Tumor drug resistance is an important problem in the failure of chemotherapy and targeted drug therapy, which is a complex process involving chromatin remodeling. SWI/SNF is one of the most studied ATP-dependent chromatin remodeling complexes in tumorigenesis, which plays an important role in the coordination of chromatin structural stability, gene expression, and post-translation modification. However, its mechanism in tumor drug resistance has not been systematically combed. SWI/SNF can be divided into 3 types according to its subunit composition: BAF, PBAF, and ncBAF. These 3 subtypes all contain two mutually exclusive ATPase catalytic subunits (SMARCA2 or SMARCA4), core subunits (SMARCC1 and SMARCD1), and regulatory subunits (ARID1A, PBRM1, and ACTB, etc.), which can control gene expression by regulating chromatin structure. The change of SWI/SNF complex subunits is one of the important factors of tumor drug resistance and progress. SMARCA4 and ARID1A are the most widely studied subunits in tumor drug resistance. Low expression of SMARCA4 can lead to the deletion of the transcription inhibitor of the BCL2L1 gene in mantle cell lymphoma, which will result in transcription up-regulation and significant resistance to the combination therapy of ibrutinib and venetoclax. Low expression of SMARCA4 and high expression of SMARCA2 can activate the FGFR1-pERK1/2 signaling pathway in ovarian high-grade serous carcinoma cells, which induces the overexpression of anti-apoptosis gene BCL2 and results in carboplatin resistance. SMARCA4 deletion can up-regulate epithelial-mesenchymal transition (EMT) by activating YAP1 gene expression in triple-negative breast cancer. It can also reduce the expression of Ca²⁺ channel IP3R3 in ovarian and lung cancer, resulting in the transfer of Ca²⁺ needed to induce apoptosis from endoplasmic reticulum to mitochondria damage. Thus, these two tumors are resistant to cisplatin. It has been found that verteporfin can overcome the drug resistance induced by SMARCA4 deletion. However, this inhibitor has not been applied in clinical practice. Therefore, it is a promising research direction to develop SWI/SNF ATPase targeted drugs with high oral bioavailability to treat patients with tumor resistance induced by low expression or deletion of SMARCA4. ARID1A deletion can activate the expression of ANXA1 protein in HER2+ breast cancer cells or down-regulate the expression of progesterone receptor B protein in endometrial cancer cells. The drug resistance of these two tumor cells to trastuzumab or progesterone is induced by activating AKT pathway. ARID1A deletion in ovarian cancer can increase the expression of MRP2 protein and make it resistant to carboplatin and paclitaxel. ARID1A deletion also can up-regulate the phosphorylation levels of EGFR, ErbB2, and RAF1 oncogene proteins.The ErbB and VEGF pathway are activated and EMT is increased. As a result, lung adenocarcinoma is resistant to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). Although great progress has been made in the research on the mechanism of SWI/SNF complex inducing tumor drug resistance, most of the research is still at the protein level. It is necessary to comprehensively and deeply explore the detailed mechanism of drug resistance from gene, transcription, protein, and metabolite levels by using multi-omics techniques, which can provide sufficient theoretical basis for the diagnosis and treatment of poor tumor prognosis caused by mutation or abnormal expression of SWI/SNF subunits in clinical practice.

Aim To investigate the changes in the proliferation and apoptosis of Siha cells after knocking down Rho GTPase-activating protein 30(ARHGAP30).Methods After designing specific shARHGAP30 primers and connecting them to the pLKO.1 vector,we transformed them into Escherichia coli competent cells,then co-transfecting them with lentiviral helper plasmids into HEK-293T cells.We collected and filtered cell supernatant to obtain the vi-rus to infect Siha cells.RT-qPCR and Western blot were used to detect knockdown efficiency,as well as changes in the expression of Bax and Bcl-2 after trans-fection.The CCK-8 method was employed to measure the proliferation level of cells after knockdown.Results After successful construction of a lentiviral plasmid with knockdown of the ARHGAP30 gene and establish-ment of stably transfected Siha cells,ARHGAP30 tran-scription and translation(P＜0.01)in Siha cells de-creased,Bax/Bcl-2 significantly decreased(P＜0.01),indicating decreased apoptosis and increased cell proliferation(P＜0.01).Conclusions This study suggests the involvement of ARHGAP30 in the proliferation and apoptosis of Siha cells,and regulating the ARHGAP30 gene may interfere with the occurrence and development of cervical cancer.

Objective:To investigate the safety and efficacy of laparoscopic simultaneous bilateral adrenalectomy in treating ectopic ACTH syndrome (ACTH)caused by medullary thyroid carcinoma(MTC).Methods:A 56-year-old male patient was admitted after MTC surgery and 7 months of general fatigue. The patient had a history of two open thyroid surgeries for medullary thyroid carcinoma, with previous pathological reports indicating lymph node metastasis in the upper mediastinum and mediastinum, accompanied by weak cytoplasmic expression of ACTH and negative CRH staining. After the operation, the patient developed diabetes, hypertension, and hypokalemia. Upon admission, the patient presented with a blood pressure reading of 200/95 mmHg (1 mmHg = 0.133 kPa), a weight of 61.5 kg, a height of 160 cm, a body mass index (BMI)of 24.02 kg/cm 2, and a waist circumference of 83 cm. Laboratory tests revealed the following: blood potassium level of 2.71 mmol/L, blood calcium level of 1.47 mmol/L, parathyroid hormone level of 6.0 pg/ml, fasting blood glucose level of 10.51 mmol/L, glycated hemoglobin level of 8.2%, blood calcitonin level exceeding 2 000 pg/ml, and blood CEA level of 70.8 μg/L. The plasma ACTH levels at 8∶00, 16∶00, and 24∶00 were 189.0, 125.0, and 65.0 pg/ml, respectively. Serum cortisol levels at 08∶00, 16∶00, and 24∶00 were 429.30, 408.14, and 446.61 μg/L, respectively. The 24-hour urine free cortisol measurement was 1 200 μg, and after the midnight 1mg dexamethasone suppression test at 8∶00, the plasma ACTH level was 183.0 pg/ml, and the serum cortisol level was 538.27 μg/L. The aldosterone level in standing position after 2 hours was 8.2 pg/ml. There were no significant abnormality in catecholamine hormone detection or thyroid function in blood and urine samples. An 18F-FDG-PET/CT examination showed multiple lymph node metastases in the neck, while an abdominal CT scan revealed bilateral adrenal hyperplasia. Enhanced MRI revealed pituitary gland thinning, and lung CT and sputum culture examinations showed scattered multiple lung infections. After a multidisciplinary discussion, the patient was diagnosed with EAS, postoperative MTC metastasis, diabetes, hypertension, hypokalemia, pulmonary infection, mild anemia, liver dysfunction, hypoparathyroidism, and hypocalcemia. The patient were accepted laparoscopic bilateral adrenalectomy via an abdominal approach under general anesthesia. The left adrenal gland was removed first, followed by the right adrenal gland after repositioning. Results:The surgery was successful with a surgical duration of approximately 60 minutes and an intraoperative bleeding volume of about 20 ml. No surgical complications occurred during the perioperative period. Pathological examination confirmed nodular hyperplasia of the adrenal cortex and bilateral adrenal medullary hyperplasia with negative ACTH staining. After a 3-month postoperative follow-up, blood calcitonin levels remained above 2000 pg/ml. The blood ACTH levels at 1 week, 1 month, and 3 months after surgery were 183.0, 220.0, and 731.0 pg/ml, respectively. However, hypertension, diabetes, and hypokalemia rapidly improved. One month after surgery, blood pressure was 100/80 mmHg, fasting blood glucose was 4.4 mmol/L, and blood potassium was 3.87 mmol/L. Pulmonary infection showed improvement, and no adrenal crisis occurred. Glucocorticoid replacement therapy consisted of 20 mg of hydrocortisone tablets in the morning and 10 mg in the afternoon, and thyroid hormone replacement therapy involved daily administration of 100 μg of levothyroxine. Genetic testing revealed heterozygous mutations in the Ret gene. The patient is currently undergoing clinical trial treatment with Ret inhibitors.Conclusions:Based on the data from this case and existing literature reports, laparoscopic simultaneous bilateral adrenalectomy might be safe and effective treatment option for EAS caused by unresectable MTC metastasis. It can correct hypertension, diabetes, and hypokalemia and increase the opportunity for MTC treatment.

This article reports a case of prenatal diagnosis of fetal Costello syndrome. At 11 weeks of gestation, the fetal nuchal translucency thickness was 2.5 mm. At 26 +1 weeks of gestation, ultrasound indicated that the fetal abdominal circumference was significantly enlarged, suggesting fetal overgrowth. Subsequent regular ultrasound follow-ups revealed polyhydramnios, enlarged fetal kidneys, and macroglossia after 30 +5 weeks of gestation. Whole-exome sequencing of the family detected a c.34G>A(p.Gly12Ser) mutation in the fetal HRAS gene, which was pathogenic and not present in either parent. Based on clinical manifestations, the fetus was diagnosed with Costello syndrome. After genetic counseling, the pregnant woman opted for termination of the pregnancy.

Objective: Whether peripheral blood 5-hydroxytrptamine (5-HT) levels serve as biomarker for depression diagnosis/response evaluation has not been well determined. This work was explored to address this inconclusive issue. Methods: Animals were randomized into normal control group (NC, n = 10) and chronic unpredictable mild stress model group (CUMS-model, n = 20), respectively. Animals in CUMS-model group were subjected to chronic stress, then they were randomly subdivided into CUMS subgroup and CUMS + fluoxetine subgroup (CUMS + FLX). After FLX treatment, blood and tissues were collected. 5-HT and relevant protein expression were measured. Results: In mice model, there was a significant increase in serum and a significant reduction in plasma 5-HT levels in CUMS-model group versus NC group, while platelet 5-HT levels change little. After FLX treatment, serum and platelet 5-HT levels were significantly decreased in CUMS + FLX subgroup, while plasma 5-HT levels had not much change versus CUMS subgroup. Chronic stress enhanced colon and platelet serotonin transporter (SERT) expression and FLX treatment mitigated SERT expression. In rats’ model, there was a significant increase in serum 5-HT levels while plasma and platelet 5-HT levels showed little change in CUMS group versus NC group. After FLX treatment, serum, plasma and platelet 5-HT levels were significantly decreased in CUMS + FLX subgroup versus CUMS subgroup. The profile of relevant proteins expression changed by FLX were like those in mice. Conclusion Serum 5-HT levels might serve as a potential biomarker for depression diagnosis, meanwhile serum and platelet 5-HT levels might respond to antidepressant treatment.

Objective: Whether peripheral blood 5-hydroxytrptamine (5-HT) levels serve as biomarker for depression diagnosis/response evaluation has not been well determined. This work was explored to address this inconclusive issue. Methods: Animals were randomized into normal control group (NC, n = 10) and chronic unpredictable mild stress model group (CUMS-model, n = 20), respectively. Animals in CUMS-model group were subjected to chronic stress, then they were randomly subdivided into CUMS subgroup and CUMS + fluoxetine subgroup (CUMS + FLX). After FLX treatment, blood and tissues were collected. 5-HT and relevant protein expression were measured. Results: In mice model, there was a significant increase in serum and a significant reduction in plasma 5-HT levels in CUMS-model group versus NC group, while platelet 5-HT levels change little. After FLX treatment, serum and platelet 5-HT levels were significantly decreased in CUMS + FLX subgroup, while plasma 5-HT levels had not much change versus CUMS subgroup. Chronic stress enhanced colon and platelet serotonin transporter (SERT) expression and FLX treatment mitigated SERT expression. In rats’ model, there was a significant increase in serum 5-HT levels while plasma and platelet 5-HT levels showed little change in CUMS group versus NC group. After FLX treatment, serum, plasma and platelet 5-HT levels were significantly decreased in CUMS + FLX subgroup versus CUMS subgroup. The profile of relevant proteins expression changed by FLX were like those in mice. Conclusion Serum 5-HT levels might serve as a potential biomarker for depression diagnosis, meanwhile serum and platelet 5-HT levels might respond to antidepressant treatment.

Objective To investigate the neurodevelopmental characteristics of children with autism spectrum disorder(ASD),analyze the correlation between neurodevelopmental indicators and cerebral blood flow(CBF),and explore the potential mechanisms of neurodevelopment in ASD children.Methods A retrospective study was conducted on 145 children aged 2-6 years with newly-diagnosed ASD.Scores from the Gesell Developmental Diagnosis Scale and the Autism Behavior Checklist(ABC)and CBF results were collected to compare gender differences in the development of children with ASD and analyze the correlation between CBF and neurodevelopmental indicators.Results Fine motor and personal-social development quotient in boys with ASD were lower than those in girls with ASD(P<0.05).Gross motor development quotient in ASD children was negatively correlated with CBF in the left frontal lobe(r=-0.200,P=0.016),right frontal lobe(r=-0.279,P=0.001),left parietal lobe(r=-0.208,P=0.012),and right parietal lobe(r=-0.187,P=0.025).The total ABC score was positively correlated with CBF in the left amygdala(r=0.295,P<0.001).Conclusions Early intervention training should pay attention to gender and developmental structural characteristics for precise intervention in ASD children.CBF has the potential to become a biological marker for assessing the severity of ASD.

Objective:To investigate the major considerations of domestic orthopaedic trauma surgeons in China when they diagnose and treat Mason type Ⅱ radial head fractures.Methods:A questionnaire survey was conducted from January 15, 2022 to January 16, 2022 using the convenience sampling method among domestic orthopedic trauma surgeons in China. The survey covered the surgeons' basic information, evaluation of Mason type Ⅱ radial head fractures, treatment preferences, and surgical indications recognized.Results:The present survey retrieved 474 eligible questionnaires. 358 surgeons (75.5%, 358/474) believed that the Morrey modified classification for Mason type Ⅱ radial head fracture could properly guide their diagnosis and treatment. 460 surgeons (97.0%, 460/474) believed that diagnosis of the fracture should be based on a combination of elbow X-ray and elbow CT examinations. Young age (80.2%, 380/474), dominant side involvement (66.2%, 314/474), concomitant ipsilateral upper limb injury (78.7%, 373/474), large fracture displacement (67.7%, 321/474), separation of fracture fragments from the main bone (91.6%, 434/474), and fracture involvement area >30% (81.6%, 387/474) were the main factors considered by the orthopedic trauma surgeons when they chose surgical treatment. Large fracture displacement (71.7%, 340/474), especially large articular steps (83.5%, 443/474), separation of fracture fragments from the main bone (75.9%, 360/474), and limited forearm rotation or joint clicking (82.7%, 392/474) found during physical examination were recognized as surgical indications for Mason type Ⅱ fracture by orthopedic trauma surgeons.Conclusion:Domestic orthopedic trauma surgeons in China prefer surgical treatment for Mason type Ⅱ radial head fractures with loss of cortical contact and large displacement, especially large articular steps.

Objective:To investigate the current status and developing trends of study of adult radial head fracture and its treatment.Methods:The literature related to radial head fracture from January 2010 to September 2022 was reviewed through Web of science database. A bibliometric method and visualization software were used to study all the data collected and the 100 most-cited studies related to the treatment of radial head fracture to understand the research status, related cooperation, research trends and research hotspots in the field of adult radial head fracture.Results:A total of 387 studies were included, with a citation frequency of 4,982 times, an average citation frequency of 12.9 times for each study, and an H index of 36. The most studies were published in 2020 (38 studies). The citation frequency increased year by year, reaching the highest (783 times) in 2019. For the 100 most-cited studies, the citation frequency was 2,235 times, and the average citation frequency was 22.4 times for each study. The United States (100 studies), Harvard University (30 studies), Journal of Shoulder and Elbow Surgery (69 studies), and Ring D (19 studies) were, respectively, the most contributing country/region, institution, journal, and author. The country/region, institution, and author that participated the most in the collaboration were, respectively, the United States, Amphia Hospital, and Eygendaal D. Radial head fractures of Mason types Ⅱ and Ⅲ and combined with other elbow fractures and dislocations have attracted the intense attention since 2010. The current research hotspots are combined injuries and radial head prosthesis. Conclusion:Analysis of the bibliometric characteristics of the literature related to adult radial head fracture since 2010 displays the current research status and research hotspots to help following researchers to fully understand the historical development and recent hotspots in the field of adult radial head fracture.

In recent years, polysaccharides have received much attention because of their high safety and good immunological activity. The study of polysaccharide in vivo process is a key scientific problem that needs to be solved for polysaccharide drug development. Some progress has been made in the field of polysaccharide pharmacokinetics and immunomodulation. However, due to the lack of both chromogenic and light-absorbing groups and the complex molecular structure of polysaccharides, the in vivo processes and immunomodulatory mechanisms of polysaccharides have been slow to be investigated. The effective combination of multiple techniques can break the bottleneck of difficult tracing and unknown immunomodulatory mechanism of polysaccharides in vivo, and promote the development and utilization of polysaccharides. In this paper, we systematically summarize the key techniques in the study of polysaccharide in vivo processes and immunomodulatory mechanisms in order to provide technical references and research ideas for the study of polysaccharide in vivo processes and immunomodulatory mechanisms.