Double pituitary adenomas: report of two cases and systematic review of the literature.

Objective: Double pituitary adenomas (DPA) are a rare clinical condition, and our knowledge of them is limited. Missing the second lesion leading to incomplete biochemical remission after surgery is an important challenge in DPA management. This study aims to analyze independent prognostic factors in DPA patients and summarize clinical experiences to prevent surgical failure. Methods: Two cases of DPA patients with Cushing's disease diagnosed and surgically treated at Peking Union Medical College Hospital are reported. A literature review was performed on the online database Pubmed, and 57 DPA patients from 22 retrieved articles were included. Demographic characteristics, endocrine manifestations, diagnostic methods, tumor size, and immunohistochemical features of 59 patients were analyzed. Binary logistic regression models were used to identify independent prognostic factors affecting postoperative biochemical remission. Results: Among 59 DPA patients, the mean ± SD age was 43.64 ± 14.42 years, with 61.02% being female (n = 36). The most common endocrine manifestations were Cushing's syndrome (23/59, 38.98%) and acromegaly (20/59, 33.90%). The most prevalent immunohistochemical types were ACTH-immunopositive (31/118, 26.27%) and GH-immunopositive (31/118, 26.27%) tumors. Microadenomas (<1cm) were the most frequent in terms of tumor size (62/92, 67.39%). The detection rate for double lesions on 3.0T MRI was 50.00% (14/28), which significantly higher than 1.5T MRI (P = 0.034). Univariate analysis revealed that female, Cushing's syndrome and only single lesion detected by surgical exploration were associated with significantly worse prognosis (P<0.05). Multivariate analysis identified double lesion detected by surgical exploration (OR = 0.08, P = 0.003) and contiguous type tumor (OR = 0.06, P = 0.017) as independent protective factors for DPA patients. Conclusions: The double lesion detected by surgical exploration is independently associated with a better prognosis for DPA patients. Comprehensive intraoperative exploration are crucial measures to avoid missing causative lesions.

IRF3 activates RB to authorize cGAS-STING-induced senescence and mitigate liver fibrosis.

Cytosolic double-stranded DNA surveillance by cyclic GMP-AMP synthase (cGAS)-Stimulator of Interferon Genes (STING) signaling triggers cellular senescence, autophagy, biased mRNA translation, and interferon-mediated immune responses. However, detailed mechanisms and physiological relevance of STING-induced senescence are not fully understood. Here, we unexpectedly found that interferon regulatory factor 3 (IRF3), activated during innate DNA sensing, forms substantial endogenous complexes in the nucleus with retinoblastoma (RB), a key cell cycle regulator. The IRF3-RB interaction attenuates cyclin-dependent kinase 4/6 (CDK4/6)-mediated RB hyperphosphorylation that mobilizes RB to deactivate E2 family (E2F) transcription factors, thereby driving cells into senescence. STING-IRF3-RB signaling plays a notable role in hepatic stellate cells (HSCs) within various murine models, pushing activated HSCs toward senescence. Accordingly, IRF3 global knockout or conditional deletion in HSCs aggravated liver fibrosis, a process mitigated by the CDK4/6 inhibitor. These findings underscore a straightforward yet vital mechanism of cGAS-STING signaling in inducing cellular senescence and unveil its unexpected biology in limiting liver fibrosis.

Study on analgesic effect of anterior quadratus lumborum block at lateral supra-arcuate ligament and transversus abdominis plane block in analgesia in patients undergoing laparoscopic partial hepatectomy / 天津医药

Objective To observe the effect of ultrasound-guided anterior quadratus lumborum block at lateral supra-arcuate ligament(QLB-LSAL)and transversus abdominis plane block(TAPB)on analgesia and recovery quality after laparoscopic partial hepatectomy(LPH).Methods Fifty-eight patients underwent elective LPH were selected and divided into the quadratus lumborum group or the transversus abdominis group randomly,with 29 patients in each group.The quadratus lumborum group received bilateral QLB-LSAL,and the transversus abdominis group received bilateral subcostal TAPB block before surgery.Both groups received 20 mL of 0.33%ropivacaine on each side.All patients used patient-controlled intravenous analgesia(PCIA)postoperatively.The numeric rating scale(NRS)scores for rest and movement were recorded at 2,4,6,12,24 and 48 hours postoperatively,as well as the Quality of Recovery-15(QoR-15)scores at 1 day preoperatively,1 and 3 days postoperatively.The perioperative anesthetic agent consumption,PCIA pressing frequency,remedial analgesia use in 48 h,postoperative nausea and vomiting(PONV)incidence and time of first out-of-bed mobilization were also recorded.Results Compared with the transversus abdominis group,the quadratus lumborum group had lower movement NRS scores at 2,4,6,12,24 and 48 hours postoperatively,and lower rest NRS scores at 2,4,6,12 and 24 hours postoperatively(P＜0.05).The quadratus lumborum group had higher QoR-15 scores at 1 and 3 days postoperatively(P＜0.05).Patients in the quadratus lumborum group had reduced perioperative remifentanil and sufentanil consumption,postoperative 48-hour rescue analgesia use,PCIA pressing frequency,PONV incidence and time of first out-of-bed mobilization(P＜0.05).Conclusion QLB-LSAL block provides superior analgesic effects and recovery quality compared to TAPB block after LPH.

Clinical characteristics of 25 non-perinatal adult patients with Listeria monocytogenes infection / 中华传染病杂志

Objective:To investigate the clinical characteristics of non-perinatal adult patients with Listeria monocytogenes (LM) infection. Methods:Twenty-five non-perinatal adult patients who were etiologically confirmed as listeriosis in Tangdu Hospital, Fourth Military Medical University during January 2010 and July 2023 were enrolled in this study. The characteristics of demographic data, underlying diseases, clinical manifestations, laboratory indicators, cranial imaging examination, anti-microbial therapeutic schemes and clinical outcomes were retrospectively analyzed. The clinical characteristics were compared between patients with Listeria septicemia and Listerial meningoencephalitis, as well as between survival and death patients. Independent samples t test and Mann-Whitney U test were used for statistical analysis. Results:The age of enrolled patients was (52.84±12.17) years. Eighteen patients were male, and seven patients were female. The major clinical manifestations included fever (23/25(92%)), headache (15/25 (60%)), disorder of consciousness (12/25(48%)) and vomiting (8/25(32%)). Thirteen (52%) patients had underlying diseases (including hematological diseases, autoimmune disorders, solid neoplasms, and liver cirrhosis, etc). There were no significant differences in blood routine test, aminotransferase, protein levels, renal function, electrolyte, blood glucose, and inflammatory indicators between patients with Listeria septicemia and Listerial meningoencephalitis (all P>0.05). The platelet count in the death group was significantly higher than that in the recovery group ((243.10±92.96)×10 9/L vs (157.80±75.55)×10 9/L, t=2.45, P=0.022). There were also no significant differences in blood biochemical index and inflammatory indicators between these two groups (all P>0.05). Cranial imaging examination of patients with Listerial meningoencephalitis manifested as intracranial infection, cerebral edema/hydrocephalus or cerebral hernia. All nineteen patients with Listerial meningoencephalitis had elevated cerebrospinal fluid (CSF) pressure (220.0(130.0, 290.0) mmH 2O (1 mmH 2O=0.009 8 kPa)), elevated CSF total cell count (522.0(350.0, 783.0)×10 6/L), elevated CSF white blood cell count (356.0(266.0, 668.0)×10 6/L), and CSF protein level (1 817.0(822.5, 6 000.0) mg/L). Fifteen patients had reduced CSF chloride level ((111.70±8.51) mmol/L). Ten patients had decreased CSF glucose level (3.71(1.45, 7.11) mmol/L). The drug sensitivity results of blood and CSF cultures revealed that LM was sensitive to ampicillin. One case was resistance to penicillin, three cases were resistance to meropenem, while three cases were resistance to trimethoprim-sulfonamide. Thirteen cases out of seventeen recovery patients were administered with ampicillin or penicillin-based therapy. Conclusions:When patients with underlying diseases or immune dysfunction suffered with clinical symptoms such as high fever, central nervous system infection, they should be alert to the possibility of listeriosis. Early administration of ampicillin-based therapeutic strategy is beneficial for clinical recovery of the patients.

Analysis of visual acuity status and difference in children of the same age from different areas of Xi'an City / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To understand the current status and differences in visual acuity of children of the same age from different regions of Xi'an, and to take an effective basis for the prevention of children's myopia.METHODS: Random stratified sampling was used to select the uncorrected distance visual acuity and computed dioptric data of 41 285 children aged 6-12 from 6 towns, 10 urban and rural areas and 112 country schools screened by Xi'an Central Hospital in December 2022.RESULTS: The myopia detection rate in different regions of Xi'an is 47.16% in towns, 38.59% in urban and rural areas, and 32.29% in the country, and the total myopia rate is 37.50%. The myopia rate of 6-12 years old in towns is higher than that in urban and rural areas, and that of urban and rural areas is higher than that of country; the myopia rate of girls is higher than that of boys; myopia rate increases with age; mild myopia: the myopia rate in towns is significantly higher than that of the urban and rural areas and the country; high myopia: the myopia rate in the country is significantly higher than that of the towns and the urban and rural areas. The total rate of deficient hyperopia reserves in different regions of Xi'an is 92.08% in towns, 93.67% in urban and rural areas, and 90.92% in the country, and the total rate of deficient hyperopia reserves is 92.09%. The rate of deficient hyperopia reserves at the age of 6-12 is higher in the urban and rural areas than in the towns, and higher in the towns than in the country; the total rate of deficient hyperopia reserve is higher in girls than in boys; it is the peak period of the development of hyperopia reserve rate before the age of 8.CONCLUSION: The total myopia rate and the total vision reserve deficiency rate of 6-12 years old in different regions of Xi'an are different, and 8-9 years old is the accelerated period of myopia development, and the peak of deficient hyperopia reserve is before the age of 8 years old. With the growth of age, the myopia rate shows a certain growth trend, and the rate of deficient hyperopia reserve shows a decreasing trend after reaching the peak. The total myopia rate and insufficient acuity reserve rate of girls are higher than those of boys.

Application research of ultrasound oblique axis plane guidance technique in PICC puncture / 中华护理杂志

Objective To explore the application efficacy and safety of oblique ultrasound-guided techniques in PICC puncture,in order to provide guidance and references for clinical application.Methods Through convenient sampling,654 patients from a tertiary A hospital in Zhejiang Province from March to December 2022 were selected as the study subjects.The random numbers were generated through Excel table functions and they were randomly grouped into 3 groups:A,B,and C.The ultrasound short axis method,long axis method,and oblique axis method were employed to guide PICC puncture catheterization,respectively.The success rate of PICC puncture,the number of subcutaneous adjustments of the puncture needle,puncture time,and the occurrence of puncture complications(such as hematoma,puncture of the posterior wall of blood vessels,accidental injury to arteries,and accidental injury to nerves)were recorded during the catheterization process in 3 groups.Results A total of 654 patients completed the study,including 215 in group A,219 in group B,and 220 in group C.The success rate of first-time puncture in the group C(86.36％)was higher than that in group A(73.95％)and group B(63.93％),and there was a statistically significant difference among 3 groups(P＜0.001).The subcutaneous adjustment frequency of the puncture needle was 1(1,1)in group C,1(1,2)in group A,and 1(1,2)in group B.The difference between 3 groups was statistically significant(P＜0.001);the puncture time of group C was shorter than that of group A and group B,and the difference was statistically significant(P＜0.001).There was a statistically significant difference in the puncture time between 3 groups(P＜0.017);the pairwise comparison of the number of subcutaneous needle adjustments and the success rate of a puncture between 3 groups showed that there was a statistical difference between group C and group A,and between group C and group B(P＜0.017),while there was no statistical difference between group A and group B(P＞0.017).There was statistical significance(P＜0.05)among 3 groups in terms of complications such as accidental nerve injury and puncture of the contralateral vascular wall by puncture needle,but there was no statistical significance in terms of accidental arterial injury and hematoma occurrence among 3 groups.Conclusion Compared with the short axis approach and the long axis approach,the ultrasound oblique axis approach guided PICC puncture has statistical differences in the success rate of a puncture and the incidence of puncture complications,etc.It is recommended to use the ultrasound oblique axis approach during PICC puncture.

Efficacy of Solifenacin in Children with Idiopathic Overactive Bladder / 中山大学学报(医学科学版)

ObjectiveTo explore the efficacy of Solifenacin in the treatment of children with idiopathic overactive bladder （OAB）. MethodsThe study included 67 children with idiopathic OAB treated in the urology clinic of our hospital from March 2022 to March 2023. After at least 2-week-long behavioral therapy showed no significant therapeutic effect， 52 of the cases in the trial group were given oral Solifenacin 5 mg once daily and the other 15 cases in the control group continued the behavioral therapy. The cases in trial group were subdivided into OAB-dry group （27 cases without urinary incontinence） and OAB-wet group （25 cases with urinary incontinence）. The 3-day micturition diary， OAB Symptom Scores （OABSS） and the adverse reactions were recorded and analyzed before， at Weeks 2， 4， 8 and 12 after the treatment. ResultsOf all the 67 cases who completed a 3-month follow-up， 44 were cured including 41 in the trial group and 3 in the control group， 4 presented with adverse reactions. After the 3-month follow-up， the OABSS declined markedly in trial group than in control group （Z=4.524， P<0.001）； the cure rates in trial group and control group are 78.8% and 20% respectively， with significant difference （χ2=15.367， P<0.001）. At each follow-up，we found increased mean voided volume （F=9.707， P<0.001）， reduced mean voiding frequency during daytime （F=3.837， P=0.009） and decreased voiding urgency （χ2=482.835， P<0.001）. After the 3-month follow-up， the cure rates in OAB-dry group and OAB-wet group are 81.5% and 76% respectively， with no significant difference （χ2=0.234， P=0.629）. ConclusionsIn children with idiopathic OAB， oral Solifenacin 5 mg once daily could significantly increase mean voided volume， reduce mean voiding frequency during daytime， relieve symptoms of urinary urgency and lead to fewer adverse reactions， but is not significantly effective for the treatment of urinary incontinence in OAB-wet children .

Risk factors for pulmonary infection in patients with acute-on-chronic liver failure and establishment of a predictive model / 临床肝胆病杂志

ObjectiveTo investigate the risk factors for pulmonary infection in patients with acute-on-chronic liver failure （ACLF）， and to establish a predictive model. MethodsA retrospective analysis was performed for 585 ACLF patients who were admitted to Department of Infectious Diseases， The Second Affiliated Hospital of Air Force Medical University， from January 2009 to September 2022， and according to the condition of pulmonary infection after admission， they were divided into infection group with 213 patients and non-infection group with 372 patients. The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between two groups， and the chi-square test was used for comparison of categorical data between groups. The clinical data of these patients were collected. Univariate and multivariate Logistic regression analyses were used to investigate the risk factors for pulmonary infection in ACLF patients and establish a predictive model， and the receiver operating characteristic （ROC） curve was plotted to assess the predictive value of the model. The Hosmer-Lemeshow test was used to evaluate the degree of fitting of the model， and the ROC curve and the area under the ROC curve （AUC） were used to assess the predictive performance of the model. ResultsAmong the 585 patients with ACLF， 213 experienced pulmonary infection， with an infection rate of 36.41%. The multivariate logistic analysis showed that upper gastrointestinal bleeding （odds ratio ［OR］=2.463， P=0.047）， infection at other sites （OR=2.218， P=0.004）， femoral vein catheterization （OR=2.520， P<0.001）， and combined use of two or more antibiotics （OR=2.969， P<0.001） were risk factors for pulmonary infection in ACLF patients. These factors were included in the risk factor predictive model of Logit （P）=-1.869+0.901×upper gastrointestinal bleeding+0.755×infection at other sites+0.924×femoral vein catheterization+1.088×combined use of two or more antibiotics. The ROC curve analysis showed that the model had a good predictive value （Hosmer-Lemeshow χ2=3.839， P=0.698）， with an AUC of 0.753 （95% confidence interval： 0.700 — 0.772）. ConclusionThere is a relatively high incidence rate of pulmonary infection in patients with ACLF， and upper gastrointestinal bleeding， spontaneous peritonitis， femoral vein catheterization， and combined use of two or more antibiotics are related risk factors. The model established based on these factors can effectively predict the onset of pulmonary infection in ACLF patients.

Application effect and safety analysis of unilateral laminectomy and bilateral decompression under unilateral biportal endoscopy and microendoscope in lumbar spinal stenosis / 中国内镜杂志

Objective To analyze the efficacy and safety of unilateral laminectomy and bilateral decompression under unilateral biportal endoscopy(UBE)and microendoscope(MED)in lumbar spinal stenosis.Methods 80 patients with lumbar spinal stenosis from January 2021 to December 2022 were selected and divided into two groups by numerical table method,the control group and the study group,and the number of cases was 40.The grouping method was random number table method.The control group was treated with unilateral laminectomy and bilateral decompression under MED,while the study group was treated with unilateral laminectomy and bilateral decompression under UBE.Operation time,intraoperative blood loss,Oswestry disability index(ODI)and visual analogue scale(VAS)of lumbago and leg pain were obtained before surgery,1,3 months after surgery and at the last follow-up,efficacy and complications were compared between the two groups.Result There were no significant differences in operative time and blood loss between the study group and the control group(P>0.05).1,3 months after surgery and at the last follow-up,ODI in both groups were lower than those before surgery(P<0.05),but there was no difference between the study group and the control group(P>0.05).The VAS of lumbago and leg pain in both groups were lower than those before surgery(P<0.05),at 1,3 months after surgery and the last follow-up,and the study group was significantly lower than the control group(P<0.05).The excellent and good rate of clinical treatment in the study group was 97.50%,and there was no difference compared with 92.50%in the control group(P>0.05).The complication rate of the study group was 2.50%,significantly lower than that of the control group(15.00%)(P<0.05).Conclusion Unilateral laminectomy and bilateral decompression under the UBE and MED have similar efficacy in the treatment of lumbar spinal stenosis,both of which can effectively promote functional recovery,but UBE can reduce pain more effectively and has fewer postoperative complications.

The regulatory effect of morphine postconditioning in left stellate ganglion on remodeling after myocardial infarction / 中国药理学通报

Aim To investigate the regulatory effect of morphine postconditioning in the LSG on remodeling after myocardial infarction. Methods SD rats were randomly divided into four groups: sham operation group (Sham), myocardial infarction group (MI), myocardial infarction + saline group (Control) and myocardial infarction + morphine postconditioning group (MI + Morphine) . The rat MI model was constructed by ligating the left anterior descending coronary artery, and then morphine was given to the LSG by percutaneous posterior approach. After four weeks, the changes of cardiac function in rats were detected by ultrasound. Masson staining was used to detect fibrosis changes; the expression of Collagen I and Collagen III protein was detected by Western blot. The mRNA expression of ANP and BNP was detected by RT-qPCR. The expression of JJLOR in LSG was detected by immunofluorescence. The concentration of catecholamine in plasma and myocardial tissue was detected by ELISA. Results Compared with the sham group, the cardiac function of the MI group was significantly impaired, the myocardial tissue showed significant fibrosis changes, and the concentration of catecholamine in plasma and myocardial tissue significantly increased. Compared with the control group, the MI + Morphine group reduced myocardial fibrosis collagen deposition in rats after MI, inhibited the expression of ANP and BNP in myocardial tissue, reduced the concentration of catecholamine, and improved the cardiac function of MI rats. Immunofluorescence results showed that JJLOR was expressed in LSG after MI and increased after morphine postconditioning. Conclusions This study shows that morphine postconditioning in the LSG has a protective effect on myocardial remodeling after myocardial infarction. The mechanism may be related to the activation of JJLOR in the LSG by morphine and the reduction of catecholamine release from sympathetic nerve endings.

Expression of GDNF and AR in Testicular Peritubular Cells of Surgery-induced Cryptorchidism Mice / 中山大学学报(医学科学版)

ObjectiveTo investigate the expression of glial cell line-derived neurotrophic factor （GDNF） and androgen receptor （AR） in testicular peritubular cells （TPCs） of cryptorchidism mouse models and explore the theoretical significance of cryptorchidism-induced spermatogenesis dysfunction. MethodsA total of 30 five-week-old male ICR rats were divided randomly by using random number table method into 6 groups. Cryptorchidism was surgically induced in 3 randomly selected groups and the other 3 groups underwent sham surgery as the control groups. On days 4， 7 and 14 after surgery， we harvested the mice testes of the 3 groups and their corresponding control groups， then measured the testicular volumes， analyzed the testicular histopathology and detected the mRNA and protein expression levels of AR and GDNF in TPCs by immunofluorescence， real-time PCR and Western blot. ResultsIn normal control groups， on days 4， 7 and 14 after surgery， the testicular volumes were （125.58±19.22） mm3，（123.45±20.12） mm3， （140.09±13.62） mm3 ， respectively. Clear layers of spermatogenic cells were well arranged and abundant sperm cells were found. Peritubular cells were morphologically homogeneous， with slim-spindle appearance and normal cell thickness. The mRNA expression levels of AR were 1.00±0.05， 1.06±0.07 and 1.19±0.13； GDNF mRNA 1.00±0.04， 1.09±0.05， and 1.10±0.07. The protein expression levels of AR were 1.01±0.01， 0.79±0.02 and 1.01±0.04； GDNF protein （18.68±0.43） pg/mL， （14.39±0.36） pg/mL and （16.88±0.37） pg/mL. In cryptorchidism groups， on days 4， 7 and 14 after surgery， the testicular volumes were （115.64±3.91） mm3， （69.51±14.97） mm3 and （44.86±5.56） mm3， respectively. Spermatogenic cells were disorganized， seminiferous tubules were disrupted， peritubular cells shrank， bent and fractured. The mRNA expression levels of AR were 0.76±0.06， 0.53±0.04， and 0.29±0.02； GDNF mRNA 0.72±0.05， 0.42±0.02 and 0.30±0.03. The protein expression levels of AR were 0.54±0.02， 0.98±0.04 and 0.31±0.01； GDNF protein （8.50±0.34） pg/mL， （17.44±0.32） pg/mL and （6.83±0.34） pg/mL. Statistically significant differences （P < 0.05） were found in 7-day and 14-day testicular volumes between control and cryptorchidism groups but not in the 4-day testicular volume （P > 0.05）. Testicular volumes， AR and GDNF mRNA and protein expression in control groups had no statistically significant difference （P > 0.05）， while those in cryptorchidism groups showed a trend of gradual decline in the amount and the differences between groups were statistically significant （P < 0.05）. ConclusionsIn surgery-induced cryptorchidism mice， after the induction， the expression of AR and GDNF in TPCs showed a gradual decrease over time. AR and GDNF play a major role in mediating the TPCs damage in cryptorchidism. This study provides a theoretical basis for mechanism researches of cryptorchidism-induced spermatogenesis dysfunction.

Anoikis regulator GLI2 promotes NC cell immunity escape by TGF-ß-mediated non-classic hedgehog signaling in colorectal cancer: based on artificial intelligence and big data analysis.

BACKGROUND: Anoikis is a speed-limited procedure to inhibit tumor metastasis during epithelial-mesenchymal transition (EMT). Previous studies have explored anoikis-related genes (ARG) in predicting prognosis and distinguishing tumoral immunity in many types of cancer. However, the role of ARGs in regulating NK cell exhaustion (NKE) and in predicting chemotherapy sensitivity is not clear. Therefore, it is necessary to work on it. METHODS: Gene expression profiles and clinical features are collected from TCGA and GEO, and data analysis is performed in R4.2.0. RESULTS: The ARGs-based no-supervised learning algorithm identifies three ARG subgroups, amongst which the prognosis is different. WCGNA and Artificial intelligence (AI) are applied to construct an NKE-related drug sensitivity stratification and prognosis identification model in digestive system cancer. Pathways association analysis screens out GLI2 is a key gene in regulating NKE by non-classic Hedgehog signaling (GLI2/TGF-ß/IL6). In vitro experiments show that down-regulation of GLI2 enhances the CAPE-mediated cell toxicity and accompanies with down-regulation of PD-L1, tumor-derive IL6, and snial1 whereas the expression of cleaved caspas3, cleaved caspase4, cleaved PARP, and E-cadherin are up-regulated in colorectal cancer. Co-culture experiments show that GLI2- decreased colorectal tumor cells lead to down-regulation of TIM-3 and PD1 in NK cells, which are restored by TGF-bate active protein powder. Besides, the Elisa assay shows that GLI2-decreased colorectal tumor cells lead to up-regulation of IFN-gamma in NK cells.

Thrombotic events and prophylactic anticoagulation in pediatric patients with COVID-19: a systematic review and meta-analysis.

BACKGROUND: Venous thromboembolism (VTE) can occur in children with COVID-19, and the efficacy and safety of prophylactic anticoagulant therapy are uncertain. This study aimed to assess the incidence of VTE in pediatric patients with COVID-19, the association of D-dimer with thrombus formation, and the effectiveness and safety of prophylactic anticoagulation treatment. METHODS: We systematically searched databases from January 2020 to February 2023. A systematic review and meta-analysis were conducted to determine the incidence of VTE in children and evaluate the efficacy and safety of prophylactic anticoagulant therapy. RESULTS: Thirteen cohort studies and one clinical trial were included. The pooled incidence rate of VTE in affected children was 1.5% (95% CI 0.4-2.9%). Children with D-dimer levels five times higher than normal had a higher risk of VTE (OR 4.92, 95% CI 1.60-15.11). Prophylactic anticoagulant therapy did not significantly reduce the risk of VTE (OR 1.35, 95% CI 0.74-2.49). The safety of prophylactic anticoagulant therapy was relatively high, with major bleeding and all-cause mortality rates below 0.1% (95% CI 0.0-0.2%). CONCLUSIONS: The incidence of VTE in children with COVID-19 is low, and prophylaxis based on ISTH standards is reasonable. Low-molecular-weight heparin (LMWH) for VTE prevention has a high level of safety. However, more high-quality studies are needed to understand the impact of anticoagulant therapy on VTE incidence in pediatric patients with COVID-19.

Advances in genetic abnormalities, epigenetic reprogramming, and immune landscape of intracranial germ cell tumors.

Intracranial germ cell tumors (IGCTs) are a rare subtype of central nervous system neoplasms that predominantly affect young individuals and exhibit a higher incidence in East Asia. IGCTs can be pathologically divided into two main categories: germinomas and non-germinomatous germ cell tumors (NGGCTs). Despite the scarcity of this disease, recent advancements in molecular biology techniques have facilitated the discovery of the inherent genetic and molecular characteristics of IGCTs. Somatic mutations that result in the activation of the KIT/RAS/MAPK and PI3K/AKT/mTOR pathways, chromosomal instability leading to characteristic changes in chromosomal fragments (notably 12p gain), and potentially diagnostic miRNAs (such as miR-371a-3p) may provide valuable insights for the efficient diagnosis, targeted therapy, and prognosis evaluation of IGCTs. Additionally, transcriptomic and methylomic analyses have provided new perspectives on the intrinsic development of IGCTs, further elucidating their equivalence with GCTs at other sites. The evaluation of the tumor immune landscape may guide prognosis prediction and immunotherapy for IGCT patients. Nevertheless, current research still faces challenges such as the absence of basic laboratory research systems, a single source of large sample research data, and a limited overall volume of research. The incorporation of larger sample sizes, the implementation of more innovative evaluation systems, and the employment of novel experimental methods are urgently required to become the focus of future research.

BCL2A1 is associated with tumor-associated macrophages and unfavorable prognosis in human gliomas.

B-cell lymphoma 2-related protein A1 (BCL2A1) is a member of the BCL-2 family. Previous studies have shown that BCL2A1 is closely related to the tumorigenesis and resistance to chemotherapy of multiple solid tumors, such as breast cancer. However, the expression pattern and potential biological function of BCL2A1 in glioma remain unknown. For the first time, we found that the expression of BCL2A1 was higher in human glioma tissues than in normal brain tissues (NBTs) in both public datasets and an in-house cohort. High BCL2A1 expression was associated with advanced WHO grade, IDH 1/2 wild type and the mesenchymal (ME) subtype, and its overexpression in glioma predicted resistance to temozolomide (TMZ) chemotherapy and unfavorable prognosis. In addition, Gene set enrichment analysis (GSEA), Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated that BCL2A1 was significantly correlated with the immune response and immune-related pathways, and BCL2A1 expression was positively correlated with microenvironmental parameters (immune, stromal, and ESTIMATE scores) and macrophage infiltration. Interestingly, bioinformatic prediction and immunohistochemical/immunofluorescence staining analysis revealed that BCL2A1 expression was obviously associated with the tumor-associated macrophages (TAMs) markers CD68 and CCL2. Notably, knockdown of BCL2A1 significantly inhibited cell proliferation of U87 and U251 in vitro, induced smaller tumor size and prolonged survival time of mice in vivo. Co-culture experiments of macrophages and GBM cells showed that BCL2A1 knockdown inhibited macrophage migration. Meanwhile, knockdown of BCL2A1 was associated with low expression of CD68 and CCL2 in intracranial xenograft model. This may suggest that BCL2A1 promotes the progression of glioma and influences the prognosis of patients by participating in TAMs infiltration. In conclusion, these findings suggest that BCL2A1 could serve as a promising prognostic indicator and immunotherapy target in gliomas.

Advances in the role of gut microbiota in the regulation of the tumor microenvironment (Review).

As a protector of human health, the gut microbiota plays an important role in the development of the immune system during childhood, and the regulation of dietary habits, metabolism and immune system during adulthood. Dysregulated gut flora is not pathogenic, but it can weaken the protective effect of the immune system and cause various diseases. The tumor microenvironment is a physiological environment formed during tumor growth, which provides nutrients and growth factors necessary for tumor growth. As an important factor affecting the tumor microenvironment, the intestinal microflora affects the development of tumors through the mechanisms of gut and microflora metabolites, gene toxins and signaling pathways. The present article aimed to review the components and mechanisms of action, clinical applications, and biological targets of gut microbiota in the regulation of the tumor microenvironment. The present review provides novel insights for the future use of intestinal flora, to regulate the tumor microenvironment, to intervene in the occurrence, development, treatment and prognosis of tumors.

TMEM2 induces epithelial-mesenchymal transition and promotes resistance to temozolomide in GBM cells.

Glioblastoma multiforme (GBM) is the most common intracranial malignant tumor and is notorious for its poor prognosis. An important element in the short overall survival of GBM patients is the lack of understanding the pathogenesis and progression of tumor and deficiency biomarkers that can be used for early diagnosis and therapeutic sensitivity monitoring. Studies have shown that transmembrane protein 2 (TMEM2) is participated in tumorigenesis of various human tumors, including rectal and breast cancers. Although Qiuyi Jiang et al. have reported that TMEM2 combined with IDH1/2 and 1p19q can predict the survival time of glioma patients based on bioinformatics, its expression and biological role of glioma remain unclear. In our study, we investigated the effect of TMEM2 expression level on glioma malignancy in public datasets and an independent internal dataset. We revealed TEMM2 expression was higher in GBM tissues than in non-tumor brain tissues (NBT). Moreover, the increase in TMEM2 expression level was closely related to tumor malignancy. The survival analysis showed that TMEM2 high expression reduces survival time in all glioma patients, including GBM and LGG patients. Subsequent experiments demonstrated that knockdown TMEM2 inhibited proliferation of GBM cells. In addition, we analyzed TMEM2 mRNA levels in different GBM subtypes, and demonstrated that TMEM2 expression was upregulated in mesenchymal subtype. Meanwhile, bioinformatics analysis and transwell assay indicated that knockdown TMEM2 suppressed epithelial-mesenchymal transition (EMT) in GBM. Importantly, Kaplan-Meier analysis demonstrated that TMEM2 high expression reduced the treatment response to TMZ in GBM patients. Knockdown of TMEM2 alone did not reduce apoptosis GBM cells, but significant apoptotic cells were observed in the group treated with additional TMZ. These studies may contribute to improving the accuracy of early diagnosis and evaluating the effectiveness of TMZ treatment in GBM patients.

Apalutamide for metastatic castration-sensitive prostate cancer: final analysis of the Asian subpopulation in the TITAN trial.

The final analysis of the phase 3 Targeted Investigational Treatment Analysis of Novel Anti-androgen (TITAN) trial showed improvement in overall survival (OS) and other efficacy endpoints with apalutamide plus androgen deprivation therapy (ADT) versus ADT alone in patients with metastatic castration-sensitive prostate cancer (mCSPC). As ethnicity and regional differences may affect treatment outcomes in advanced prostate cancer, a post hoc final analysis was conducted to assess the efficacy and safety of apalutamide in the Asian subpopulation. Event-driven endpoints were OS, and time from randomization to initiation of castration resistance, prostate-specific antigen (PSA) progression, and second progression-free survival (PFS2) on first subsequent therapy or death. Efficacy endpoints were assessed using the Kaplan-Meier method and Cox proportional-hazards models without formal statistical testing and adjustment for multiplicity. Participating Asian patients received once-daily apalutamide 240 mg ( n = 111) or placebo ( n = 110) plus ADT. After a median follow-up of 42.5 months and despite crossover of 47 placebo recipients to open-label apalutamide, apalutamide reduced the risk of death by 32% (hazard ratio [HR]: 0.68; 95% confidence interval [CI]: 0.42-1.13), risk of castration resistance by 69% (HR: 0.31; 95% CI: 0.21-0.46), PSA progression by 79% (HR: 0.21; 95% CI: 0.13-0.35) and PFS2 by 24% (HR: 0.76; 95% CI: 0.44-1.29) relative to placebo. The outcomes were comparable between subgroups with low- and high-volume disease at baseline. No new safety issues were identified. Apalutamide provides valuable clinical benefits to Asian patients with mCSPC, with an efficacy and safety profile consistent with that in the overall patient population.

Fatostatin induces ferroptosis through inhibition of the AKT/mTORC1/GPX4 signaling pathway in glioblastoma.

Glioblastoma multiforme (GBM) is the most common and fatal primary malignant central nervous system tumor in adults. Although there are multiple treatments, the median survival of GBM patients is unsatisfactory, which has prompted us to continuously investigate new therapeutic strategies, including new drugs and drug delivery approaches. Ferroptosis, a kind of regulated cell death (RCD), has been shown to be dysregulated in various tumors, including GBM. Fatostatin, a specific inhibitor of sterol regulatory element binding proteins (SREBPs), is involved in lipid and cholesterol synthesis and has antitumor effects in a variety of tumors. However, the effect of fatostatin has not been explored in the field of ferroptosis or GBM. In our study, through transcriptome sequencing, in vivo experiments, and in vitro experiments, we found that fatostatin induces ferroptosis by inhibiting the AKT/mTORC1/GPX4 signaling pathway in glioblastoma. In addition, fatostatin inhibits cell proliferation and the EMT process through the AKT/mTORC1 signaling pathway. We also designed a p28-functionalized PLGA nanoparticle loaded with fatostatin, which could better cross the blood-brain barrier (BBB) and be targeted to GBM. Our research identified the unprecedented effects of fatostatin in GBM and presented a novel drug-targeted delivery vehicle capable of penetrating the BBB in GBM.