In this comprehensive review, we delve into the evolution of drug delivery systems in reproductive medicine with a focus on the emerging role of exosomes, a class of extracellular vesicles. Exosomes offer unique advantages in overcoming these challenges due to their inherent biocompatibility, stability, and ability to facilitate targeted delivery. This review provides a detailed examination of exosome biogenesis and their function in cellular communication, setting the stage for understanding their potential as drug delivery vehicles. We explore the mechanisms through which exosomes can be loaded with small molecule drugs and the benefits they offer over synthetic nanoparticles. The review highlights groundbreaking case studies that illustrate the successful application of exosome-mediated drug delivery in reproductive health, including enhancing fertility treatments, supporting gamete and embryo development, and facilitating maternal-fetal communication. This study aims to provide a precise understanding of how exosomal drug delivery can revolutionize treatments for reproductive health disorders, paving the way for future therapeutic applications. Lastly, we touch upon the promising therapeutic implications of exosomal delivery for proteins and genes, offering a window into future treatments for reproductive health disorders.

BACKGROUND: Changes in white matter (WM) underlie the neurocognitive damages induced by a human immunodeficiency virus (HIV) infection. This study aimed to examine using a bundle-associated fixel-based analysis (FBA) pipeline for investigating the microstructural and macrostructural alterations in the WM of the brain of HIV patients. METHODS: This study collected 93 HIV infected patients and 45 age/education/handedness matched healthy controls (HCs) at the Beijing Youan Hospital between January 1, 2016 and December 30, 2016.All HIV patients underwent neurocognitive evaluation and laboratory testing followed by magnetic resonance imaging (MRI) scanning. In order to detect the bundle-wise WM abnormalities accurately, a specific WM bundle template with 56 tracts of interest was firstly generated by an automated fiber clustering method using a subset of subjects. Fixel-based analysis was used to investigate bundle-wise differences between HIV patients and HCs in three perspectives: fiber density (FD), fiber cross-section (FC), and fiber density and cross-section (FDC). The between-group differences were detected by a two-sample t -test with the false discovery rate (FDR) correction ( P <0.05). Furthermore, the covarying relationship in FD, FC and FDC between any pair of bundles was also accessed by the constructed covariance networks, which was subsequently compared between HIV and HCs via permutation t -tests. The correlations between abnormal WM metrics and the cognitive functions of HIV patients were explored via partial correlation analysis after controlling age and gender. RESULTS: Among FD, FC and FDC, FD was the only metric that showed significant bundle-wise alterations in HIV patients compared to HCs. Increased FD values were observed in the bilateral fronto pontine tract, corona radiata frontal, left arcuate fasciculus, left corona radiata parietal, left superior longitudinal fasciculus III, and right superficial frontal parietal (SFP) (all FDR P <0.05). In bundle-wise covariance network, HIV patients displayed decreased FD and increased FC covarying patterns in comparison to HC ( P <0.05) , especially between associated pathways. Finally, the FCs of several tracts exhibited a significant correlation with language and attention-related functions. CONCLUSIONS Our study demonstrated the utility of FBA on detecting the WM alterations related to HIV infection. The bundle-wise FBA method provides a new perspective for investigating HIV-induced microstructural and macrostructural WM-related changes, which may help to understand cognitive dysfunction in HIV patients thoroughly.
Humans ; HIV ; HIV Infections ; Cognition ; Brain ; White Matter

BACKGROUND: The prevalence of hypertension is high among Chinese adults, thus, identifying non-hypertensive individuals at high risk for intervention will help to improve the efficiency of primary prevention strategies. METHODS: The cross-sectional data on 9699 participants aged 20 to 80 years were collected from the China National Health Survey in Gansu and Hebei provinces in 2016 to 2017, and they were nonrandomly split into the training set and validation set based on location. Multivariable logistic regression analysis was performed to develop the diagnostic prediction model, which was presented as a nomogram and a website with risk classification. Predictive performances of the model were evaluated using discrimination and calibration, and were further compared with a previously published model. Decision curve analysis was used to calculate the standardized net benefit for assessing the clinical usefulness of the model. RESULTS: The Lasso regression analysis identified the significant predictors of hypertension in the training set, and a diagnostic model was developed using logistic regression. A nomogram with risk classification was constructed to visualize the model, and a website ( https://chris-yu.shinyapps.io/hypertension_risk_prediction/ ) was developed to calculate the exact probabilities of hypertension. The model showed good discrimination and calibration, with the C-index of 0.789 (95% confidence interval [CI]: 0.768, 0.810) through internal validation and 0.829 (95% CI: 0.816, 0.842) through external validation. Decision curve analysis demonstrated that the model was clinically useful. The model had a higher area under receiver operating characteristic curves in training and validation sets compared with a previously published diagnostic model based on Northern China population. CONCLUSION This study developed and validated a diagnostic model for hypertension prediction in Gansu Province. A nomogram and a website were developed to make the model conveniently used to facilitate the individualized prediction of hypertension in the general population of Han and Yugur.
Adult ; Humans ; Asian People ; China/epidemiology* ; Cross-Sectional Studies ; Health Surveys ; Hypertension/epidemiology* ; Nomograms ; Ethnicity

Objective: To investigate the origin of infection and risk factors of a case with SARS-CoV-2 infection associated with overseas countries in the Ningbo-Zhoushan Port, Zhejiang Province, so as to provide the evidence for improving the COVID-19 control measures at ports. Methods: Ningbo Center for Disease Control and Prevention ( CDC ) and Beilun CDC conducted case finding and epidemiological surveys immediately after being informed. The general information, history of vaccination and the travel during the latest 14 days were collected from the positive case, and all close contacts were tracked. Saliva samples were collected for SARS-CoV-2 nucleic acid testing and whole-genome sequencing, and the sequencing results were aligned with the GISAID's EpiCoV database. The origin of infection and transmission route of the positive case was investigated. Results: A case was identified positive for SARS-CoV-2 nucleic acid during company M's routine screening in the Ningbo-Zhoushan Port on August 10, 2021, and was confirmed positive for SARS-CoV-2 nucleic acid by Beilun CDC and Ningbo CDC on August 11. Whole-genome sequencing showed SARS-CoV-2 B.1.617.2 ( Delta ) variant, which shared the highest homology with the virus sequence uploaded by Russia on June, 2021 ( Russia/MOW-RII-MH27356S/2021 ). The case was a bundling worker for overseas container ships, and reported communicated with foreign boatmen and contacted materials without protected interventions on the SINOKOR AKITA Container Ship between August 4 and 5, 2021. This ship anchored at Vladivostok, Russia from July 27 to 29, anchored at Ningbo Harbor on August 4, and departed on August 5. Then, 11 boatmen from this ship were tested positive for SARS-CoV-2 nucleic acid on August 8. One asymptomatic case was reported in this epidemic; 254 close contacts and 617 secondary close contacts were identified, and all were tested negative for SARS-CoV-2 nucleic acid. No new cases with SARS-CoV-2 infections were detected until August 25, 2021, and the emergency response was therefore terminated. Conclusions The infection was a sporadic COVID-19 epidemic associated with overseas countries, which was caused by Delta variant infection through contacts with foreign boatmen or materials by a bundling worker in Ningbo-Zhoushan Port; fortunately, no epidemic spread occurred. Intensified closed-loop management and increased frequency of SARS-CoV-2 nucleic acid test among high-risk populations, and improving the precision and rapid emergency treatment of COVID-19 epidemics are required for the containment of COVID-19 at ports.

BACKGROUND: Acquired immune deficiency syndrome (AIDS)-related non-Hodgkin lymphoma (AR-NHL) is a high-risk factor for morbidity and mortality in patients with AIDS. This study aimed to determine the prognostic factors associated with overall survival (OS) and to develop a prognostic nomogram incorporating computed tomography imaging features in patients with acquired immune deficiency syndrome-related non-Hodgkin lymphoma (AR-NHL). METHODS: A total of 121 AR-NHL patients between July 2012 and November 2019 were retrospectively reviewed. Clinical and radiological independent predictors of OS were confirmed using multivariable Cox analysis. A prognostic nomogram was constructed based on the above clinical and radiological factors and then provided optimum accuracy in predicting OS. The predictive accuracy of the nomogram was determined by Harrell C-statistic. Kaplan-Meier survival analysis was used to determine median OS. The prognostic value of adjuvant therapy was evaluated in different subgroups. RESULTS: In the multivariate Cox regression analysis, involvement of mediastinal or hilar lymph nodes, liver, necrosis in the lesions, the treatment with chemotherapy, and the CD4 ≤100 cells/μL were independent risk factors for poor OS (all P < 0.050). The predictive nomogram based on Cox regression has good discrimination (Harrell C-index = 0.716) and good calibration (Hosmer-Lemeshow test, P = 0.620) in high- and low-risk groups. Only patients in the high-risk group who received adjuvant chemotherapy had a significantly better survival outcome. CONCLUSION A survival-predicting nomogram was developed in this study, which was effective in assessing the survival outcomes of patients with AR-NHL. Notably, decision-making of chemotherapy regimens and more frequent follow-up should be considered in the high-risk group determined by this model.
Acquired Immunodeficiency Syndrome ; Humans ; Lymphoma, Non-Hodgkin ; Neoplasm Staging ; Nomograms ; Prognosis ; Retrospective Studies

Activating metabolite glutamate receptor 8 (mGluR8) has anti-hyperpathia effect in central nervous system, however, studies of effects in gastrointestinal tract are rare. Visceral hypersensitivity is one of the pathogenesis factors of irritable bowel syndrome (IBS). Aims: To investigate the effect and potential mechanism of activating mGluR8 on visceral hypersensitivity in neonatal maternally separated (NMS) rats. Methods: Twenty-four male newborn SD rats were randomly divided into normal control (NC) group, NMS group and mGluR8 agonist (S)-3, 4-DCPG group (3, 10 mg/kg). Newborn rats were subjected to 3 hours daily maternal separation on postnatal day 2-14 to establish the NMS model; in (S)-3, 4-DCPG group, (S)-3, 4-DCPG (3 or 10 mg/kg) were administered 1 hour prior to the visceral sensitivity test in NMS rats. Abdominal withdrawal reflex (AWR) score and abdominal electromyography (EMG) activity were used to measure visceral sensitivity. mGluR8 mRNA and protein expressions in colon mucosa were measured by RT-PCR and Western blotting, respectively; TNF-α, IL-1β and IL-6 mRNA expressions in colon mucosa were measured by RT-PCR. The protein expression of myeloperoxidase (MPO) was measured by immunohistochemistry. Results: AWR score and EMG activity in NMS group were significantly higher than those in NC group under different colorectal distension (CRD) pressure. AWR score and EMG activity were significantly decreased in (S)-3, 4-DCPG group. mGluR8 mRNA and protein expressions in NMS group were significantly higher than those in NC group (P<0.05). Compared with NMS group, TNF-α mRNA expression was significantly decreased in 3 mg/kg (S)-3, 4-DCPG group (P<0.05), and MPO protein expression was significantly decreased in 10 mg/kg (S)-3, 4-DCPG group (P<0.05). Conclusions: Activating mGluR8 attenuates visceral hypersensitivity in NMS rats, the mechanism may be related to decrease of pro-inflammatory cytokine TNF-α.

Objective:To understand the seroepidemiological characteristics of pertussis in healthy population in Ningbo, and estimate the overall incidence of pertussis.Methods:A cross-sectional survey method was used in this study. A total of 1 206 healthy residents in 9 age groups were stratified randomly selected from 3 counties of Ningbo. Serum samples were collected from the subjects, and the pertussis toxin immunoglobulin G antibody (PT-IgG) levels were measured quantitatively by enzyme-linked immunosorbent assay (ELISA).Results:The mean PT-IgG seropositive rate in the subjects was 0.91% (95% CI:0.45%-1.63%) with a geometric mean titer (GMT) of 3.10 (95% CI:2.86-3.36) IU/ml. The seropositive rates ranged from 0.00% to 1.68%, and the GMTs ranged from 2.08 IU/ml to 5.28 IU/ml in 9 age groups. The incidence rate of pertussis was estimated to be 4 572.81 per 100 000 in age group ≥5 years (95% CI:1 807.30 per 100 000-9 348.12 per 100 000), and the peak of estimated incidence rates were found in age group 5- years (9 301.62 per 100 000, 95% CI:1 121.77 per 100 000-33 154.68 per 100 000) and age group ≥50 years old (8 967.02 per 100 000, 95% CI: 1 059.45 per 100 000-31 845.94 per 100 000). Conclusions:The actual incidence of pertussis was high in Ningbo in 2019. As a result of waning immunity after vaccination, pertussis can occur in adolescents and adults. The pertussis surveillance should be strengthened and the pertussis vaccination strategy should be improved.

Objective:To investigate a cluster epidemic of COVID-19 after a mass gathering activity in Ningbo of Zhejiang province and analyze the transmission chain and status of infection cases of different generations.Methods:The tracking of all the close contacts of the first COVID-19 case and epidemiological investigation were conducted on January 29, 2020 after a cluster epidemic of COVID-19 related with a Buddhism rally on January 19 (the 1.19 rally) in Ningbo occurred. The swabs of nose/throat of the cases and close contacts were collected and tested for nucleic acids by real-time fluorescence quantitative RT-PCR.Results:From January 26 to February 20, 2020, a total of 67 COVID-19 cases and 15 asymptomatic infection cases related with the 1.19 rally were reported in Ningbo. The initial case was the infection source who infected 29 second generation cases and 4 asymptomatic infection cases, in whom 23 second generation cases and 3 asymptomatic infection cases once took bus with the initial case, the attack rate was 33.82% (23/68) and the infection rate was 38.24% (26/68). The risks of suffering from COVID-19 and being infected were 28.91 times and 26.01 times higher in rally participants taking bus with initial case compared with those taking no bus with initial case. In this epidemic, 37 third+generation cases and 11 related asymptomatic infection cases occurred, the attack rate was 2.88% (37/1 283) and the infection rate was 4.76% (48/1 008). The main transmission routes included vehicle sharing and family transmission.Conclusion:It was a cluster epidemic of COVID-19 caused by a super spreader in a massive rally. The epidemic has been under effective control.

Objective To evaluate the clinical efficacy of percutaneous piercing cortical bone at fracture ends and local injection of autologous concentrated bone marrow aspirate (cBMA) and platelet rich plasma (PRP) in the treatment of delayed fracture union.Methods A retrospective study was performed on the clinical data of 34 patients with delayed fracture union who had been treated at Department of Orthopaedics,Luoyang Zhenggu Hospital of Henan Province from April 2014 to February 2017.They were 26 males 8 females,aged from 18 to 63 years (average,36.7 years).There were 15 femoral,11 tibial,5 humerus and 3 ulnar fractures.According to the Weber-Crech classification,14 cases belonged to the type of rich blood supply-active end hypertrophy and 20 to the type of poor blood supply and malnutrition.There were 28 closed and 6 open fractures.Of this cohort,21 cases had their primary fixation,7 had revision once,4 had revision twice,and 2 had revision more than thrice;19 cases had intramedullary fixation,12 had plate fixation and 3 had external fixation.Autologous iliac bone grafting was performed previously in 19 cases.Kirschner wire was used under fluoroscopy to pierce percutaneously the cortical bone at fracture ends;bone marrow blood and peripheral venous blood were collected to prepare autologous cBMA and PRP which were to be injected locally at the fracture ends after mixture.At the last follow-up,the patients were evaluated by visual analogue scale (VAS),SF-36 health survey summary scores and modified Radiographic Union Score for Tibia (RUST).Results The patients were followed up for 12 to 42 months (average,21.5 months).Thirty-one patients healed after surgery,yielding a healing rate of 91.2％.The healing time averaged 5.3 months (from 4 to 10 months).No patient reported such complications as infection or neurovascular injury.At the last follow-up,the VAS scores of the 34 patients were 1.3 ± 0.6 points,significantly lower than the preoperative 5.4 ± 3.6 points (P ＜ 0.05);the postoperative SF-36 scores 74.8 ± 16.5 points,significantly increased than the preoperative 44.8 ± 15.6 scores (P ＜ 0.05);the RUST scores 3.3 ± 0.4 points,significantly higher than the preoperative 1.6 ± 0.8 points (P ＜ 0.05).Conclusions Minimally invasive percutaneous piercing of K-wire on the cortical bone at the fracture ends may result in fluid leakage and restart bone healing process.At the same time,local injection of autologous cBMA and PRP may increase the number and concentration of local bone marrow mesenchymal stem cells and growth factors,promoting fracture healing.

The family doctor system is a collection of the rules and operating patterns formed during the interaction between the top design of "universal health coverage" and the "contractual experiment" at primary level. Its optimization and upgrading call for continuous attention to primary policy response. A questionnaire survey was made to medical workers at primary healthcare institutions in Zhejiang,to learn the comments and willingness of participation of family doctors for the contractual service policy. The survey found the poor policy response roots in such constraints as lack of effective connection between top level and primary level,poor incentive design,and delayed supporting policies. In view of upgrading supplier policy response,the authors recommended feasible strategies to optimize policy response, namely priori decision-making,process control,both hard and soft tactics,and parallel efforts for both internal and external sides.