Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.

Diabetic retinopathy (DR) is a diabetic ocular complication that can lead to poor vision and blindness. This experiment aimed to investigate the ameliorative effect and its mechanism of Panax notoginseng saponins (PNS) eye drops on streptozotocin (STZ)-induced non-proliferative diabetic retinopathy (NPDR) in rats. All experiments were approved by the Animal Research Committee of Shanghai University of Traditional Chinese Medicine. Animal welfare and the animal experimental protocols were strictly consistent with related ethics regulations of Shanghai University of Traditional Chinese Medicine (No. PZSHUTCM 211115004). Diabetes mellitus was induced by a single intraperitoneal injection of STZ into rats. Two months later, PNS solution was dropped binocular twice per day at 6 h intervals at dose of 20, 40, and 80 mg·kg^-1 continuously for 1 month. The morphological structure and activation of microglia of the retina were observed by hematoxylin-eosin staining and immunohistochemical assay. The disruption of the blood-retina barrier (BRB) was conducted by the Evans blue dye leakage assay. The number of acellular capillaries in the retina was assessed by digesting and hematoxylin-eosin staining assay. The number of retinal leukocyte adhesion was observed by fluorescein isothiocyanate-coupled concanavalin A lectin labeling assay. The serum expression of inflammatory factors was measured using enzyme-linked immunosorbent assay. Western blot experiments were used to detect the expression of relevant proteins in retinal tissue and transcriptional activation of nuclear factor kappa-B (NF-κB). The results revealed that PNS eye drops significantly increased the thickness of the retina, decreased the number of acellular capillaries, and up-regulated the expression of the tight junction proteins claudin-1 and occludin, thereby alleviating BRB damage. In addition, PNS eye drops were also able to significantly reduce leukocyte adhesion and microglia activation, the expression of inflammatory factors in serum, and the nuclear translocation of retinal p65 proteins, effectively inhibiting the occurrence of retinal inflammation. The above results showed that PNS eye drops played a role in improving NPDR by inhibiting the activation of the NF-κB signaling pathway and reducing inflammation.

By using thioflavin T(ThT)as displacement-based fluorescent probes,three kinds of aptasensors were constructed for rapid detection of three kinds of small molecules such as ochratoxin A(OTA),aflatoxin B1(AFB1)and adenosine.In the absence of target molecule,ThT bound with the aptamer to form an aptamer-ThT complex and exhibited a significant fluorescence response.Upon the addition of target molecule,because of the higher affinity between target and aptamer than that between ThT and the aptamer,ThT was displaced by the target molecule from the aptamer-ThT complex,resulting in weakened fluorescence signal.Based on this principle,the target molecule could be detected quantitatively.Further study through circular dichroism spectra showed that there was no significant change in the conformation of the aptamer after addition of ThT or target molecules.The stoichiometric ratios of ThT to OTAapt,AFB1apt and Adeapt measured through the method of equimolar continuous variation was 1∶1,1∶1 and 2∶1,respectively,and their dissociation constants were all larger than those between the target molecule and its aptamer.Therefore,the principle of this detection method was the displacement of fluorescent probe(ThT)in aptamer-ThT complex by target molecule,resulting in decrease of fluorescence intensity.Under optimal experimental conditions,the limits of detection(LODs)were 0.8 nmol/L for OTA,1.3 nmol/L for AFB1,and 0.10 μmol/L for adenosine,respectively.This method was label-free,simple to operate,with low cost,good selectivity and high sensitivity.The developed assay kit based on this method could be used for actual sample detection.

Objective:To explore the relationship between preterm labor with different causes and cerebral perfusion in different regions of interest in very preterm infants.Methods:This was a prospective cohort study. A total of 145 preterm infants with gestational age of 28-31 +6 weeks who were hospitalized in the Neonatology Department of the Third Affiliated Hospital of Zhengzhou University within 24 h after birth from April 2022 to May 2023 were selected for the study, and were categorized into the iatrogenic preterm labor group ( n=55), spontaneous preterm labor with premature rupture of the membranes (PROM) group ( n=47), and spontaneous preterm labor with intact membranes group ( n=43) according to the cause of preterm labor. Cerebral blood flow (CBF) values in the cortex and deep gray matter of different regions of interest (frontal lobe, temporal lobe, parietal lobe, occipital lobe, thalamus, and basal ganglia) were measured using the arterial spin labeling technique in the very preterm infants in each group. One-way analysis of variance, Kruskal-Wallis H test and Bonferroni correction, Chi-square test or Fisher's exact probability method, analysis of covariance, and LSD test were used to compare the differences in CBF among the groups. Results:The differences in the incidence of complications such as cerebral white matter injury, Ⅰ-Ⅱ grade intracranial hemorrhage, and late-onset sepsis during hospitalization among the three groups of preterm infants were not statistically significant (all P>0.05). In the iatrogenic preterm labor group, compared with the spontaneous preterm labor with PROM group, CBF [in units of ml/ (100 g·min)] was higher in regions of interest such as the right temporal lobe [20.5 (16.1-24.6) vs. 17.1 (14.5-23.0)], bilateral parietal lobe [left side: 22.4 (17.1-25.3) vs. 16.9 (14.4-24.1); right side: 23.0 (18.2-27.4) vs. 17.0 (14.0-22.2)], right occipital lobe [22.1 (18.6-29.5) vs. 19.4 (13.7-24.5)], bilateral basal ganglia [left side: 33.0 (29.1-36.3) vs. 24.9 (22.9-33.1); right side: 32.8 (29.0-37.0) vs. 26.1 (22.3-35.0)], and bilateral thalamus [left side: 39.2 (36.0-45.0) vs. 32.6 (25.1-42.2); right side: 38.6 (34.6-44.1) vs. 32.0 (25.4-44.9)] (Bonferroni corrected, all P<0.017). Compared with the spontaneous preterm labor group with intact membranes, CBF in the iatrogenic preterm labor group was higher in the cortex and deep gray matter of regions of interest such as bilateral frontal lobe [left side: 21.4 (18.3-25.3) vs. 17.0 (12.0-22.2); right side: 22.1 (16.7-25.0) vs. 15.9 (12.0-23.3)], temporal lobe [left side: 21.4 (17.0-24.8) vs. 18.4 (14.0-22.0); right side: 20.5 (16.1-24.6) vs. 17.3 (13.3-22.3)], parietal lobe [left side: 22.4 (17.1-25.3) vs. 15.3 (10.4-20.8); right side: 23.0 (18.2-27.4) vs. 15.7 (11.1-23.6)], occipital lobe [left side: 22.7 (18.8-28.4) vs. 18.2 (11.4-23.4); right side: 22.1 (18.6-29.5) vs. 19.6 (14.0-25.8)], basal ganglia [left side: 33.0 (29.1-36.3) vs. 27.7 (19.1-32.4); right side: 32.8 (29.0-37.0) vs. 27.7 (21.5-33.0)] and thalamus [left side: 39.2 (36.0-45.0) vs. 33.9 (26.0-43.7); right side: 38.6 (34.6-44.1) vs. 33.3 (27.8-40.4)] (Bonferroni corrected, all P<0.017). Analysis of covariance revealed that the cause of preterm birth had a significant effect on CBF values in the cortex and deep gray matter of very preterm infants ( P=0.007), and that iatrogenic preterm birth elevated CBF perfusion in the localized cerebral cortex and deep gray matter of very preterm infants as compared to the spontaneous preterm births with PROM group and spontaneous preterm births with intact membranes group (LSD test, all P<0.05). Conclusion:Cerebral blood perfusion in very preterm infants is related to the causes leading to preterm birth, and local cortical and deep gray matter blood perfusion levels in the brain are increased in those with iatrogenic preterm birth compared to spontaneous preterm birth.

With the rapid development of computer technology, numerical simulation has gradually become an important method to study drying process and improve drying equipment. Using computer to simulate the drying process of traditional Chinese medicine(TCM) is characterized by intuitiveness, scientificity, and low cost, which serves as an auxiliary means for technical innovation in TCM drying. This paper summarizes the theories of different drying methods and the research status of numerical simulation in drying, introduces the modeling methods and software of numerical simulation, and expounds the significance of numerical simulation modeling in shortening the research and development cycle, improving drying equipment, and optimizing drying parameters. However, the current numerical simulation method for drying process has problems, such as low accuracy, lack of quantitative indicators for the control of simulation results on the process, and insufficient in-depth research on the mechanism of drug quality changes. Furthermore, this paper put forward the application prospect of numerical simulation in TCM drying, providing reference for the further study of numerical simulation in this field.
Medicine, Chinese Traditional ; Drugs, Chinese Herbal ; Desiccation

A comprehensive analytical method based on ultra-fast liquid chromatography coupled with triple quadrupole/linear ion trap tandem mass spectrometry(UFLC-QTRAP-MS/MS) was established for simultaneous determination of the content of 45 bioactive constituents including flavonoids, alkaloids, amino acids, phenolic acids, and nucleosides in Epimedium brevicornum. The multiple bioactive constituents in leaves, petioles, stems and rhizomes of E. brevicornum were analyzed. The gradient elution was performed at 30 ℃ in an XBridge~® C_(18) column(4.6 mm×100 mm, 3.5 μm) with 0.4% formic acid aqueous solution-acetonitrile as the mobile phase at a flow rate of 0.8 mL·min~(-1). Single factor experiment and response surface methodology were employed to optimize the extraction conditions. Multivariate statistical analyses including systematic cluster analysis(SCA), principal component analysis(PCA), partial least squares discriminant analysis(PLS-DA), and one-way analysis of variance(One-way ANOVA) were carried out to classify the samples from different parts and identify different constituents. Grey relation analysis(GRA) and entropy weight-TOPSIS analysis were performed to build a multi-index comprehensive evaluation model for different parts of E. brevicornum. The results showed that there was a good relationship between the mass concentrations of 45 constituents and the corresponding peak areas, with the correlation coefficients(r) not less than 0.999 0. The precision, repeatability, and stability of the established method were good for all the target constituents in this study, with the relative standard deviations(RSDs) less than 5.0%(0.62%-4.9%) and the average recovery of 94.51%-105.7%. The above results indicated that the bioactive constituents varied in different parts of E. brevicornum, and the overall quality followed the trend of leaves > petioles > rhizomes > stems. This study verified the rationality of the Chinese Pharmacopoeia(2020 edition) stipulating that the medicinal part of E. brevicornum is the leaf. Moreover, our study indicated that the rhizome had the potential for medicinal development. The established method was accurate and reliable, which can be used to comprehensive evaluate and control the quality of E. brevicornum. This study provides data reference for clarifying the medicinal parts and rationally utilizing the resources of E. brevicornum.
Chromatography, High Pressure Liquid ; Epimedium ; Tandem Mass Spectrometry ; Chromatography, Liquid ; Multivariate Analysis

BACKGROUND: Rheumatoid arthritis (RA), a chronic systemic autoimmune disease, is characterized by synovitis and progressive damage to the bone and cartilage of the joints, leading to disability and reduced quality of life. This study was a randomized clinical trial comparing the outcomes between withdrawal and dose reduction of tofacitinib in patients with RA who achieved sustained disease control. METHODS: The study was designed as a multicenter, open-label, randomized controlled trial. Eligible patients who were taking tofacitinib (5 mg twice daily) and had achieved sustained RA remission or low disease activity (disease activity score in 28 joints [DAS28] ≤3.2) for at least 3 months were enrolled at six centers in Shanghai, China. Patients were randomly assigned (1:1:1) to one of three treatment groups: continuation of tofacitinib (5 mg twice daily); reduction in tofacitinib dose (5 mg daily); and withdrawal of tofacitinib. Efficacy and safety were assessed up to 6 months. RESULTS: Overall, 122 eligible patients were enrolled, with 41 in the continuation group, 42 in the dose-reduction group, and 39 in the withdrawal group. After 6 months, the percentage of patients with a DAS28-erythrocyte sedimentation rate (ESR) of <3.2 was significantly lower in the withdrawal group than that in the reduction and continuation groups (20.5%, 64.3%, and 95.1%, respectively; P  < 0.0001 for both comparisons). The average flare-free time was 5.8 months for the continuation group, 4.7 months for the dose reduction group, and 2.4 months for the withdrawal group. CONCLUSION: Withdrawal of tofacitinib in patients with RA with stable disease control resulted in a rapid and significant loss of efficacy, while standard or reduced doses of tofacitinib maintained a favorable state. TRIAL REGISTRATION Chictr.org, ChiCTR2000039799.
Humans ; Quality of Life ; China ; Arthritis, Rheumatoid/drug therapy* ; Piperidines/therapeutic use* ; Treatment Outcome ; Antirheumatic Agents/therapeutic use* ; Pyrroles/therapeutic use*

Objective: To analyze the prevalence and the risk factors of fungal sepsis in 25 neonatal intensive care units (NICU) among preterm infants in China, and to provide a basis for preventive strategies of fungal sepsis. Methods: This was a second-analysis of the data from the "reduction of infection in neonatal intensive care units using the evidence-based practice for improving quality" study. The current status of fungal sepsis of the 24 731 preterm infants with the gestational age of <34⁺⁰ weeks, who were admitted to 25 participating NICU within 7 days of birth between May 2015 and April 2018 were retrospectively analyzed. These preterm infants were divided into the fungal sepsis group and the without fungal sepsis group according to whether they developed fungal sepsis to analyze the incidences and the microbiology of fungal sepsis. Chi-square test was used to compare the incidences of fungal sepsis in preterm infants with different gestational ages and birth weights and in different NICU. Multivariate Logistic regression analysis was used to study the outcomes of preterm infants with fungal sepsis, which were further compared with those of preterm infants without fungal sepsis. The 144 preterm infants in the fungal sepsis group were matched with 288 preterm infants in the non-fungal sepsis group by propensity score-matched method. Univariate and multivariate Logistic regression analysis were used to analyze the risk factors of fungal sepsis. Results: In all, 166 (0.7%) of the 24 731 preterm infants developed fungal sepsis, with the gestational age of (29.7±2.0) weeks and the birth weight of (1 300±293) g. The incidence of fungal sepsis increased with decreasing gestational age and birth weight (both P<0.001). The preterm infants with gestational age of <32 weeks accounted for 87.3% (145/166). The incidence of fungal sepsis was 1.0% (117/11 438) in very preterm infants and 2.0% (28/1 401) in extremely preterm infants, and was 1.3% (103/8 060) in very low birth weight infants and 1.7% (21/1 211) in extremely low birth weight infants, respectively. There was no fungal sepsis in 3 NICU, and the incidences in the other 22 NICU ranged from 0.7% (10/1 397) to 2.9% (21/724), with significant statistical difference (P<0.001). The pathogens were mainly Candida (150/166, 90.4%), including 59 cases of Candida albicans and 91 cases of non-Candida albicans, of which Candida parapsilosis was the most common (41 cases). Fungal sepsis was independently associated with increased risk of moderate to severe bronchopulmonary dysplasia (BPD) (adjusted OR 1.52, 95%CI 1.04-2.22, P=0.030) and severe retinopathy of prematurity (ROP) (adjusted OR 2.55, 95%CI 1.12-5.80, P=0.025). Previous broad spectrum antibiotics exposure (adjusted OR=2.50, 95%CI 1.50-4.17, P<0.001), prolonged use of central line (adjusted OR=1.05, 95%CI 1.03-1.08, P<0.001) and previous total parenteral nutrition (TPN) duration (adjusted OR=1.04, 95%CI 1.02-1.06, P<0.001) were all independently associated with increasing risk of fungal sepsis. Conclusions: Candida albicans and Candida parapsilosis are the main pathogens of fungal sepsis among preterm infants in Chinese NICU. Preterm infants with fungal sepsis are at increased risk of moderate to severe BPD and severe ROP. Previous broad spectrum antibiotics exposure, prolonged use of central line and prolonged duration of TPN will increase the risk of fungal sepsis. Ongoing initiatives are needed to reduce fungal sepsis based on these risk factors.
Infant ; Infant, Newborn ; Humans ; Birth Weight ; Intensive Care Units, Neonatal ; Retrospective Studies ; Tertiary Care Centers ; Infant, Extremely Low Birth Weight ; Gestational Age ; Infant, Extremely Premature ; Sepsis/epidemiology* ; Retinopathy of Prematurity/epidemiology* ; Bronchopulmonary Dysplasia/epidemiology*

Management and treatment of terminal metastatic castration-resistant prostate cancer (mCRPC) remains heavily debated. We sought to investigate the efficacy of programmed cell death 1 (PD-1) inhibitor plus anlotinib as a potential solution for terminal mCRPC and further evaluate the association of genomic characteristics with efficacy outcomes. We conducted a retrospective real-world study of 25 mCRPC patients who received PD-1 inhibitor plus anlotinib after the progression to standard treatments. The clinical information was extracted from the electronic medical records and 22 patients had targeted circulating tumor DNA (ctDNA) next-generation sequencing. Statistical analysis showed that 6 (24.0%) patients experienced prostate-specific antigen (PSA) response and 11 (44.0%) patients experienced PSA reduction. The relationship between ctDNA findings and outcomes was also analyzed. DNA-damage repair (DDR) pathways and homologous recombination repair (HRR) pathway defects indicated a comparatively longer PSA-progression-free survival (PSA-PFS; 2.5 months vs 1.2 months, P = 0.027; 3.3 months vs 1.2 months, P = 0.017; respectively). This study introduces the PD-1 inhibitor plus anlotinib as a late-line therapeutic strategy for terminal mCRPC. PD-1 inhibitor plus anlotinib may be a new treatment choice for terminal mCRPC patients with DDR or HRR pathway defects and requires further investigation.
Male ; Humans ; Prostate-Specific Antigen ; Treatment Outcome ; Prostatic Neoplasms, Castration-Resistant/drug therapy* ; Immune Checkpoint Inhibitors/therapeutic use* ; Retrospective Studies

OBJECTIVE: To verify the consistency between the digital manufacturing simple intraoral Gothic arch-tracing device and the traditional intraoral Gothic arch-tracing device in determining the centric relation of complete dentures restoration. METHODS: Ten outpatients with edentulous jaws were selec-ted, and the centric relation of the patients was determined by digital manufacturing of simple intraoral Gothic arch-tracing device (T1) and traditional intraoral Gothic arch-tracing device (T2); the difference of clinical operation time between the two methods was recorded; the upper and lower edentulous jaw plaster models were scanned with two kinds of centric relation, the Standard Triangle Language (STL) files imported into Geomagic studio software to apply the best fitting of multiple points of the both upper jaw models, the fitted STL files imported into the 3 shape viewer software, and the maximum position deviations of the vertical, labial (buccal) and lingual directions of the mandibular midline area and molar areas in T1 and T2 groups measured. During the clinical complete dentures try-in, we observed whether there was midline deviation in the mouth of T1 group and T2 group, and whether the occlusion of posterior teeth was stable or not. RESULTS: The mean time spent on determining the centric relation of T1 and T2 groups was (41.90±2.64) min, (57.50±2.37) min respectively. Paired t test was conducted in the two groups, P < 0.01 with significant statistical difference; The mean maximum position deviation between T1 group and T2 group of the midline mandibular region in labial lingual direction was (0.32±0.14) mm, that was (0.40±0.23) mm in vertical direction; the mean maximum position deviation of molar area in buccal lingual direction was (0.35±0.23) mm and that was (0.33±0.20) mm in vertical direction. In the vertical and horizontal directions, the maximum position deviation of mandibles between group T1 and group T2 was controlled within 0.5 mm. In the process of clinical complete dentures try-in, there was no deviation from the center line of dentures. There was not warping, swinging and other poor stability phenomena in T1 and T2 groups. CONCLUSION The digital manufacturing of simple intraoral Gothic arch-tracing device can be used to determine the centric relation of complete dentures, which can not only save time of clinical operation, but also ensure the accuracy of the centric relation.
Humans ; Centric Relation ; Jaw Relation Record/methods* ; Denture, Complete ; Mouth, Edentulous ; Jaw, Edentulous