In this study, we explored the pharmacological effects of Siwu Decoction in treating premature ovarian insufficiency(POI) and its molecular mechanism based on the mitophagy pathway modulated and mediated by estrogen receptor(ER) subtypes. Female Balb/c mice were divided into a control group, model group, as well as high-dose and low-dose groups of Siwu Decoction. The POI mice model was constructed by intraperitoneal injection of cisplatin. The high-dose and low-dose groups of Siwu Decoction were administered intragastrically with Siwu Decoction each day for 14 days. During this period, we monitored the estrous cycle and body weight of the mice and calculated the ovarian index. The morphology of the ovaries was detected by hematoxylin-eosin(HE) staining, and the number of primordial follicles was counted. The apoptosis of the ovarian tissue was detected by TUNEL staining. The expression levels of anti-Müllerian hormone(AMH), apoptosis-associated and mitophagy-associated proteins, ER subtypes, and the expression levels of key proteins of its mediated molecular pathways were detected by Western blot and immunohistochemistry. KGN cells were divided into a control group, model group, Siwu Decoction group, and gene silencing group. The apoptosis model was induced by H_2O_2, and PTEN-induced putative kinase 1(PINK1) gene silencing was induced by siRNA transfection. The Siwu Decoction group and gene silencing group were added to the medium containing Siwu Decoction. Cell viability was detected by CCK-8 assay. Cell senescence was detected by senescence-associated-β-galactosidase. The expression levels of apoptosis-associated and mitophagy-associated proteins were detected by Western blot. The results of in vivo experiments showed that compared with the model group, the mice in the high-dose and low-dose groups of Siwu Decoction significantly recovered the rhythm of the estrous cycle, and the levels of ovarian index, number of primordial follicles, and expression of AMH, representative indexes of ovarian function, were significantly higher, suggesting that the level of ovarian function was significantly improved. The expression levels of the apoptosis-related proteins, cytochrome C(Cyt C), cysteinyl aspartate specific proteinase 3(caspase 3), B-cell lymphoma-2(Bcl-2)-associated X(Bax), and mitophagy-associated indicator(Beclin 1) were significantly decreased, and the expression levels of Bcl-2 was significantly elevated. The positive area of TUNEL was significantly reduced, suggesting that the apoptosis level of the ovaries was significantly reduced. The expression levels of PINK1, Parkin, and sequestosome 1(p62) were significantly reduced, suggesting that the level of ovarian mitophagy was significantly down-regulated. The expression levels of ERα and ERβ were significantly elevated, and the ratio of ERα/ERβ was significantly reduced. The expression levels of key proteins in the pathway, phosphoinositide 3-kinase(PI3K) and protein kinase B(Akt), were significantly reduced, suggesting that the regulation of ER subtypes and the mediation of PI3K/Akt pathway were the key mechanisms. In vitro experiments showed that compared with the model group, the proportion of senescent cells in the Siwu Decoction group was significantly reduced. Cyt C, caspase 3, Beclin 1, Parkin, and p62 were significantly reduced, which was in line with in vivo experimental results. The proportion of senescent cells and the expression level of the above proteins were further significantly reduced after PINK1 silencing. It can be seen that Siwu Decoction can regulate the expression level and proportion of ER subtypes in KGN cells, then mediate the PI3K/Akt pathway to inhibit excessive mitophagy and apoptosis, and exert therapeutic effects of POI.
Animals ; Female ; Drugs, Chinese Herbal/administration & dosage* ; Mitophagy/drug effects* ; Primary Ovarian Insufficiency/physiopathology* ; Mice ; Mice, Inbred BALB C ; Humans ; Receptors, Estrogen/genetics* ; Apoptosis/drug effects* ; Ovary/metabolism* ; Signal Transduction/drug effects* ; Anti-Mullerian Hormone/genetics*

OBJECTIVES: To evaluate the effectiveness of single-balloon and double-balloon enteroscopy in diagnosing pediatric small bowel diseases and assess the diagnostic efficacy of computed tomography enterography (CTE) for small bowel diseases using enteroscopy as the reference standard. METHODS: Clinical data from 576 children who underwent enteroscopy at Hunan Children's Hospital between January 2017 and December 2023 were retrospectively collected. The children were categorized based on enteroscopy type into the single-balloon enteroscopy (SBE) group (n=457) and double-balloon enteroscopy (DBE) group (n=119), and the clinical data were compared between the two groups. The sensitivity and specificity of CTE for diagnosing small bowel diseases were evaluated using enteroscopy results as the standard. RESULTS: Among the 576 children, small bowel lesions were detected by enteroscopy in 274 children (47.6%).There was no significant difference in lesion detection rates or complication rates between the SBE and DBE groups (P>0.05), but the DBE group had deeper insertion, longer procedure time, and higher complete small bowel examination rate (P<0.05). The complication rate during enteroscopy was 4.3% (25/576), with 18 cases (3.1%) of mild complications and 7 cases (1.2%) of severe complications, which improved with symptomatic treatment, surgical, or endoscopic intervention. Among the 412 children who underwent CTE, the sensitivity and specificity for diagnosing small bowel diseases were 44.4% and 71.3%, respectively. CONCLUSIONS SBE and DBE have similar diagnostic efficacy for pediatric small bowel diseases, but DBE is preferred for suspected deep small bowel lesions and comprehensive small bowel examination. Enteroscopy in children demonstrates relatively good overall safety. CTE demonstrates relatively low sensitivity but comparatively high specificity for diagnosing small bowel diseases.
Retrospective Studies ; Treatment Outcome ; Double-Balloon Enteroscopy/statistics & numerical data* ; Single-Balloon Enteroscopy/statistics & numerical data* ; Humans ; Male ; Female ; Child ; Operative Time ; Tomography, X-Ray Computed/statistics & numerical data* ; Sensitivity and Specificity ; Intestine, Small/surgery* ; Intestinal Diseases/surgery*

The growth of three plague phages from Qinghai Plateau in two Yersinia pestis strains(plague vaccine strains EV76 and 614F)and four non-Yersinia pestis strains(Yersinia pseudotuberculosis PTB3,PTB5,Escherichia coli V517,and Yersinia enterocolitica 52302-2)were detected through a micromethod based on the OmniLogTM microbial identification system and by the drop method,to provide a scientific basis for future ecological studies and classification based on the host range.For plague vaccine strains EV76 and 614F,successful phage infection and subsequent phage growth were observed in the host bacte-rium.Diminished bacterial growth and respiration and a concomitant decrease in color were observed with the OmniLogTM mi-crobial identification system at 33 ℃ for 48 h.Yersinia pseudotuberculosis PTB5 was sensitive to Yersinia pestis phage 476,but Yersinia pseudotuberculosis PST5 was insensitive to phage 087 and 072204.Three strains of non-Yersinia pestis(Yersinia pseudotuberculosis PTB3,Escherichia coli V517,and Yersinia enterocolitica 52302-2)were insensitive to Yersinia pestis pha-ges 087,072204,and 476 showed similar growth curves.The growth of phages 476 and 087,as determined with the drop method,in two Yersinia pestis strains(plague vaccine strains EV76 and 614F)and four non-Yersinia pestis strains(Yersinia pseudotuberculosis PTB3,Escherichia coli V517,and Yersin-ia enterocolitica 52302-2)showed the same results at 37 ℃,on the basis of comparisons with the OmniLogTM microbial i-dentification system;in contrast,phages 072204 did not show plaques on solid medium at 37 ℃ with plague vaccine strains EV76 and 614F.Determination based on the OmniLogTM detection system can be used as an alternative to the traditional determination of the host range,thus providing favorable application val-ue for determining the interaction between the phage and host bacteria.

Digital intraoral scanning is a hot topic in the field of oral digital technology.In recent years,digital intra-oral scanning has gradually become the mainstream technology in orthodontics,prosthodontics,and implant dentistry.The precision of digital intraoral scanning and the accuracy and stitching of data collection are the keys to the success of the impression.However,the operators are less familiar with the intraoral scanning characteristics,imaging process-ing,operator scanning method,oral tissue specificity of the scanned object,and restoration design.Thus far,no unified standard and consensus on digital intraoral scanning technology has been achieved at home or abroad.To deal with the problems encountered in oral scanning and improve the quality of digital scanning,we collected common expert opin-ions and sought to expound the causes of scanning errors and countermeasures by summarizing the existing evidence.We also describe the scanning strategies under different oral impression requirements.The expert consensus is that due to various factors affecting the accuracy of digital intraoral scanning and the reproducibility of scanned images,adopting the correct scanning trajectory can shorten clinical operation time and improve scanning accuracy.The scanning trajec-tories mainly include the E-shaped,segmented,and S-shaped methods.When performing fixed denture restoration,it is recommended to first scan the abutment and adjacent teeth.When performing fixed denture restoration,it is recommend-ed to scan the abutment and adjacent teeth first.Then the cavity in the abutment area is excavated.Lastly,the cavity gap was scanned after completing the abutment preparation.This method not only meets clinical needs but also achieves the most reliable accuracy.When performing full denture restoration in edentulous jaws,setting markers on the mucosal tissue at the bottom of the alveolar ridge,simultaneously capturing images of the vestibular area,using different types of scanning paths such as Z-shaped,S-shaped,buccal-palatal and palatal-buccal pathways,segmented scanning of dental arches,and other strategies can reduce scanning errors and improve image stitching and overlap.For implant restora-tion,when a single crown restoration is supported by implants and a small span upper structure restoration,it is recom-mended to first pre-scan the required dental arch.Then the cavity in the abutment area is excavated.Lastly,scanning the cavity gap after installing the implant scanning rod.When repairing a bone level implant crown,an improved indi-rect scanning method can be used.The scanning process includes three steps:First,the temporary restoration,adjacent teeth,and gingival tissue in the mouth are scanned;second,the entire dental arch is scanned after installing a standard scanning rod on the implant;and third,the temporary restoration outside the mouth is scanned to obtain the three-di-mensional shape of the gingival contour of the implant neck,thereby increasing the stability of soft tissue scanning around the implant and improving scanning restoration.For dental implant fixed bridge repair with missing teeth,the mobility of the mucosa increases the difficulty of scanning,making it difficult for scanners to distinguish scanning rods of the same shape and size,which can easily cause image stacking errors.Higher accuracy of digital implant impres-sions can be achieved by changing the geometric shape of the scanning rods to change the optical curvature radius.The consensus confirms that as the range of scanned dental arches and the number of data concatenations increases,the scanning accuracy decreases accordingly,especially when performing full mouth implant restoration impressions.The difficulty of image stitching processing can easily be increased by the presence of unstable and uneven mucosal mor-phology inside the mouth and the lack of relatively obvious and fixed reference objects,which results in insufficient ac-curacy.When designing restorations of this type,it is advisable to carefully choose digital intraoral scanning methods to obtain model data.It is not recommended to use digital impressions when there are more than five missing teeth.

Objective To observe the clinical efficacy of Shuangye San(the prescription mainly composed of Mori Folium and Nelumbinis Folium)in the treatment of type 2 diabetes mellitus(T2DM)complicated with non-alcoholic fatty liver disease(NAFLD)of spleen deficiency and phlegm stasis type.Methods A total of 80 patients with T2DM complicated with NAFLD of spleen deficiency and phlegm stasis type were randomly divided into a treatment group and a control group,with 40 cases in each group.The control group was treated with conventional western medicine for lowering blood glucose and lipid,protecting liver and lowering enzymes.The treatment group was treated with the granules of Shuangye San orally on the basis of treatment for the control group.The course of treatment lasted for three months.The changes of traditional Chinese medicine(TCM)syndrome scores,homeostasis model assessment of insulin resistance(HOMA-IR),fasting insulin(FINS),fasting blood glucose(FBG),2-hour postprandial blood glucose(2hPG),glycosylated hemoglobin(HbA1C),total cholesterol(TC),triglyceride(TG),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C),liver function indicators and B-ultrasound grading of fatty liver in the two groups were observed before and after treatment.After treatment,the clinical efficacy and safety of the two groups were evaluated.Results(1)After three months of treatment,the total effective rate of the treatment group was 85.00％(34/40),and that of the control group was 70.00％(28/40).The intergroup comparison(tested by chi-square test)showed that the efficacy of the treatment group was significantly superior to that of the control group(P＜0.01).(2)After treatment,the scores of TCM symptoms of obese physique,heaviness and weakness in the limbs,shortness of breath and unwilling to talk,tightness and stabbing pain in the chest,abdominal distension and poor appetite in the two groups were decreased compared with those before treatment(P＜0.05),and the decrease of TCM syndrome scores in the treatment group was significantly superior to that in the control group(P＜0.05).(3)After treatment,the levels of glucose and lipid metabolism indicators of FINS,HOMA-IR,FBG,2hPG,HbA1C,TC,TG and LDL-C in the two groups were significantly decreased compared with those before treatment(P＜0.05),and the level of HDL-C was significantly increased compared with that before treatment(P＜0.05).The decrease of FINS,HOMA-IR,FBG,2hPG,HbA1C,TC,TG and LDL-C levels and the increase of HDL-C levels in the treatment group were significantly superior to those in the control group(P＜0.05).(4)After treatment,the levels of liver function indicators of alanine aminotransferase(ALT),aspartate aminotransferase(AST)and gamma-glutamyl transpeptidase(GGT)in the two groups were significantly decreased compared with those before treatment(P＜0.05),and the decrease of liver function indicators in the treatment group was significantly superior to that in the control group(P＜0.05).(5)After treatment,the B-ultrasound grading of fatty liver of the two groups was significantly improved compared with that before treatment(P＜0.05),and the improvement of fatty liver B-ultrasound grading in the treatment group was significantly superior to that in the control group,and the difference was statistically significant(P＜0.05).(6)During the treatment,there were no adverse reactions such as impairment of liver and kidney function and abnormalities in routine blood,urine and stool test in the two groups.Conclusion Shuangye San exerts certain effect in the treatment of T2DM complicated with NAFLD of spleen deficiency and phlegm stasis type.It can alleviate the clinical symptoms of patients,correct the disorder of glucose and lipid metabolism,and improve liver function and fatty liver B-ultrasound grading.

As a novel tumor treatment,photodynamic therapy(PDT)has been widely used in clinical treatment of a variety of tumors due to its advantages,such as fewer adverse reactions,precise targeting and repeatability of treatment.Unlike conventional treatments,such as surgery,chemotherapy and radiotherapy,PDT not only eliminates the primary tumor but also effectively inhibits metastatic tumors by activating the body's immune response.However,the PDT-activated immune response is influenced by multiple factors,including the localization and dose of photosensitizer in the cells,light parameters,oxygen concentration in the tumor,and the integrity of immune function.This review summarizes the mechanisms behind the PDT-activated anti-tumor immune response,systematically examines the key influencing factors on the immune effect of PDT,and discusses the future development direction of PDT in cancer treatment.

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.

Purpose::Cerebral edema (CE) is the main secondary injury following traumatic brain injury (TBI) caused by road traffic accidents (RTAs). It is challenging to be predicted timely. In this study, we aimed to develop a prediction model for CE by identifying its risk factors and comparing the timing of edema occurrence in TBI patients with varying levels of injuries.Methods::This case-control study included 218 patients with TBI caused by RTAs. The cohort was divided into CE and non-CE groups, according to CT results within 7 days. Demographic data, imaging data, and clinical data were collected and analyzed. Quantitative variables that follow normal distribution were presented as mean ± standard deviation, those that do not follow normal distribution were presented as median (Q 1, Q 3). Categorical variables were expressed as percentages. The Chi-square test and logistic regression analysis were used to identify risk factors for CE. Logistic curve fitting was performed to predict the time to secondary CE in TBI patients with different levels of injuries. The efficacy of the model was evaluated using the receiver operator characteristic curve. Results::According to the study, almost half (47.3%) of the patients were found to have CE. The risk factors associated with CE were bilateral frontal lobe contusion, unilateral frontal lobe contusion, cerebral contusion, subarachnoid hemorrhage, and abbreviated injury scale (AIS). The odds ratio values for these factors were 7.27 (95% confidence interval ( CI): 2.08 -25.42, p = 0.002), 2.85 (95% CI: 1.11 -7.31, p = 0.030), 2.62 (95% CI: 1.12 -6.13, p = 0.027), 2.44 (95% CI: 1.25 -4.76, p = 0.009), and 1.5 (95% CI: 1.10 -2.04, p = 0.009), respectively. We also observed that patients with mild/moderate TBI (AIS ≤ 3) had a 50% probability of developing CE 19.7 h after injury (χ 2= 13.82, adjusted R2 = 0.51), while patients with severe TBI (AIS > 3) developed CE after 12.5 h (χ 2= 18.48, adjusted R2 = 0.54). Finally, we conducted a receiver operator characteristic curve analysis of CE time, which showed an area under the curve of 0.744 and 0.672 for severe and mild/moderate TBI, respectively. Conclusion::Our study found that the onset of CE in individuals with TBI resulting from RTAs was correlated with the severity of the injury. Specifically, those with more severe injuries experienced an earlier onset of CE. These findings suggest that there is a critical time window for clinical intervention in cases of CE secondary to TBI.

The testis,as one of the important reproductive organs in men,has two major functions of secreting androgens and producing sperm.Androgen and spermatogenesis are the key factors for the evaluation of the testicular function.The lack of androgen or the decline of spermatogenic function is both a symbolic manifestation and a"product"of testis aging.In order to gain a deeper in-sight into the relationship between testis aging and overall health,this article reviews the relevant literature based on the correlation of androgen deficiency with various systemic diseases and the belief in the impacts of testis aging on the health of the cardiovascular and nervous systems through different channels,the development and progression of metabolic diseases,orthopedic diseases,PCa,kidney disease,peptic ulcer and other diseases.All these suggest that adequate attention should be paid to the studies of male reproductive health and its impact on overall health,so as to provide some new ideas and evidence for clinical diagnosis and treatment of relevant conditions.

Protein phosphorylation modification is an important mechanism of physiological regulation that is closely related to protein biological functions. In particular, protein kinases are responsible for catalyzing the phosphorylation process of proteins, and phosphatases are responsible for catalyzing the dephosphorylation process of phosphorylation-modified proteins, which together mediate the achievement of dynamic and reversible phosphorylation modifications of proteins. Abnormal phosphorylation levels of proteins contribute to the development of many diseases, such as cancer, neurodegenerative diseases, and chronic diseases. Therefore, rational design of small molecules to regulate protein phosphorylation is an important approach for disease treatment. Based on the mechanism of protein phosphorylation regulation, small molecule drug design strategies can be classified into three types, protein kinase modulators, phosphatase modulators, and bifunctional molecules with proximity-mediated mechanism. This review emphasizes the above three small molecule design strategies for targeting protein phosphorylation regulation, including molecular design ideas, research progress and current challenges, and provides an outlook on small molecule modulators targeting protein phosphorylation modification.