Insulin-like growth factor 2 (IGF2) is a critical endocrine mediator implicated in male reproductive physiology. To investigate the correlation between IGF2 protein levels and various aspects of male infertility, specifically focusing on sperm quality, inflammation, and DNA damage, a cohort of 320 male participants was recruited from the Women's Hospital, Zhejiang University School of Medicine (Hangzhou, China) between 1 st January 2024 and 1 st March 2024. The relationship between IGF2 protein concentrations and sperm parameters was assessed, and Spearman correlation and linear regression analysis were employed to evaluate the independent associations between IGF2 protein levels and risk factors for infertility. Enzyme-linked immunosorbent assay (ELISA) was used to measure IGF2 protein levels in seminal plasma, alongside markers of inflammation (tumor necrosis factor-alpha [TNF-α] and interleukin-1β [IL-1β]). The relationship between seminal plasma IGF2 protein levels and DNA damage marker phosphorylated histone H2AX (γ-H2AX) was also explored. Our findings reveal that IGF2 protein expression decreased notably in patients with asthenospermia and teratospermia. Correlation analysis revealed nuanced associations between IGF2 protein levels and specific sperm parameters, and low IGF2 protein concentrations correlated with increased inflammation and DNA damage in sperm. The observed correlations between IGF2 protein levels and specific sperm parameters, along with its connection to inflammation and DNA damage, underscore the importance of IGF2 in the broader context of male reproductive health. These findings lay the groundwork for future research and potential therapeutic interventions targeting IGF2-related pathways to enhance male fertility.
Humans ; Male ; Insulin-Like Growth Factor II/metabolism* ; Infertility, Male/genetics* ; DNA Damage ; Adult ; Inflammation/metabolism* ; Spermatozoa/metabolism* ; Semen Analysis ; Semen/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Histones/metabolism* ; Interleukin-1beta/metabolism*

The efficient production of L-glutamate is dependent on the product's rapid efflux, hence researchers have recently concentrated on artificially modifying its transport system and cell membrane wall structure. Considering the unique composition and structure of the cell wall of Corynebacterium glutamicum, we investigated the effects of CmpLs on L-glutamate synthesis and transport in SCgGC7, a constitutive L-glutamate efflux strain. First, the knockout strains of CmpLs were constructed, and it was confirmed that the deletion of CmpL1 and CmpL4 significantly improved the performance of L-glutamate producers. Next, temperature-sensitive L-glutamate fermentation with the CmpL1 and CmpL4 knockout strains were carried out in 5 L bioreactors, where the knockout strains showcased temperature-sensitive characteristics and enhanced capacities for L-glutamate production under high temperatures. Notably, the CmpL1 knockout strain outperformed the control strain in terms of L-glutamate production, showing production and yield increases of 69.2% and 55.3%, respectively. Finally, the intracellular and extracellular metabolites collected at the end of the fermentation process were analyzed. The modification of CmpLs greatly improved the L-glutamate excretion and metabolic flux for both L-glutamate production and transport. Additionally, the CmpL1 knockout strain showed decreased accumulation of downstream metabolites of L-glutamate and intermediate metabolites of tricarboxylic acid (TCA) cycle, which were consistent with its high L-glutamate biosynthesis capacity. In addition to offering an ideal target for improving the stability and performance of the industrial strains for L-glutamate production, the functional complementarity and redundancy of CmpLs provide a novel target and method for improving the transport of other metabolites by modification of the cell membrane and cell wall structures in C. glutamicum.
Corynebacterium glutamicum/genetics* ; Glutamic Acid/biosynthesis* ; Fermentation ; Metabolic Engineering ; Bacterial Proteins/metabolism* ; Bioreactors/microbiology* ; Gene Knockout Techniques

Objective To investigate the clinical characteristics and prognosis of pneumococcal meningitis(PM),and drug sensitivity of Streptococcus pneumoniae(SP)isolates in Chinese children.Methods A retrospective analysis was conducted on clinical information,laboratory data,and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country.Results Among the 160 children with PM,there were 103 males and 57 females.The age ranged from 15 days to 15 years,with 109 cases(68.1% )aged 3 months to under 3 years.SP strains were isolated from 95 cases(59.4% )in cerebrospinal fluid cultures and from 57 cases(35.6% )in blood cultures.The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87)and 27% (21/78),respectively.Fifty-five cases(34.4% )had one or more risk factors for purulent meningitis,113 cases(70.6% )had one or more extra-cranial infectious foci,and 18 cases(11.3% )had underlying diseases.The most common clinical symptoms were fever(147 cases,91.9% ),followed by lethargy(98 cases,61.3% )and vomiting(61 cases,38.1% ).Sixty-nine cases(43.1% )experienced intracranial complications during hospitalization,with subdural effusion and/or empyema being the most common complication[43 cases(26.9% )],followed by hydrocephalus in 24 cases(15.0% ),brain abscess in 23 cases(14.4% ),and cerebral hemorrhage in 8 cases(5.0% ).Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old,with rates of 91% (39/43)and 83% (20/24),respectively.SP strains exhibited complete sensitivity to vancomycin(100% ,75/75),linezolid(100% ,56/56),and meropenem(100% ,6/6).High sensitivity rates were also observed for levofloxacin(81% ,22/27),moxifloxacin(82% ,14/17),rifampicin(96% ,25/26),and chloramphenicol(91% ,21/23).However,low sensitivity rates were found for penicillin(16% ,11/68)and clindamycin(6% ,1/17),and SP strains were completely resistant to erythromycin(100% ,31/31).The rates of discharge with cure and improvement were 22.5% (36/160)and 66.2% (106/160),respectively,while 18 cases(11.3% )had adverse outcomes.Conclusions Pediatric PM is more common in children aged 3 months to under 3 years.Intracranial complications are more frequently observed in children under 1 year old.Fever is the most common clinical manifestation of PM,and subdural effusion/emphysema and hydrocephalus are the most frequent complications.Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates.Adverse outcomes can be noted in more than 10% of PM cases.SP strains are high sensitivity to vancomycin,linezolid,meropenem,levofloxacin,moxifloxacin,rifampicin,and chloramphenicol.[Chinese Journal of Contemporary Pediatrics,2024,26(2):131-138]

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Objective:To investigate the safety,efficacy,and prognosis of high-dose melphalan in combination with autologous hematopoietic stem cell transplantation (ASCT) for the treatment of multiple myeloma (MM). Methods:The clinical data of 17 patients with newly diagnosed MM who underwent ASCT as first-line consolidation therapy at the Yijishan Hospital of Wannan Medical College from March 2020 to October 2022 were retrospectively analyzed. The safety,efficacy,and prognosis of this treatment approach were evaluated. Results:Of the 17 patients,10 were male and 7 were female,with a median age of 56 (45-64) years. The stem cell engraftment rate was 100％,with a median neutrophil engraftment time of+10 (9-12) days and a median platelet engraftment time of+12 (10-21) days. The incidence of oral mucositis and intestinal infection after transplantation was 100％,with 2 cases of pulmonary infection,1 case of urinary tract infection,1 case of skin infection,and 11 cases of transient elevation of serum amylase. After transplantation,13 patients achieved a complete response (CR) or better,and the CR rate showed an increasing trend compared to before transplantation (13/17 vs 8/17;P=0.078). The median follow-up time was 18 (6-36) months,and 15 patients survived without progression,1 patient experienced disease progression,and 1 patient died due to clinical relapse and abandonment of treatment. The 2-year overall survival (OS) rate and progression-free survival (PFS) rate were approximately 90.0％ and 83.9％,respectively. Conclusion:High-dose melphalan in combination with ASCT as first-line consolidation therapy for MM can enhance the depth of patient response,further improve therapeutic efficacy,and the transplant-related complications are controllable,making it a viable option worth promoting in clinical practice.

Objective To investigate the medication rules of tradition Chinese medicine for the treatment of ulcerative colitis(UC)at remission stage by data mining method,thus to provide reference for clinical prescription and medication.Methods The clinical research or medical case report of UC remission treated by Chinese medicine issued in CNKI,Wanfang Data and VIP from July 2000 to December 2022 were retrieved.Excel 2019 was used to analyze the frequency statistics,and the distribution of the nature,flavor and meridian tropism of the prescribed drugs in the included literature.Modeler 18.0 and SPSS Statistics 26.0 were used for association rules and cluster analysis,and Cytoscape 3.9.1 was used to construct the network diagram of the associated drugs.Results A total of 121 articles were included in the analysis,involving 167 drugs,of which 24 drugs were frequently used,mainly including Atractylodis Macrocephalae Rhizoma,Poria,Aucklandiae Radix,Coptidis Rhizoma,Codonopsis Radix,Paeoniae Radix Alba,Coicis Semen,Astragali Radix,Glycyrrhizae Radix et Rhizoma Praeparata cum Melle,Angelicae Sinensis Radix,Citri Reticulatae Pericarpium,and Dioscoreae Rhizoma.According to the therapeutic actions,the drugs were mainly classified into deficiency-supplementing drugs,heat-clearing drugs,qi-regulating drugs,urination-promoting and dampness-percolating drugs,blood-stanching drugs,exterior-relieving drugs,interior-warming drugs,astringent drugs,dampness-resolving drugs,and blood-activating and stasis-resolving drugs.The medicinals were mainly warm,mild and cold in nature,and were sweet,bitter and pungent in flavor.Most of the drugs had the meridian tropism of the spleen,stomach,lung and liver.A total of 25 drug association rules were mined out,and five prescriptions were obtained after cluster analysis.Conclusion The Chinese medicine prescriptions for the treatment of UC remission usually deprive from the classical formulas such as Shenling Baizhu San,Sishen Pills,and Tongxie Yaofang.The compatibility of drugs reflects the thoughts of treating UC remission from the perspective of spleen,and embodies the therapies of strengthening the spleen and removing dampness,promoting qi and regulating blood,and focusing on tonifying ministerial fire and supporting yang in the later stage,which has the characteristics of treating both symptoms and root causes simultaneously by using multiple drugs through multiple methods.

Abstract Allergic diseases can occur in all systems of the body, covering the whole life cycle, from children to adults and to old age, can be lifelong onset and even fatal in severe cases. Children account for the largest proportion of the victims of allergic disease, Children s allergies start from scratch, ranging from mild to severe, from less to more, from single to multiple systems and systemic performance, so the prevention and treatment of allergic diseases in children is of great importance, which can not only prevent high risk allergic conditions from developing into allergic diseases, but also further block the process of allergy. At present, there is no consensus on the management system of allergic children in kindergartens and primary schools. The "Consensus on Allergy Management and Prevention in Kindergartens and Primary Schools", which includes the organizational structure, system construction and management of allergic children, provides evidence informed recommendations for the long term comprehensive management of allergic children in kindergartens and primary schools, and provides a basis for the establishment of the prevention system for allergic children.

Humans ; Asthma/drug therapy* ; Biological Therapy

Objective: To examine the feasibility and surgical approach of removing type D trigeminal schwannoma through nasal cavity and nasal sinus under endoscope. Methods: Eleven patients with trigeminal schwannoma who were treated in the Department of Otorhinolaryngology, Qilu Hospital of Shandong University from December 2014 to August 2021 were analyzed retrospectively in this study. There were 7 males and 4 females, aged (47.5±13.5) years (range: 12 to 64 years). The neoplasm involved the pterygopalatine fossa, infratemporal fossa, ethmoidal sinus, sphenoid sinus, cavernous sinus, and middle cranial fossa. The size of tumors were between 1.6 cm×2.0 cm×2.0 cm and 5.7 cm×6.0 cm×6.0 cm. Under general anesthesia, the tumors were resected through the transpterygoid approach in 4 cases, through the prelacrimal recess approach in 4 cases, through the extended prelacrimal recess approach in 2 cases, and through the endoscopic medial maxillectomy approach in 1 case. The nasal endoscopy and imaging examination were conducted to detect whether neoplasm recurred or not, and the main clinical symptoms during follow-up. Results: All the surgical procedures were performed under endonasal endoscope, including Gross total resection in 10 patients. The tumor of a 12-year-old patient was not resected completely due to huge tumor size and limited operation space. One patient was accompanied by two other schwannomas located in the occipital region and the ipsilateral parotid gland region originating from the zygomatic branch of the facial nerve, both of which were removed concurrently. After tumor resection, the dura mater of middle cranial fossa was directly exposed in the nasal sinus in 2 cases, including 1 case accompanied by cerebrospinal fluid leakage which was reconstructed by a free mucosal flap obtained from the middle turbinate, the other case was packed by the autologous fat to protect the dura mater. The operation time was (M(IQR)) 180 (160) minutes (range: 120 to 485 minutes). No complications and deaths were observed. No recurrence was observed in the 10 patients with total tumor resection during a 58 (68) months' (range: 10 to 90 months) follow-up. No obvious change was observed in the facial appearance of all patients during the follow-up. Conclusion: Type D trigeminal schwannoma involving pterygopalatine fossa and infratemporal fossa can be removed safely through purely endoscopic endonasal approach by selecting the appropriate approach according to the size and involvement of the tumor.
Male ; Female ; Humans ; Child ; Retrospective Studies ; Endoscopy/methods* ; Nasal Cavity/surgery* ; Neurilemmoma/surgery* ; Cranial Nerve Neoplasms/surgery*

Cerebral small vessel disease (CSVD) is a senile brain lesion caused by the abnormal structure and function of arterioles, venules and capillaries in the aging brain. The etiology of CSVD is complex, and disease is often asymptomatic in its early stages. However, as CSVD develops, brain disorders may occur, such as stroke, cognitive dysfunction, dyskinesia and mood disorders, and heart, kidney, eye and systemic disorders. As the population continues to age, the burden of CSVD is increasing. Moreover, there is an urgent need for better screening methods and diagnostic markers for CSVD, in addition to preventive and asymptomatic- and mild-stage treatments. Integrative medicine (IM), which combines the holistic concepts and syndrome differentiations of Chinese medicine with modern medical perspectives, has unique advantages for the prevention and treatment of CSVD. In this review, we summarize the biological markers, ultrasound and imaging features, disease-related genes and risk factors relevant to CSVD diagnosis and screening. Furthermore, we discuss IM-based CSVD prevention and treatment strategies to stimulate further research in this field.
Humans ; Integrative Medicine ; Brain/pathology* ; Cerebral Small Vessel Diseases/pathology* ; Stroke/complications* ; Cognitive Dysfunction/complications* ; Magnetic Resonance Imaging