The anterior cingulate cortex (ACC) has recently been proposed as a key player in the representation of itch stimuli. However, to date, little is known about the contribution of specific ACC interneuron populations to itch processing. Using c-Fos immunolabeling and in vivo Ca²⁺ imaging, we reported that both histamine and chloroquine stimuli-induced acute itch caused a marked enhancement of vasoactive intestinal peptide (VIP)-expressing interneuron activity in the ACC. Behavioral data indicated that optogenetic and chemogenetic activation of these neurons reduced scratching responses related to histaminergic and non-histaminergic acute itch. Similar neural activity and modulatory role of these neurons were seen in mice with chronic itch induced by contact dermatitis. Together, this study highlights the importance of ACC VIP⁺ neurons in modulating itch-related affect and behavior, which may help us to develop novel mechanism-based strategies to treat refractory chronic itch in the clinic.
Animals ; Pruritus/physiopathology* ; Vasoactive Intestinal Peptide/metabolism* ; Interneurons/metabolism* ; Gyrus Cinguli/metabolism* ; Mice ; Male ; Mice, Inbred C57BL ; Histamine ; Chloroquine ; Optogenetics ; Mice, Transgenic

Aortic valve stenosis,as a common heart valve disease,progresses rapidly and has a poor clinical prognosis.In the case of combined acute heart failure,the pumping function of the heart is severely impaired,which may lead to a significant decrease in cardiac output,resulting in a state of shock.Transcatheter aortic valve replacement(TAVR)has become a first-line treatment for elderly patients with aortic valve stenosis since its first successful case in 2002.In China,with the advancement of technology and the strengthening of physician training,the capacity of grassroots hospitals in TAVR treatment is increasing.This case reports a patient with severe aortic valve stenosis accompanied by acute heart failure and shock status who received emergency TAVR treatment at a grassroots hospital.Due to limitations in conditions,TAVR was urgently implemented without extracorporeal circulation and extracorporeal membrane oxygenation support.The patient's blood pressure immediately rose to 105/65 mmHg after valve dilation during surgery,and the postoperative symptoms were significantly relieved.Follow up color Doppler ultrasound showed that the stenosis was relieved and the heart function was significantly improved.The success of this surgery provides a reference for emergency TAVR treatment in patients with severe aortic valve stenosis and heart failure in grassroots hospitals.

Psoriasis is a refractory disease mainly co-acted by immune,genetic and environment.Tumor necrosis factor α (TNF-α)-related biologics have brought the landmark advances in the treatment of psoriasis;however,the anti-TNF-α therapy has the adverse response,its limitation may be related to the different bio-logical functions exerted by activation of TNF-α different receptors.Tumor necrosis factor receptor 2 (TNFR2) is one of the key receptors for TNF-α,and after binding to TNF-α,it can activate multiple signaling pathways such as NF-κB,PI3K/Akt,MAPK,STAT3,etc.,which are involved in the regulation of inflamma-tion,epidermal homeostasis,cellular apoptosis,cellular proliferation,cellular autophagy and other biological processes.It is suggested that TNFR2 is closely related to the occurrence and development of psoriasis.Previ-ous studies have often overlooked the role of TNFR2 in anti-TNF-α therapies;therefore,this article reviews the structure and signaling pathways of TNFR2,research advances in the disease,and its relationship with psoriasis to provide new references for exploring the pathogenesis and treatment of psoriasis.

Aim To investigate the effects of angelica sinensis polysaccharide (ASP) antagonizing 5-fluorou-raeil (5-FU) on spleen stress erythropoiesis in mice and its related mechanism. Methods C57BL/6J mice aged 6-8 weeks were randomly divided into control group, ASP group, 5-FU group and ASP + 5-FU group. The mouse body weight during the modeling pe-riod was recorded, and peripheral blood routine and the number of mononuclear cells in the bone marrow of femur were measured. Histopathology of spleen was de-tected, also the index and cellularity of spleen were analyzed. BFU-E of spleen mononuclear cells was counted. The number of F4/80

Objective: Retrospective analysis of the efficacy and influencing factors of bladder preservation integrated therapy for unresectable invasive bladder cancer confined to the pelvis was done, also including the bladder function preservation and adverse effects analysis. Methods: Sixty-nine patients with unresectable locally invasive bladder cancer who received radiotherapy-based combination therapy from March 1999 to December 2021 at our hospital were selected. Among them, 42 patients received concurrent chemoradiotherapy, 32 underwent neoadjuvant chemotherapyand 43 with transurethral resection of bladder tumors (TURBT) prior to radiotherapy. The late adverse effect of radiotherapy, preservation of bladder function, replase and metastasis and survival were followed-up. Cox proportional hazards models were applied for the multifactorial analysis. Results: The median age was 69 years. There were 63 cases (91.3%) of uroepithelial carcinoma, 64 of stage Ⅲ and 4 of stage Ⅳ. The median duration of follow-up was 76 months. There were 7 grade 2 late genito urinary toxicities, 2 grade 2 gastrointestinal toxicities, no grade 3 or higher adverse events occurred. All patients maintained normal bladder function, except for 8 cases who lost bladder function due to uncontrolled tumor in the bladder. Seventeen cases recurred locally. There were 11 cases in the concurrent chemoradiotherapy group with a local recurrence rate of 26.2% (11/42) and 6 cases in the non-concurrent chemoradiotherapy group with a local recurrence rate of 22.2% (6/27), and the difference in local recurrence rate between the two groups was not statistically significant (P=0.709). There were 23 cases of distant metastasis (including 2 cases of local recurrence with distant metastasis), including 10 cases in the concurrent chemoradiotherapy group with a distant metastasis rate of 23.8% (10/42) and 13 cases in the non-concurrent chemoradiotherapy group with a distant metastasis rate of 48.1% (13/27), and the distant metastasis rate in the non-concurrent chemoradiotherapy group was higher than that in the concurrent chemoradiotherapy group (P=0.036). The median 5-year overall survival (OS) time was 59 months and the OS rate was 47.8%. The 5-year progression-free survival (PFS) time was 20 months and the PFS rate was 34.4%. The 5-year OS rates of concurrent and non-concurrent chemoradiotherapy group were 62.9% and 27.6% (P<0.001), and 5-year PFS rates were 45.4% and 20.0%, respectively (P=0.022). The 5-year OS rates of with or without neoadjuvant chemotherapy were 78.4% and 30.1% (P=0.002), and the 5-year PFS rates were 49.1% and 25.1% (P=0.087), respectively. The 5-year OS rates with or without TURBT before radiotherapy were 45.5% and 51.9% (P=0.233) and the 5-year PFS rates were 30.8% and 39.9% (P=0.198), respectively. Multivariate Cox regression analysis results showed that the clinical stage (HR=0.422, 95% CI: 0.205-0.869) was independent prognostic factor for PFS of invasive bladder cancer. The multivariate analysis showed that clinical stages (HR=0.278, 95% CI: 0.114-0.678), concurrent chemoradiotherapy (HR=0.391, 95% CI: 0.165-0.930), neoadjuvant chemotherapy (HR=0.188, 95% CI: 0.058-0.611), and recurrences (HR=10.855, 95% CI: 3.655-32.638) were independent prognostic factors for OS of invasive bladder cancer. Conclusion: Unresectable localized invasive bladder cancer can achieve satisfactory long-term outcomes with bladder-preserving combination therapy based on radiotherapy, most patients can retain normal bladder function with acceptable late adverse effects and improved survival particularly evident in patients with early, concurrent chemoradiotherapy and neoadjuvant chemotherapy.
Humans ; Aged ; Treatment Outcome ; Retrospective Studies ; Combined Modality Therapy ; Chemoradiotherapy/methods* ; Urinary Bladder Neoplasms/radiotherapy* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Neoplasm Staging

The purpose of this study was to explore the effect and mechanism of dihydromyricetin (DHM) on Parkinson's disease (PD)-like lesions in type 2 diabetes mellitus (T2DM) rats. The T2DM model was established by feeding Sprague Dawley (SD) rats with high-fat diet and intraperitoneal injection of streptozocin (STZ). The rats were intragastrically administered with DHM (125 or 250 mg/kg per day) for 24 weeks. The motor ability of the rats was measured by balance beam experiment, the changes of dopaminergic (DA) neurons and the expression of autophagy initiation related protein ULK1 in the midbrains of the rats were detected by immunohistochemistry, and the protein expression levels of α-synuclein (α-syn), tyrosine hydroxylase (TH), as well as AMPK activation level, in the midbrains of the rats were detected by Western blot. The results showed that, compared with normal control, the rats with long-term T2DM exhibited motor dysfunction, increased α-syn aggregation, down-regulated TH protein expression, decreased number of DA neurons, declined activation level of AMPK, and significantly down-regulated ULK1 expression in the midbrain. DHM (250 mg/kg per day) treatment for 24 weeks significantly improved the above PD-like lesions, increased AMPK activity, and up-regulated ULK1 protein expression in T2DM rats. These results suggest that DHM may improve PD-like lesions in T2DM rats by activating AMPK/ULK1 pathway.
Rats ; Animals ; Parkinson Disease ; Rats, Sprague-Dawley ; AMP-Activated Protein Kinases ; Diabetes Mellitus, Type 2 ; Autophagy-Related Protein-1 Homolog

Objective To evaluate the risk factors for development of primary hepatic carcinoma(PHC)in patients with hepatitis B virus-related liver cirrhosis.Methods The cases of hepatitis B virus-related liver cirrhosis combined with PHC and hepatitis B virus-related liver cirrhosis alone were retrospectively analyzed in the Second Affiliated Hospital of Nanchang University.A total of 151 patients with hepatitis B virus-related liver cirrhosis combined with PHC were included in observation group and 136 patients with hepatitis B virus-related liver cirrhosis alone were included in control group.We have down the analysis of risk factors by χ2 test,t test and Logistic regression model.Results The clinical data of the two groups of patients showed statistically significant differences in six indicators,including gender,hepatitis B virus e antibodies(Anti-HBe),liver function grading(Child-Pugh),alpha-fetoprotein(AFP),blood glucose,and blood type,through univariate analysis(P<0.05).The results of multivariate unconditional Logistic regression analysis showed that AFP(OR=5.046,2.716,and 9.373,P<0.01)and Anti-HBe positive(OR=2.305,1.075,and 4.945,P<0.01)were risk factors for primary liver cancer.Conclusion Male shows a more possibility of occurrence of PHC than female.The positive Anti-HBe is the independent risk factors for PHC.The probability of PHC in Child-Pugh stage A is higher than that in Child-Pugh stage B and C.

N ⁶-methyladenosine (m⁶A) modification is critical for mRNA splicing, nuclear export, stability and translation. Fat mass and obesity-associated protein (FTO), the first identified m⁶A demethylase, is critical for cancer progression. Herein, we developed small-molecule inhibitors of FTO by virtual screening, structural optimization, and bioassay. As a result, two FTO inhibitors namely 18077 and 18097 were identified, which can selectively inhibit demethylase activity of FTO. Specifically, 18097 bound to the active site of FTO and then inhibited cell cycle process and migration of cancer cells. In addition, 18097 reprogrammed the epi-transcriptome of breast cancer cells, particularly for genes related to P53 pathway. 18097 increased the abundance of m⁶A modification of suppressor of cytokine signaling 1 (SOCS1) mRNA, which recruited IGF2BP1 to increase mRNA stability of SOCS1 and subsequently activated the P53 signaling pathway. Further, 18097 suppressed cellular lipogenesis via downregulation of peroxisome proliferator-activated receptor gamma (PPARγ), CCAAT/enhancer-binding protein alpha (C/EBPα), and C/EBPβ. Animal studies confirmed that 18097 can significantly suppress in vivo growth and lung colonization of breast cancer cells. Collectively, we identified that FTO can work as a potential drug target and the small-molecule inhibitor 18097 can serve as a potential agent against breast cancer.

OBJECTIVE: To evaluate the protective effect of excretory-secretory proteins from Trichinella spiralis muscle larvae (Ts-MES) on sepsis-induced myocardial injury in mice. METHODS: Eighty male BALB/C mice were randomized equally into sham-operated group, myocardial injury group, Ts-MES treatment group and dexamethasone treatment group. In the latter 3 groups, sepsis-induced myocardial injury models were established by cecal ligation and perforation; the sham operation was performed by exposure of the cecum without ligation or perforation. Forty minutes after the operation, the mice were given intraperitoneal injections 150 μL PBS, 20 μg TS-MES or 0.3 mg/kg dexamethasone as indicated. At 12 h after the operation, 6 mice were randomly selected from each group for echocardiography, and 8 mice were used for observing the survival rate within 72 h. The remaining 6 mice were examined for myocardial pathologies with HE staining and serum levels of NTPro-BNP and cTnI with ELISA; the expressions of TNF-α, IL-6, IL-10 and TGF-β in the serum and myocardial tissue were detected using ELISA and qRT-PCR. RESULTS: Compared with the sham-operated mice, the septic mice showed significantly decreased cardiac function indexes (LVEF, LVFS, and E/A) with lowered survival rate within 72 h (P < 0.001) and significantly higher myocardial injury scores and serum levels of NTPro-BNP and cTnI (P < 0.01). Treatment with TS-MES significantly improved the cardiac function and 72-h survival rate (P < 0.05) and lowered the myocardial injury scores and serum levels of NTPro-BNP and cTnI (P < 0.05) in the septic mice. Compared with the sham-operated mice, the septic mice had obviously increased TNF-α and IL-6 levels in the serum and myocardial tissue (P < 0.001), which were significantly lowered by treatment with TS-MES (P < 0.05). TS-MES and dexamethasone both increased the levels of IL-10 and TGF-β in the septic mice, but the changes were significant only in TS-MES-treated mice (P < 0.05). CONCLUSION Ts-MES are capable of protecting against myocardial injury in septic mice by reducing the production of pro-inflammatory cytokines and enhancing the levels of regulatory cytokines.
Animals ; Cytokines ; Dexamethasone ; Heart Injuries ; Interleukin-10 ; Interleukin-6 ; Larva ; Male ; Mice ; Mice, Inbred BALB C ; Myocardium ; Sepsis ; Transforming Growth Factor beta ; Trichinella spiralis ; Tumor Necrosis Factor-alpha

Inhalational anesthetics have been the default agents for general anesthesia maintenance for several decades. However, with advances in total intravenous anesthesia (TIVA) and a growing body of evidence on the potential benefits of TIVA, anesthesiologists need to question this paradigm. Some of the benefits of propofol-based TIVA, such as its antiemetic properties and patients’ smooth emergence, are widely acknowledged. A growing body of evidence suggests that TIVA may potentially benefit the immune system and cancer outcomes. From an existential health perspective, there is evidence that inhalational agents have a materially higher global warming potential than propofol-based TIVA. Despite the compelling potential benefits of propofol-based TIVA, there are barriers to its widespread adoption. To examine the applicability of TIVA as a mainstay agent more rigorously, we discuss the safety and applicability of propofol-based TIVA in the context of complex major abdominal surgery, specifically, liver resection surgery. We also discuss the use of propofol-based TIVA in liver resection surgery with a broad, integrated approach, addressing general and specific clinical considerations, economic factors, and operating room turnover.