Objective: To explore the clinical safety and efficacy of a single-position robot-assisted radical nephroureterectomy (RRUN) in the treatment of upper tract urothelial carcinoma (UTUC). Methods: A retrospective study was conducted on 136 UTUC patients who underwent RRUN (n=35) and laparoscopic radical nephroureterectomy (LRUN，n=101) in our hospital during Dec.2020 and Aug.2023.The perioperative and safety indicators of the two groups were compared.The intravesical recurrence-free survival (IVRFS)，recurrence-free survival (RFS)，and overall survival (OS) of the two groups were compared using Kaplan-Meier method. Results: There were no significant differences in the baseline data between the two groups (P>0.05).All surgeries were successfully completed without conversion to open surgery.RRUN demonstrated superior perioperative outcomes compared to LRUN in overall postoperative complication rate [37.1%(13/35) vs. 56.4%(57/101)]，postoperative hospital stay [6(5,7) days vs. 7(6,8) days]，and catheter indwelling time [3(2，4) days vs. 4(3，5) days]，with statistically significant differences (P<0.05).Safety indicators of both surgical approaches were similar (P>0.05).Survival analysis showed no significant difference in oncological outcomes between the two groups [IVRFS (1 year：92.1%，2 years：85.2%)，RFS (1 year:82.4%，2 years:74.9%)，OS (1 year:90.6%，2 years:84.2%)] (P>0.05). Conclusion: Compared with retroperitoneal LRUN，single-position RRUN for UTUC demonstrates comparable safety and oncological efficacy，while offering significant advantages in perioperative outcomes such as reducing postoperative complication rate and shortening hospital stay.

This paper aims to study the effect of Ziziphi Spinosae Semen extracts on chronic unpredictable mild stress(CUMS)-induced depression-like and insomnia behavior models of mice. The CUMS-induced depression-like and insomnia behavior model of mice was established by CUMS treatment for three weeks. The mice were randomly divided into control group, model group, positive drug diazepam group(2 mg·kg~(-1)), as well as low-dose group(1.95 g·kg~(-1)), medium-dose group(3.9 g·kg~(-1)), and high-dose group(7.8 g·kg~(-1)) of Ziziphi Spinosae Semen extracts, with 18 mice in each group. On the 15th day of modeling, the drug was administered intragastrically once a day for one week. Then, the pentobarbital sodium cooperative righting experiment, open field experiment, and elevated plus maze experiment were carried out, respectively. The contents of neurotransmitters 5-hydroxytryptamine(5-HT) and 5-hydroxyindoleacetic acid(5-HIAA) in serum and thalamus of mice, as well as the levels of corticotropin releasing hormone(CRH), adrenocorticotropic hormone(ACTH), and corticosterone(CORT) in serum, were determined by enzyme-linked immunosorbent assay(ELISA). The neuron damage in the hippocampus of mice was observed by hematoxylin-eosin(HE) staining and Nissl staining. Western blot was used to detect the expressions of tryptophan hydroxylase 2(TPH2), serotonin transporter(SERT), monoamine oxidase A(MAOA), five prime repressors under dual repression binding protein 1(Freud1), synaptic plasticity-related proteins [cellular gene FOS(C-FOS), postsynaptic density protein 95(PSD95), synapsin 1(SYN1), and activity-regulated cytoskeleton-associated gene(ARC)], blood-brain barrier(BBB) permeability-related proteins [zonula occludens 1(ZO-1), occludin, and claudin 1], inflammatory factors [NOD-, LRR-and pyrin domain-containing protein 3(NLRP3), apoptosis-associated speck-like protein(ASC), gasdermin D(GSDMD), caspase-3, and caspase-8], and antioxidant factors [nuclear factor erythroid 2-related factor 2(NRF2) and heme oxygenase 1(HO1)] in thalamic tissue of mice. The results indicated that compared with that in the model group, the sleep latency was significantly shortened, and the sleep duration was significantly prolonged in each dose group of Ziziphi Spinosae Semen extracts. The number of visits to the central area of the open field and the distance and time of visits were significantly increased in each dose group of Ziziphi Spinosae Semen extracts. In addition, the proportion of distance and time of entering the open arm area of the elevated plus maze was significantly increased in each dose group of Ziziphi Spinosae Semen extracts. The contents of 5-HT and 5-HIAA in serum and thalamus of mice increased to varying degrees in each dose group of Ziziphi Spinosae Semen extracts; the contents of CRH, ACTH, and CORT in serum of mice were significantly decreased. The protein expression of TPH2 was significantly increased. The protein expression of MAOA, SERT, and Freud1 was significantly decreased. Ziziphi Spinosae Semen extracts could also significantly reduce the protein expression of C-FOS but significantly increase the protein expression of PSD95, ARC, and SYN1. They could reduce the pathological damage of the hippocampus in mice and significantly increase the protein expression of ZO-1, occluding, and claudin 1. The protein expression of NLRP3, GSDMD, ASC, caspase-3, and caspase-8 in the thalamic tissue of mice was significantly decreased, and the protein expression of HO1 and NRF2 was significantly increased. In conclusion, Ziziphi Spinosae Semen extracts could effectively improve sleep disorders and depression-like behaviors in CUMS-induced model mice, which may be related to regulating the 5-HT anabolism process and hypothalamic-pituitary-adrenal(HPA) axis-related hormone levels, reducing pathological damage in the hippocampus, improving synaptic plasticity, repairing BBB integrity, and alleviating inflammatory response and oxidative stress damage.
Animals ; Ziziphus/chemistry* ; Mice ; Male ; Depression/psychology* ; Drugs, Chinese Herbal/administration & dosage* ; Sleep Initiation and Maintenance Disorders/psychology* ; Stress, Psychological/complications* ; Behavior, Animal/drug effects* ; Humans ; Disease Models, Animal

This study explores the effect of total secondary ginsenosides(TSG) on apoptosis and energy metabolism in H9c2 cells under hypoxia and its potential mechanisms. H9c2 cell viability was observed and the apoptosis rate was calculated to determine suitable intervention concentrations of TSG, antimycin A complex(AMA), and coenzyme Q10(CoQ10), along with the duration of hypoxia. H9c2 cells at the logarithmic phase were divided into a normal group, a model group, a TSG group, an AMA group, a TSG+AMA group, and a CoQ10 group. All groups, except the normal group, were treated with their respective intervention drugs and cultured under hypoxic conditions. Adenosine triphosphate(ATP) content and creatine kinase(CK) activity were measured using an ATP chemiluminescence assay kit and a CK colorimetric assay kit. Flow cytometry was used to assess apoptosis rates, and Western blot evaluated the expression levels of apoptosis-related proteins, including B-cell lymphoma 2(Bcl-2), Bcl-2-associated X protein(Bax), cysteinyl aspartate-specific protease(caspase)-3, caspase-8, and caspase-9, as well as mitochondrial biogenesis-related proteins peroxisome proliferator-activated receptor-γ coactivator 1α(PGC-1α), estrogen-related receptor-α(ERRα), nuclear respiratory factor(NRF)-1, NRF-2, peroxisome proliferator activated receptor-α(PPARα), and Na~+-K~+-ATPase. RT-PCR was employed to analyze the mRNA expression of mitochondrial biogenesis factors, including PGC-1α, ERRα, NRF-1, NRF-2, PPARα, mitochondrial transcription factor A(TFAM), mitochondrial cytochrome C oxidase 1(COX1), and mitochondrial NADH dehydrogenase subunit 1(ND1), ND2. The selected intervention concentrations were 7.5 μg·mL~(-1) for TSG, 10 μmol·L~(-1) for AMA, and 1×10~(-4) mol·L~(-1) for CoQ10, with a hypoxia duration of 6 h. Compared with the normal group, the model group showed decreased ATP content and CK activity, increased apoptosis rates, decreased Bcl-2 expression, and increased Bax, caspase-3, caspase-8, and caspase-9 expression in H9c2 cells. Additionally, the protein and mRNA expression levels of mitochondrial biogenesis-related factors(PGC-1α, ERRα, NRF-1, NRF-2, PPARα), mRNA expression of TFAM, COX1, and ND1, ND2, and protein expression of Na~+-K~+-ATPase in mitochondrial DNA, were also reduced. In the TSG and CoQ10 groups, ATP content and CK activity increased, and apoptosis rates decreased compared with those in the model group. The TSG group showed decreased protein expression of apoptosis-related proteins Bax, caspase-3, caspase-8, and caspase-9, increased protein and mRNA expression of mitochondrial biogenesis factors PGC-1α, ERRα, NRF-1, and PPARα, and increased NRF-2 protein expression and TFAM mRNA expression in mitochondrial DNA. Conversely, in the AMA group, ATP content and CK activity decreased, the apoptosis rate increased, Bcl-2 expression decreased, and Bax, caspase-3, caspase-8, and caspase-9 expression increased, alongside reductions in PGC-1α, ERRα, NRF-1, NRF-2, PPARα protein and mRNA expression, as well as TFAM, COX1, ND1, ND2 mRNA expression and Na~+-K~+-ATPase protein expression. Compared with the TSG group, the TSG+AMA group exhibited decreased ATP content and CK activity, increased apoptosis rates, decreased Bcl-2 expression, and increased Bax, caspase-3, caspase-8, and caspase-9 expression, along with decreased PGC-1α, ERRα, NRF-1, NRF-2, and PPARα protein and mRNA expression and TFAM, COX1, and ND1, ND2 mRNA expression. Compared with the AMA group, the TSG+AMA group showed increased CK activity, decreased apoptosis rate, increased Bcl-2 expression, and decreased Bax, caspase-8, and caspase-9 expression. Additionally, the protein and mRNA expression of PGC-1α, ERRα, NRF-1, PPARα, mRNA expression of TFAM, COX1, ND1, ND2, and Na~+-K~+-ATPase protein expression increased. In conclusion, TSG enhance ATP content and CK activity and inhibit apoptosis in H9c2 cells under hypoxia, and the mechanisms may be related to the regulation of PGC-1α, ERRα, NRF-1, NRF-2, PPARα, and TFAM expression, thus promoting mitochondrial biogenesis.
Apoptosis/drug effects* ; Ginsenosides/pharmacology* ; Energy Metabolism/drug effects* ; Mitochondria/metabolism* ; Animals ; Rats ; Cell Line ; Cell Hypoxia/drug effects* ; Organelle Biogenesis ; Adenosine Triphosphate/metabolism* ; Humans ; Cell Survival/drug effects*

The innate immune sensor NLRP3 inflammasome overactivation is involved in the pathogenesis of ulcerative colitis. PGAM5 is a mitochondrial phosphatase involved in NLRP3 inflammasome activation in macrophages. However, the role of PGAM5 in ulcerative colitis and the mechanisms underlying PGAM5 regulating NLRP3 activity remain unknown. Here, we show that PGAM5 deficiency ameliorates dextran sodium sulfate (DSS)-induced colitis in mice via suppressing NLRP3 inflammasome activation. By combining APEX2-based proximity labeling focused on PGAM5 with quantitative proteomics, we identify NEK7 as the new binding partner of PGAM5 to promote NLRP3 inflammasome assembly and activation in a PGAM5 phosphatase activity-independent manner upon inflammasome induction. Interfering with PGAM5-NEK7 interaction by punicalagin inhibits the activation of the NLRP3 inflammasome in macrophages and ameliorates DSS-induced colitis in mice. Altogether, our data demonstrate the PGAM5-NEK7 interaction in macrophages for NLRP3 inflammasome activation and further provide a promising therapeutic strategy for ulcerative colitis by blocking the PGAM5-NEK7 interaction.

Based on the natures and flavors of herbal medicinals recorded in Shen Nong's Classic of the Materia Medica （《神农本草经》）； Miscellaneous Records of Famous Physicians （《名医别录》）， this study analyzed the characte-ristics of the natures， flavors and combination of medicinals of the two-herb compound formulas in Treatise on Cold Damage and Miscellaneous Diseases （《伤寒杂病论》）.Finally， 31 compound formulas were included， and it was found that the nature and flavor of the herbs in these two-herb compound formulas are closely related to the functions of the compound formulas， such as the common pairing of the acrid and the sweet herbs to warm yang and transform qi， the acrid and the bitter herbs in pairs to regulate and harmonize cold and heat， the sweet and the bitter in pairs to remove dampness and clear heat， the acrid and the acrid in pairs to arrest vomiting and direct qi downward， and the sour and the sweet in pairs to slow the urgent and relieve pain. Regardless of the deficiency or excess nature of the disease， the corresponding two-herb compound formulas often aim to reinforce healthy qi while eliminating pathogenic factors， with some formulas showcasing a unique correspondence between the disease pattern and the symptoms addressed.

This study design of specific identification primers for the ITS2 sequence of F. ussuriensis. The reaction system and conditions were optimized, and PCR-nucleic acid test strips were constructed to realize the visual detection of F. ussuriensis Bark. Through molecular cloning and sequencing technology, we constructed a positive control for F. ussuriensis DNA and formulated quality standards. The established method was evaluated for sensitivity, specificity and reproducibility, and the authenticity of the commercially available samples was identified. Results demonstrated that based on the ITS2 sequences, F. ussuriensis and its mixed forgeries could be distinguished. The PCR products of the authentic F. ussuriensis on test strips showed two bands in the T and C lines, while the pseudo products and negative control showed only one band in the C line, which was consistent with the results of agarose gel electrophoresis. The specificity was 100%, and the sensitivity of the PCR-nucleic acid test strip was up to 0.1 ng·μL^-1, which was 10 times higher than that of the gel electrophoresis assay. 11 out of 16 commercially available samples of F. ussuriensis were qualified, and 5 were unqualified. Collectively, the PCR-nucleic acid test strip method established in this study is specific, rapid, accurate and visualized, which can provide a new technical idea for the detection of F. ussuriensis.

Objective:To investigate the feasibility of expectant management of different degrees of vaginal fluid in pregnant women with premature rupture of membranes in the second trimester.Methods:A retrospective cohort study was conducted to collect 103 pregnant women who were diagnosed with premature rupture of membranes in the second trimester of pregnancy and insisted on continuing the pregnancy in Shanxi Bethune Hospital from July 2012 to July 2022. According to the degree of vaginal fluid, pregnant women were divided into rupture group (with typical vaginal fluid, 48 cases) and leakage group (without typical vaginal fluid, 55 cases). The rupture latency (the time from rupture of membranes to termination of pregnancy), gestational weeks of termination, indications and methods of termination of pregnancy, maternal infection related indicators and perinatal outcomes were compared between the two groups. Univariate regression model was used to analyze the correlation between different degrees of vaginal fluid in pregnant women with premature rupture of membranes and maternal and neonatal outcomes.Results:(1) Obstetric indicators: there was no significant difference in the gestational age of rupture of membranes between the two groups ( P>0.05). However, the proportion of rupture latency >28 days in the leakage group was significantly higher than that in the rupture group [42% (23/55) vs 13% (6/48); χ2=33.673, P<0.001], and the incidence of pregnancy termination ≥28 weeks was significantly higher [47% (26/55) vs 19% (9/48); χ2=9.295, P=0.002]. (2) Indications and methods of termination: the incidence of progressive reduction of amniotic fluid as the indication for termination in the leakage group was significantly lower than that in the rupture group [22% (12/55) vs 42% (20/48); χ2=4.715, P=0.030], and the incidence of full-term termination in the leakage group was significantly higher than that in the rupture group [31% (17/55) vs 12% (6/48); χ2=5.008, P=0.025], while there were no significant differences in the indications of termination of pregnancy, including amniotic cavity infection, uterine contraction failure and fetal distress between the two groups (all P>0.05). The incidence of induced labor or spontaneous contraction in the leakage group was significantly lower than that in the rupture group [53% (29/55) vs 81% (39/48); χ2=9.295, P=0.002], while the cesarean section rate and vaginal delivery rate were similar between the two groups (both P>0.05). (3) Infection related indicators: the incidence of amniotic cavity infection in the leakage group was significantly higher than that in the rupture group [31% (17/55) vs 13% (6/48); χ2=4.003, P=0.045]. However, there were no significant differences in the elevation of inflammatory indicators, the positive rate of cervical secretion bacterial culture and the incidence of tissue chorioamnionitis between the two groups (all P>0.05). (4) Perinatal outcomes: the live birth rate in the leakage group was significantly higher than that in the rupture group [51% (28/55) vs 27% (13/48); χ2=5.119, P=0.024]. The proportion of live births with 1-minute Apgar score >7 in the leakage group was significantly higher than that in the rupture group [38% (21/55) vs 17% (8/48); χ2=4.850, P=0.028]. However, there were no significant differences in the birth weight of live births and the incidence of neonatal complications between the two groups (all P>0.05). (5) Univariate regression analysis showed that compared with the rupture group, the leakage group had a higher risk of pregnancy termination at ≥28 gestational weeks ( RR=2.521, 95% CI: 1.314-4.838; P=0.002), amniotic infection ( RR=2.473, 95% CI: 1.061-5.764; P=0.025), perinatal survival ( RR=1.880, 95% CI: 1.104-3.199; P=0.014). Conclusion:Compared with pregnant women with typical vaginal fluid in the second trimester of premature rupture of membranes, expectant treatment for pregnant women with atypical vaginal fluid is more feasible, which could effectively prolong the gestational weeks and improve the perinatal live birth rate.

Objectives The combined use of bedaquiline and delamanid(BDQ-DLM)is limited by an increased risk of prolonging the QTc interval.We retrospectively evaluated patients who received DLM/BDQ-containing regimens at a TB-specialized hospital.We aimed to present clinical efficacy and safety data for Chinese patients. Methods This case-control study included patients with multidrug-resistant tuberculosis(MDR-TB)treated with BDQ alone or BDQ plus DLM. Results A total of 96 patients were included in this analysis:64 in the BDQ group and 32 in the BDQ+DLM group.Among the 96 patients with positive sputum culture at the initiation of BDQ alone or BDQ combined with DLM,46 patients(71.9%)in the BDQ group and 29(90.6%)in the BDQ-DLM group achieved sputum culture conversion during treatment.The rate of sputum culture conversion did not differ between the two groups.The time to sputum culture conversion was significantly shorter in the BDQ-DLM group than in the BDQ group.The most frequent adverse event was QTc interval prolongation;however,the frequency of adverse events did not differ between the groups. Conclusion In conclusion,our results demonstrate that the combined use of BDQ and DLM is efficacious and tolerable in Chinese patients infected with MDR-TB.Patients in the BDQ-DLM group achieved sputum culture conversion sooner than those in the BDQ group.

Objective:To observe the correlation between retinal capillary density and retinal thickness in the macula and spherical equivalent (SE) in school-age children.Methods:A cross-sectional study. From May to December 2022, 182 school-age children who visited the ophthalmology department of the First Affiliated Hospital of Zhengzhou University were included. There were 95 males and 87 females. The age ranged from 6 to 12 years, and the spherical equivalent (SE) was +0.50 to -6.00 D. They were divided into three groups based on the SE of the right eyes: 54 eyes in emmetropia group (+0.50≤SE<-0.50 D), 71 eyes in low myopia group (-0.50≤SE<-3.00 D), and 57 eyes in moderate myopia group (-3.00≤SE≤-6.00 D). The macular area of 6 mm×6 mm was scanned using swept-source optical coherence tomography angiography and was divided into three concentric rings centered on the fovea, including the macular central fovea (0-1 mm diameter), inner ring (1-3 mm diameter) and outer ring (3-6 mm diameter). The retinal thickness and blood flow density of superficial vascular plexus (SVP) and deep vascular plexus (DVP) in different zones within 6 mm of the macular area were measured. The relationships between SE and SVP, DVP and retinal thickness in each ring region were investigated by univariate and multivariate linear regression analyses, smooth curve fitting, and threshold effects.Results:There were significant differences in the SVP ( F=6.64, 26.06, 22.69) and DVP ( F=7.97, 25.01, 5.09) of macular central fovea, inner ring and outer ring among the emmetropia, low myopia and moderate myopia groups ( P<0.05). Univariate linear regression analysis showed that the SVP ( β=-0.56,-1.17, -0.79) and DVP ( β=-1.03, -0.93, -0.45) of the three regions were positively correlated with SE ( P<0.05). After smooth curve fitting, threshold effect analysis and multivariate linear regression analysis, the SVP and DVP in the macular central fovea were linearly positively correlated with SE ( β=-0.91, -1.40; P<0.05), and SVP and DVP in the inner ring and outer ring showed an inverted U-shaped curve relationship with SE with the inflection (<3.00 D). When the SE was less than <3.00 D, the SVP and DVP in the inner ring and outer ring were positively correlated with SE ( P<0.05). When the SE was higher than -3.00 D, except for the DVP in the inner ring region, the other parameters were negatively correlated with SE ( P<0.05). There were significant differences in retinal thickness of the inner ring and outer ring ( F=5.47, 16.36; P<0.05), and no significant difference in the macular central fovea among the emmetropia, low and moderate myopia groups ( F=2.16, P>0.05). By using univariate and multivariate linear regression analyses, the retinal thickness in the inner ring and outer ring were negatively correlated with SE ( β =1.99, 3.05; P<0.05). However, no correlation was found between retinal thickness and SE in the macular central fovea ( β=-1.65, P>0.05). Conclusions:In school-age children with SE between +0.50 D and -6.00 D, the retinal capillaries density of the macular central fovea gradually increase, and increase first and then decrease in the inner ring and outer ring with increasing SE. The retinal thickness of inner ring and outer ring gradually decrease and not change significantly in the macular central fovea.