Background During pregnancy, negative emotions such as anxiety and depression may induce cortisol disruption. Cortisol can be transmitted to the fetus through the placental barrier, thereby affecting the neurodevelopment of the offspring. Objective To investigate the relationship between placental cortisol, maternal depression during pregnancy, and neurodevelopment of 3-month-old infants. Methods From September 2022 to September 2023, 171 pregnant women ordered routine prenatal checks at the obstetrics outpatient department of a tertiary hospital in Ningxia were selected using a prospective cohort design. After providing informed consent, these women participated in a questionnaire survey that covered general individual characteristics, prenatal depression, and sleep quality. At birth, placental samples were collected to measure cortisol levels using ELISA kits. Follow-up assessments on the neurodevelopmental of 3-month-old infants were conducted using the Warning Sign for Children Mental and Behavioral Development. LASSO regression analysis was conducted to screen the influencing factors of depression during pregnancy. Huber regression analysis was then applied to assess potential linear relationship between depression during pregnancy and placental cortisol levels. Log-binomial regression was used to analyze the linear relationships between cortisol levels and neurodevelopmental delay in 3-month-old infants. Additionally, a mediation effect model was fitted using R 4.3.3 to assess possible mediating role of cortisol in the association between prenatal depression and neurodevelopmental delay in 3-month-old infants. Results The positive rate of prenatal depression was 33.33%. Nine factors affecting prenatal depression were identified by LASSO regression, including rural residence, high school education or above, extroverted personality characteristics, moderate early pregnancy reactions, baby sex expectation, prenatal anxiety, family dysfunction, exposure to stressful life events during pregnancy, and moderate prenatal sleep quality. The Huber regression model showed a positive linear correlation between prenatal depression and placental cortisol (P<0.05). With or without controlling confounding factors, the results of log-binomial regression modeling showed that cortisol levels were associated with a reduced risk of neurodevelopmental delay in 3-month-old infants (crude model: RR=0.988, 95%CI: 0.9768, 0.9996, P＜0.05; adjusted model: RR=0.988, 95%CI: 0.9764, 0.9993, P＜0.05). A mediating effect of placental cortisol between prenatal depression and the risk of neurodevelopmental delay in 3-month-old offspring was found statistically significant (P=0.045), accounting for 67.0% of the total effect. Conclusion Prenatal depression is associated with elevated placental cortisol levels, and higher cortisol levels are found to be related to a lower risk of neurodevelopmental delay in infants. Placental cortisol mediates the relationship between prenatal depression and infant neurodevelopment.

Periodontal bone defects, primarily caused by periodontitis, are highly prevalent in clinical settings and manifest as bone fenestration, dehiscence, or attachment loss, presenting a significant challenge to oral health. In regenerative medicine, harnessing developmental principles for tissue repair offers promising therapeutic potential. Of particular interest is the condensation of progenitor cells, an essential event in organogenesis that has inspired clinically effective cell aggregation approaches in dental regeneration. However, the precise cellular coordination mechanisms during condensation and regeneration remain elusive. Here, taking the tooth as a model organ, we employed single-cell RNA sequencing to dissect the cellular composition and heterogeneity of human dental follicle and dental papilla, revealing a distinct Platelet-derived growth factor receptor alpha (PDGFRA) mesenchymal stem/stromal cell (MSC) population with remarkable odontogenic potential. Interestingly, a reciprocal paracrine interaction between PDGFRA⁺ dental follicle stem cells (DFSCs) and CD31⁺ Endomucin⁺ endothelial cells (ECs) was mediated by Vascular endothelial growth factor A (VEGFA) and Platelet-derived growth factor subunit BB (PDGFBB). This crosstalk not only maintains the functionality of PDGFRA⁺ DFSCs but also drives specialized angiogenesis. In vivo periodontal bone regeneration experiments further reveal that communication between PDGFRA⁺ DFSC aggregates and recipient ECs is essential for effective angiogenic-osteogenic coupling and rapid tissue repair. Collectively, our results unravel the importance of MSC-EC crosstalk mediated by the VEGFA and PDGFBB-PDGFRA reciprocal signaling in orchestrating angiogenesis and osteogenesis. These findings not only establish a framework for deciphering and promoting periodontal bone regeneration in potential clinical applications but also offer insights for future therapeutic strategies in dental or broader regenerative medicine.
Receptor, Platelet-Derived Growth Factor alpha/metabolism* ; Humans ; Neovascularization, Physiologic/physiology* ; Dental Sac/cytology* ; Single-Cell Analysis ; Transcriptome ; Mesenchymal Stem Cells/metabolism* ; Bone Regeneration ; Animals ; Dental Papilla/cytology* ; Periodontium/physiology* ; Stem Cells/metabolism* ; Regeneration ; Angiogenesis

Mesangial cell proliferation is an early pathological indicator of diabetic nephropathy (DN). Growing evidence highlights the pivotal role of paired-related homeobox 1 (Prrx1), a key regulator of cellular proliferation and tissue differentiation, in various disease pathogenesis. Notably, Prrx1 is highly expressed in mesangial cells under DN conditions. Both in vitro and in vivo studies have demonstrated that Prrx1 overexpression promotes mesangial cell proliferation and contributes to renal fibrosis in db/m mice. Conversely, Prrx1 knockdown markedly suppresses hyperglycemia-induced mesangial cell proliferation and mitigates renal fibrosis in db/db mice. Mechanistically, Prrx1 directly interacts with the Yes-associated protein 1 (YAP) promoter, leading to the upregulation of YAP expression. This upregulation promotes mesangial cell proliferation and exacerbates renal fibrosis. These findings emphasize the crucial role of Prrx1 upregulation in high glucose-induced mesangial cell proliferation, ultimately leading to renal fibrosis in DN. Therefore, targeting Prrx1 to downregulate its expression presents a promising therapeutic strategy for treating renal fibrosis associated with DN.

Benign prostatic hyperplasia(BPH)is one of the major chronic complications of type 2 diabetes mellitus(T2DM),and sex steroid hormones are common risk factors for the occurrence of T2DM and BPH.The profiles of sex steroid hormones are simultaneously quantified by LC-MS/MS in the clinical serum of patients,including simple BPH patients,newly diagnosed T2DM patients,T2DM complicated with BPH patients and matched healthy individuals.The G protein-coupled estrogen receptor(GPER)inhibitor G15,GPER knockdown lentivirus,the YAP1 inhibitor verteporfin,YAP1 knockdown/overexpression lentivirus,targeted metabolomics analysis,and Co-IP assays are used to investigate the molecular mechanisms of the disrupted sex steroid hormones homeostasis in the pathological process of T2DM complicated with BPH.The homeostasis of sex steroid hormone is disrupted in the serum of patients,accompanying with the proliferated prostatic epithelial cells(PECs).The sex steroid hormone metabolic profiles of T2DM patients complicated with BPH have the greatest degrees of separation from those of healthy individuals.Elevated 17β-estradiol(E2)is the key contributor to the disrupted sex steroid hormone homeostasis,and is significantly positively related to the clinical characteristics of T2DM patients complicated with BPH.Activating GPER by E2 via Hippo-YAP1 signaling exacerbates high glucose(HG)-induced PECs prolifer-ation through the formation of the YAP1-TEAD4 heterodimer.Knockdown or inhibition of GPER-mediated Hippo-YAP1 signaling suppresses PECs proliferation in HG and E2 co-treated BPH-1 cells.The anti-proliferative effects of verteporfin,an inhibitor of YAP1,are blocked by YAP1 overexpression in HG and E2 co-treated BPH-1 cells.Inactivating E2/GPER/Hippo/YAP1 signaling may be effective at delaying the progression of T2DM complicated with BPH by inhibiting PECs proliferation.

A retrospective analysis was made on clinical data of a case of familial dysalbuminemic hyperthyroxinemia (FDH) treated at Hebei Children′s Hospital in August 2021.The patient, female, 4 years and 2 months old, was diagnosed with growth retardation.Genetic sequencing of the child and her immediate family revealed a heterozygous mutation, c.725G>A(p.R242H) in exon 7 of the albumin gene, which confirmed the diagnosis of FDH.The growth and development of the girl were monitored regularly.Early identification and diagnosis of FDH can prevent misdiagnosis or improper antithyroid medication from affecting children′s growth and development, and growth hormone therapy is effective for children with FDH who are slow growing.

Objective To systematically evaluate the efficacy and safety of finerenone in treating the pa-tients with heart failure.Methods The databases of Pubmed,Embase,Cochrane Library,Web of Science and Scopus were retrieved.The retrieval time was from the establishment of the database to April 21,2024.The data of randomized controlled trials(RCTs)on finerenone in treating heart failure were collected.After screening the literatures and extracting the data,the Jadad scale and Cochrane bias risk assessment tool were used to evaluate the quality of included literatures.The RevMan5.4 software was adopted to conduct the meta analysis.Results Five RCTs involving in a total of 2 518 patients with heart failure were finally included.In the aspect of effectiveness outcome indicators,there was no statistical difference in improving NT-proBNP lev-els and cardiovascular mortality risk between finerenone and eplerenone(P＞0.05).Compared with placebo,finerenone could reduce the ris k of first hospitalization due to heart failure(RR=0.68,95％CI:0.49-0.94,P=0.02)and the risk of cardiovascular composite endpoint event(RR=0.79,95％CI:0.64-0.98,P=0.03).In the aspects of safe outcome indicators,the occurrence risk of adverse events of finerenone was slight-ly lower than that of placebo(RR=0.95,95％CI:0.90-1.01),the risk of finerenone induced hyperkalemia was slightly lower than that of eplerenone(RR=0.90,95％CI:0.46-1.76),but the difference was not statis-tically significant(P＞0.05).Finerenone had a higher risk for causing hyperkalemia than placebo(RR=2.07,95％CI:1.46-2.95,P＜0.01).Conclusion Finerenone could reduce the NT-proBNP level,risk of first time HHF and the cardiovascular composite endpoint event,moreover its safe and tolerance are good.

Objective To optimize the immune scheme of SARS-CoV-2 RBD recombinant protein vaccine based on P.pastoris,and investigate the effect of different adjuvants on neutralizating antibody(NAb)titer,in order to provide reference for the continuous optimization research of SARS-CoV-2 vaccine.Methods The RBD protein was selected and the corresponding gene fragment was synthesized,which was constructed into the pPICZαA plasmid,and the plasmid was integrated into the genome of P.pastoris after linear transforma-tion for recombinant expression.The obtained recombinant protein vaccine was combined with different adju-vants to immunize mice to evaluate its immunogenicity.Results Both the target proteins wtRBD and Delta RBD were able to achieve satisfactory overexpression through the P.pastoris system.Compared with the 42 d interval,the IgG antibody titer at the 28 d interval increased by 1.8 times(44 923 vs.80 507).After 3 doses of immunization at an interval of 28 d,the geometric mean titer of NAb for Delta variant was 2.5 times higher than that at an interval of 42 days(2 191 vs.891).After immunization with Delta RBD recombinant protein vaccine combined with aluminum adjuvant,the NAb geometric mean titer for Delta variants reached 32 255(2 167-88 084).When using 5 μg or 30 μg Delta RBD immunization,the NAb titers of the aluminum adju-vant+CpG adjuvant group were about 10 times higher than those of the aluminum adjuvant group alone.Af-ter the third immunization,there was no significant difference in Delta RBD specific IgG titers between the 5 μg antigen group and the 30 μg antigen group(P＞0.05).Conclusion Both wtRBD and Delta RBD prepared based on P.pastoris could be used as effective antigens,with three doses of vaccine administered at a 28 day in-terval being the most effective.The combined immunization of Delta RBD recombinant protein with aluminum adjuvant+CpG adjuvant could obtain higher titers of NAb to exert immune effects on SARS-CoV-2 and its va-riants,providing some reference for the continuous optimization research of SARS-CoV-2 vaccines.

The occurrence of benign prostate hyperplasia(BPH)was related to disrupted sex steroid hormones,and metformin(Met)had a clinical response to sex steroid hormone-related gynaecological disease.How-ever,whether Met exerts an antiproliferative effect on BPH via sex steroid hormones remains unclear.Here,our clinical study showed that along with prostatic epithelial cell(PEC)proliferation,sex steroid hormones were dysregulated in the serum and prostate of BPH patients.As the major contributor to dysregulated sex steroid hormones,elevated dihydrotestosterone(DHT)had a significant positive rela-tionship with the clinical characteristics of BPH patients.Activation of adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK)by Met restored dysregulated sex steroid hormone homeostasis and exerted antiproliferative effects against DHT-induced proliferation by inhibiting the formation of androgen receptor(AR)-mediated Yes-associated protein(YAP1)-TEA domain transcription factor(TEAD4)heterodimers.Met's anti-proliferative effects were blocked by AMPK inhibitor or YAP1 over-expression in DHT-cultured BPH-1 cells.Our findings indicated that Met would be a promising clinical therapeutic approach for BPH by inhibiting dysregulated steroid hormone-induced PEC proliferation.

OBJECTIVE To identify, synthesize and analyze the structure of unknown impurities unique to bromhexine hydrochloride injection and set the impurities as known impurity to control. METHODS The structure of unknown impurities was derived through two-dimensional liquid chromatography tandem mass spectrometry(2DLC-HRMS/MS), and the source of impurities was derived based on the product's prescription process. The mechanism of impurities generation was analyzed, and impurity monomers were obtained through directional synthesis. The structure of impurities was confirmed using techniques such as 2DLC-HRMS/MS and nuclear magnetic resonance. Finally, HPLC was used to verify the analysis method of impurities. RESULTS It was confirmed that such impurities were produced in a reaction between bromhexine and the excipient glucose. The correction factor of the two impurities were 2.2 and 2.4, the analytical method was specific and reproducible. CONCLUSION Name the two injection specific impurities as impurity 1 and impurity 2 respectively, and use them as known impurities to be included in the standard, calculate the impurity content using the self control and correction factor method. This study is of great significance in guiding the impurity control of bromhexine hydrochloride injection and the screening of excipient glucose.

Objective To evaluate the effect of prone ventilation in children with severe pneumonia at high altitude.Methods By convenience sampling method,80 children with severe pneumonia hospitalized in intensive care department of a tertiary A children's hospital in Xining,Qinghai Province from June 2021 to June 2023 were selected as the study subjects,and the regional randomization group method was used to divide into a test group and a control group with 40 cases in each group.On the basis of routine care,the test group received prone ventilation once a day for 6 to 12 h;the control group received supine ventilation.Respiratory mechanical parameters(oxygenation index,oxygen saturation,arterial oxygen partial pressure,arterial CO2 partial pressure),mechanical ventilation duration and safety parameters(incidence of unplanned extubation,stress injury)at 6 h and 12 h of mechanical ventilation were compared.Results There were no shedding cases.The interaction between oxygenation index,blood oxygen saturation and arterial oxygen partial pressure(P＜0.05)in the 2 groups was compared(P＞0.05).The results of simple effect analysis showed that at 6 h,the oxygen saturation and oxygenation index in the test group were higher than those in the control group,and the difference was statistically significant(P＜0.05).At 12 h of mechanical ventilation,the oxygenation index,blood oxygen saturation and arterial oxygen partial pressure in the test group were higher than those in the control group,and the difference was statistically significant(P＜0.05).The time of mechanical ventilation in the test group was102.00(60.00,153.00)h and 126.00(108.00,156.00)h in the control group,and the difference was statistically significant(P=0.013).The incidence of unplanned extubation and pressure injury were compared,and the differences in 2 groups were not significant(P＞0.05).Conclusion Prone ventilation in children with severe pneumonia at high altitude is safe and feasible,which is helpful to improve the respiratory function and shorten the time of mechanical ventilation.