Humans ; Gastrointestinal Microbiome ; Constipation/therapy* ; Probiotics/therapeutic use* ; Patients

Objective We aimed to observe the differences in the effects of different acupuncture technique on the endometrium of mice with simple endometrial hyperplasia model and to explore the potential mechanisms. Methods According to the random number tables,32 female C57BL/6J mice were divided into a blank control group,a model group,a quick needle group and a retaining needle group,with 8 mice in each group. A mouse model of simple endometrial hyperplasia was established using bilateral ovariectomy combined with estrogen loading. In the quick needle group,mice were punctured at the bilateral for "Yinbai"(SP1) points and withdrawn immediately,with the treatmeat performed once every other day for a total of 12 times. In the retaining needle group,mice were punctured at the bilateral "Yinbai"(SP1) points and the needles were retained for 15 min each time,with the treatment also performed once every other day for a total of 12 times. After the intervention,samples were collected. HE staining was used to observe morphological changes in the mouse uterine tissue;ELISA was used to detect serum estradiol level;flow cytometry was used to detect the ratio of M1 and M2 macrophages(M1/M2) and immunohistochemical method was used to measure the expression of CD86 and CD206 in uterine tissue;and Western blotting was used to detect the expression of interleukin-13 (IL-13) and interferon-γ(IFN-γ) in uterine tissue. Results The endometrium of mice in the model group showed simple hyperplasia. Compared with the blank control group,the endometrium of the model group was thickened (P<0.01);the level of estradiol in the serum was increased (P<0.01);M1/M2 in uterine tissues was decreased (P<0.01),the expression of CD86 was decreased (P<0.01),and the positive expression of CD206 was increased (P<0.01);and the level of IFN-γ protein expression in uterine tissues was decreased (P<0.01),and the expression of IL-13 protein was increased (P<0.01). Compared with the model group,the endometrial thicknesses of the quick needle group and the retaining needle group were reduced (P<0.05),the levels of estradiol in serum were reduced (P<0.05),M1/M2 in uterine tissues increased (P<0.01),and the reduction of CD206 positive expression,and IL-13 protein expression reduced (P<0.01);the level of CD86 positive expression,IFN-γ protein expression increased (P<0.01). Compared with the quick needle group,IL-13 protein expression increased in the retaining needle group (P<0.01).Conclusion Both quick needle and retaining needle may be through the regulation of the expression of IFN-γ and IL-13,thus prompting the polarization of macrophages from M2 to M1 type,inhibiting the pro-cell proliferative ability and tissue repair ability of M2 type macrophages,thus reducing the degree of endometrial hyperplasia,and the quick needle group was superior to the retaining needle group in regulating the expression of IL-13.

Objective: To examine the causal relationship between body mass index (BMI) and 25 types of autoimmune diseases (ADs) using Mendelian randomization (MR) study method. Methods: The genome-wide association study (GWAS) data for BMI and 25 types of ADs were obtained from IEU OPEN GWAS database. Single nucleotide polymorphisms (SNPs) related to BMI were used as instrumental variables, 25 types of ADs were used as study outcomes, and MR analysis was performed using inverse variance weighted (IVW) method. Heterogeneity was evaluated using Cochran's Q test, horizontal pleiotropy was tested using MR-Egger regression and MR-PRESSO, and results robustness was verified with leave-one-out method. Results: Cochran's Q test showed heterogeneity of MR analysis results (P<0.05), and a random effect model was employed. The results of MR analysis showed that elevated BMI increased the incidence risks of type 1 diabetes mellitus (OR=1.519, 95%CI: 1.281-1.801), IgA nephropathy (OR=1.227, 95%CI: 1.134-1.327), adult Still disease (OR=1.002, 95%CI: 1.001-1.003), multiple sclerosis (OR=1.303, 95%CI: 1.115-1.523), narcolepsy (OR=1.029, 95%CI: 1.017-1.040), Hashimoto thyroiditis (OR=1.561, 95%CI: 1.391-1.751), autoimmune hepatitis (OR=1.481, 95%CI: 1.076-2.038), rheumatoid arthritis (OR=1.209, 95%CI: 1.054-1.386), psoriasis vulgaris (OR=1.719, 95%CI: 1.427-2.070) and pernicious anemia (OR=1.001, 95%CI: 1.000-1.002). No causal relationship was found with other ADs (all P>0.05). MR-Egger regression identified no horizontal pleiotropy of instrumental variables (all P>0.05), while MR-PRESSO test identified partial horizontal pleiotropy (all P<0.05), which remained consistent with the original results after adjustment (P>0.05). Leave-one-out analysis showed results robustness. Conclusion There are causal relationship among BMI and type 1 diabetes mellitus, IgA nephropathy, adult Still disease, multiple sclerosis, narcolepsy, Hashimoto thyroiditis, autoimmune hepatitis, rheumatoid arthritis, psoriasis vulgaris and pernicious anemia.

Objective To investigate the effect of body mass index(BMI)on the clinicopathological characteristics of patients with idiopathic membranous nephropathy(IMN).Methods A total of 261 patients with IMN were divided into the normal group(66 cases),the overweight group(105 cases)and the obese group(90 cases)according to BMI.Clinical and renal pathological data of patients were compared between the three groups.The correlation between BMI and clinicopathological indexes was analyzed by Pearson or Spearman's correlation.The influencing factors of estimated glomerular filtration rate(eGFR)were analyzed by multiple linear regression,and the influencing factors of interstitial fibrosis(IF),tubular atrophy(TA),glomerulosclerosis(GS)and mesangial cell proliferation(MCP)were analyzed by binary Logistic regression.Results Compared with the normal group,the prevalence of diabetes mellitus,triglycerides(TG)and low-density lipoprotein cholesterol(LDL-C)were elevated in the overweight group.The prevalence of hypertension,hemoglobin(HGB),uric acid(UA),LDL-C,TG,24-h urinary protein(UTP)and serum complement 3(C3)were elevated,and high-density lipoprotein cholesterol(HDL-C)was decreased in the obese group(P＜0.05).The prevalence of hypertension,UA,TG and serum C3 were elevated in the obese group compared to the overweight group(P＜0.05).The glomerular basement membrane(GBM)thickness was higher in the obese group and the overweight group than that in the normal group,and the proportion of GS and IF was higher in the obese group than that in the normal group(P＜0.05).BMI was positively correlated with hypertension,TG,LDL-C,serum C3,UTP,GS,IF,MCP and deposition in the mesangial region of C3,and negatively correlated with HDL-C(P＜0.05).Multiple linear regression analysis showed that age,blood urea nitrogen(BUN),anti-phospholipase A2 receptor antibody(anti-PLA2R),UTP and TA were independent risk factors of eGFR.Binary Logistic regression analysis showed that elevated BMI,age,UTP and serum creatinine(Scr)were independent risk factors for IF.Age,Scr and elevated UA were independent risk factors for TA.Elevated BMI and decreased eGFR were independent risk factors for GS.Elevated BMI was an independent risk factor for MCP.There was no significant difference in the treatment protocol of IMN patients between the three groups.Conclusion Obesity can exacerbate multiple clinical and pathological outcomes in IMN patients.

Objective To explore the mediating role of depression between uremic toxins and cognitive function in end-stage renal disease(ESRD)patients,so as to provide a basis for early clinical intervention.Methods A retrospective study involved 49 predialysis ESRD patients diagnosed in the Nephrology Department of The First Affiliated Hospital of Xi'an Jiaotong University between August 2018 and October 2021,along with 50 healthy controls(HC).General information of the two groups was collected.Montreal Cognitive Assessment(MoCA),Auditory Verbal Learning Test-Huashan Version(AVLT-H),Trail Making Test A(TMT-A),Beck Depression Inventory(BDI),and Beck Anxiety Inventory(BAI)were used to collect data on cognitive function,anxiety,and depression in both groups.Serological indicators in the ESRD group were used to clarify the impact of uremic toxins on cognitive function.PROCESS v3.4.1 was applied to explore the relationship between uremic toxins,depression,and cognitive function,as well as the mediating effect of depression.Results Significant differences were found between the ESRD group and the HC group in MoCA total score(P＜0.001),AVLT-H(word learning;short-term delay;long-term delay,P＜0.001;word recognition,P=0.001),TMT-A(P＜0.001),BDI(P＜0.001),and BAI(P=0.009).Cystatin C was a negative influencing factor for short-term delay in AVLT-H(B＝-0.834,P=0.019),while BDI was a negative influencing factor for long-term delay in AVLT-H(B=-0.102,P=0.002),word recognition in AVLT-H(B=-0.071,P＜0.001),and MoCA total score(B=-0.135,P=0.002).BDI partially mediated the effect of cystatin C on short-term delay in AVLT-H(total effect,c=-0.3346;direct effect,c'=-0.223 5;mediating effect,a×b=-0.111 0;and mediating effect proportion,33.2％)and long-term delay in AVLT-H(total effect,c=-0.318 7;direct effect,c'=-0.218 8;mediating effect,a×b=-0.099 9;and mediating effect proportion,31.3％).Conclusion ESRD patients experience cognitive decline as well as anxiety and depression.Cystatin C and depression are both negative influencing factors for cognitive decline in ESRD patients.Cystatin C indirectly affects cognitive function in ESRD patients through depression.

Objective:To investigate the pregnancy outcomes of different treatment methods for triplet pregnancies with different chorionicities.Methods:A retrospective study was conducted on 97 triplet pregnancies who visited and delivered at the Department of Obstetrics, the Third Affiliated Hospital of Zhengzhou University, from January 1, 2017, to November 30, 2023. The pregnancies were categorized based on chorionicity into monochorionic triamniotic (MCTA) ( n=24), dichorionic triamniotic (DCTA) ( n=33), and trichorionic triamniotic (TCTA) ( n=40). They were further divided into expectant management group ( n=46), reduction to twins group ( n=40), and reduction to singleton group ( n=11) based on the treatment method. Pregnancy outcomes were compared among the groups. Statistical analysis were performed using t-test, corrected t-test, one-way analysis of variance and LSD test, Kruskal-Wallis test and Mann-Whitney U test, Chi-square test, continuity correction Chi-square test, Fisher's exact test, and Bonferroni correction. Results:(1) Comparison of pregnancy outcomes with different treatment methods for the same chorionicity: In MCTA, there were no statistically significant differences in gestational age at delivery, live birth rate before 37 weeks, live birth rate before 32 weeks, neonatal birth weight, and incidence of severe neonatal complications between the expectant management group and the reduction to monochorionic diamniotic (MCDA) group (all P>0.05). In DCTA, compared to the reduction to singleton group, the expectant management group had lower gestational age at delivery [(31.8±2.7) vs. (37.9±1.3) weeks, U=－3.66] and neonatal birth weight [(1 604.3±422.6) vs. (2 997.1±598.9) g, U=－3.84] (both P<0.05), but higher live birth rate before 37 weeks (9/10 vs.1/8, Bonferroni correction, P<0.017). The expectant management group showed a trend towards higher rates of pregnancy complications (5/10 vs. 2/15 and 0/8) and severe neonatal complications [37.0% (10/27) vs. 10.7% (3/28) and 0/7] compared to the groups reduced to dichorionic diamniotic (DCDA) twins and singletons. However, the differences between the groups were not statistically significant (all P>0.017). In TCTA, compared to the expectant management group, the reduction to DCDA group had a higher gestational age at delivery [(37.1±0.9) vs. (34.1±2.7) weeks, t'=－4.36], and increased neonatal birth weight [(2 647.5±377.8) vs. (1 902.5±459.9) g, t'=－6.98] (both P<0.05). The incidence of maternal pregnancy complications [3/15 vs. 54.2% (13/24)] and live birth rate before 37 weeks [3/15 vs. 66.7% (16/24)] were lower (Fisher's exact test, both P<0.05). (2) Comparison of pregnancy outcomes with different chorionicities for the same treatment method: In the expectant management group, the DCTA group had the lower neonatal birth weight compared to the MCTA and TCTA groups [(1 604.3±422.6) vs. (1 948.3±573.4) and (1 902.5±459.9) g, LSD test, both P<0.05]. In the fetal reduction group, the TCTA group had higher neonatal birth weight compared to the MCTA and DCTA groups [(2 657.6±373.3) vs. (2 000.8±443.3) and (2 078.8±799.9) g, U=－2.91 and U=－3.12] (both P<0.05). Conclusions:The appropriate treatment method for triplet pregnancies should be selected based on chorionicity. Expectant management is recommended for MCTA, fetal reduction is suggested for DCTA to improve pregnancy outcomes. For TCTA, the pregnant woman should be informed of the risks of preterm birth associated with expectant management, who should then decide whether to undergo fetal reduction.

Methcathinone (MCAT) belongs to the designer drugs called synthetic cathinones, which are abused worldwide for recreational purposes. It has strong stimulant effects, including enhanced euphoria, sensation, alertness, and empathy. However, little is known about how MCAT modulates neuronal activity in vivo. Here, we evaluated the effect of MCAT on neuronal activity with a series of functional approaches. C-Fos immunostaining showed that MCAT increased the number of activated neurons by 6-fold, especially in sensory and motor cortices, striatum, and midbrain motor nuclei. In vivo single-unit recording and two-photon Ca²⁺ imaging revealed that a large proportion of neurons increased spiking activity upon MCAT administration. Notably, MCAT induced a strong de-correlation of population activity and increased trial-to-trial reliability, specifically during a natural movie stimulus. It improved the information-processing efficiency by enhancing the single-neuron coding capacity, suggesting a cortical network mechanism of the enhanced perception produced by psychoactive stimulants.
Mice ; Animals ; Reproducibility of Results ; Neurons ; Sensation ; Perception

Rituximab is currently used as a first-line therapy for phospholipase A 2 receptor-associated membranous nephropathy due to its good efficacy and safety. Although the remission rate after rituximab treatment is more than 60%, nearly 40% patients still do not respond to treatment. We used obinutuzumab to treat 3 cases of rituximab resistant PLA 2R-associated membranous nephropathy. After the first dose of 1 000 mg with or without additional dose, the amount of anti-PLA 2R antibody and urinary protein decreased significantly and the adverse reactions were mild. The results show that obinutuzumab has a certain therapeutic effect on rituximab resistant PLA 2R-associated membranous nephropathy, but the time of follow-up observation is short and can only be used as individual cases, which needs to be confirmed by a large sample and high-quality prospective cohort study.

Objective:To investigate the effects of personalized intermittent energy restriction (IER) diet on sleep related gut microbiome in obese patients.Methods:In this single-arm clinical trial, a total of 35 obese patients who visited Henan Provincial People′s Hospital from April to November 2018 were recruited as research subjects. They underwent a strict 32-day IER diet intervention, divided into 4 stages of 8 days each. Nutritional recipes were formulated and nutritious meals were provided to each obese patient with timed meals, including 55% carbohydrates, 15% protein, and 30% fat per meal. In stages 1, 2, 3, and 4, patients were provided with 2/3, 1/2, 1/3, and 1/4 of their previous calorie intake every other day, respectively, with meals at 8:00 and 16:00. During the remaining time, patients were allowed unrestricted eating at home. Physiological indicators (weight, body mass index, body fat percentage, waist circumference, hip circumference, fasting blood glucose, glycosylated hemoglobin, blood pressure, triglycerides, total cholesterol, high-density lipoprotein, low-density lipoprotein and Pittsburgh Sleep Quality Index (PSQI) scores were observed before and after the intervention. Gut microbiota changes were analyzed using metagenomic sequencing technology, and Spearman′s correlation analysis was used to assess the correlation between significantly different bacterial species and PSQI scores.Results:After the intervention, the body weight, body mass index, and PSQI scores of obese patients were all significantly lower than before intervention [(89.92±14.98) vs (97.53±15.67) kg, (31.94±3.95) vs (34.64±4.05) kg/m 2, (3.43±1.16) vs (5.42±2.27)], the abundance of gut microbiota was significantly higher after the intervention (all P<0.05). There were 45 significantly different bacterial species before and after the intervention, of which 6 bacterial species ( Enterobacter cloacae, Escherichia coli, Odoribacter splanchnicus, Oribacterium sinus, Streptococcus gordonii, and Streptococcus parasanguinis) showed significantly positive correlations with PSQI scores ( r=0.476, 0.475, 0.369, 0.391, 0.401, 0.423) (all P<0.05), and they were mainly enriched in the glutamate and tryptophan synthesis pathways. Conclusions:The personalized IER diet intervention can improve the sleep of obese patients while reducing weight, possibly mediated by changes in gut microbiota through the glutamate and tryptophan pathways.

Objective:To explore the predictive value of transvaginal ultrasound measurement of cervical length (CL) in the first and second trimester on spontaneous preterm birth in singleton pregnant women.Methods:This study retrospectively recruited 2 254 singleton pregnancies without severe comorbidities at Peking University First Hospital from January 2019 to June 2019. CL was measured for all subjects using transvaginal ultrasound in the first (11-13 +6 weeks) and second trimester (21-23 +6 weeks). Differences in CL between women with preterm (preterm group) and full-term delivery (full-term group) as well as the CL during the first and second trimester were compared. The independent risk factors for preterm birth and the predictive value of CL in the first and second trimester for spontaneous preterm birth were also explored. Fisher's exact test, t-test, χ2 test, and logistic regression analysis, etc, were adopted for statistical analysis. Results:(1) For the 2 254 subjects, CL measured in the first trimester and second trimester were (36.1±4.2) mm (22.4-52.6 mm) and (36.9±5.3) mm (2.9-59.7 mm), respectively. The incidence of short cervix in the first trimester and second trimester were 0.31% (7/2 254) and 1.46% (33/2 254), respectively. When CL was ≤25.0 mm ( OR=43.92, 95% CI:6.83-282.49) or >25.0-≤30.3 mm ( OR=6.59, 95% CI:1.97-22.0) in the first trimester, the risk of short cervix increased in the second trimester (both P<0.05). (2) The total incidence of preterm delivery was 3.06% (69/2 254). CL and the incidence of short cervix did not differ significantly in the first trimester between the preterm and full-term group [(35.2±4.5) and (36.1±4.1) mm, t=－1.78, P=0.076; 1.5% (1/69) and 0.3% (6/2 185), χ 2=2.98, P=0.084]. Compared with the full-term group, CL was shorter and the incidence of short cervix was higher in the second trimester in the preterm group [(33.6±6.7) vs (37.0±5.2) mm, t=－5.12;8.7% (6/69) vs 1.2% (27/2 185), χ 2=25.80, P<0.001]. (3) Multivariate regression analysis showed that age ≥35 years ( OR=2.05, 95% CI:1.22-3.46), history of spontaneous preterm birth ( OR=25.25, 95% CI:5.01-127.28), conception assisted by reproductive technology ( OR=10.39, 95% CI:2.39-50.33), and short cervix during the second trimester were independent risk factors for premature delivery. (4) There was no significant difference in the risk of preterm delivery when comparing to those with CL≤25.0 mm, >25.0-≤30.3 mm, >30.3-≤33.0 mm, >33.0-≤35.7 mm, >35.7-≤38.7 mm women with CL>38.7 mm during the first trimester (all P>0.05). The risk of premature delivery was relatively increased for those with CL≤25.0 mm,>25.0-≤29.5 mm, >29.5-≤33.6 mm, >33.6~≤36.8 mm, >36.8~≤40.1 mm during the second trimester compared to those with CL>40.1 mm [ OR (95% CI):17.64 (4.99-62.32), 6.89 (2.11-22.55), 3.58 (1.34-9.59), 4.04 (1.58-10.32), 3.34 (1.28-8.67), respectively , all P<0.05]. (5) When CL≤25.0 mm and ≤29.5 mm in the second trimester were used as the cut-off value, the prediction of preterm delivery was with a sensitivity of 8.70% and 17.39%, specificity of 98.80% and 95.29%, positive predictive value of 18.20% and 10.43%, negative predictive value of 97.16% and 97.34%, and the accuracy rate of 96.01% and 92.90%, respectively. Conclusions:There were no significant differences in CL and the incidence of short cervix during the first trimester among women with preterm or full-term delivery. CL in the first trimester is not an independent risk factor for preterm birth, but the risk of short cervix in the second trimester is increased when CL≤30.3 mm in the first trimester. The shorter the cervix during the second trimester, the greater the risk of preterm birth.