Objective:To explore the clinical and electrophysiological characteristics of peripheral neuropathy in prediabetic patients.Methods:Subjects aged 20-65 years with high-risk factors of impaired glycemia enrolled in Beijing Tiantan Hospital, Capital Medical University from 2019 to 2022 were recruited to conduct oral glucose tolerance test, after excluding other causes of neuropathy or radiculopathy. Patients with impaired fasting glucose or impaired glucose tolerance were defined by American Diabetes Association criteria. These patients were divided into clinical polyneuropathy (PN) and clinical non-PN groups, according to the 2010 Toronto consensus criteria and the presence of PN symptoms and signs or not. Nerve conduction studies (NCS), F wave, sympathetic skin response (SSR), R-R interval variation (RRIV) and current perception thresholds (CPT) were performed and the abnormal rate was compared between different electrodiagnostic methods and between clinical subgroups.Results:Among the 73 prediabetic patients ultimately enrolled, only 20 (27.4%) can be diagnosed as clinical PN according to the Toronto consensus criteria. The abnormal rate of CPT (68.5%, 50/73) was significantly higher than those of F wave (2.7%, 2/73), lower limb NCS (0, 0/73), upper limb NCS changes of carpal tunnel syndrome (26.0%, 19/73), SSR (6.8%, 5/73) and RRIV (5.5%, 4/73; McNemar test, all P<0.001). With sinusoid-waveform current stimuli at frequencies of 2 000 Hz, 250 Hz and 5 Hz, the CPT device was used to measure cutaneous sensory thresholds of large myelinated, small myelinated and small unmyelinated sensory fibers respectively. CPT revealed a 21.9% (16/73) abnormal rate of unmyelinated C fiber in the hands of prediabetic patients, significantly higher than that of large myelinated Aβ fibers [8.2% (6/73), χ2=5.352, P=0.021]. Both abnormal rates of small myelinated Aδ [42.5% (31/73)] and unmyelinated C fibers [39.7% (29/73)] in the feet of prediabetic patients were significantly higher than that of large myelinated Aβ fibers [11.0% (8/73), χ2=18.508, 15.965, both P<0.001]. Compared with the clinical non-PN group, the abnormal rates of CPT [90.0% (18/20) vs 60.4% (32/53), χ2=5.904, P=0.015] and SSR [20.0% (4/20) vs 1.9% (1/53), P=0.016) were significantly higher in the clinical PN group. Conclusions:Peripheral neuropathies in prediabetic patients are usually asymptomatic or subclinical, and predispose to affect unmyelinated and small myelinated sensory fibers. Selective electrodiagnostic measurements of small fibers help to detect prediabetic neuropathies in the earliest stages of the disease.

Objective To investigate the effect of ursodeoxycholic acid(UDCA)on the symptoms after severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection in patients with primary biliary cholangitis(PBC)and their family member.Methods A questionnaire survey was conducted to collect related information from 171 PBC patients who attended The First Affiliated Hospital of Air Force Medical University before March 22,2023 and 128 family members,including demographic information,comorbidities,UDCA administration,SARS-CoV-2 infection,vaccination,symptoms,therapeutic medication,and the changes in liver disease-related symptoms.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 or the Fisher's exact test was used for comparison of categorical data between two groups.Results The median age was 51 years in the PBC patients and 49 years in the family members,with no significant difference between the two groups(P>0.05).Compared with the family member group,the PBC group had significantly lower body mass index(22.2±2.4 kg/m2 vs 23.3±2.9 kg/m2,P<0.001)and proportion of male individuals(10%vs 55%,P<0.001).All PBC patients received UDCA at a dose of 13—15 mg/kg,and SARS-CoV-2 infection rate was 100%in both groups.The family members had a significantly higher SARS-CoV-2 vaccination rate than the PBC patients(91%vs 57%,P<0.001).Compared with the family members,the PBC patients had significantly milder symptoms of sneezing,nasal obstruction,chest pain,and abnormal taste(P<0.05).Compared with the family members,the PBC patients had significantly lower rates of use of compound cold medicine(11%vs 20%,P<0.05)and Lianhua Qingwen capsules(12%vs 21%,P<0.05).For the PBC patients after SARS-CoV-2 infection,the liver disease-related symptoms such as fatigue,abdominal distension,dry mouth and dry eyes,pruritus,and yellow skin were aggravated by 37%,2%,27%,10%,and 3%,respectively.Conclusion Compared with the immediate family members of PBC patients who do not take UDCA,the PBC patients receiving UDCA do not show a reduction in SARS-CoV-2 infection rate,but UDCA may have a certain effect on alleviating infection-related symptoms in such patients.PBC patients may still experience the aggravation of liver disease-related symptoms after SARS-CoV-2 infection,and the long-term effect on PBC patients after SARS-CoV-2 infection should be taken seriously in clinical practice.

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis complex and is mainly manifested as pulmonary tuberculosis. Mycobacterium tuberculosis is characterized by high pathogenicity and drug resistance due to its high viability and lethality, and multidrug-resistant tuberculosis caused by it has become a global public health problem. Early and effective treatment is essential to prevent the emergence of drug-resistant strains. Commonly employed methods for the screening and diagnosis of TB include: clinical signs, imaging examinations (chest X-ray, computed tomography), sputum culture (L-J medium, BACTEC liquid culture system), and immunological tests (lipoarabinomannan antigen test, tuberculin skin test, interferon-gamma release test). In recent years, emerging molecular diagnostic methods such as GeneXpert MTB/RIF assay, loop-mediated isothermal amplification (LAMP), linear probe assay, and whole-genome sequencing have been used to diagnose and characterize TB. These methods not only identify Mycobacterium tuberculosis but also detect mutation sites associated with resistance to first-line anti-tuberculosis drugs (isoniazid, rifampicin, etc.), providing new possibilities for the diagnosis of drug-resistant Mycobacterium tuberculosis. In this paper, the advantages and disadvantages of some commonly used detection methods for tuberculosis are first reviewed, aiming at assisting clinicians to diagnose and treat the disease in a timely manner. Secondly, this paper explores the prospects of the latest high-throughput detection methods for drug-resistant Mycobacterium tuberculosis.

Neurogenesis decline in hippocampal dentate gyrus (DG) participates in stress-induced depressive-like behaviors, but the underlying mechanism remains poorly understood. Here, we observed low-expression of NOD-like receptor family pyrin domain containing 6 (NLRP6) in hippocampus of stress-stimulated mice, being consistent with high corticosterone level. NLRP6 was found to be abundantly expressed in neural stem cells (NSCs) of DG. Both Nlrp6 knockout (Nlrp6^-/-) and NSC-conditional Nlrp6 knockout (Nlrp6CKO) mice were susceptible to stress, being more likely to develop depressive-like behaviors. Interestingly, NLRP6 was required for NSC proliferation in sustaining hippocampal neurogenesis and reinforcing stress resilience during growing up. Nlrp6 deficiency promoted esophageal cancer-related gene 4 (ECRG4) expression and caused mitochondrial dysfunction. Corticosterone as a stress factor significantly down-regulated NLRP6 expression, damaged mitochondrial function and suppressed cell proliferation in NSCs, which were blocked by Nlrp6 overexpression. ECRG4 knockdown reversed corticosterone-induced NSC mitochondrial function and cell proliferation disorders. Pioglitazone, a well-known clinical drug, up-regulated NLRP6 expression to inhibit ECRG4 expression in its protection against corticosterone-induced NSC mitochondrial dysfunction and proliferation restriction. In conclusion, this study demonstrates that NLRP6 is essential to maintain mitochondrial homeostasis and proliferation in NSCs, and identifies NLRP6 as a promising therapeutic target for hippocampal neurogenesis decline linked to depression.

Objective:To introduce and validate the Pediatric Nausea Assessment Tool (PeNAT) and the Baxter Retching Faces Scale (BARF) in the assessment of chemotherapy induced nausea in Chinese children with malignant neoplasms, and to explore the cut-off value for rescue antiemetic.Methods:A prospective descriptive study was conducted, 244 children in Sun Yat-sen University Cancer Center with malignant neoplasms who received chemotherapy were selected by convenience sampling from July to August 2021. PeNAT, BARF, Visual Analogue Scale (VAS) and the Faces Pain Scale-Revised(FPS-R) were used to assess the severity of nausea and pain before and after chemotherapy, before and 30-60 minutes after the use of rescue antiemetic or analgesic. After chemotherapy, the children also were asked the changes of nausea severity and whether antiemetic was needed.Results:A test-retest reliability was conducted on the patients with the same severity of nausea before and after chemotherapy, and the intraclass correlation coefficient of the PeNAT and BARF were 0.940 (both P<0.05). After chemotherapy, the PeNAT and BARF were 1.5(1.0, 2.0) and 2.0(0, 2.0) points, which were significantly higher than the 1.0(1.0, 1.0) and 0(0, 0) points before chemotherapy ( Z = - 9.19, - 9.09, both P<0.01). The PeNAT and BARF of 11 cases receiving antiemetic before medication were 4.0 (4.0, 6.0) and 3.0(2.0, 4.0) points, which were higher than the 0(0, 2.0) and 1.0(1.0, 2.0) points without antiemetic ( Z = - 4.03, - 3.86, both P<0.05). After chemotherapy, the correlation coefficients between PeNAT or BARF and VAS-nausea were r = 0.933, 0.957 (both P<0.01), and FPS-R were r = 0.192, 0.189 (both P<0.05). After using antiemetic, PeNAT and BARF were 2.0(2.0, 3.0) and 2.5(2.0, 4.0) points, which were significant different than the 3.0(3.0, 3.8) and 4.0(4.0, 8.0) points before using antiemetic ( Z = - 2.97, - 2.83, both P<0.05). According ROC curves and cut-off values, it was determined that PeNAT≥3 and BARF≥4 had clinical significance and require clinical intervention. Conclusions:PeNAT and BARF have excellent reliability and validity in the assessment of chemotherapy induced nausea in children with malignant neoplasms, they can effectively identify the requirement of rescue antiemetic, and evaluate the efficacy of antiemetic.

The occurrence of eosinophilic leukemia complicated with cardiogenic embolism and L?ffler endocarditis are relatively rare.Early accurate diagnosis and prompt treatment can improve the its prognosis.When patients have symptoms of neurological impairment accompanied by increased eosinophils,the rare etiological type of cerebral infarction should be actively screened.Further improvements are needed in the examination of bone marrow smears,detection of fusion genes associated with leukemia,screening for L?ffler endocarditis,and identification of intraventricular thrombi.In this case,the main manifestations of eosinophilic leukemia were cardiogenic embolism and L?ffler endocarditis.After active treatment,the symptoms improved,and the eosinophil count returned to normal.This study summarizes the case data of this patient and combines it with a literature review,with the hope of raising clinicians'understanding of this rare disease.

OBJECTIVE The abnormal amyloid-β(Aβ)and oxidative stress assiociated with the progression of Alzheimer disease(AD).Quercetin has been reported to possess antioxidant and anti-inflammatory properties in neurodegenerative disorders.In this present study,we designed to characterize the mechanisms by which quer-cetin exerts neuroprotective effects in murine neuroblas-toma N2a cells stably expressing human Swedish mutant amyloid precursor protein(N2a/APP).METHODS N2a/APP cells were treated with quercetin at concentrations of 10,20 and 50 μ mol·L-1 for 24 h.Cell viability was examined with CCK-8 assays.The protein levels of ERK1/2 and Akt were detected by Western blotting.Intra-cellular reactive oxygen species(ROS)was detected by a fluorescent probe 2,7-dichlorofluorescein diacetate(DCFH-DA).The mitochondrial membrane potential(Δψ m)in N2a/APP cells was detected by using JC-1 staining method.Immunofluorescence was used to detect the generation of 8-hydroxy-2′-deoxyguanosine(8-OHdG)and 4-hydroxynonenal(4-HNE).RESULTS Quercetin attenuated the enhancement of p-ERK1/2,reductions of p-Akt,and decreased levels of APP expression.More-over,quercetin alleviated loss of mitochondria membrane potential(MMP)since it attenuates these oxidative stress,as reflected in the levels of ROS,4-HNE and 8-OHdG,was elevated in N2a/APP cells and these effects were again ameliorated by quercetin.CONCLUSION Neuroprotection by quercetin in N2a/APP cells involves normalizing the impaired mitochondrial function and reducing oxidative stress via inactivation of the ERK1/2 and activation of the Akt pathways.

Objective:To construct a nomogram model for nasopharyngeal bleeding risk in nasopharyngeal carcinoma patients underwent radiotherapy, and to verify the application value of the model.Methods:From June 2020 to December 2021, 317 nasopharyngeal carcinoma patients underwent radiotherapy in the First Affiliated Hospital of Zhengzhou University were enrolled by the convenience sampling method, and divided into the bleeding group and the non-bleeding group according to the occurrence of nasopharyngeal hemorrhage bleeding. Univariate analysis and Logistic regression analysis were used to analyze the independent risk factors of nasopharyngeal hemorrhage patients underwent radiotherapy, and a nomogram model was constructed. Correction curve, Hosmer- Lemeshow ( H- L) goodness fit test and receiver operating characteristic (ROC) curve were used to evaluate the predictive efficiency of the model, and the area under ROC curve was calculated. Results:Multivariate Logistic regression analysis results showed that hypertension, skull base invasion, synchronous chemotherapy, anterior field+skull base irradiation, tumor rectum growth and average radiation dose≥70 Gy were the independent risk factors of nasopharyngeal hemorrhage in nasopharyngeal carcinoma patients underwent radiotherapy ( P<0.05). H- L goodness fit test results showed that there was no significant difference between the calibration curve predicted by the nomogram model and the ideal model curve (χ 2=3.469, P=0.614), and the area under ROC curve was 0.778 (95% CI: 0.705-0.947) . Conclusions:Hypertension, skull base invasion, synchronous chemotherapy, anterior field+skull base irradiation, tumor crypt growth and radiation dose≥70 Gy were the independent risk factors for nasopharyngeal hemorrhage in nasopharyngeal cancer patients underwent radiotherapy. The nomogram model constructed in this study has good differentiation and accuracy, which can provide a reference for medical staffs to develop targeted intervention strategies.

Objective:To summarize the clinical characteristics, causes of misdiagnosis and preventive measures of infectious mononucleosis (IM) in children, and to improve the ability of clinicians in early diagnosis of IM in children.Methods:The clinical data of 468 children with IM in Xi′an Children′s Hospital from January 2018 to December 2021 were retrospectively analyzed, including general situation, disease onset, diagnosis and misdiagnosis.Results:Among the 468 children, 33 cases were clinically diagnosed and 435 cases were a definitely diagnosed; 281 males (60.04%) and 187 females (39.96%); the incidence rate was highest in preschool children (43.80%, 205/468) and in autumn (33.12%, 155/468). The first symptoms were fever (52.99%, 248/468), eyelid edema (15.38%,72/468) and neck mass (14.96%, 70/468). The fever rate was 90.38% (423/468), and the median time of first fever appearance was on the first (first, second) day of disease course, and the median duration of fever was 6 (4, 8) d. The median time of first visit was on the third (first, fifth) day of disease course, and the time of diagnosis was on the seventh (fifth, ninth) day of disease course. Blood routine examination showed that the proportion of white blood cell count increased was 51.92% (243/468), the proportion of lymphocytes increased was 61.75% (289/468), and the proportion of abnormal lymphocytes increased (≥10%) in peripheral blood was 58.97% (276/468). The lymphocyte subsets of 364 children were detected, the rate of helper T lymphocytes (Th cells) decreased was 80.22% (292/364), the rate of suppressor T lymphocytes (Ts cells) increased was 99.45% (362/364), the value and decreased rate of Th cells/Ts cells were 0.24 (0.16, 0.40) and 100.00% (364/364), rate of B lymphocytes decreased was 93.96% (342/364), rates of natural killer cells decreased and increased were 35.16% (128/364) and 0.55% (2/364). The misdiagnosis rate was 55.13% (258/468), and the misdiagnosis time was on the fifth (fourth, seventh) day of disease course. Among the 258 misdiagnosed children, 105 cases (40.70%) were misdiagnosed as upper respiratory tract infection, 65 cases (25.19%) as acute suppurative tonsillitis, 27 cases (10.47%) as acute cervical lymphadenitis or neck mass.Conclusions:Due to the complex and diverse clinical manifestations of IM in children, it is easy to be misdiagnosed in the early stage of the disease. So, it is necessary for clinicians to master the clinical characteristics of IM in children, constantly improve the level of diagnosis and treatment, and reduce the misdiagnosis rate.

Aging-elevated DNMT3A R882H-driven clonal hematopoiesis (CH) is a risk factor for myeloid malignancies remission and overall survival. Although some studies were conducted to investigate this phenomenon, the exact mechanism is still under debate. In this study, we observed that DNMT3A R878H bone marrow cells (human allele: DNMT3A R882H) displayed enhanced reconstitution capacity in aged bone marrow milieu and upon inflammatory insult. DNMT3A R878H protects hematopoietic stem and progenitor cells from the damage induced by chronic inflammation, especially TNFα insults. Mechanistically, we identified that RIPK1-RIPK3-MLKL-mediated necroptosis signaling was compromised in R878H cells in response to proliferation stress and TNFα insults. Briefly, we elucidated the molecular mechanism driving DNMT3A R878H-based clonal hematopoiesis, which raises clinical value for treating DNMT3A R882H-driven clonal hematopoiesis and myeloid malignancies with aging.