BACKGROUND:Our previous studies have shown that the poly(hydroxybutyrate- co-hydroxyvalerate) - sol-gel bioactive glass (PHBV-SGBG) has good biocompatibility and promote bone tissue repair, but its specific role in periodontal tissue regeneration has not been investigated. OBJECTIVE:To investigate the periodontal regenerative effects of a PHBV-SGBG scaffold in beagle dogs. METHODS:Alveolar bone defects (5 mm×5 mm) were surgicaly created bilateraly at the buccal side of the mandibular third and fourth premolars of four beagle dogs. PHBV-SGBG scaffold was randomly filed in the defects as experimental group and nothing was put into the contralateral as control group. Histological and scanning electron microscopy observations, cone-beam CT evaluation and the Ca/P concentration ratio analysis were processed at 2, 4, 8 and 12 weeks after surgery. RESULTS AND CONCLUSION:After surgery, the height of the regenerated tissue increased with time in both groups, and the regenerated tissue height in the experiment group was higher than that in the control group (P < 0.05). At 12 weeks after surgery, the Ca/P concentration ratio of the experiment group was close to that in the normal tissue (P > 0.05), but higher than that of the control group (P < 0.05); the histological observation showed that the regenerated tissue of the experimental group was close to the normal tissue, and the regenerated tissue of the control group tended to be mature, with a smal amount of new blood vessels. Under the scanning electron microscope, no scaffold structure was visible in the experimental group with the presence of bone lacuna at 8 weeks after surgery, while in the control group, there was no bone lacuna and obvious osteoblasts; at 12 weeks after surgery, the structure of the regenerated tissue of experimental group was more regular and close to the normal tissue with no remarkable osteoblasts, and in the control group, the regenerated tissue was disordered, with several cavity. These results show that the PHBV-SGBG scaffold can enhance periodontal bone regeneration effectively.

Objective To explore the impact of early repetitive painful procedures on subsequent pain behaviors and physiological indicators in full-term infants.Methods Sixty-two full-term neonates were enrolled (male 36 cases,female 26 cases) from the medical center of neonatal care at Nanjing Children's Hospital Affiliated to Nanjing Medical University from March to May in 2009.The data of all painful procedures were performed on those neonates and their responses to them were collected by using digital video recording were collected.The Neonatal Facial Coding System C(NFCS) and Neonatal Infant Pain Scale(NIPS) were used prospectively to evaluate the pain response to painful procedures.Results The average experience of pain caused by operation on newborn at the hospital was 56.5 times (12-249 times),and the daily average was 5.9 times (4-26 times).After they were exposed to more than 10 repetitive pain procedures,the full-term neonates showed the declining pain response assessed by NFCS and NIPS during the subsequent painful procedures (NFCS:P10=0.012,P20=0.015,P30=0.041;NIPS:P10=0.006,P20=0.015,P30=0.049),and the temporarily enhanced pain response was observed in the preparation phase of the subsequent painful procedures (NFCS:P2＜0.001,P3＜0.001,P4=0.004,P5=0.009;NIPS:P2＜0.001,P3＜0.001,P4=0.045,P5 =0.031).Bnt there was no difference in preparation phase.There was no alternation in latency and crying time after repetitiing painful procedures,but the proportion of crying neonates in the preparation phase of the painful procedures was increased(P=0.032).Conclusions After exposed to repetitive pain,full-term neonates expressed hypoalgesia during subsequent painful procedures,but the temporary irritation was enhanced during the following phases exposed to stress.

Objective To evaluate the effects of repetitive noxious stimuli during the neonatal period on the pain sensitivity during adulthood in rats.Methods Twenty pathogen-free male neonatal SpragueDawley rats,weighing 6.2-6.8 g,were randomly divided into 2 groups (n=10 each) using a random number table:control group (group C) and repetitive noxious stimuli group (group RNS).In RNS group,neonatal rats sequentially received needle pricks into the dorsal surface of 4 paws at 6 h intervals with a 28 G needle per day during the first postnatal week.In group C,the animals received non-painful tactile stimuli with cotton tip rub.At the age of 10 weeks,complete Freund' s adjuvant was injected into the plantar surface of the right hind paw to induce inflammatory pain.Before injection,and at 24 h and 7 days after injection (T0-2),the mechanical and thermal thresholds were measured,and alcohol preference test was performed for assessment of the behavior at T2.Results The mechanical threshold of the right paws was significantly lower at T1.2 than that of the left paws in the two groups.Compared to group C,the mechanical threshold of the left and right paws at T0-2 and thermal threshold of the right paws at T1 were significantly decreased,and alcohol intake was increased in group RNS.Conclusion Repetitive noxious stimuli during the neonatal period can lead to increase in the pain sensitivity during adulthood in rats.

Objective To establish the fingerprints and formononetin content determination method for Caulis Spatholobi from different habitats by high performance liquid chromatography ( HPLC) , thus to control the quality of Caulis Spatholobi. Methods Reversed phase-high performance liquid chromatography (RP-HPLC) for fingerprint was performed on Feini Gen RedClassical AQ-C18 column ( 4.6 mm × 250 mm, 5 μm) with acetonitrile-0.1%acetic acid solution as the mobile phase by gradient elution, and the detection wavelength was 260 nm. High performance liquid chromatography-diode array detector ( HPLC-DAD) for the determination of formononetin content was performed on AcclaimTM 120-C18 column ( 4.6 mm × 250 mm, 5 μm) with acetonitrile-water solution by isocratic elution, the detection wavelength was 254 nm, the flow rate was 1.0 mL/min and the column temperature was 25℃. Results The standard fingerprint of Caulis Spatholobi was set up through the evaluation of the fingerprints of 24 batches of Caulis Spatholobi samples from different habitats. Thirteen common peaks were identified with reference to formononetin peak, and the content of formononetin was determined by HPLC-DAD method. The similarity of the fingerprints of Caulis Spatholobi from different habitats and their formononetin content had great differences. Conclusion The established method is simple, accurate, highly sensitive, and repeatable, and can be applied for the quality control of Caulis Spatholobi.

Purpose: This study aimed to investigate reproductive concerns among breast cancer patients of reproductive age, analyze the influencing factors, explore the relationship between coping styles, fear of progression (FOP), and reproductive concerns, and identify the multiple effects of coping styles on the relationship between FOP and reproductive concerns among Chinese breast cancer patients. Methods: A cross-sectional, descriptive study was conducted among breast cancer patients in four tertiary grade A hospitals in Fujian, China, from January 2022 to September 2022. A total of 210 patients were recruited to complete paper-based questionnaires, which included the general data questionnaires, the Reproductive Concerns After Cancer Scale (RCACS), the Fear of Progression Questionnaire-Short Form (FOP-Q-SF), and the Medical Coping Modes Questionnaire (MCMQ). Structural equation models were utilized to evaluate the multiple effects of coping styles on FOP and reproductive concerns. Results: Reproductive concerns in breast cancer patients had a mean score of 53.02 (SD, 10.69), out of a total score of 90, and coping styles for cancer (confrontation, avoidance) were closely associated with FOP and reproductive concerns. FOP showed a significant positive correlation with reproductive concerns (r = .52, p < .01). At the same time, confrontation was significantly negatively correlated with both FOP (r = −.28, p < .01) and reproductive concerns (r = −.39, p < .01). Avoidance was positively correlated to both FOP (r = .25, p < .01) and reproductive concerns (r = .34, p < .01). The impact of FOP on reproductive concerns is partially mediated by confrontation and avoidance, with effect sizes of .07 and .04, respectively. These mediating factors account for 22.0% of the total effect. Conclusions The FOP directly impacted reproductive concerns, while coping styles could partially mediate the association between FOP and reproductive concerns. This study illustrates the role of confrontation and avoidance in alleviating reproductive concerns, suggesting that it is necessary to focus on the changes in reproductive concerns among reproductive-age breast cancer patients. Healthcare professionals can improve disease awareness and reduce patients' FOP, thereby promoting positive psychological and coping behaviors and ultimately alleviating reproductive concerns.

Objective To study the effects of painful procedures during neonatal period on rats' hippocampal gene expression in later life.Method A total of 28 newborn male rats were randomly assigned into two equal groups.From day1 (P1) to day7(P7) after birth,rats in the pain group received four times of needle acupuncture at the foot everyday,simulating the infants' experience in the NICU.Rats in control group were touched at the same side of the foot with a cotton swab.Transcriptome sequencing of the hippocampus of the two groups were examined on day 8 (P8) and day 21 (P21).The gene expression profiles were established and the differentially expressed genes were screened for functional analysis.Quantitative Real-time polymerase chain reaction (qRT-PCR) was used to confirm these differentially expressed genes (GABRB1,GRIN2A,IL1 RAPL1) related to pain-stimulated response or brain cognition,and one of the key genes was further verified using Western blotting.Result The sequencing results showed that there were only 6 differentially expressed genes in hippocampal tissues of rats on P8 in the two groups.Howerer,the number increased to 53 on P21 and 85.0％ of these genes were down-regulated (45/53).Gene Ontology (GO) function enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis showed that the differentially expressed genes were mainly expressed on the cell membrane,voltage-gated ion channels,synapses,neurotransmitter receptors,immune responses,etc.The qRT-PCR and Western-blot results of key genes were consistent with the transcriptome sequencing.Conclusion Pain stimuli at an early stage after birth may trigger differentially expression of voltage-gated ion channel proteins,neurotransmitter receptors,and some key genes such as GABRB1 on hippocampal synaptic cell membranes in rats.These phenomenon may provide initial explanation for the molecular mechanism of early pain stimuli on neonatal brain development.

Objective:To investigate the effects of enriched environments on behavioral development at toddler period of preterm who had experienced early repeated operative pain.Methods:A cross-sectional study was conducted. A total of 80 high-risk preterm children of 2 years of age, who had experienced repeated pain stimuli in the neonatal intensive care unit (NICU), were enrolled as preterm group from the High-risk Children Clinic of Children′s Hospital of Nanjing Medical University from October 2016 to March 2021. Furthermore, 39 full-term healthy children, aged 2 years, who were undergoing routine check-ups during the same period, were selected as the full-term group. The preterm group was further divided into preterm intervention group and preterm non-intervention group based on the implementation of enriched environment interventions. Data of neonatal characteristics from 3 groups were collected. Growth and development indicators at the age of 2 years were measured. Neuropsychological development evaluated by Gesell developmental scale. Behavioral development evaluated by child behavior check list. The salivary cortisol levels in response to novelty (baseline, task, end) were collected. The family environment, including maternal parenting pressure, were evaluated through a survey questionnaire. One-way ANOVA and least significant difference (LSD) tests were used to compare physical development, maternal parenting stress, Gesell neuropsychological development, and behavioral problems among the 3 groups. A repeated-ANOVA and LSD tests were employed to compare the patterns of salivary cortisol secretion. Pearson correlation analysis was used to explore the influencing factors related to neuropsychological and behavioral development and cortisol level.Results:There were 44 cases in the preterm intervention group (17 males, gestational age of (31.3±2.8) weeks), and 36 in the preterm non-intervention group (29 males, gestational age of (32.5±2.6) weeks). The full-term group consisted of 39 children (23 males, gestational age of (39.3±2.1) weeks). At 2 years of age, the height, weight, and head circumference of the preterm intervention group and non-intervention group were all lower than those of the full-term group (all P<0.05).The Gesell developmental schedule showed that the preterm non-intervention group scored all lower in gross motor, fine motor, adaptive, language and personal-social domains compared to the full-term group (91±7 vs. 97±6, 88±9 vs. 94±6, 89±8 vs. 99±8, 84±10 vs. 100±15, 89±7 vs. 95±6), with statistical significance (all P<0.01). The preterm intervention group scored all higher than the preterm non-intervention group in gross motor, fine motor, adaptive and language domains (all P<0.05), with no significant difference compared to the full-term group (all P>0.05). The number of needle painful procedures during hospitalization in NICU of the non-intervention group was negatively correlated to the adaptive development quotient ( r=-0.48, P<0.05). Furthermore, the preterm non-intervention group exhibited higher scores in social withdrawal, depression, somatic complaints, aggression, and destructive behaviors compare to the full-term group and preterm intervention group ( F=8.07, 5.67, 7.72, 7.90, 7.06; all P<0.05); while the preterm intervention group showed no significant difference compared to full-term group (all P>0.05). Behavioral problems (social withdrawal and depression) in the preterm non-intervention group were positively correlated with maternal parenting stress ( r=0.66, 0.50; both P<0.05). In response to novel visual stimuli and cognitive challenges, the preterm non-intervention group had significantly higher salivary cortisol levels compared to the full-term group ( P=0.006), which were negatively correlated with the frequency of early painful procedures ( r=-0.83, -0.80; both P<0.01). There was no significant difference in cortisol secretion pattern between the intervention group and the full-term group ( P=0.772). Conclusion:Enriched environmental interventions can improve neuropsychological development, decrease behavioral problems, and down-regulate consistent high cortisol response to task in preterm infants who have experienced repeated procedural pain in the NICU by the age of 2 years.

Genome-scale metabolomics analysis is increasingly used for pathway and function dis-covery in the post-genomics era.The great potential offered by developed mass spectrometry(MS)-based technologies has been hindered,since only a small portion of detected metabolites were iden-tifiable so far.To address the critical issue of low identification coverage in metabolomics,we adopted a deep metabolomics analysis strategy by integrating advanced algorithms and expanded reference databases.The experimental reference spectra and in silico reference spectra were adopted to facilitate the structural annotation.To further characterize the structure of metabolites,two approaches were incorporated into our strategy,i.e.,structural motif search combined with neutral loss scanning and metabolite association network.Untargeted metabolomics analysis was performed on 150 rice cultivars using ultra-performance liquid chromatography coupled with quadrupole-Orbitrap MS.Consequently,a total of 1939 out of 4491 metabolite features in the MS/MS spectral tag(MS2T)library were annotated,representing an extension of annotation coverage by an order of magnitude in rice.The differential accumulation patterns of flavonoids between indica and japon-ica cultivars were revealed,especially O-sulfated flavonoids.A series of closely-related flavonolignans were characterized,adding further evidence for the crucial role of tricin-oligolignols in lignification.Our study provides an important protocol for exploring phytochemical diversity in other plant species.