Objective Pancreatic cancer(PC)is a malignant tumor of the digestive tract that is difficult to diagnose early,easily metastasizes and relapses,and resistant to conventional chemotherapy.PC is a very difficult disease to treat.The key regulatory factors of PC resistance,such as epithelial-mesenchymal transition phenotypic cells,tumor stem cells,and miRNAs,have been reviewed in the past few years,and some new regulatory factors have been discovered as supplements.This review mainly focuses on the characteristics and properties of the key regulatory factors of PC chemotherapy resistance including long noncoding RNAs,nuclear factor KB and exosomes,drug resistance mechanisms,and treatment related strategies,and future treatment directions were predicted.

OBJECTIVE: To observe the effect of acupotomy on the fat infiltration degree of lumbar multifidus muscle (LMM) in patients with lumbar disc herniation after percutaneous transforaminal endoscopic discectomy (PTED). METHODS: A total of 104 patients with lumbar disc herniation treated with PTED were randomly divided into an observation group (52 cases, 3 cases dropped off) and a control group (52 cases, 4 cases dropped off). Patients of both groups received rehabilitation training of two weeks 48 h after PTED treatment. The observation group was treated with acupotomy (L₃-L₅ Jiaji [EX-B 2]) once within 24 h after PTED. In the two groups, the fat infiltration cross sectional area (CSA) of LMM was compared before and 6 months after PTED, the visual analogue scale (VAS) score and Oswestry disability index (ODI) score were observed before and 1, 6 months after PTED. The correlation between fat infiltration CSA of LMM in each segment and VAS score was analyzed. RESULTS: Six months after PTED, the fat infiltration CSA of LMM in L₄/L₅ and the total L₃-S₁ segments of the observation group was lower than that before PTED (P<0.05), and the fat infiltration CSA of LMM in L₄/L₅ of the observation group was lower than the control group (P<0.01). One month after PTED, the ODI and VAS scores of the two groups were lower than those before PTED (P<0.01), and those in the observation group were lower than the control group (P<0.05). Six months after PTED, the ODI and VAS scores of the two groups were lower than those before PTED and 1 month after PTED (P<0.01), and those in the observation group were lower than the control group (P<0.01). There was a positive correlation between the fat infiltration CSA of LMM in the total L₃-S₁ segments and VAS scores in the two groups before PTED (r = 0.64, P<0.01). Six months after PTED, there was no correlation between the fat infiltration CSA of LMM in each segment and VAS scores in the two groups (P>0.05). CONCLUSION Acupotomy can improve the fat infiltration degree of LMM, pain symptoms and activities of daily living in patients with lumbar disc herniation after PTED.
Humans ; Intervertebral Disc Displacement ; Activities of Daily Living ; Paraspinal Muscles ; Treatment Outcome ; Lumbar Vertebrae ; Retrospective Studies ; Endoscopy ; Diskectomy ; Acupuncture Therapy

Objectives: . Reactive oxygen species in the stria vascularis (SV) of the cochlea may be involved in the pathogenesis of sensorineural hearing loss. However, the effects of oxidative stress on SV endothelial cells (SV-ECs) remain largely unknown, and no feasible in vitro cell culture model exists for the functional study of SV-ECs. Methods: . We isolated primary SV-ECs from the SV of neonatal mice. The apoptosis-reducing effects of fibronectin in SV-ECs cultured with serum-free medium were determined using β-galactosidase staining and flow cytometry. SV-ECs incubated in serum-free medium were treated with various H2O2 concentrations to evaluate the effects of H2O2 on their viability. The secretome of SV-ECs treated with or without H2O2 (100 μM or 500 μM) was analyzed using high-resolution mass spectrometry. The function of the SV-EC secretome was evaluated by a macrophage assay. Results: . We successfully isolated and characterized the SV-ECs. Treatment with H2O2 at concentrations up to 500 μM for 2 hours and further incubation with serum-free medium in plates precoated with fibronectin showed no significant effect on apoptosis. Compared to the control SV-ECs, the amount of differential proteins in the secretome of SV-ECs stimulated with 500 μM H2O2 was much higher than in those treated with 100 μM H2O2. Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analyses suggested that the proteins differentially expressed in SV-ECs treated with 500 μM H2O2 were involved in the regulation of multiple signaling pathways and cellular processes. The secretome of H2O2-stimulated SV-ECs exhibited significant pro-inflammatory effects on macrophages. Conclusion . We successfully established an in vitro serum-free culture method, identified the differential proteins released by oxidative stress-induced ECs and their functions, and revealed the pro-inflammatory effects of the secretome of H2O2-stimulated SV-ECs. Therefore, SV-ECs might elicit immunoregulatory effects on bystander cells in the microenvironment of oxidative stress-induced cochlea, especially cochlear macrophages.

The 3-succinate-30-stearyl glycyrrhetinic acid(18-GA-Suc) was inserted into glycyrrhetinic acid(GA)-tanshinone Ⅱ_A(TSN)-salvianolic acid B(Sal B) liposome(GTS-lip) to prepare liver targeting compound liposome(Suc-GTS-lip) mediated by GA receptors. Next, pharmacokinetics and tissue distribution of Suc-GTS-lip and GTS-lip were compared by UPLC, and in vivo imaging tracking of Suc-GTS-lip was conducted. The authors investigated the effect of Suc-GTS-lip on the proliferation inhibition of hepatic stellate cells(HSC) and explored their molecular mechanism of improving liver fibrosis. Pharmacokinetic results showed that the AUC_(Sal B) decreased from(636.06±27.73) μg·h·mL~(-1) to(550.39±12.34) μg·h·mL~(-1), and the AUC_(TSN) decreased from(1.08±0.72) μg·h·mL~(-1) to(0.65±0.04) μg·h·mL~(-1), but the AUC_(GA) increased from(43.64±3.10) μg·h·mL~(-1) to(96.21±3.75) μg·h·mL~(-1). The results of tissue distribution showed that the AUC_(Sal B) and C_(max) of Sal B in the liver of the Suc-GTS-lip group were 10.21 and 4.44 times those of the GTS-lip group, respectively. The liver targeting efficiency of Sal B, TSN, and GA in the Suc-GTS-lip group was 40.66%, 3.06%, and 22.08%, respectively. In vivo imaging studies showed that the modified liposomes tended to accumulate in the liver. MTT results showed that Suc-GTS-lip could significantly inhibit the proliferation of HSC, and RT-PCR results showed that the expression of MMP-1 was significantly increased in all groups, but that of TIMP-1 and TIMP-2 was significantly decreased. The mRNA expressions of collagen-I and collagen-Ⅲ were significantly decreased in all groups. The experimental results showed that Suc-GTS-lip had liver targeting, and it could inhibit the proliferation of HSC and induce their apoptosis, which provided the experimental basis for the targeted treatment of liver fibrosis by Suc-GTS-lip.
Humans ; Liposomes ; Hepatic Stellate Cells ; Glycyrrhetinic Acid/pharmacology* ; Liver ; Liver Cirrhosis/genetics* ; Collagen/pharmacology*

Objective: To investigate the influence of extending the waiting time on tumor regression after neoadjuvant chemoradiology (nCRT) in patients with locally advanced rectal cancer (LARC). Methods: Clinicopathological data from 728 LARC patients who completed nCRT treatment at the First Affiliated Hospital, Naval Medical University from January 2012 to December 2021 were collected for retrospective analysis. The primary research endpoint was the sustained complete response (SCR). There were 498 males and 230 females, with an age (M(IQR)) of 58 (15) years (range: 22 to 89 years). Logistic regression models were used to explore whether waiting time was an independent factor affecting SCR. Curve fitting was used to represent the relationship between the cumulative occurrence rate of SCR and the waiting time. The patients were divided into a conventional waiting time group (4 to <12 weeks, n=581) and an extended waiting time group (12 to<20 weeks, n=147). Comparisons regarding tumor regression, organ preservation, and surgical conditions between the two groups were made using the t test, Wilcoxon rank sum test, or χ² test as appropriate. The Log-rank test was used to elucidate the survival discrepancies between the two groups. Results: The SCR rate of all patients was 21.6% (157/728). The waiting time was an independent influencing factor for SCR, with each additional day corresponding to an OR value of 1.010 (95%CI: 1.001 to 1.020, P=0.031). The cumulative rate of SCR occurrence gradually increased with the extension of waiting time, with the fastest increase between the 9^th to <10^th week. The SCR rate in the extended waiting time group was higher (27.9%(41/147) vs. 20.0%(116/581), χ²=3.901, P=0.048), and the organ preservation rate during the follow-up period was higher (21.1%(31/147) vs. 10.7%(62/581), χ²=10.510, P=0.001). The 3-year local recurrence/regrowth-free survival rates were 94.0% and 91.1%, the 3-year disease-free survival rates were 76.6% and 75.4%, and the 3-year overall survival rates were 95.6% and 92.2% for the conventional and extended waiting time groups, respectively, with no statistical differences in local recurrence/regrowth-free survival, disease-free survival and overall survival between the two groups (χ²=1.878, P=0.171; χ²=0.078, P=0.780; χ²=1.265, P=0.261). Conclusions: An extended waiting time is conducive to tumor regression, and extending the waiting time to 12 to <20 weeks after nCRT can improve the SCR rate and organ preservation rate, without increasing the difficulty of surgery or altering the oncological outcomes of patients.

OBJECTIVE: To compare the clinical efficacy between acupuncture combined with western medication and simple western medication for ocular myasthenia gravis (OMG), and to explore its possible mechanism. METHODS: A total of 60 patients of ocular myasthenia gravis were randomized into an acupuncture combined with western medication group (30 cases, 1 case dropped off) and a western medication group (30 cases, 2 cases dropped off). Oral pyridostigmine bromide tablet and prednisone acetate tablet were given in the western medication group. On the basis of the treatment in the western medication group, Tongdu Tiaoqi acupuncture (acupuncture for unblocking the governor vessel and regulating qi ) was applied at Baihui (GV 20), Fengfu (GV 16), Hegu (LI 4), Zusanli (ST 36), etc. in the acupuncture combined with western medication group, once a day, 6 days a week. The treatment was given 8 weeks in both groups. Before and after treatment, the OMG clinical absolute score was observed, electrophysiological indexes of orbicularis oculi (value of mean jitter, percentage of jitter >55 μs and percentage of blocks) were measured by single-fiber electromyography (SFEMG), serum levels of acetylcholine receptor antibody (AChR-Ab), interferon-gamma (IFN-γ) and interleukin-4 (IL-4) were detected by ELISA method. RESULTS: After treatment, the OMG clinical absolute scores, values of mean jitter, percentages of jitter >55 μs, percentages of blocks and serum levels of AChR-Ab, IFN-γ and IL-4 were decreased compared before treatment in both groups (P<0.05), and those in the acupuncture combined with western medication group were lower than the western medication group (P<0.05). CONCLUSION Acupuncture combined with western medication can effectively improve ptosis, palpebra superior fatigability, eye movement disorder and neuromuscular junction dysfunction in patients with ocular myasthenia gravis, the therapeutic effect is superior to simple western medication. Its mechanism may be related to down-regulating serum levels of AChR-Ab, IFN-γ and IL-4 and promoting the recovery of orbicularis oculi function.
Acupuncture Therapy ; Facial Muscles ; Humans ; Interferon-gamma ; Interleukin-4 ; Myasthenia Gravis/drug therapy*

Primary immunodeficiency diseases (PID) is a congenital disease caused by single gene germline mutation related to the immune system. PID patients have immune dysregulation, and are susceptible to infectious diseases, autoimmune diseases, autoimmune diseases, allergic diseases, and malignant tumors. The first symptom of some PID patients is atopic disease, therefore they go to the department of allergy, department of pediatrics and other relevant departments. How to identify and diagnose PID in allergic patients, to reduce diagnosis delay and prevent disease aggravation are the abilities that allergists, pediatricians, and doctors in other relevant departments need to master. This article summarizes the warning signs of PID in allergic patients and the mechanism of allergy combined with PID, and then summarizes the common types of PID in allergic patients, the evaluation, treatment and prevention in patients with PID and allergy.
Autoimmune Diseases ; Child ; Humans ; Hypersensitivity/therapy* ; Immunologic Deficiency Syndromes/therapy* ; Primary Immunodeficiency Diseases/therapy*

Antibodies, Monoclonal, Humanized/adverse effects* ; Humans ; Immune Checkpoint Inhibitors/adverse effects* ; Myocarditis/drug therapy*

Hodgkin Disease/pathology* ; Humans ; Lung/pathology* ; Lymphoma, B-Cell/pathology*

Objective: To explore the clinical manifestations and genetic characteristics of patients with epilepsy and episodic ataxia caused by SCN2A gene variation. Methods: The clinical data of seizure manifestation, imaging examination and genetic results of 5 patients with epilepsy and (or) episodic ataxia because of SCN2A gene variation admitted to the Department of Pediatrics, the Third Affiliated Hospital of Zhengzhou University from July 2017 to January 2021 were analyzed retrospectively. Results: Among 5 patients, 4 were female and 1 was male. The onset age of epilepsy ranged from 4 days to 8 months. There were 2 cases of benign neonatal or infantile epilepsy and 3 cases of epileptic encephalopathy, in whom 1 case had development retardation,1 case transformed from West syndrome to infantile spasm and another one transformed from infantile spasm to Lennox-Gastaut syndrome. One case of benign neonatal-infantile epilepsy was characterized by neonatal onset seizures and episodic ataxia developed at the age of 78 months. Electroencephalograms at first visit of 5 cases showed that 2 cases were normal, 1 case had focal epileptic discharge, and 2 cases had multi-focal abnormal discharge with peak arrhythmia. The brain magnetic resonance imaging (MRI) of 3 cases were nomal, 1 case was abnormal (brain atrophy with decreased white matter) and the results of 1 case was unknown. The follow-up time ranged from 17 months to 89 months. Four cases of epilepsy were controlled and 1 case died at 2 years of age. Two cases had normal intelligence and motor development, 2 had moderate to severe intelligence retardation and motor critical state, and 1 had moderate to severe intelligence and motor development retardation. SCN2A gene variations were identified in all cases. There were 4 missense variations and 1 frameshift variation. Three variations had not been reported so far, including c.4906A>G,c.3643G>T,c.638delT. Conclusions: Variations in SCN2A gene can cause benign neonatal or infantile epilepsy and epileptic encephalopathy. Some children develop episodic ataxia with growing age. The variation of SCN2A gene is mainly missense variation.
Ataxia/genetics* ; Child ; Electroencephalography ; Epilepsy/genetics* ; Female ; Humans ; Infant ; Infant, Newborn ; Male ; Mutation ; NAV1.2 Voltage-Gated Sodium Channel/genetics* ; Retrospective Studies ; Spasms, Infantile/genetics*