AIM To establish an UPLC-MS/MS method for simultaneous content determination of protocatechuic acid,epicatechin,chlorogenic acid,quercitrin,gaultherin and gaultheroside A in Gaultheria leucocarpa var.yunnanensis.METHODS The analysis was performed on a 40℃thermostatic Waters BEH C18 column(100 mm×2.1 mm,1.7 μm),with the mobile phase comprising of water(containing 0.1%formic acid)-acetonitrile(containing 0.1%formic acid)flowing at 0.3 mL/min in a gradient elution manner,and electron spray inoization source was adopted in positive and negative ion scanning with multiple reaction monitoring(MRM)mode.Hierarchical cluster analysis(HCA)and principal component analysis(PCA)was used to screen important components that affect the quality of medicinal materials.RESULTS Six constituents showed good linear relationships within their own ranges(R2≥0.998 2),whose average recoveries were 98.76%-101.88%with the RSDs of 1.0%-2.5%.The constituents of G.leucocarpa in the roots and aerial parts were quite different.Gaultherin,epicatechin and protocatechuic acid may be the quality mark constituents of G.leucocarpa.CONCLUSION This accurate and efficient method can be used for the quality control of G.leucocarpa.

ObjectiveMetabolomics was used to reveal the mechanism of Aconiti Lateralis Radix Praeparata（ALRP） in attenuating toxicity by processing from the aspects of amino acid metabolism， oxidative stress and energy metabolism by analyzing multiple metabolic pathways. MethodTwenty-four rats were randomly divided into control group， raw group and processed group， 8 rats in each group. The raw and processed group were given with 0.64 g·kg^-1 of raw ALRP and processed ALRP respectively every day， the control group was given with an equal amount of normal saline once a day. After continuous administration for 7 days， the urine， serum and heart tissue of rats were collected. Pathological examination of the heart was carried out using hematoxylin-eosin（HE） staining， and the activities of lactate dehydrogenase（LDH） and creatine kinase-MB（CK-MB） in serum and cardiac tissues were detected by microplate assay and immunoinhibition assay. The effects of ALRP on rat heart before and after processing were compared and analyzed. Ultra performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS） was used to perform urine metabolomics analysis， and multivariate statistical analysis was used to screen for differential metabolites related to ALRP in attenuating toxicity by processing， and pathway enrichment analysis was carried out to explore the processing mechanism. ResultHE staining showed that no obvious pathological changes were observed in the heart tissue of the control group， while obvious infiltration of inflammatory cells such as plasma cells and granulocytes was observed in the heart tissue of the raw group， indicating that the raw ALRP had strong cardiotoxicity. There was no significant difference in HE staining of heart tissue between the processed group and the control group， indicating that the toxicity of ALRP was significantly reduced after processing. Compared with the control group， the activities of LDH and CK-MB were significantly increased in serum and heart tissue of the raw group， and those were significantly decreased in serum and heart tissue of the processed group， suggesting that the myocardial toxicity of processed ALRP was reduced. A total of 108 endogenous differential metabolites associated with the raw ALRP were screened using multivariate statistical analysis in positive and negative modes， of which 51 differential metabolites were back-regulated by the processed ALRP. Biological analysis of the key regulatory pathways and associated network changes showed that the pathways related to toxicity of ALRP mainly included tryptophan metabolism， arginine and proline metabolism， phenylalanine metabolism， aminoacyl-tRNA biosynthesis， alanine， aspartate and glutamate metabolism， etc. The metabolic pathways related to the attenuation of processed ALRP mainly included aminoacyl-tRNA biosynthesis， tryptophan metabolism， phenylalanine， tyrosine and tryptophan biosynthesis， phenylalanine metabolism and caffeine metabolism. ConclusionThe processing technology of ALRP in Guilingji can significantly attenuate the cardiotoxicity of raw products， the mechanism mainly involves amino acid metabolism， oxidative stress and energy metabolism， which can provide experimental bases for the research related to the mechanism of toxicity reduction of ALRP by processing and its clinical safety applications.

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.

Objective To analyze the molecular markers of various nuclei in the human basal ganglia and the differentially expressed genes(DEGs)among different nuclei,gender,and Parkinson's disease(PD),followed by the biological function annotations of the DEGs.Methods Forty-five specimens of basal ganglia from 10 human postmortem brains were divided into control and PD groups,and the control group was further categorized into female and male groups.RNA from each sample was extracted for high-throughput transcriptome sequencing.Bioinformatic analysis was conducted to identify molecular markers of each nuclei in the control group,nuclei-specific,gender-specific,and PD-specific DEGs,followed by gene enrichment analysis and functional annotation.Results Sequencing analysis revealed top DEGs such as DRD1,FOXG1,and FAM183A in the caudate;SLC6A3,EN1,SLC18A2,and TH in the substantia nigra;MEPE and FGF10 in the globus pallidus;and SLC17A6,PMCH,and SHOX2 in the subthalamic nucleus.In them,putamen showed some overlapping DEGs with caudate,such as DRD1 and FOXG1.A significant number of DEGs were identified among different nuclei in the control group,with the highest number between caudate and globus pallidus(9321),followed by putamen and globus pallidus(6341),caudate and substantia nigra(6054),and substantia nigra and subthalamic nucleus(44).Gene enrichment analysis showed that downregulated DEGs between caudate and globus pallidus were significantly enriched in processes like myelination of neurons and cell migration.Upregulated DEGs between putamen and globus pallidus were enriched processes like chemical synaptic transmission and regulation of membrane potential,while downregulated DEGs were enriched in myelination and cell adhesion.Upregulated DEGs between caudate and substantia nigra were enriched in processes like chemical synaptic transmission and axonal conduction,while downregulated DEGs were enriched in myelination of neurons.Totally 468,548,1402,333,and 341 gender-specific upregulated DEGs and 756,988,2532,444,and 1372 downregulated DEGs were identified in caudate,putamen,substantia nigra,globus pallidus,and subthalamus nucleus.Gene enrichment analysis revealed upregulated DEGs mostly enriched in pathways related to immune response and downregulated DEGs in chemical synaptic transmission.At last,709,852,276,507,and 416 PD-specific upregulated DEGs and 830,2014,1218,836,and 1730 downregulated DEGs were identified in caudate,putamen,substantia nigra,globus pallidus,and subthalamus nucleus.Gene enrichment analysis revealed upregulated DEGs mostly enriched in apoptotic regulation and downregulated DEGs in chemical synaptic transmission and action potential regulation.Conclusion We identified and analysed the molecular markers of different human basal ganglia nuclei,as well as DEGs among different nuclei,different gender,and between control and PD.

Objective:To explore the potential causal relationship between gut microbiota and teratozoospermia.Methods:We searched the database of Genome-Wide Association Study(GWAS)for gut microbiota-and teratozoospermia-related data.We used gut microbiota as an exposure factor,determined the instrumental variables according to the GWAS data on 18 340 participants released by the MiBioGen Alliance,and derived the outcome variables from the European data on teratozoospermia,with a sample size of 85 716,including 915 cases and 209 006 controls.Using inverse-variance weighting(IVW),MR-Egger regression and the weighted median estimator(WME),we performed two-sample Mendelian randomization(MR)analysis on the retrieved data,and estimated the causal relationship between gut microbiota and teratozoospermia based on the β value.Results:Two-sample MR analysis indicated that the class Erysipelotrichia,family Erysipelotrichaceae,family Streptococcaceae,genus Coprococcusl,genus Ruminococcaceae UCG009,genus Streptococcus,order Clostridialesm and order Erysipelotrichales were causally related with the increased risk,while the family Porphyromonadaceae with the decreased risk of teratozoospermia.Conclusion:The class Erysipelotrichia,family Erysipe-lotrichaceae,family Streptococcaceae,genus Coprococcusl,genus Ruminococcaceae UCG009,genus Streptococcus,order Clostridia-lesm and order Erysipelotrichales are one of the causes of teratozoospermia,related to the increased risk of the condition,while the family Porphyromonadaceae has a protective effect on sperm morphology,reducing the risk of teratozoospermia.

Objective:Analyze the isolation and antimicrobial resistance of Candida auris.Methods:Using matrix-assisted laser desorption ionization time-of-flight mass spectrometry, 10 clinically isolated strains of Candida auris were identified in Nanfang Hospital of Southern Medical University between September and December 2023. Additionally, their resistance to multiple antifungal drugs, specimen source, and patient prognosis were analyzed. Results:All 10 isolates were identified as Candida auris by mass spectrometry. The drug sensitivity test showed that 10 strains were resistant to fluconazole, 3 strains were resistant to amphotericin B, and all were sensitive to Echinocandins. The samples came from various sources; except for 2 patients who were in good condition, 1 patient with stable condition were discharged, and 1 patient died, the remaining 6 patients voluntarily discharged due to worsening of their condition. Conclusions:Candida auris can be identified by mass spectrometry. It was found that Candida auris had high resistance to fluconazole and no resistance to echinocanthin.

Objective:By analyzing the clinical phenotypic characteristics and gene sequences of two patients with Treacher Collins syndrome（TCS）, the biological causes of the disease were determined. Then discuss the therapeutic effect of hearing intervention after bone bridge implantation. Methods:All clinical data of the two family members were collected, and the patients signed the informed consent. The peripheral blood of the proband and family members was extracted, DNA was extracted for whole exome sequencing, and Sanger sequencing was performed on the family members for the mutation site.TCOF1genetic mutations analysis was performed on the paitents. Then, the hearing threshold and speech recognition rate of family 2 proband were evaluated and compared under the sound field between bare ear and wearing bone bridge. Results:In the two pedigrees, the probands of both families presented with auricle deformity, zygomatic and mandibular hypoplasia, micrognathia, hypotropia of the eye fissure, and hypoplasia of the medial eyelashes. The proband of Family 1 also presents with specific features including right-sided narrow anterior nasal aperture and dental hypoplasia, which were consistent with the clinical diagnosis of Treacher Collins syndrome. Genetic testing was conducted on both families, and two heterozygous mutations were identified in the TCOF1 gene: c. 1350_1351dupGG（p. A451Gfs*43） and c. 4362_4366del（p. K1457Efs*12）, resulting in frameshift mutations in the amino acid sequence. Sanger sequencing validation of the TCOF1 gene in the parents of the proband in Family 1 did not detect any mutations. Proband 1 TCOF1 c. 1350_1351dupGG heterozygous variants have not been reported previously. The postoperative monosyllabic speech recognition rate of family 2 proband was 76%, the Categories of Auditory Performance（CAP） score was 6, and the Speech Intelligibility Rating（SIR） score was 4. Assessment using the Meaningful Auditory Integration Scale（MAIS） showed notable improvement in the patient's auditory perception, comprehension, and usage of hearing aids. Evaluation using the Glasgow Children's Benefit Inventory and quality of life assessment revealed significant improvements in the child's self care abilities, daily living and learning, social interactions, and psychological well being, as perceived by the parents. Conclusion:This study has elucidated the biological cause of Treacher Collins syndrome, enriched the spectrum of TCOF1 gene mutations in the Chinese population, and demonstrated that bone bridge implantation can improve the auditory and speech recognition rates in TCS patients.
Child ; Humans ; Mandibulofacial Dysostosis/genetics* ; Quality of Life ; Speech ; Parents ; Mutation ; Nuclear Proteins/genetics* ; Phosphoproteins/genetics*

OBJECTIVE: To compare the clinical efficacy between the combined therapy of fire needling and cupping, and western medication on herpes zoster of acute stage, as well as the effects on Th17 and Treg cells and inflammatory factors, i.e. IL-10 and IL-17 in the peripheral blood. METHODS: Eighty patients with herpes zoster of acute stage were randomly divided into a combined therapy (fire needling plus cupping) group and a western medication group, 40 cases in each one. In the combined therapy group, the pricking and scattering techniques with fire needle were used at ashi points and Jiaji (EX-B 2) corresponding to the affected spinal segments; afterwards, cupping therapy was delivered. The combined treatment was given once daily. In the western medication group, valaciclovir hydrochloride tablet and vitamin B₁ tablet were administered orally. The duration of treatment in each group was 10 days. Before each treatment from day 1 to day 10 and on day 11 , the score of symptoms and physical signs was observed in the two groups separately. Before each treatment from day 1 to day 10 and on day 11, 30, 60, the score of visual analogue scale (VAS) and skin lesion indexes were observed in the two groups. On day 60, the incidence of postherpetic neuralgia was recorded in the two groups. The levels of Th17 and Treg cells, Th17/Treg ratio in the peripheral blood, as well as serum levels of IL-10 and IL-17 were detected before and after treatment in the two groups. The clinical efficacy was compared between the two groups. RESULTS: From day 6 to day 10 during treatment and on day 11, the scores of symptoms and physical signs in the combined therapy group were lower than those of the western medication group (P<0.05, P<0.01). On day 3, day 6 to day 10 during treatment and day 11, day 30, VAS scores in the combined therapy group were lower than those of the western medication group (P<0.05, P<0.01). On day 60, the incidence of postherpetic neuralgia in the combined therapy group was lower compared with that in the western medication group (P<0.05). The blister arresting time and scabbing time in the combined therapy group were shorter than those of the western medication group (P<0.05). After treatment, the level of Th17, and Th17/Treg ratio in the peripheral blood, as well as the serum levels of IL-10 and IL-17 were all lower in comparison with those in the western medication group (P<0.05). The curative and remarkably effective rate was 82.5% (33/40) in the combined therapy group, higher than 62.5% (25/40) in the western medication group (P<0.05). CONCLUSION The early application of fire needling combined with cupping therapy can effectively treat herpes zoster of acute stage, relieve pain, and reduce the incidence of postherpetic neuralgia, which may be related to reducing the levels of Th17 and Treg cells, and Th17/Treg ratio in the peripheral blood, as well as the serum levels of IL-10 and IL-17 so that the cellular immune balance is modulated.
Humans ; Neuralgia, Postherpetic ; Acupuncture Therapy/methods* ; Interleukin-10 ; Interleukin-17 ; T-Lymphocytes, Regulatory ; Cupping Therapy ; Th17 Cells ; Herpes Zoster/therapy* ; Treatment Outcome ; Tablets

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*

AIM: To investigate the risk factors associated with neovascular glaucoma(NVG)after pars plana vitrectomy(PPV)for proliferative diabetic retinopathy(PDR).METHODS: The PDR patients who received 23G PPV treatment at Shenyang He Eye Specialist Hospital from October 2015 to September 2020 and were followed up for at least 12mo with complete data were retrospectively collected. The patients were divided into two groups according to the occurrence of NVG during follow-up. The preoperative and intraoperative variables between two groups were compared. The cumulative hazard ratio for NVG was evaluated. RESULTS: A total of 151 PDR patients(169 eyes)with a mean follow-up of 18.07±12.55(1～79)mo were included, of which 30(17.8%)eyes developed NVG, the mean time of occurrence was 6.27±4.01(1～17)mo, and 50%(15 eyes)of NVG occurred within 5mo after vitrectomy. The cumulative hazard ratios of NVG at postoperative 3, 6 and 12mo were 4.8%, 12.6% and 18.1%, respectively. Multivariate logistic regression analysis showed that preoperative best corrected visual acuity(OR=3.077, 95%CI: 1.203～7.869, P=0.019), preoperative iris rubeosis(OR=7.897, 95%CI: 1.313～47.498, P=0.024), and contralateral NVG(OR=22.108, 95%CI: 1.562～312.861, P=0.022)were risk factors with the occurrence of NVG, while the number of intraoperative retinal laser photocoagulation(OR=0.772, 95%CI: 0.666～0.893, P=0.001)was the protective factor with the occurrence of NVG.CONCLUSIONS: The incidence of NVG in PDR eyes after PPV was 17.8%, of which 50% occurred within 5mo after surgery. PDR eyes with poor baseline visual acuity, iris rubeosis, and contralateral NVG are prone to postoperative NVG, and sufficient intraoperative retinal laser photocoagulation has a certain protective effect. PDR eyes after PPV should be closely followed up for 1a.