Polycystic ovary syndrome (PCOS) is the predominant cause of subfertility in reproductive-aged women; however, its pathophysiology remains unknown. Neurotensin (NTS) is a member of the gut-brain peptide family and is involved in ovulation; its relationship with PCOS is unclear. Here, we found that NTS expression in ovarian granulosa cells and follicular fluids was markedly decreased in patients with PCOS. In the in vitro culture of cumulus-oocyte complexes, the neurotensin receptor 1 (NTSR1) antagonist SR48692 blocked cumulus expansion and oocyte meiotic maturation by inhibiting metabolic cooperation and damaging the mitochondrial structure in oocytes and surrounding cumulus cells. Furthermore, the ERK1/2-early growth response 1 pathway was found to be a key downstream mediator of NTS/NTSR1 in the ovulatory process. Animal studies showed that in vivo injection of SR48692 in mice reduced ovulation efficiency and contributed to irregular estrus cycles and polycystic ovary morphology. By contrast, NTS partially ameliorated the ovarian abnormalities in mice with dehydroepiandrosterone-induced PCOS. Our findings highlighted the critical role of NTS reduction and consequent abnormal NTSR1 signaling in the ovulatory dysfunction of PCOS, suggesting a potential strategy for PCOS treatment.
Polycystic Ovary Syndrome/physiopathology* ; Female ; Animals ; Neurotensin/metabolism* ; Receptors, Neurotensin/antagonists & inhibitors* ; Mice ; Ovulation/drug effects* ; Humans ; Granulosa Cells/metabolism* ; Adult ; Oocytes/metabolism* ; MAP Kinase Signaling System ; Signal Transduction ; Follicular Fluid/metabolism* ; Disease Models, Animal ; Gonadotropin-Releasing Hormone/analogs & derivatives*

BACKGROUND:With the application and development of 3D printing technology in medicine,orthopedic internal fixation surgery has become precise and individualized.The equal-scale fracture model obtained by 3D printing technology was simulated and planned before surgery,realizing the leap from traditional 2D images to more vivid and detailed three-dimensional objects.It allows the surgeon to understand the fracture type in advance and rehearse the reduction sequence,so as to realize the individualized implementation of fracture surgery,optimize the surgical process,bring better postoperative recovery and less surgical complications. OBJECTIVE:To compare clinical efficacy of three 3D printed models combined with computerized virtual repositioning technology to assist incision reduction bone plate internal fixation and traditional incision reduction bone plate internal fixation in the treatment of Robinson II B2 clavicle fracture. METHODS:Eighty patients with Robinson II B2 clavicle fracture were randomly divided into trial group(n=40)and control group(n=40).In the trial group,three kinds of 3D printing models(affected clavicle fracture model,computer simulation clavicle fracture reduction model,clavicle mirror model of healthy side)combined with computer virtual reduction technology were used for preoperative in vitro surgery rehearsal.Finally,3D printing was used for clavicle mirror model of healthy side to advance bending and select bone plates for internal fixation.In the control group,open reduction plate internal fixation was applied.The time from admission to surgery,intraoperative blood loss,operation time,frequency of fluoroscopy,number of bends of the bone plate,fracture healing time,complications,and visual analog scale score and Constant score before and after surgery were compared between the two groups. RESULTS AND CONCLUSION:The time from admission to operation in the trial group was greater than that in the control group(P<0.05).Operation time,intraoperative fluoroscopy frequency and bending times of the bone plate in the trial group were lower than those in the control group(P<0.05).The trial group had faster fracture healing and fewer complications(P<0.05).There was no significant difference in intraoperative blood loss between the two groups(P>0.05).Constant score of the two groups had an increasing trend with time(F=613.50,P<0.001),but the difference between the groups was not statistically significant(F=0.08,P=0.78),and there was no interaction between the measurement times and the group assignment(F=0.27,P=0.66).The visual analog scale score decreased with time(F=1 149.55,P<0.001),but there was no significant difference between groups(F=0.02,P=0.88),and there was no interaction between the number of measurements and the group assignment(F=1.02,P=0.36).The results show that the use of 3D printed model combined with computer virtual reduction technology for preoperative rehearsal can shorten the operation time,reduce the number of intraoperative fluoroscopy frequency and the times of bone plate bending,and have the advantages of faster fracture healing,fewer complications,and similar functional recovery to the traditional incision reduction bone plate internal fixation.

Approximately 140 million people worldwide are homozygous carriers of APOE4 (ε4), a strong genetic risk factor for late onset familial and sporadic Alzheimer's disease (AD), 91% of whom will develop AD at earlier age than heterozygous carriers and noncarriers. Susceptibility to AD could be reduced by targeted editing of APOE4, but a technical basis for controlling the off-target effects of base editors is necessary to develop low-risk personalized gene therapies. Here, we first screened eight cytosine base editor variants at four injection stages (from 1- to 8-cell stage), and found that FNLS-YE1 variant in 8-cell embryos achieved the comparable base conversion rate (up to 100%) with the lowest bystander effects. In particular, 80% of AD-susceptible ε4 allele copies were converted to the AD-neutral ε3 allele in human ε4-carrying embryos. Stringent control measures combined with targeted deep sequencing, whole genome sequencing, and RNA sequencing showed no DNA or RNA off-target events in FNLS-YE1-treated human embryos or their derived stem cells. Furthermore, base editing with FNLS-YE1 showed no effects on embryo development to the blastocyst stage. Finally, we also demonstrated FNLS-YE1 could introduce known protective variants in human embryos to potentially reduce human susceptivity to systemic lupus erythematosus and familial hypercholesterolemia. Our study therefore suggests that base editing with FNLS-YE1 can efficiently and safely introduce known preventive variants in 8-cell human embryos, a potential approach for reducing human susceptibility to AD or other genetic diseases.
Humans ; Apolipoprotein E4/genetics* ; Cytosine ; Mutation ; Blastocyst ; Heterozygote ; Gene Editing ; CRISPR-Cas Systems

Objective To investigate the characteristics of pathogenic bacteria in cancer patients with severe infection after radiotherapy and chemotherapy and the application value of metagenomic next-generation sequencing(NGS)in the detection of pathogenic bacteria.Methods A total of 112 patients with severe infection after malignant tumor radiation and chemotherapy admitted to Department of Critical Care Medicine of Wuwei Tumor Hospital from October 2019 to August 2023 were selected as the research objects.A total of 150 specimens from suspected infection sites were collected and tested by traditional etiology and NGS.The characteristics of pathogenic bacteria in severe infection of cancer patients after chemoradiotherapy and the application value of NGS in pathogen detection were analyzed.Results Among 150 samples of 112 patients with severe infection after radiotherapy and chemotherapy,the highest proportion of respiratory system infection was 51.79%(58 cases),followed by 25.89%(29 cases)of bloodstream infection,the lowest central nervous system infection rate was 1.79%(2 cases).Gram-negative bacteria were the most common pathogenic bacteria[NGS 35.33%(53 cases),traditional pathogen detection 23.33%(35 cases)],followed by Gram-positive bacteria[NGS 20.67%(31 cases),traditional pathogen detection 12.00%(18 cases)],and multi-drug resistant bacteria infection rate was more than 80.00%,multi-drug resistant fungal infection rate also reached 28.57%.In the patients with severe infection after radiotherapy and chemotherapy,the positive rate of pathogenic bacteria of NGS was significantly higher than that of traditional pathogen detection[87.33%(131/150)vs.42.67%(64/150),P＜0.01],and the positive detection rate of Gram-negative bacteria,Gram-positive bacteria,fungi and other pathogens was significantly higher than that of traditional pathogen detection[Gram-negative bacteria:35.33%(53/150)vs.23.33%(35/150),Gram-positive bacteria:20.67%(31/150)vs.12.00%(18/150),fungi:22.67%(34/150)vs.6.67%(10/150),others:8.67%(13/150)vs.0.67%(1/150),both P＜0.05].Conclusions The detection rate of pathogenic bacteria of NGS in patients with severe infection after radiotherapy and chemotherapy was significantly higher than that of traditional pathogen detection.The distribution and drug resistance of pathogenic bacteria in severe infection after radiotherapy and chemotherapy are unique,and strengthening the detection of pathogenic bacteria is helpful to improve the curative effect.

Objective:To investigate and analyse the current status of screening and management of diabetic kidney disease (DKD) in six provinces and cities in China.Methods:The qualitative research method of focus group interview was adopted, based on the semi-structured interview outline, the clinical medical and disease control personnel in Tianjin, Chongqing, Gansu, Hubei, Heilongjiang, and Guangdong were interviewed. The interview transcripts were analyzed using thematic analysis, and MAXQDA analysis software was used for data management and analysis.Results:A total of 6 interviews were conducted with 49 interviewees. Forty respondents (81.6%) claimed that DKD screening was critical; 53.1% think that it was not easy for patients to obtain DKD screening services; 40.8%, 26.5% and 14.3% of the people believed that the technology of DKD screening services was moderate, simple or very simple, respectively. Of the respondents,16.3% thought that the cost of DKD screening service was relatively expensive, while 83.7% thought that the cost was inexpensive; 75.5% of the respondents believed that the patients could receive early DKD screening service. The factors of fully implementing medical reform policies, changing concepts and actively serving patients, and integrating external resources in medical and health institutions at all levels and of all types were conducive to the development of DKD screening and management services. The lack of technology and personnel for DKD screening services at the grassroots level, the lack of trust in the service capabilities of grassroots medical institutions by patients, the low level of patient awareness, and the novel coronavirus infection epidemic had an adverse impact on the development of DKD screening and management services.Conclusion:The screening and management services for DKD are relatively limited in China, and there is a significant fragmentation in the management and care of diabetes and DKD.

Objective:To investigate the factors that contribute to acute lung injury(ALI)following thoracoscopic surgery in elderly patients with esophageal cancer.Methods:This study retrospectively analyzed the clinical data of 300 elderly patients with esophageal cancer who were treated in the hospital between June 2018 and June 2022.The baseline data of the patients were recorded and they were divided into two groups: ALI group and non-ALI group based on the postoperative complication of ALI.The study compared the baseline data of the two groups and used Logistic regression analysis to identify the influencing factors of ALI after thoracoscopic surgery in elderly patients with esophageal cancer.Results:This study involving 300 elderly patients with esophageal cancer found that 35 had ALI while 265 did not.Multiple Logistic regression analysis revealed that age increase( OR=1.573, P=0.031), a large number of lymph nodes cleaned( OR=3.145, P=0.008), and long tracheal intubation time( OR=1.108, P=0.028)were identified as risk factors for ALI in elderly esophageal cancer patients after thoracoscopic surgery.Conversely, high albumin levels were found to be a protective factor( OR=0.434, P=0.035). Conclusions:The incidence of acute lung injury(ALI)following thoracoscopic surgery in elderly patients with esophageal cancer is significantly high.Several factors contribute to this risk, including patient age, the number of lymph nodes cleaned, albumin level, and tracheal intubation time.

C-X-C motif chemokine receptor 4 (CXCR4) plays a key role in various physiological functions, such as immune processes and disease development, and can influence angiogenesis, proliferation, and distant metastasis in tumors. Recently, several radioligands, including peptides, small molecules, and nanoclusters, have been developed to target CXCR4 for diagnostic purposes, thereby providing new diagnostic strategies based on CXCR4. Herein, we focus on the recent research progress of CXCR4-targeting radioligands for tumor diagnosis. We discuss their application in the diagnosis of hematological tumors, such as lymphomas, multiple myelomas, chronic lymphocytic leukemias, and myeloproliferative tumors, as well as nonhematological tumors, including tumors of the esophagus, breast, and central nervous system. Additionally, we explored the theranostic applications of CXCR4-targeting radioligands in tumors. Targeting CXCR4 using nuclear medicine shows promise as a method for tumor diagnosis, and further research is warranted to enhance its clinical applicability.

ObjectiveTo explore the effect of oleanolic acid （OA） on water metabolism in mice with water-dampness retention caused by spleen deficiency and the mechanism. MethodThe 60 SPF Kunming （KM） mice were randomized into blank group （n=10） and modeling group （n=50）. Through long-term living in damp place and irregular diet， water-dampness retention caused by spleen deficiency was induced in modeling mice. Then the model mice were randomly classified into model group， natural recovery group， and low-dose， medium-dose， and high-dose OA groups. The mice in the blank group， model group， and natural recovery group were given （ig） 10 mL·kg^-1·d^-1 normal saline， and mice in the low-dose， medium-dose， and high-dose OA groups received 50， 100， 200 mg·kg^-1·d^-1 OA， respectively. The intervention lasted 7 days. Before and after modeling and administration， the general conditions of the mice were observed and body weight of mice was measured. The water content in feces and tissues was detected with the oven-drying method， and water load index and organ coefficient were measured with the weighing method. Enzyme-linked immunosorbent assay （ELISA） was employed to detect the urinary D-xylose excretion， serum gastrin （GAS）， total protein （TP）， albumin （ALB）， total cholesterol （TC）， high-density lipoprotein cholesterol （HDL-C）， low-density lipoprotein cholesterol （LDL-C）， interleukin-6 （IL-6）， antidiuretic hormone （AVP）， aquaporin 1 （AQP1） in renal medulla， and liver Na⁺-K⁺-ATPase. At the same time， OA was docked with ALB， IL-6， AQP1， and Na⁺-K⁺-ATPase. ResultCompared with the blank group， the model group showed withered hair， emaciation， laziness， bradykinesia， slow weight growth， infrequent spontaneous activities， high water content in feces and tissues， low weight loss after water loading， high coefficient of each organ （P<0.05， P<0.01）. Moreover， the model group had less urinary D-xylose excretion， lower serum levels of GAS， TP， ALB， and HDL-C， higher levels of TC， LDL-C， AVP， and IL-6， lower expression of Na⁺-K⁺-ATPase in the liver， and higher expression of AQP1 in renal medulla than the blank group （P<0.05， P<0.01）. The three OA groups demonstrated better general conditions， faster weight gain， more frequent spontaneous activities， lower water content in feces and tissues， larger weight loss after water loading， and lower coefficient of each organ than the model group （P<0.05， P<0.01）. Moreover， compared with the model group， the three OA groups had high D-xylose excretion， high serum levels of GAS， TP， ALB， and HDL-C， low serum levels of TC， LDL-C， AVP， and IL-6， high expression of Na⁺-K⁺-ATPase in liver， and low expression of AQP1 in renal medulla （P<0.05， P<0.01）. The recovery in each OA group was better than that in natural recovery group. Molecular docking results also confirmed that OA had high binding affinity with ALB， IL-6， AQP1， and Na⁺-K⁺-ATPase. ConclusionOA can alleviate the abnormal water metabolism in mice with water-dampness retention caused by spleen deficiency， which lays a basis for its potential clinical application.

Objective:To explore the effects of multidimensional pain intervention model on postoperative pain in patients with perianal abscess.Methods:Totally 106 patients with perianal abscess who were admitted to the China-Japan Friendship Hospital from March 2020 to March 2022 were selected by convenience sampling and divided into observation group and routine group according to the admission time, with 53 patients in each group. Patients in the routine group received routine nursing care, while patients in the observation group were treated with a multidimensional pain intervention model based on the care provided to the routine group. The postoperative Numerical Rating Scale (NRS) and Depression-Anxiety-Stress Scale 21 (DASS-21) scores were compared between the two groups.Results:The NRS scores of the observation group at 1, 3, 5 and 7 days after surgery were all lower than those of the routine group, and the differences were statistically significant ( P<0.05) ; the DASS-21 scores of the observation group were lower than those of the routine group at 1 and 7 days after surgery, with statistically significant differences ( P<0.05) . Conclusions:The multidimensional pain intervention model can ameliorate postoperative pain and negative emotions of patients with perianal abscess.

Genome-wide physical protein-protein interaction(PPI)mapping remains a major chal-lenge for current technologies.Here,we reported a high-efficiency BiFC-seq method,yeast-enhanced green fluorescent protein-based bimolecular fluorescence complementation(yEGFP-BiFC)coupled with next-generation DNA sequencing,for interactome mapping.We first applied yEGFP-BiFC method to systematically investigate an intraviral network of the Ebola virus.Two-thirds(9/14)of known interactions of EBOV were recaptured,and five novel interactions were discovered.Next,we used the BiFC-seq method to map the interactome of the tumor protein p53.We identified 97 interactors of p53,more than three-quarters of which were novel.Furthermore,in a more complex background,we screened potential interactors by pooling two BiFC libraries together and revealed a network of 229 interactions among 205 proteins.These results show that BiFC-seq is a highly sensitive,rapid,and economical method for genome-wide interactome map-ping.