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.

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 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.

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.

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.

Objective To explore the optimal method for preparing fresh and fixed skeletal muscle tissues,and to lay an experimental foundation for the rapid diagnosis of and research into the pathogenesis of skeletal muscle diseases.Methods The tibialis anterior muscle was extracted from C57BL/6J mice.Fresh tissue was treated by direct rapid freezing in liquid nitrogen,embedding combined with liquid nitrogen freezing,and foreign body alkane treatment combined with liquid nitrogen freezing.Fixed tissues were pre-treated by direct embedding with embedding agent combined with rapid liquid nitrogen freezing.The frozen sections were stained with hematoxylin and eosin.The cross-sectional areas of ice crystals and muscle fibers were calculated to evaluate the effects of the different pre-treatment method.Results The morphology of the muscle fiber bundles was disrupted and numerous ice crystal vacuoles were observed in fresh tissues after direct liquid nitrogen freezing and foreign body alkane treatment combined with liquid nitrogen freezing.In contrast,the muscle fiber bundles were intact and dense and there were no ice crystals in tissues treated with embedding agent combined with rapid liquid nitrogen freezing,indicating that this pre-treatment method was suitable for preparing fresh skeletal muscle tissue.Fixed tissue treated with embedding agent and liquid nitrogen freezing also showed complete muscle fiber bundles and no ice crystals.Conclusions Treatment of fresh and fixed skeletal muscle tissues with embedding agent combined with rapid liquid nitrogen freezing preserves muscle fiber bundles,with no ice crystals.Tissues prepared by this method are thus suitable for further examinations,such as immunohistochemistry and immunofluorescence.This method will therefore aid the accurate and rapid diagnosis of and research into the pathogenesis of skeletal muscle diseases.

Traumatic supraorbital fissure syndrome (TSOFS) is a symptom complex caused by nerve entrapment in the supraorbital fissure after skull base trauma. If the compressed cranial nerve in the supraorbital fissure is not decompressed surgically, ptosis, diplopia and eye movement disorder may exist for a long time and seriously affect the patients′ quality of life. Since its overall incidence is not high, it is not familiarized with the majority of neurosurgeons and some TSOFS may be complicated with skull base vascular injury. If the supraorbital fissure surgery is performed without treatment of vascular injury, it may cause massive hemorrhage, and disability and even life-threatening in severe cases. At present, there is no consensus or guideline on the diagnosis and treatment of TSOFS that can be referred to both domestically and internationally. To improve the understanding of TSOFS among clinical physicians and establish standardized diagnosis and treatment plans, the Skull Base Trauma Group of the Neurorepair Professional Committee of the Chinese Medical Doctor Association, Neurotrauma Group of the Neurosurgery Branch of the Chinese Medical Association, Neurotrauma Group of the Traumatology Branch of the Chinese Medical Association, and Editorial Committee of Chinese Journal of Trauma organized relevant experts to formulate Chinese expert consensus on the diagnosis and treatment of traumatic supraorbital fissure syndrome ( version 2024) based on evidence of evidence-based medicine and clinical experience of diagnosis and treatment. This consensus puts forward 12 recommendations on the diagnosis, classification, treatment, efficacy evaluation and follow-up of TSOFS, aiming to provide references for neurosurgeons from hospitals of all levels to standardize the diagnosis and treatment of TSOFS.

Objective:To evaluate the efficacy and safety of mild hypothermia for patients with severe traumatic brain injury (sTBI).Methods:PubMed, Embase, Cochrane Library, Web of Science, China Biology Medicine Disc, China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, and VIP Database were searched for prospective randomized controlled researches on mild hypothermia and normothermia for patients with sTBI. The search time was from the establishment of the databases to February 2023. RevMan 5.3 software was used for Meta-analysis. The evaluation indicators included literature search results, basic characteristics and quality of the literature, poor prognosis rate and mortality at 6 and 12 months after treatment, incidence of pulmonary infection, arrhythmia, thrombocytopenia, intracranial infection, renal insufficiency, gastrointestinal ulcer/bleeding and electrolyte disorder during the treatment, and publication bias.Results:A total of 16 papers involving 2 640 patients were included, comprising 1 381 patients in the mild hypothermia group and 1 259 patients in the normothermia group. The poor prognosis rate in the mild hypothermia group was significantly lower than that in the normothermia group at 6 and 12 months after treatment ( RR=0.81, 95% CI 0.69, 0.95, P<0.01; RR=0.65, 95% CI 0.51, 0.84, P<0.01). There was no significant difference in the mortality between the two groups at 6 and 12 months after treatment ( RR=0.81, 95% CI 0.61, 1.08, P>0.05; RR=0.69, 95% CI 0.47, 1.03, P>0.05). In contrast with the the normothermia group, in the mild hypothermia group the incidence of pulmonary infection was significantly different ( RR=1.18, 95% CI 1.04, 1.34, P<0.01); the incidence of arrhythmia was not significantly different ( RR=1.35, 95% CI 0.73, 2.49, P>0.05); the incidence of thrombocytopenia was significantly different ( RR=1.78, 95% CI 1.34, 2.37, P<0.01); the incidence of intracranial infection was not significantly different ( RR=1.32, 95% CI 0.54, 3.23, P>0.05); the incidence of renal insufficiency was not significantly different ( RR=1.22, 95% CI 0.71, 2.09, P>0.05); the incidence of gastrointestinal ulcer/bleeding was not significantly different ( RR=0.98, 95% CI 0.73, 1.31, P>0.05); the incidence of electrolyte disorders was not significantly different ( RR=1.39, 95% CI 1.00, 1.94, P>0.05). The funnel plot was approximately symmetrical and the scattered points were concentrated in the narrow area in the upper part of the funnel plot, suggesting no publication bias. Conclusions:In comparison with normothermia for sTBI, mild hypothermia can not reduce the mortality at 6 and 12 months after treatment, but it can reduce the incidence of poor prognosis at 6 and 12 months after treatment. Moreover, mild hypothermia has no obvious effect on the incidence of arrhythmia, intracranial infection, renal insufficiency, gastrointestinal ulcer/bleeding, and electrolyte disorder, but it can increase the incidence of pulmonary infection and thrombocytopenia.