.213 kgCO_2eq·kg~(-1). In addition, the carbon emission is the highest in the production stage, in which the consumption of ethanol solvents makes the greatest contribution to the carbon footprint, accounting for 25.71%, more than one-fourth of the total carbon footprint. The second contribution was from the treatment process of TCM residues, accounting for 19.67%, closely followed by wastewater treatment(17.71%), the consumption of hot steam(17.43%), and drinking water(16.90%). The consumption of electric power and packaging materials has a smaller carbon emission of 2.58%. In particular, the carbon emission caused by the consumption of packaging materials is only 0.04%, which is negligible. The results of the study are expected to provide a reference for TCM enterprises to carry out research on the carbon footprint of products, offer ideas for collaborative innovation in reducing pollution and carbon emissions throughout the entire industry chain of TCM, and develop new quality productivity of modern TCM industry based on green and low-carbon manufacturing.
Morus/chemistry* ; Plant Leaves/chemistry* ; Carbon Footprint ; Drugs, Chinese Herbal/chemistry* ; Plant Extracts/analysis* ; Medicine, Chinese Traditional

OBJECTIVE: To evaluate the clinical efficacy of self-made anatomical tower-shaped pads combined with splint plaster fixation in the treatment of unstable 2nd to 5th metacarpal fractures and to provide a reference for clinical practice. METHODS: A retrospective analysis was conducted on 98 patients with unstable 2nd to 5th metacarpal fractures treated with self-made anatomical tower-shaped pads combined with splint plaster fixation between January 2019 and December 2022. There were 74 males and 24 females, aged from 19 to 63 years old with an average of (41.58±7.23) years old. The total active movement (TAM) score was used to evaluate the metacarpophalangeal joint function. Complications and fracture healing time were recorded. RESULTS: All patients were followed up for a period ranging from 1 to 5 months, with an average duration of (3.45±1.03) months. Among the 98 patients, anatomical alignment was achieved in 75 patients, with 68 patients still maintaining anatomical alignment after fixation removal. Functional alignment was achieved in 23 patients, with 20 patients maintaining functional alignment even after fixation removal. There were 10 patients with displacement after reduction. The average fracture healing time was (5.78±1.14) weeks, and the fracture healed well without any angular or rotational deformities. TAM score was utilized to assess the hand function of patients 3 months post-treatment. The extension range of motion (10.72±1.35)° and flexion range of motion (83.19±4.08)° of the metacarpophalangeal joint were significantly higher than the pre-treatment values of (8.25±0.68)° and (70.35±2.36)°, respectively. These differences were statistically significant (P<0.05). TAM outcomes were excellent in 92 cases, good in 5, fair in 1, and poor in none. CONCLUSION The implementation of self-made anatomical tower-shaped pad combined with splint plaster fixation is effective for the conservative management of unstable 2nd to 5th metacarpal fractures.
Humans ; Male ; Female ; Adult ; Middle Aged ; Metacarpal Bones/surgery* ; Splints ; Retrospective Studies ; Fractures, Bone/therapy* ; Casts, Surgical ; Young Adult ; Fracture Fixation, Internal/instrumentation*

Nonobstructive azoospermia (NOA), one of the most severe types of male infertility, etiology often remains unclear in most cases. Therefore, this study aimed to detect four biallelic detrimental variants (0.5%) in the minichromosome maintenance domain containing 2 ( MCMDC2 ) genes in 768 NOA patients by whole-exome sequencing (WES). Hematoxylin and eosin (H&E) demonstrated that MCMDC2 deleterious variants caused meiotic arrest in three patients (c.1360G>T, c.1956G>T, and c.685C>T) and hypospermatogenesis in one patient (c.94G>T), as further confirmed through immunofluorescence (IF) staining. The single-cell RNA sequencing data indicated that MCMDC2 was substantially expressed during spermatogenesis. The variants were confirmed as deleterious and responsible for patient infertility through bioinformatics and in vitro experimental analyses. The results revealed four MCMDC2 variants related to NOA, which contributes to the current perception of the function of MCMDC2 in male fertility and presents new perspectives on the genetic etiology of NOA.
Humans ; Male ; Azoospermia/genetics* ; Meiosis/genetics* ; Spermatogenesis/genetics* ; Adult ; Exome Sequencing ; Microtubule-Associated Proteins/genetics* ; Alleles ; Infertility, Male/genetics*

Objective To evaluate the efficacy and safety of systemic thrombolysis(ST)and standard anticoagulation(SA)in the treatment of lower extremity fracture complicated with distal deep vein thrombosis(DDVT).Methods We retrospectively analyzed the clinical data of 60 patients with lower extremity fracture complicated with DDVT treated from January 2021 to December 2023.When the lower limb venography indicated a calf thrombus burden score ≥3 points,a retrievable inferior vena cava filter(IVCF)was successfully placed in the healthy femoral vein before orthopedic surgery.The patients who received further anticoagulant or thrombolytic therapy after surgery were allocated into a ST group(n=30,urokinase ST and SA)and a SA group(n=30,only SA).The two groups were compared in terms of calf thrombus burden score,thrombus dissolution rate,IVCF placement time,IVCF retrieval rate,intercepted thrombi,hemoglobin level,platelet count,D-dimer level,and complications.Results There was no statistically significant difference in the calf thrombus burden score between the two groups before treatment(P=0.431).However,after treatment,the scores in both groups decreased(both P<0.001),with the ST group showing lower score than the SA group(P=0.002).The thrombus dissolution rate in the ST group was higher than that in the SA group(P<0.001).There was no statistically significant difference in the IVCF placement time between the two groups(P=0.359),and the IVCF retrieval rate was 100% in both groups.The ST group had fewer intercepted thrombi than the SA group(P=0.002).There was no statistically significant difference in hemoglobin level(P=0.238),platelet count(P=0.914),or D-dimer level(P=0.756)between the two groups before treatment.However,after treatment,both groups showed an increase in platelet count(both P<0.001)and a decrease in D-dimer level(both P<0.001).There was no statistically significant difference in the occurrence of complications between the two groups(P=0.704).Conclusions Both SA and ST demonstrate safety and efficacy in the treatment of lower extremity fractures complicated with DDVT,serving as valuable options for clinical application.Compared with SA,ST not only enhances the thrombus dissolution in the calf but also mitigates the risk of thrombosis associated with IVCF.
Humans ; Venous Thrombosis/therapy* ; Retrospective Studies ; Thrombolytic Therapy/methods* ; Male ; Female ; Middle Aged ; Fractures, Bone/complications* ; Lower Extremity/injuries* ; Anticoagulants/therapeutic use* ; Aged ; Treatment Outcome ; Adult

Objective:To evaluate the correlation between the degree of posterior longitudinal ligament (PLL) injury and various parameters of vertebral body injury in patients with thoracolumbar burst fractures.Methods:A total of 48 patients with thoracolumbar burst fractures were admitted to the Spine Surgery Center of the Second Affiliated Hospital of Inner Mongolia Medical University between December 2022 and January 2024. The cohort consisted of 31 males and 17 females, with a mean age of 44.1±11.8 years (range, 18-65 years). Based on the PLL injury grading method proposed by Sun Zhaoyun, patients were classified into three groups: mild, moderate, and severe. However, due to an insufficient number of patients in the severe group ( n=3), the moderate and severe groups were combined for statistical analysis, resulting in two groups: mild, and moderate-to-severe. Patient demographic and clinical data were collected. Local kyphosis (LK), inversion angle (IA), horizontal rotation angle (HRA), increased interspinous distance (IISD), anterior vertebral body compression ratio (AVBCR), posterior vertebral body compression ratio (PVBCR), middle vertebral body compression ratio (MVBCR), the ratio of height of bone fragment (RHBF), the ratio of width of bone fragment (RWBF), and mid-sagittal canal diameter compression ratio (MSDCR) were measured. Statistical analyses were performed using SPSS 25.0. Categorical variables were expressed as frequency (percentage) and analyzed using chi-square and Fisher exact tests. Continuous variables were tested for normality, with non-normally distributed data analyzed using the rank-sum test and expressed as median (interquartile range). Multivariate logistic regression analysis was performed to identify independent risk factors, and receiver operating characteristic (ROC) curves were plotted to calculate the area under the curve (AUC) to evaluate predictive performance. Results:Among the 48 patients, only 3 were found to have severe PLL injury, necessitating the combination of the moderate and severe groups for statistical purposes. Patients in the moderate-to-severe group demonstrated significantly higher AVBCR, PVBCR, RHBF, MVBCR, MSDCR, and IA compared to the mild group ( P<0.05). Multivariate logistic regression identified AVBCR, PVBCR, MSDCR, and IA as independent risk factors for moderate-to-severe PLL injury ( OR>1, P<0.05). ROC curve analysis revealed that AVBCR, PVBCR, MSDCR, IA, and their combined index could effectively predict moderate-to-severe PLL injury ( P<0.05). Notably, the combined index showed superior predictive performance (AUC=0.970) compared to individual parameters. Threshold values were determined as follows: AVBCR>45.30%, PVBCR>12.17%, MSDCR>27.13%, IA>5.90°, and the combined index >0.61, indicating PLL damage. Conclusion:AVBCR, PVBCR, MSDCR, IA, and their combined index are significantly associated with moderate-to-severe PLL injury in thoracolumbar burst fractures. The combined index demonstrates superior predictive ability compared to single parameters, providing a reliable tool for assessing PLL integrity.

Objective Exploring the effect of Percutaneous angular vertebroplasty(PCVP)on functional recovery in elderly patients with osteoporotic vertebral compression fractures(OVCF).Methods Retrospective selection of clinical data from 108 OVCF patients admitted to our hospital from August 2020 to December 2022.According to the different surgical methods,52 cases were divided into a control group(percutaneous vertebroplasty)and an observation group(percutaneous vertebroplasty)with 56 cases;Compare the recovery of vertebral body function,imaging related parameters,functional impairment and lumbar function,surgical related conditions,gait,and complications between the two groups.Results The intraoperative blood loss in the observation group was less than that in the control group[(10.65±3.52)ml vs.(13.11±3.66)ml,P＜0.05],the number of intraoperative fluoroscopy was less than that of control group[(14.21±4.27)vs.(17.04±4.25),P＜0.05],there was no statistically significant difference in the total clinical effective rate between the observation group of 89.28％and the control group of 86.53％(P＞0.05).After 2 months of surgery,the imaging related parameters,functional impairment,lumbar function,surgical and gait related conditions in the control group were better than those in the control group(P＜0.05).There was no statistically significant difference in the incidence of incision infection,nerve root injury,and recurrent fractures between the two groups(P＞0.05),but the leakage rate of bone cement in the observation group was lower than that in the control group(P＜0.05).Conclusion Both surgeries can effectively improve the level of lumbar vertebral function in OVCF patients.PVCP has advantages in increasing the height of the anterior and posterior edges of the vertebral body,reducing the Cobb angle,and relatively fewer intraoperative fluoroscopy times and bleeding.The incidence of bone cement leakage is lower,making it more safe.