Dysregulated RNA splicing is a well-recognized characteristic of colorectal cancer (CRC); however, its intricacies remain obscure, partly due to challenges in profiling full-length transcript variants at the single-cell level. Here, we employ high-depth long-read scRNA-seq to define the full-length transcriptome of colorectal epithelial cells in 12 CRC patients, revealing extensive isoform diversities and splicing alterations. Cancer cells exhibited increased transcript complexity, with widespread 3'-UTR shortening and reduced intron retention. Distinct splicing regulation patterns were observed between intrinsic-consensus molecular subtypes (iCMS), with iCMS3 displaying even higher splicing factor activities and more pronounced 3'-UTR shortening. Furthermore, we revealed substantial shifts in isoform usage that result in alterations of protein sequences from the same gene with distinct carcinogenic effects during tumorigenesis of CRC. Allele-specific expression analysis revealed dominant mutant allele expression in key oncogenes and tumor suppressors. Moreover, mutated PPIG was linked to widespread splicing dysregulation, and functional validation experiments confirmed its critical role in modulating RNA splicing and tumor-associated processes. Our findings highlight the transcriptomic plasticity in CRC and suggest novel candidate targets for splicing-based therapeutic strategies.
Humans ; Colorectal Neoplasms/metabolism* ; RNA Isoforms/metabolism* ; Single-Cell Analysis ; RNA Splicing ; Gene Expression Regulation, Neoplastic ; RNA, Neoplasm/metabolism* ; Transcriptome

Objective:To evaluate the efficacy of ultrasound-guided semispinalis capitis plane (SCP) block for treatment of occipital neuralgia (ON).Methods:This was a prospective study. Ninety patients of both sexes, aged 29-66 yr, suffering ON for 3 months-6 yr in Zibo Municipal Hospital from January 2022 to December 2023, were divided into 3 groups ( n=30 each) using a random number table method: combination of greater occipital nerve (GON) block and the third occipital nerve (TON) block group (group GT), SCP block via the medial head of semispinalis capitis muscle (SCM) group (group Sm), and SCP block via the space between obliquus capitis inferior and C 2, 3 facet joint (OCI-C 2, 3) group (group OC). In GT group, the analgesic and anti-inflammatory compound solution 2.5 ml was injected around GON in the SCM-OCI space at the C 2 level of the cervical vertebra and at the lateral surface of C 2, 3 facet joint. In Sm group, the analgesic and anti-inflammatory compound solution 5 ml was injected into the medial head of SCM at the level of C 1. In OC group, the analgesic and anti-inflammatory compound solution 5 ml was injected into the OCI-C 2, 3 space in the deep part of SCM. The Visual Analogue Scale (VAS) score and Pittsburgh Sleep Quality Index (PSQI) score were recorded before treatment (T 1) and at 1, 3, 7, 10 and 14 days after treatment (T 2-6), and then the rates of pain relief and improvement in sleep quality were calculated. The time spent in blocking, onset time of blocking, completion time of blocking, duration of block, and occurrence of adverse reactions within 24 h after block were recorded. Results:There were no significant differences in VAS scores and PSQI scores at T 1-3 and T 5-6 among the three groups ( P>0.05), and VAS and PSQI scores were significantly higher at T 4 in Sm group than in OC and GT groups ( P<0.05). Compared with GT group, the time spent in blocking was significantly shortened, the onset time and completion time of block was prolonged, and the duration of block was shortened in Sm group, and the time spent in blocking was significantly shortened, the onset time and completion time of block was shortened ( P<0.05), and no significant change was found in the duration of block in OC group ( P>0.05). No severe complications were observed in the three groups. Conclusions:Compared with the combination of GON and TON blocks, ultrasound-guided SCP block for treating ON is simple and highly safe, SCP block via the OCI-C 2, 3 space has rapid onset and long duration, leading to significant improvements in pain and sleep quality, and it can be used as the first-choice block method for treating ON.

Objective To evaluate the quality of life of patients with type 2 diabetes mellitus in Weifang City, Shandong Province and to explore its influencing factors. Methods A multistage stratified random sampling method was used to investigate patients in endocrine outpatient clinics in four medical institutions in Weifang from July to September 2022. The survey included general information, multi-dimensional evaluation of quality of life with the EQ-5D-5L scale, calculation of health utility values, and analysis of influencing factors using Tobit regression models. Results A total of 397 patients with type 2 diabetes were included in the present investigation, with health utility value of 0.82±0.21 points and visual analogue scale (VAS) score of 79.47±12.81 points. Pain or discomfort, anxiety or depression were more prominent in the study population. Age, diabetic complications, BMI, daily need for care, social support, and daily level of glycemic control were factors influencing health-related quality of life in patients with type 2 diabetes. Conclusion In the actual treatment of type 2 diabetes patients, an emphasis should be placed on protecting elderly type 2 diabetic patients, preventing and controlling the occurrence and development of diabetic complications, and improving daily blood glucose control to further improve the health-related quality of life of the population.

BACKGROUND: High-grade serous ovarian cancer (HGSOC) is the biggest cause of gynecological cancer-related mortality because of its extremely metastatic nature. This study aimed to explore and evaluate the characteristics of candidate factors associated with the metastasis and progression of HGSOC. METHODS: Transcriptomic data of HGSOC patients' samples collected from primary tumors and matched omental metastatic tumors were obtained from three independent studies in the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were selected to evaluate the effects on the prognosis and progression of ovarian cancer using data from The Cancer Genome Atlas (TCGA) database. Hub genes' immune landscapes were estimated by the Tumor Immune Estimation Resource (TIMER) database. Finally, using 25 HGSOC patients' cancer tissues and 10 normal fallopian tube tissues, immunohistochemistry (IHC) was performed to quantify the expression levels of hub genes associated with International Federation of Gynecology and Obstetrics (FIGO) stages. RESULTS: Fourteen DEGs, ADIPOQ , ALPK2 , BARX1 , CD37 , CNR2 , COL5A3 , FABP4 , FAP , GPR68 , ITGBL1 , MOXD1 , PODNL1 , SFRP2 , and TRAF3IP3 , were upregulated in metastatic tumors in every database while CADPS , GATA4 , STAR , and TSPAN8 were downregulated. ALPK2 , FAP , SFRP2 , GATA4 , STAR , and TSPAN8 were selected as hub genes significantly associated with survival and recurrence. All hub genes were correlated with tumor microenvironment infiltration, especially cancer-associated fibroblasts and natural killer (NK) cells. Furthermore, the expression of FAP and SFRP2 was positively correlated with the International Federation of Gynecology and Obstetrics (FIGO) stage, and their increased protein expression levels in metastatic samples compared with primary tumor samples and normal tissues were confirmed by IHC ( P = 0.0002 and P = 0.0001, respectively). CONCLUSIONS This study describes screening for DEGs in HGSOC primary tumors and matched metastasis tumors using integrated bioinformatics analyses. We identified six hub genes that were correlated with the progression of HGSOC, particularly FAP and SFRP2 , which might provide effective targets to predict prognosis and provide novel insights into individual therapeutic strategies for HGSOC.
Humans ; Female ; Ovarian Neoplasms/pathology* ; Prognosis ; Gene Expression Profiling ; Transcriptome ; Tumor Microenvironment ; Receptors, G-Protein-Coupled/therapeutic use* ; Tetraspanins/genetics* ; Protein Kinases ; Integrin beta1/therapeutic use*

Objective:To observe the anatomical characteristics of the semispinalis capitis plane (SCP) to provide a reference for clinically effective implementation of ultrasound-guided SCP block.Methods:Ultrasound scanning was performed in six certain districts of SCP in 30 healthy volunteers (60 sides). The key point was to examine and describe the anatomical characteristics of semispinalis capitis (SCA), deep space of SCA and structures within the space.Results:(1) Transverse scanning at the posterior arch of atlas revealed that the SCA was separated into medial and lateral head by an oblique thick septum; in the space between SCA and obliquus capitis inferior (SCA-OCI), the third occipital nerve (TON) and the greater occipital nerve (GON) were separated by a fascia.There was often a branch of occipital vein between them.The distance from TON to GON was (12.9±0.6) mm.(2) Transverse scanning at the lamina of axis revealed that the axial image of SCA and the structures in SCA-OCI space were similar to the results previously described in (1). The distance from TON to GON was (12.1±0.5) mm.(3) Sagittal scanning beside the spinous process of axis revealed that SCA was separated into superior and inferior belly by a septum which connected to the end of axis spinous process.(4) Sagittal scanning at the C 2, 3 facet joint revealed that in the space between OCI and C 2, 3 facet joint (OCI-C 2, 3) beneath SCA, there was no septum between TON and GON.The distance from TON to GON was (8.0±0.5) mm.(5) Transverse scanning at the lamina of C 4 revealed that in the space between SCA and semispinalis cervicis, the deep cervical artery and vein were observable except medial branch of C 4, and the characteristics of the short axis of the SCA belly were similar to the results previously described in (1). (6) Transverse scanning at the lamina of C 5 revealed that the view was similar to the results previously described in (5). The posterior branch of C 5 nerve was not found. Conclusions:SCP is rich in fascia, and blood vessels often pass through the deep surface space of SCA under ultrasound.The anatomical structure is complex, and there is individual variation.Grasping its ultrasonic anatomical characteristics is helpful in safely and effectively implementing ultrasound-guided SCP block.

Objective: To investigate the optimal setting value of the minimum segment area(MSA) based on the Monaco planning system in the static intensity modulated radiotherapy(IMRT) plan for cervical cancer to improve the accuracy of radiotherapy planning for cervical cancer. Methods: A retrospective collection of 10 patients with cervical cancer was performed using the Monaco treatment planning system to design fixed five-field static intensity modulation plans with MSA of 1, 2, 4, 10, 20, 50, 80, and 100 cm2. Each patient received eight radiotherapy plans. The radiotherapy plan with an MSA of 2 cm2was used as the control group to compare the radiotherapy plans with other MSA settings. Under the premise that other optimization objective functions and constraints were the same, only the set value of MSA was changed, and the statistical methods for analyzing of variance and post-hoc comparison were used to study the impact of MSA on radiotherapy plans. Results: When MSA was in the range of 10～20 cm2, compared with the control group, the dose of target area and organ-at-risk did not change significantly, but the number of monitor units and subfields began to decrease. When MSA starts from 50 cm2, compared with the control group, the maximum dose(D2%) and the average dose(Dmean) in the target area both increased, and the uniformity index(homogeneity index, HI) and conformity index(conformity index, CI) began to deteriorate. Except for the small intestine average dose(Dmean) that changed slightly with MSA, the exposure to other organs at risk increased with the increase of MSA(P<0.05); the number of monitor units and subfields generally decreased with the increase of MSA. Conclusion In the design of a static intensity modulation plan for cervical cancer based on a Monaco treatment planning system, the optimal setting range for the MSA setting value is 10～20 cm2.

Based on the characteristics of medical imaging specialty, this paper introduces in detail several features of standardized residency training in the Department of Radiology in our hospital, from the aspects of teaching purpose, preliminary preparation and specific implementation, namely, the morning reading and analysis of difficult cases, the analysis of postoperative cases and missed diagnosis cases, and the teaching reading. At the same time, it also deeply analyzes the advantages, existing problems and solutions of this teaching practice. In order to provide reference for improving the teaching quality of the standardized residency training in the Department of Radiology.

Objective To investigate the association of ideal cardiovascular health metrics with the incidence rate of nonalcoholic fatty liver disease (NAFLD), and to provide a basis for the prevention and control of NAFLD. Methods A prospective cohort study was conducted for the data of 50 511 employees of Kailuan Group who participated in physical examination from July 2006 to June 2007, and the onset of NAFLD was observed during follow-up once every two years. A one-way analysis of variance was used for comparison of normally distributed continuous data between multiple groups, and the Kruskal-Wallis H test used for comparison of continuous data with skewed distribution between multiple groups; the chi-square test was used for comparison of categorical data between groups. The subjects were divided into four groups according to the quartile of cardiovascular health score (CHS), and person-year incidence rate was used to calculate the incidence rate of NAFLD in each group. Restricted cubic spline (RCS) curve was used to calculate the dose-response relation between continuous variables and outcome events; the Cox proportional hazards model was used to analyze hazard ratio ( HR ) and 95% confidence interval ( CI ) in each group and investigate the effect of ideal cardiovascular health metrics on the incidence rate of NAFLD. Results During the mean follow-up time of 5.58 years, a total of 15 265 cases of NAFLD were observed, and the incidence rate of NAFLD was 77.88/1000 person-year in the Q1 group, 61.33/1000 person-year in the Q2 group, 46.37/1000 person-year in the Q3 group, and 33.69/1000 person-year in the Q4 group. RCS results showed a non-linear relationship between CHS continuous variable and the risk of NAFLD ( P < 0.05). The multivariate Cox proportional risk model analysis showed that compared with the Q1 group in terms of the risk of NAFLD, the Q2, Q3, and Q4 groups had an HR of 0.78 (95% CI 0.74~0.81), 0.57 (95% CI 0.54~0.59), and 0.38 (95% CI 0.36~0.41), respectively, and similar results were observed in subjects stratified by sex and age. The analysis of each component showed that ideal body mass index ( HR =0.37, 95% CI : 0.36~0.39), ideal blood glucose ( HR =0.80, 95% CI : 0.77~0.84), ideal blood pressure ( HR =0.72, 95% CI : 0.69~0.75), ideal cholesterol ( HR =0.86, 95% CI : 0.83~0.89), and ideal diet ( HR =0.94, 95% CI : 0.90~0.99) were protective factors against NAFLD. Conclusion Ideal cardiovascular health metrics are protective factors against NAFLD, and maintaining a healthy lifestyle may help to prevent the onset of NAFLD.

OBJECTIVE: To analyze the hematological characteristics of Chinese METHODS: Hemoglobin electrophoresis and blood routine test were used to analyze the hematological indexes of all peripheral blood samples，PCR-Flow fluorescent hybridization and Gap-PCR were used to detect the globin gene mutations and the data were analyzed statistically. RESULTS: The 3 types of deletion β- Thalassemia patients were showed as hypochromic small cell anemia. The MCH and MCV values of Taiwan type β-thalassemia patients were the lowest. The results of hemoglobin electrophoresis showed that the increasing of HbF was found in all of the 3 types. Except for the decreasing of Hb A2 in Chinese CONCLUSION Through analyze the hematological characteristics, it can be provide that the guidance for the differential diagnosis and genetic consultation of the three commonest deletion β-thalassemia in Chinese.
China ; Diagnosis, Differential ; Fetal Hemoglobin ; Humans ; Mutation ; Thalassemia ; beta-Thalassemia/genetics*

Qingxin Lianzi Yin （QXLZY）， as an ancient classical formula for clearing the heart and nourishing the Yin， was composed of nine herbs （Scutellariae Radix， Ophiopogonis Radix， Lycii Cortex， Plantaginis Semen， Glycyrrhizae Radix et Rhizoma Praeparata Cum Melle， Nelumbinis Semen， Poria， Astragali Radix and Ginseng Radix et Rhizoma）， coming from Prescriptions of the Bureau of Taiping People's Welfare Pharmacy. It could clear away the heart-fire， promote the interaction of the heart and kidney， replenish Qi and Yin， and stop strangury-turbidity. It was used to treat gonorrhea of urination， seminal emission， restlessness， wasting-thirst and so on. At present， the usage and dosage of QXLZY and its addition and subtraction are different in clinical practice. Most of the studies just focus on its clinical efficacy， and there is few review literature reflecting its historical evolution. Based on this， this paper systematically clarified the historical evolution， composition， preparation， interpretation， function， and modern clinical application of QXLZY. This work has been explained the historical evolution of QXLZY， and found that it was wildly used in modern clinical， especially suitable for the treatment of chronic urinary system diseases. At the same time， QXLZY also had significant therapeutic effects on neurasthenia， stomatitis， diabetic nephropathy and other aspects. Through the comprehensive analysis of ancient and modern literature， this work explores the true connotation of QXLZY from the perspective of traditional Chinese medicine theory， which can point out the direction of the clinical application and positioning of this famous classical formula after it comes into the market， and also can provide reference basis for its subsequent in-depth research and development.