[SRSF2 promotes glioblastoma cell proliferation by inducing alternative splicing of FSP1 and inhibiting ferroptosis].

Objective: To investigate the effect of serine/arginine-rich splicing factor 2 (SRSF2) on ferroptosis and its possible mechanism in glioblastoma cells. Methods: The online database of gene expression profiling interactive analysis 2 (GEPIA 2) and Chinese Glioma Genome Atlas were used to analyze the expression of SRSF2 in glioblastoma tissue and its association with patients prognosis. To validate the findings of the online databases, the pathological sections of glioblastoma and non-tumor brain tissues from Tianjin Medical University General Hospital, Tianjin, China were collected and analyzed by using immunohistochemistry. Silencing SRSF2 gene expression in glioblastoma cells by siRNA was analyzed with Western blot. The proliferation index was detected by using CCK8 assay. The rescued experiment was conducted by using expression plasmid of pcDNA3.1(+)-SRSF2. The activity of ferroptosis was assessed by using the levels of iron ions and malondialdehyde in glioblastoma cells and the changes in the ratio of glutathione to oxidized glutathione. The changes of gene expression and differential pre-mRNA alternative splicing (PMAS) induced by SRSF2 were monitored by using the third-generation sequencing technology analysis, namely Oxford nanopore technologies (ONT) sequencing analysis. Results: SRSF2 expression was higher in glioblastoma tissues than non-tumor brain tissues. Immunohistochemistry also showed a positive rate of 88.48%±4.60% in glioblastoma tissue which was much higher than the 9.97%±4.57% in non-tumor brain tissue. The expression of SRSF2 was inversely correlated with overall and disease-free disease survivals (P<0.01). The proliferation index of glioblastoma cells was significantly reduced by silencing with SRSF2 siRNA (P<0.01) and could be reversed with transfection of exogenous SRSF2. The levels of intracellulariron ions and malondialdehyde increased (P<0.05), but the glutathione/oxidized glutathione ratio and the expression of key proteins in the glutathione pathway remained unchanged (P>0.05). ONT sequencing results showed that silencing SRSF2 in glioblastoma cells could induce a significant alternative 3' splice site change on ferroptosis suppressor protein 1 (FSP1). Conclusion: SRSF2 inhibits the ferroptosis in glioblastoma cells and promotes their proliferation, which may be achieved by regulating FSP1 PMAS.

[Diagnosis and treatment understanding of Waldenström macroglobulinemia in China: a cross-sectional study].

Objective: To conduct a nationwide physician survey to better understand clinicians' disease awareness, treatment patterns, and experience of Waldenström macroglobulinemia (WM) in China. Methods: This cross-sectional study was conducted from February 2022 to July 2022 by recruiting clinicians with WM treatment experience from hematology, hematology-oncology, and oncology departments throughout China. Quantitative surveys were designed based on the qualitative interviews. Results: The study included 415 clinicians from 219 hospitals spread across thirty-three cities and twenty-two provinces. As for diagnosis, the laboratory tests prescribed by physicians for suspected WM patients were relatively consistent (92% -99% recommendation for laboratory, 79% -95% recommendation for pathology, 96% recommendation for gene testing, and 63% -83% recommendation for imaging examination). However, from a physician's perspective, there was 22% misdiagnosis occurred in clinical practice. The rate of misdiagnosis was higher in lower-level hospitals than in tertiary grade A hospitals (29% vs 21%, P<0.001). The main reasons for misdiagnosis were that WM was easily confused with other diseases, and physicians lacked the necessary knowledge to make an accurate diagnosis. In terms of gene testing in clinical practice, 96% of participating physicians believed that WM patients would require gene testing for MYD88 and CXCR4 mutations because the results of gene testing would aid in confirming diagnosis and treatment options. In terms of treatment, 55% of physicians thought that the most important goal was to achieve remission, while 54% and 51% of physicians wanted to improve laboratory and/or examination results and extend overall survival time, respectively. Among patients with treatment indications, physicians estimated that approximately 21% of them refused to receive treatment, mainly owing to a lack of affordable care and disease awareness. When selecting the most appropriate treatment regimens, physicians would consider patient affordability (63% ), comorbidity (61% ), and risk level (54% ). Regimens containing Bruton tyrosine kinase inhibitor (BTKi) were most widely recommended for both treatment-naïve and relapsed/refractory patients (94% for all patients, 95% for treatment-naïve patients, and 75% for relapsed/refractory patients), and most physicians recommended Ibrutinib (84% ). For those patients who received treatment, physicians reported that approximately 23% of patients did not comply with the treatment regimen due to a lack of affordability and disease awareness. Furthermore, 66% of physicians believe that in the future, increasing disease awareness and improving diagnosis rates is critical. Conclusions: This study is the first national physician survey of WM conducted in China. It systematically describes the issues that exist in WM diagnosis and treatment in China, such as a high rate of misdiagnosis, limited access to gene testing and new drugs, and poor patient adherence to treatment. Chinese doctors believe that improving doctors' and patients' understanding of WM is one of the most urgent issues that must be addressed right now.

[The occurrence, precaution and treatment strategies of postoperative fecal incontinence in rectal and anal diseases].

In the surgical treatment of hemorrhoids, rectal prolapse, rectal cancer, anal fissures, or anal fistulas, inadvertent damage to the nerves or muscles responsible for bowel control may potentially lead to varying degrees of fecal incontinence (FI). Surgeons need to conduct preoperative assessments based on the patient's individual condition to select an appropriate surgical plan, aiming to minimize the incidence of postoperative FI and improve the patient's postoperative quality of life as much as possible while effectively treating the disease. Additionally, the proficiency of the surgeon's skills, appropriate preoperative dietary adjustments for the patient, regular bowel habits, and exercises targeting the pelvic floor muscles all contribute to reducing the incidence of postoperative FI in patients. For patients who have already developed FI after surgery, on the basis of suitable diet, regular bowel habits, and medication, clinical practitioners can adopt such methods as biofeedback, pelvic floor muscle exercise, sacral nerve stimulation, percutaneous tibial nerve stimulation, acupuncture, injectable bulking agents, anal or vaginal inserts, transanal irrigation, surgical interventions, psychological support, etc., to individualized treatment for patients' conditions. This article, combining the literature, summarizes the current status of common diseases that may lead to postoperative FI. It elaborates on strategies for the prevention and treatment of postoperative FI, aiming to serve as a reference for peers in the field.

[Comparation of outcomes of iliac crest bone graft and accessory navicular bone graft in the Cotton osteotomy for pediatric and adolescent flexible flatfoot].

Objective: To compare the outcomes between iliac crest and accessory navicular as different bone grafts in the Cotton osteotomy in the treatment of pediatric flexible flatfoot deformity. Methods: A retrospective cohort study. The clinical data of pediatric flexible flatfoot patients with symptomatic accessory navicular received operations from July 2018 to March 2022 in Beijing Tongren Hospital were retrospectively analyzed. All the patients were treated with Cotton osteotomy. According to the different sources of bone grafting in Cotton osteotomy, the patients were divided into iliac crest group and accessory navicular group. There were 12 patients (19 feet) in iliac crest group, including 9 males and 3 females with a median age M(Q1, Q3) of 11(11, 12) years and were followed-up for 36(6, 48) months. There were 9 patients (16 feet) in accessory navicular group, including 6 males and 3 females, with a median age M(Q1, Q3) of 11(11, 11) years and were followed-up for 12(6, 17) months. Radiographic evaluations were reviewed and compared between the two groups before surgical treatment and at final follow-up, included talo-1st metatarsal angle (T1MT), talonavicular coverage angle (TNCA), talocalcaneal angle (TCA) in weight bearing anteroposterior view, and Meary angle, calcaneal Pitch angle, Kite angle, cuneiform articular angle (CAA) in weight bearing lateral view, and hindfoot alignment angle (HAA) in calcaneal long axial view. Functional scores included American Orthopedic Foot and Ankle Society (AOFAS), visual analog scale (VAS), and Maryland scores were recorded and compared before and after the operation. The complications were also recorded. Results: Total of 21 patients were successfully followed in this study. The radiographic measurements in the two groups, such as T1MT, TNCA, Meary angle, Pitch angle, Kite angle, CAA, HAA, were all significantly improved at the last follow-up when compared with those before the surgery (all P<0.05); and the AOFAS, VAS, Maryland scores in both groups were all improved after the surgery (all P<0.05). There was a significant difference in CAA alteration (∆CAA) after the operation between the two groups, the ∆CAA in iliac crest group and the accessory navicular group was 6.0°±2.6° and 4.3°±1.3°, respectively (P=0.017). There was no significant differences in the improvement of other radiographic measurements between the two groups (all P>0.05). All the patients had a successful bone union. Two patients had donor site pain in the iliac crest group and were treated conservatively. Conclusion: Compared with iliac crest bone graft, accessory navicular bone graft could achieve comparable outcomes in radiographic measurements and functional scores in the treatment of pediatric flexible flatfoot with accessory navicular pain.

[The regulation of APGAT4 on the growth and lenvatinib resistance of hepatocellular carcinoma].

Objective: To investigate the effect of 1-acyl-sn-glycerol-3-phosphate acyltransferaseδ (APGAT4) on the growth and lenvatinib resistance of hepatocellular carcinoma (HCC), and provide novel targets for HCC treatment. Methods: Using the bioinformatics methods to screen out upregulated genes in lenvatinib resistant cell lines from GEO dataset and survival related genes from TCGA dataset. Immumohistochemical staining was used to detect the expression AGPAT4 in HCC tissues, and its correlation with patients' survival. CCK8, EdU, cell cycle, and cell apoptosis assays were used to investigate the impact of role AGPAT4 on the proliferation and lenvatinib reistance of HCC cells. AGPAT4 stable knockdown cell line and subcutaneous nude mouse model were established to test the therapeutic effects of Lenvatinib. Analysis of variance was used to compare the differences between data sets. Results: APGAT4 was the common factor that predicted poor survival and Lenvatinib resistance. The mRNA and protein levels of APGAT4 were significantly upregulated in HCC tissues compared to the para-tumor tissues (P < 0.05). Using siRNA could significantly knocked down the mRNA and protein expression of APGAT4 in HCC cell lines Hep3B and HCCLM3. Compared with the control group, the proliferation ability of HCC cell lines (Hep3B and HCCLM3) in APGAT4 knockdown group was significantly inhibited, and the cell cycle was arrested in G2/M phase (P < 0.05). In addition, compared to the control group, HCC cell lines (Hep3B and HCCLM3) in APGAT4 knockdown group showed significant decrease in the Lenvatinib half maximal inhibitory concentration, and were more sensitive to lenvatinib-induced apoptosis (P < 0.05). In HCC subcutaneous nude mouse model, compared to the control group, the growth of tumor in APGAT4 knockdown group was significantly suppressed, and more apoptosis cells were induced (P < 0.05). Conclusion: APGAT4 promotes the growth and Lenvatinib resistance of HCC, which is a potential target for HCC treatment. Targeting APGAT4 treatment is conducive to inhibit the growth and Lenvatinib resistance of HCC.

[Cross-sectional study on the use of masks among occupational groups with high-risk positions for overseas import and pollution transmission].

Objective: To investigate the wearing of masks and the knowledge of masks among high-risk positions for overseas import and pollution transmission. Methods: From May 14 to 17, 2022, a convenient sampling method was used to conduct an online survey among 963 workers in high-risk positions for overseas import and pollution transmission in Beijing. The behaviors of individual use and wearing masks, the distribution and supervision of the unit, the knowledge of personal mask protection and the subjective feelings of wearing masks were analyzed. The χ(2) test and logistic regression model were used to analyze the influencing factors of the correct selection of masks. Results: The majority of the workers in high-risk positions for overseas import and pollution transmission were male (86.0%, 828/963), age concentration in 18-44 years old (68.2%, 657/963), and the majority of them had college or bachelor degrees (49.4%, 476/963). 79.4%(765/963) of the workers chose the right type of masks, female, 45-59 years old and high school education or above were the risk factors for correct selection of masks (P <0.05). Workers had good behaviors such as wearing/removing masks, but only 10.5% (101/963) could correctly rank the protective effect of different masks. 98.4% (948/963) of the workers believed that their work units had provided masks to their employees, and 99.1% (954/963) and 98.2%(946/963) of them had organized training and supervision on the use of masks, respectively. 47.4%(456/963) of the workers were uncomfortable while wearing masks. Conclusion: The overall selection and use of masks among occupational groups in high-risk positions for overseas import and pollution transmission in China need to be further standardized. It is necessary to strengthen supervision and inspection on the use of masks among occupational groups, and take improvement measures to improve the comfort of wearing masks.

[Value of (11)C-PiB PET/MRI in the evaluation of organ involvement in primary systemic light chain amyloidosis].

Objective: To analyze the value of (11)C-PiB PET/MRI for evaluating organ involvement in patients with primary light chain amyloidosis (pAL) . Methods: The clinical data of 20 patients with pAL and 3 healthy volunteers from January 2019 to October 2021 were retrospectively analyzed. The correlation between the organ involvement evaluated by clinical standards and PET/MRI was compared. The relationship between cardiac-related biological indicators, disease stage, and the maximum standardized uptake value (SUVmax) were analyzed. The relationship between 24-hour urinary protein quantification and kidney SUVmax was analyzed. Results: ①In 20 patients (18 newly diagnosed patients and 2 non-newly diagnosed patients) ,(11)C-PiB positive uptake was observed in the heart (15 patients, 75%) , lung (8 patients, 40%) , bone marrow (10 patients, 50%) , muscle (10 patients, 50%) , tongue muscle (7 patients, 35%) , thyroid (6 patients, 30%) , salivary gland (4 patients, 20%) , spleen (2 patients, 10%) , and stomach wall (1 patient, 5%) . ②Organ involvement on (11)C-PiB PET/MRI showed good correlations with the clinical evaluation criteria for the heart and bone marrow. The positive rate of PET/MRI evaluation in the lung, spleen, gland, muscle, and tongue muscle was significantly higher than the clinical criteria. However, (11)C-PiB PET/MRI has limitations in the evaluation of the nervous system and fat tissue. ③To analyze the relationship between cardiac-related biological indexes and the SUVmax of the heart in 13 newly diagnosed patients. Patients with left ventricular ejection fraction (LVEF) <50% and interventricular septal thickness (ISV) ≥1.2 cm showed a higher SUVmax than patients with LVEF ≥50% and ISV<1.2 cm (P<0.05) .There are significant differences in the SUVmax of the heart between the Mayo2004 stage and the Mayo2012 stage. The later the disease stage, the higher the SUVmax (P<0.05) . The SUVmax of the heart was positively correlated with cardiac troponin I (cTnI) and N-terminal pro-brain natriuretic peptide (NT-proBNP) (P<0.01) .There was no significant correlation between renal SUVmax and 24-hour urine protein (P>0.05) . Conclusion: Whole body (11)C-PiB PET/MRI, as a visualization system of amyloid protein, is used to qualitatively evaluate organ involvement, which can improve the level of early non-invasive diagnosis. Whole body (11)C-PiB PET/MRI can be used to perform quantitative evaluation of organ levels, especially the heart, which is expected to evaluate organ function and predict disease prognosis more accurately.

[Research progress on the application of time-restricted eating in adult obesity and related metabolic diseases].

The soaring prevalence of obesity and its complications presents a significant health care burden, and there is currently a lack of effective and sustainable treatment methods. Time-restricted eating (TRE) is a specific intermittent fasting (IF) protocol involving consistent fasting and eating periods within a 24-hour cycle. Time-restricted eating can restore robust circadian rhythms and improve metabolic health, providing an emerging dietary strategy for the prevention and treatment of obesity and related metabolic diseases. Previous TRE trials laid the groundwork, and indicate a need for further clinical research including large-scale controlled trials to determine TRE efficacy and the mechanisms by which it may affect humans.

[Clinical characteristics of patients with multiple myeloma harboring 6q deletion].

Objective: To study the clinical and cytogenetic characteristics of patients with multiple myeloma harboring 6q deletion, with the aim to determine the impact of 6q deletion on survival. Methods: This study included the retrospective analysis of 382 newly diagnosed patients with multiple myeloma in our hospital from 2014 to 2017 and compared the clinical and cytogenetic characteristics between patients with and without 6q deletion. The log-rank test and the Cox proportional hazards regression model were used to analyze prognostic factors for progression-free survival (PFS) and overall survival (OS) . Results: Compared to those without 6q, the patients with 6q deletion were older (median age, 63 vs 58 years, P=0.039) , had higher incidence of t (4; 14) (30.4% vs 16.4% , P=0.020) , and higher proportion of complex karyotypes (22.2% vs 5.3% , P=0.001) . Univariate survival analysis using the log-rank test revealed that 6q deletion was associated with shorter PFS. However, by the Cox multivariate proportional hazards regression model, 6q deletion was not an independent prognostic factor and its effect on survival was affected by age, t (4; 14) , and other risk factors. Conclusions: 6q deletion was common in elderly patients with multiple myeloma and was often accompanied by t (4;14) and complex karyotypes. However, 6q deletion was not an independent prognostic factor for multiple myeloma.

[Research advances on the effect of mechanical tension in post-traumatic hypertrophic scar formation].

Traumatic scar can not only exert influence on appearance and function of patients, but also affect psychological health status and life quality of patients to varying degrees. At present, scholars have confirmed from basic research that mechanical tension promotes the proliferation of inflammatory cells, fibroblasts, and other cells, as well as angiogenesis and epithelialization through a variety of mechanical conduction pathways and plays an important role in the formation of hypertrophic scar. Clinical studies have confirmed that surgical methods and adjuvant treatment to reduce the mechanical tension on wound can promote wound healing and inhibit hyperplasia of scar. This article summarizes the mechanism of hypertrophic scar formation, and surgical methods and adjunct means of reducing mechanical tension in traumatic wounds, aiming to provide a reference for reducing formation of hypertrophic scar in clinics.

[Clinical characteristics and prognosis of 49 newly diagnosed primary central nervous system diffuse large B-cell lymphoma].

Objective: The clinical characteristics of patients with primary central nervous system lymphoma-diffuse large B-cell lymphoma (PCNSL-DLBCL) and the effects of different treatment schemes on their survival and prognosis were analyzed retrospectively. Methods: A total of 49 patients with PCNSL-DLBCL who presented at the Tianjin Medical University General Hospital from July 2014 to December 2020 were included, and their clinical data were retrospectively analyzed. They were divided into four groups: the MTX group, the R-CDOP group, the BTKi-R-MTX group, and the RLZT group. The median overall survival (OS) and progression-free survival (PFS) were calculated, and the survival prognosis was compared by univariate and multivariate prognostic analysis. Results: The median OS time of the MTX group, the R-CDOP group, the BTKi-R-MTX group, and the RLZT group was 16.5 months, 4.5 months, 42 months, and not reached, respectively (P<0.001) . The median PFS time of the MTX group, the R-CDOP group, the BTKi-R-MTX group, and the RLZT group was 7 months, 1.5 months, 20 months, and 5 months, respectively (P=0.005) . Multivariate prognostic analysis showed that double expressor lymphoma, IESLG risk grade, and different treatment methods were the prognostic factors of PCNSL-DLBCL. Conclusion: The survival and prognosis of PCNSL-DLBCL are affected by different treatment schemes. The role of CD20 monoclonal antibody in the treatment of PCNSL-DLBCL is still controversial. The treatment scheme containing BTKi has great potential for PCNSL-DLBCL. RLZT scheme has a good prospect for elderly patients who cannot tolerate high-dose chemotherapy and radiotherapy.

Age-stratified analysis of SARS-CoV-2 infection and case fatality rate in China, Italy, and South Korea.

OBJECTIVE: We aimed to compare the characteristics of coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in China, Italy, and South Korea. MATERIALS AND METHODS: Detailed national epidemiological information of COVID-19 was retracted from the latest statistics reports from China, Italy, and South Korea. Population-based analysis of the age distribution among confirmed cases was conducted and their crude case fatality ratio in each c RESULTS: The age distributions among COVID-19 cases were relatively similar between China and Italy with primarily elderly populations infected, which were considerably different from that in South Korea with primarily younger individuals infected. Most deaths occurred among elderly individuals who were older than 60 years in both Italy (98.0%) and South Korea (87.9%), consistent with the previous data from China (81.0%). CONCLUSIONS: Most deaths occurred among elderly individuals who were over 60 in China, Italy, and South Korea. South Korea's data suggest that younger individuals might be more susceptible to SARS-CoV-2 infection, which might be fully under detected in China and Italy.

A rare case of intrauterine intussusception causing ileal atresia.

Intrauterine intussusception is a rare but evident cause of intestinal atresia and is usually detected intraoperatively. We report on a term neonate who presented to the Department of Paediatric Surgery, Sabah Women and Children's Hospital, Malaysia with delayed passage of meconium and intestinal obstruction, wherein the lower contrast showed a claw sign. This was a good clue that this neonate had intrauterine intussusception and this suspicion was confirmed upon laparotomy. We found an ileo-ileal intussusception causing ileal atresia, requiring resection and primary anastomosis.