Objective: To investigate the correlation of chemerin levels in the serum and intestinal mucosal with in- testinal mucosal inflammation in IBS-D mice . Methods: A total of 128 female C57BL/6J mice were randomly di- vided into IBS-D group and control group , with 64 mice in each group . Wire Restraint Stress method (WRS) was used to construct an animal model of IBS-D . Enzyme-linked immunosorbent assay was used to detect serum and co- lonic mucosal chemerin levels in mice . Hematoxylin-eosin (HE) staining was used to observe colonic mucosal in- flammation . Geboes value was used to evaluate the severity of colonic mucosal inflammation . Results: In the IBS- D group , the concentration of serum chemerin increased and reached the peak in the first week of the experiment ( t = 6. 538 , P < 0. 001) , and the concentration of colonic mucosa chemerin increased and reached the peak in the fourth week of the experiment ( t = 8 . 104 , P < 0. 001) ; in the first week of experiment , the colonic mucosa of IBS- D mice showed inflammatory reaction , which was the most significant in the fifth week (P < 0. 05) . Geboes score was ( 1 . 75 ±0. 50) vs (0. 55 ±0. 52) . Conclusion There is a temporal sequence between the elevation of serum and intestinal mucosal chemerin levels and the severity of intestinal mucosal inflammation , and it is hypothesized that the elevated serum and intestinal mucosal chemerin levels correlate with the onset and progression of intestinal mucosal inflammation .

Objective:To investigate the characteristics of clinical manifestations and parameters of 24 hour multichannel intraluminal impedance and pH monitoring (24 h MII-pH) in patients with low mean nocturnal baseline impedance (MNBI) of proximal esophagus.Methods:From November 4, 2014 to February 18, 2024, 308 patients who underwent 24 h MII-pH at Peking University First Hospital due to typical gastroesophageal reflux disease symptoms and(or) extra-esophageal symptoms were retrospectively enrolled. MNBI at 17 or 15 cm above the lower esophageal sphincter (LES) < 2 292 Ω was defined as low proximal esophageal impedance (LPEI), both MNBI at 17 and 15 cm above the LES ≥ 2 292 Ω was defined as normal proximal esophageal impedance (NPEI). The 24 h MII-pH parameters were compared between patients with LPEI and patients with NPEI, as well as the incidence of extra-esophageal symptoms. And the 24 h MII-pH parameters were compared between patients with and without extra-esophageal symptoms. Independent sample t-test, Mann-Whitney U test and chi-square test were used for statistical analysis. Results:Among the 308 patients, 71 patients with LPEI, 236 patients with NPEI, and 1 patient was excluded due to missing the 24 h MII-pH data; and there were 215 patients with extra-esophageal symptoms and 93 without extra-esophageal symptoms. The proportion of extra-esophageal symptoms in the LPEI patients was higher than that in the NPEI patients(81.7% (58/71) vs. 66.1% (156/236)), the times of postprandial total reflux, postprandial acid reflux detected by impedance, proximal total reflux, and proximal acid reflux in the LPEI patients were more than those in the NPEI patients (22.5 (22.8) vs. 17.0 (19.0), 10.5 (13.3) vs. 7.0 (13.0), 9.0 (12.0) vs. 5.0 (11.0), 5.0 (10.0) vs. 3.0 (7.0)), and the differences were statistically significant( χ2=6.28, Z=-1.99, -2.06, -2.26 and -2.44; all P<0.05). The times of weak acidic reflux at supine position, proximal total reflux, proximal acid reflux, and proximal non-acid reflux of the patients with extra-esophageal symptoms were more than those in patients without extra-esophageal symptoms (2.0(5.0) vs. 1.0(4.0), 6.0(13.0) vs. 4.0(10.0), 4.0(10.0) vs. 3.0(7.0), 2.0(4.0) vs. 1.0(3.0)), the MNBI at 15 cm above the LES in patients with extra-esophageal symptoms was lower than that in patients without extra-esophageal symptoms ((3 222.4±1 018.7) Ω vs. (3 512.3±1 032.1) Ω), and the differences were statistically significant ( Z=-2.32, -2.25, -2.00 and -2.13, t=-2.28; all P<0.05). Conclusions:LPEI patients have higher proportion of extra-esophageal symptoms, more times of proximal and postprandial acidic reflux. The proximal esophageal impedance and proximal reflux parameters should be emphasized in the diagnosis and treatment of patients with extra-esophageal symptoms.

Objective:To investigate the characteristics of clinical manifestations and parameters of 24 hour multichannel intraluminal impedance and pH monitoring (24 h MII-pH) in patients with low mean nocturnal baseline impedance (MNBI) of proximal esophagus.Methods:From November 4, 2014 to February 18, 2024, 308 patients who underwent 24 h MII-pH at Peking University First Hospital due to typical gastroesophageal reflux disease symptoms and(or) extra-esophageal symptoms were retrospectively enrolled. MNBI at 17 or 15 cm above the lower esophageal sphincter (LES) < 2 292 Ω was defined as low proximal esophageal impedance (LPEI), both MNBI at 17 and 15 cm above the LES ≥ 2 292 Ω was defined as normal proximal esophageal impedance (NPEI). The 24 h MII-pH parameters were compared between patients with LPEI and patients with NPEI, as well as the incidence of extra-esophageal symptoms. And the 24 h MII-pH parameters were compared between patients with and without extra-esophageal symptoms. Independent sample t-test, Mann-Whitney U test and chi-square test were used for statistical analysis. Results:Among the 308 patients, 71 patients with LPEI, 236 patients with NPEI, and 1 patient was excluded due to missing the 24 h MII-pH data; and there were 215 patients with extra-esophageal symptoms and 93 without extra-esophageal symptoms. The proportion of extra-esophageal symptoms in the LPEI patients was higher than that in the NPEI patients(81.7% (58/71) vs. 66.1% (156/236)), the times of postprandial total reflux, postprandial acid reflux detected by impedance, proximal total reflux, and proximal acid reflux in the LPEI patients were more than those in the NPEI patients (22.5 (22.8) vs. 17.0 (19.0), 10.5 (13.3) vs. 7.0 (13.0), 9.0 (12.0) vs. 5.0 (11.0), 5.0 (10.0) vs. 3.0 (7.0)), and the differences were statistically significant( χ2=6.28, Z=-1.99, -2.06, -2.26 and -2.44; all P<0.05). The times of weak acidic reflux at supine position, proximal total reflux, proximal acid reflux, and proximal non-acid reflux of the patients with extra-esophageal symptoms were more than those in patients without extra-esophageal symptoms (2.0(5.0) vs. 1.0(4.0), 6.0(13.0) vs. 4.0(10.0), 4.0(10.0) vs. 3.0(7.0), 2.0(4.0) vs. 1.0(3.0)), the MNBI at 15 cm above the LES in patients with extra-esophageal symptoms was lower than that in patients without extra-esophageal symptoms ((3 222.4±1 018.7) Ω vs. (3 512.3±1 032.1) Ω), and the differences were statistically significant ( Z=-2.32, -2.25, -2.00 and -2.13, t=-2.28; all P<0.05). Conclusions:LPEI patients have higher proportion of extra-esophageal symptoms, more times of proximal and postprandial acidic reflux. The proximal esophageal impedance and proximal reflux parameters should be emphasized in the diagnosis and treatment of patients with extra-esophageal symptoms.

Objective To investigate whether a stable and reliable hyperuricemia model can be established in mice with an ICR background via a triple-modeling method(combined potassium oxazine,hypoxanthine,and 30％yeast paste),and to evaluate the effect of the positive drug febuxostat on the model.Methods A hyperuricemia model of ICR mice was established using a single drug or double-or triple-drug combinations.Serum uric acid and creatinine concentrations,xanthine oxidase(XOD)and urate oxidase(UOX)activity,and uric acid transporter(URAT)1,glucose transporter(Glut)9,anion transporter(OAT)1,and ATP-binding box subfamily G member(ABCG)2 mRNA levels were detected to evaluate whether the hyperuricemia model was formed successfully.Results The serum uric acid levels of ICR mice were not significantly changed by potassium oxazine alone,as they showed an increase but were not significantly different to those of the 30％yeast paste diet or hypoxanthine combined groups.Serum uric acid levels in the triple administration group were significantly increased at 7 days(P＜0.01),while XOD enzyme activity had increased(P＜0.01)and UOX enzyme activity decreased(P＜0.001)at the same timepoint.There were increased expression levels of URAT1 and Glut9(P＜0.05,P＜0.001),and decreased expression levels of OAT1 and ABCG2(P＜0.001).During dynamic monitoring,the blood uric acid levels of triple administration-induced ICR mice peaked at 7 days.In addition,triple administration-induced hyperuricemia in ICR mice was sensitive to the positive drug febuxostat,which caused a significant decrease in blood uric acid levels(P＜0.001).Conclusions A hyperuricemia model in ICR mice can be stably induced by triple administration for 7 days.

ObjectiveTo explore the influence of electroacupuncture combined with point bloodletting and cupping for facial nerve function recovery in acute stage of idiopathic facial palsy （IFP）. MethodsEighty patients with IFP in the acute stage were randomly divided into 40 cases each in the treatment group and the control group. In the control group， oral prednisone acetate tablets were administered during the acute stage when the disease duration was less than 10 days； and electroacupuncture and flash cupping were provided during the recovery stage when the disease duration was more than 10 days， five times a week. For treatment group in acute stage， the stellate ganglion， vagus nerve stimulation point in the auricular cavity， Yifeng （TE 17） and Tinghui （GB 2） were needled on the affected side on the basis of the treatment of control group， with Yifeng and Tinghui connecting to electroacupuncture apparatus， once a day； point bloodletting and then cupping in Yifeng 2 times a week； in recovery stage， the treatment was the same as that of the control group. Both groups were treated until the 45th day from onset. The primary outcome was the Toronto facial grading system （SFGS）， and the secondary outcomes included house-brackmann （H-B） grade， facial disability index （FDI） score， and number of H-B grade-Ⅰ cases. Adverse events were recorded in both groups. ResultsThe SFGS scores of the patients in both groups were higher on the 10th， 30th and 45th days after onset of disease compared with those before the treatment （P＜0.05）； the H-B grade was lower on the 30th and 45th days after the onset of the disease compared with those before the treatment （P＜0.05）； and the facial disability index physical function （FDIP） and facial disability index social function （FDIS） scores were higher on the 30th and 45th days after onset of disease （P＜0.05）. SFGS scores of patients in the treatment group were significantly higher than those of the control group on the 30th and 45th days after onset （P＜0.05）； H-B grade was significantly lower than that of the control group on the 30th and 45th days after onset （P＜0.05）； and FDIP scores on the 45th day after onset， and FDIS scores on the 30th and 45th days after onset were significantly higher than those of the control group （P＜0.05）. At the end of treatment， 77.50% （31 cases） achieved H-B grade-Ⅰ in the treatment group， which was more than 55.00% （22 cases） in the control group （P＜0.05）. No adverse events occurred in either group. ConclusionElectroacupuncture combined with point bloodletting and cupping for IFP in acute stage can improve the recovery degree of facial nerve function， improve effectiveness， and show a high degree of safety.

Diabetic kidney disease(DKD)is one of the major complications of diabetes mellitus(DM),which significantly affects the survival and quality of life of DM patients.Currently,existing first-line treatment approaches for DKD are ineffective in effectively preventing the occurrence and progression of DKD.Traditional Chinese medicine(TCM)has the advantages of"ultiple pathways,multiple targets,and multiple mechanisms"in treating DKD,and has a broad prospect in the treatment of DKD.Aquaporin-2(AQP2)is a membrane channel protein widely expressed in the kidneys,and its physiological function is highly similar to the function of kidney filtration and reabsorption.Studies have found that various effective components and related formulae of Chinese medicine can improve symptoms in DKD patients by inhibiting the abnormal expression of AQP2.This article provides a review on the role of AQP2 in DKD and the research progress of TCM intervention,aiming to provide insights and references for the development of drugs related to the prevention and treatment of DKD.

Diabetic kidney disease(DKD)is one of the major complications of diabetes mellitus(DM),which significantly affects the survival and quality of life of DM patients.Currently,existing first-line treatment approaches for DKD are ineffective in effectively preventing the occurrence and progression of DKD.Traditional Chinese medicine(TCM)has the advantages of"ultiple pathways,multiple targets,and multiple mechanisms"in treating DKD,and has a broad prospect in the treatment of DKD.Aquaporin-2(AQP2)is a membrane channel protein widely expressed in the kidneys,and its physiological function is highly similar to the function of kidney filtration and reabsorption.Studies have found that various effective components and related formulae of Chinese medicine can improve symptoms in DKD patients by inhibiting the abnormal expression of AQP2.This article provides a review on the role of AQP2 in DKD and the research progress of TCM intervention,aiming to provide insights and references for the development of drugs related to the prevention and treatment of DKD.

OBJECTIVES: Hereditary spherocytosis (HS) is the most common hereditary defect of the red cell membrane, mainly characterized by anemia, jaundice, and splenomegaly. Due to the atypical clinical manifestations and negative family history of some patients, as well as the low sensitivity and specificity of traditional laboratory examinations, it is easy for it to escape diagnosis or be misdiagnosed. At present, it has been confirmed that the mutation of ANK1, SPTB, SPTA1, SLC4A1 and EPB42 genes can cause the deletion of their corresponding coding proteins, and thus lead to the defect of erythrocyte membrane. This study aims to analyze the feasibility and clinical application value of HS gene diagnosis. METHODS: Data of 26 patients from Hunan, China with HS admitted to the Department of Hematology, Second Xiangya Hospital of Central South University from January 2018 to September 2021 were retrospectively collected, and their clinical manifestations and results of laboratory examinations were analyzed. Next-generation sequencing (NGS) combined with Sanger sequencing were applied. The mutation of HS pathogenic gene and the variation of uridine diphosphate-glucuronosyl transferase 1 family polypeptide A1 (UGT1A1), a key enzyme in the regulation of bilirubin metabolism, were detected. The results of pathogenic gene variations were interpreted pathogenic gene variations in accordance with the Standards and guidelines for the interpretation of sequence variants published by the American College of Medical Genetics and Genomics (ACMG). The clinical characteristics of patients with different gene variants were analyzed, and the clinical diagnosis and genetic diagnosis were compared. RESULTS: Among the 26 patients with HS, there were 23 cases of anemia, 25 cases of jaundice, 24 cases of splenomegaly, and 14 cases of cholelithiasis. There were 16 cases with family history and 10 cases without family history. The results of HS mutation test were positive in 25 cases and negative in 1 case. A total of 18 heterozygous mutations of HS pathogenic genes were detected in 19 families, among which 14 were pathogenic, 1 was likely pathogenic and 3 were of unknown significance. SPTB mutations (12) and ANK1 mutations (4) were the most common. The main variation types were nonsense mutation (9). There were no significant differences in peripheral blood cell parameters and hemolysis indicators between the SPTB mutant group and the ANK1 mutant group (all P>0.05). The rate of splenectomy in ANK1 mutation group was higher than that in SPTB mutation group, and the difference was statistically significant (χ²=6.970, P=0.014). There were no significant differences in peripheral blood cell parameters and hemolysis indicators among different mutation types (nonsense mutation, frameshift mutation, splice site mutation and missense mutation) (all P>0.05). Among the 18 clinically confirmedpatients, there were 17 cases whose diagnosis is consistent with the genetic diagnosis. Eight patients were clinically suspected, and all of them were confirmed by detection of HS gene mutation. Twenty-four patients with HS underwent UGT1A1 mutation detection, among which 5 patients carried UGT1A1 mutation resulting in a decrease in enzyme activity, and 19 patients had normal enzyme activity. The level of total bilirubin (TBIL) in the group with reduced enzyme activity was higher than that in the group with normal enzyme activity, and the difference was statistically significant (U=22, P=0.038). CONCLUSIONS Most patients with HS have anemia, jaundice and splenomegaly, often accompanied by cholelithiasis. SPTB and ANK1 mutations are the most common mutations in HS pathogenic genes among patients in Hunan, China, and there was no significant correlation between genotype and clinical phenotype. Genetic diagnosis is highly consistent with clinical diagnosis. The decrease of UGT1A1 enzyme activity can lead to the aggravation of jaundice in HS patients. Clinical combined gene diagnosis is beneficial for the rapid and precision diagnosis of HS. The detection of UGT1A1 enzyme activity related gene variation plays an important role in evaluation of HS jaundice.
Humans ; Codon, Nonsense ; Hemolysis ; Retrospective Studies ; Splenomegaly ; Bilirubin

Objective:To evaluate the efficacy and safety of mitoxantrone hydrochloride liposome injection in the treatment of peripheral T-cell lymphoma (PTCL) in a real-world setting.Methods:This was a real-world ambispective cohort study (MOMENT study) (Chinese clinical trial registry number: ChiCTR2200062067). Clinical data were collected from 198 patients who received mitoxantrone hydrochloride liposome injection as monotherapy or combination therapy at 37 hospitals from January 2022 to January 2023, including 166 patients in the retrospective cohort and 32 patients in the prospective cohort; 10 patients in the treatment-na?ve group and 188 patients in the relapsed/refractory group. Clinical characteristics, efficacy and adverse events were summarized, and the overall survival (OS) and progression-free survival (PFS) were analyzed.Results:All 198 patients were treated with mitoxantrone hydrochloride liposome injection for a median of 3 cycles (range 1-7 cycles); 28 cases were treated with mitoxantrone hydrochloride liposome injection as monotherapy, and 170 cases were treated with the combination regimen. Among 188 relapsed/refractory patients, 45 cases (23.9%) were in complete remission (CR), 82 cases (43.6%) were in partial remission (PR), and 28 cases (14.9%) were in disease stabilization (SD), and 33 cases (17.6%) were in disease progression (PD), with an objective remission rate (ORR) of 67.6% (127/188). Among 10 treatment-na?ve patients, 4 cases (40.0%) were in CR, 5 cases (50.0%) were in PR, and 1 case (10.0%) was in PD, with an ORR of 90.0% (9/10). The median follow-up time was 2.9 months (95% CI 2.4-3.7 months), and the median PFS and OS of patients in relapsed/refractory and treatment-na?ve groups were not reached. In relapsed/refractory patients, the difference in ORR between patients with different number of treatment lines of mitoxantrone hydrochloride liposome injection [ORR of the second-line, the third-line and ≥the forth-line treatment was 74.4% (67/90), 73.9% (34/46) and 50.0% (26/52)] was statistically significant ( P = 0.008). Of the 198 PTCL patients, 182 cases (91.9%) experienced at least 1 time of treatment-related adverse events, and the incidence rate of ≥grade 3 adverse events was 66.7% (132/198), which was mainly characterized by hematologic adverse events. The ≥ grade 3 hematologic adverse events mainly included decreased lymphocyte count, decreased neutrophil count, decreased white blood cell count, and anemia; non-hematologic adverse events were mostly grade 1-2, mainly including pigmentation disorders and upper respiratory tract infection. Conclusions:The use of mitoxantrone hydrochloride liposome injection-containing regimen in the treatment of PTCL has definite efficacy and is well tolerated, and it is a new therapeutic option for PTCL patients.

Abstract As a new type of pollutant, microplastics have attracted extensive attention. Children in a critical stage of growth and development are vulnerable to microplastics. Summarzing the relevant laws and regulations and the source of microplastics, the paper demonstrates the ways of microplastics entering human body, some toxic effects of microplastics found in recent experimental studies and their potential hazards to children s health are introduced in detail.