Objective:To investigate the association between high-risk human papillomavirus (hrHPV) persistent infection and vaginal microecology.Methods:A total of 53 women were enrolled in the gynecological clinic of Beijing Obstetrics and Gynecology Hospital from January 2020 to January 2021, including 7 women without HPV and 46 women with hrHPV infection. Among the hrHPV infected women, 24 woemn who did not use any drugs were classified as the observation group and the other 22 women who were given standardized interferon vaginal administration for 3 months were regarded as the treatment group. Vaginal secretions of all women were taken for Gram-stained microecological test at the time of enrollment and at the 4, 8, and 12 month follow-up. HPV turning negative was taken as the end point of follow-up.Results:(1) Women of hrHPV persistent infection in the observation and treatmnet groups had more times of abortions ( P=0.180). (2) The hrHPV negative conversion rate was 17% (4/24) in the observation group and 36% (8/22) in the treatment group, but the difference was not significant ( P=0.183). The median hrHPV negative conversion time were 11.0 months and 7.5 months in the observation and treatment groups, respectively, and the difference was statistically significant ( P=0.001). (3) Vaginal microecology was generally normal at the time of enrollment and at the end of follow-up in women with HPV natural negative conversion in the observation group. While vaginal microecological disorders were more common in women with hrHPV persistent infection in the observation and treatmnet groups, including high vaginal pH value, poor vaginal cleanliness, poor grade of Lactobacillus and increased vaginal clutter bacteria, and the vaginal microecological situation did not improve after the 12-month follow-up. (4) In the treatment group, women who turned HPV negative within six months all had normal vaginal microecology when enrollment (5/5). While those who turned negative six months later had a higher proportion of vaginal clutter bacteria (2/3), a poor grade of Lactobacillus (2/3) and a higher proportion of vaginal dysbiosis (2/3). Conclusions:(1) Interferon therapy could shorten the negative turning time of hrHPV. (2) Women with normal vaginal microecology have the ability to naturally clear hrHPV. (3) The vaginal microecological Gram-stain test has limited value in predicting hrHPV clearance, perhaps due to its inability to detect Lactobacillus subtypes.

Objective:To establish a rat model of vulvovaginal candidiasis (VVC) and to directly observe the histopathological and ultrastructural characteristics of vaginal mucosal barrier after Candida albicans infection and treatment with Lactobacillus crispatus.Methods:Female unmated SD rats were used to establish the VVC model and divided into three groups (normal group, VVC group, and Lactobacillus group; n=6 per group). Lactobacillus group received intravaginal administration of Lactobacillus crispatus suspension, while rats in VVC group and normal group were infused with phosphate buffered solution instead. Vaginal tissues were collected on day 4 post-treatment for HE staining and transmission electron microscopy (to observe ultrastructural pathological changes). Results:The results of HE staining revealed the disruption and desquamation of vaginal epithelium, necrotic epithelial tissues, neutrophil infiltration in Candida albicans-infected rats. Lactobacillus crispatus intervention restored the damaged vaginal mucosal structure (mucosal layers and thickness) to normal levels, mucosal layers of Lactobacillus group and normal group were 9.50±1.38 vs 10.67±1.03 ( P=0.226), mucosal thickness of Lactobacillus group and normal group were (116.50±12.14) vs (130.33±13.91) μm ( P=0.211). The results of transmission electron microscopy revealed intercellular desmosome rupture, loss of microvilli and glycocalyx on superficial cells, and mitochondrial swelling in Candida albicans-infected rats. Lactobacillus crispatus intervention restored the damaged vaginal mucosal ultrastructures (mitochondria and intercellular connections, etc.) to normal levels. Conclusions:Fungal infection severely disrupte the vaginal mucosal barrier in rats. Lactobacillus crispatus could restore the vaginal mucosal barrier and epithelial ultrastructures.

Integrin α _v β ₃ is overexpressed in various tumor cells and angiogenesis. To date, no drug has been proven to target it for therapy. A first-in-human study was designed to investigate the safety, pharmacokinetics, and dosimetry of ¹⁷⁷Lu-AB-3PRGD2, a novel integrin α _v β ₃-targeting radionuclide drug with an albumin-binding motif to optimize the pharmacokinetics. Ten patients (3 men, 7 women; aged 45 ± 16 years) with integrin α _v β ₃-avid tumors were recruited to accept ¹⁷⁷Lu-AB-3PRGD2 injection in a dosage of 1.57 ± 0.08 GBq (42.32 ± 2.11 mCi), followed by serial scans to obtain its dynamic distribution in the body. Safety tests were performed before and every 2 weeks after the treatment for 6-8 weeks. No adverse event over grade 3 was observed. ¹⁷⁷Lu-AB-3PRGD2 was excreted mainly through the urinary system, with intense radioactivity in the kidneys and bladder. Moderate distribution was found in the liver, spleen, and intestines. The estimated blood half-life was 2.85 ± 2.17 h. The whole-body effective dose was 0.251 ± 0.047 mSv/MBq. The absorbed doses were 0.157 ± 0.032 mGy/MBq in red bone marrow and 0.684 ± 0.132 mGy/MBq in kidneys. This first-in-human study of ¹⁷⁷Lu-AB-3PRGD2 treatment indicates its promising potential for targeted radionuclide therapy of integrin α _v β ₃-avid tumors. It merits further studies in more patients with escalating doses and multiple treatment courses.

Objective:This study aimed to explore the serum levels of soluble programmed cell death protein 1 (sPD-1) and soluble programmed cell death-ligand 1 (sPD-L1) in patients with spontaneous intracerebral hemorrhage (ICH) and their clinical value in the prognostic analysis.Methods:This prospective cohort study included patients aged ≥18 years admitted to the department of critical care medicine at the Affiliated Hospital of Zunyi Medical University between January 2022 and October 2024 with a first episode of ICH presenting within 24 hours of onset. Patients with hemorrhage caused by other causes (e.g., tumor, medication and trauma) or incomplete data were excluded. Based on 28-day all-cause mortality, patients were divided into survival group and non-survival group. According to the 60-day neurological outcome, patients were divided into good neurological outcome group and poor neurological outcome group. Clinical and imaging data were collected, along with venous blood samples obtained within 24 hours of admission to measure serum levels of sPD-1 and sPD-L1. Predictive indicators were identified using LASSO-Logistic regression analysis was used to identify predictive indicators, and a nomogram was constructed to visualize the prediction model. Model performances were evaluated using receiver operating characteristic curves, decision curve analysis, calibration curves, and the Hosmer-Lemeshow test.Results:A total of 155 patients were included: 101 in the survival group and 54 in the death group; 56 in the favorable neurological outcome group and 99 in the poor neurological outcome group. Serum sPD-1 concentrations were significantly lower in the death group and poor neurological outcome group compared to the survival group and favorable neurological outcome group, respectively. Conversely, serum sPD-L1 concentrations were significantly higher in the death group and poor neurological outcome group compared to the survival group and favorable neurological outcome group (all P < 0.05). Serum sPD-1 and sPD-L1 were identified as predictors of 28-day mortality risk. A nomogram incorporating seven indicators—brainstem hemorrhage, hemorrhage volume, obstructive hydrocephalus, surgical intervention, admission NIHSS score, and admission serum sPD-1 and sPD-L1 levels—demonstrated superior predictive performance [AUC=0.984 (95% CI: 0.968-1.000)] compared to sPD-1 alone (AUC=0.712) or sPD-L1 alone (AUC=0.753). Serum sPD-1 was a predictor of poor 60-day neurological outcome. A nomogram incorporating obstructive hydrocephalus, admission NIHSS score, and admission serum sPD-1 level [AUC=0.818 (95% CI: 0.754-0.882)] outperformed sPD-1 alone (AUC=0.637) or sPD-L1 alone (AUC=0.602). Conclusions:Serum levels of sPD-1 were significantly lower in the non-survivors and the patients with poor neurological outcomes compared to the survivors and the patients with good neurological outcomes. However, serum levels of sPD-L1 were significantly higher in the non-survivors and the patients with poor neurological outcome. Serum sPD-1 was an independent predictor of 28-day mortality risk and 60-day poor neurological outcome; serum sPD-L1 was an independent predictor of 28-day mortality risk. A nomogram prediction model incorporating sPD-1 and sPD-L1 demonstrated good predictive performance for mortality risk and poor neurological outcome.

Objective:To investigate the association between high-risk human papillomavirus (hrHPV) persistent infection and vaginal microecology.Methods:A total of 53 women were enrolled in the gynecological clinic of Beijing Obstetrics and Gynecology Hospital from January 2020 to January 2021, including 7 women without HPV and 46 women with hrHPV infection. Among the hrHPV infected women, 24 woemn who did not use any drugs were classified as the observation group and the other 22 women who were given standardized interferon vaginal administration for 3 months were regarded as the treatment group. Vaginal secretions of all women were taken for Gram-stained microecological test at the time of enrollment and at the 4, 8, and 12 month follow-up. HPV turning negative was taken as the end point of follow-up.Results:(1) Women of hrHPV persistent infection in the observation and treatmnet groups had more times of abortions ( P=0.180). (2) The hrHPV negative conversion rate was 17% (4/24) in the observation group and 36% (8/22) in the treatment group, but the difference was not significant ( P=0.183). The median hrHPV negative conversion time were 11.0 months and 7.5 months in the observation and treatment groups, respectively, and the difference was statistically significant ( P=0.001). (3) Vaginal microecology was generally normal at the time of enrollment and at the end of follow-up in women with HPV natural negative conversion in the observation group. While vaginal microecological disorders were more common in women with hrHPV persistent infection in the observation and treatmnet groups, including high vaginal pH value, poor vaginal cleanliness, poor grade of Lactobacillus and increased vaginal clutter bacteria, and the vaginal microecological situation did not improve after the 12-month follow-up. (4) In the treatment group, women who turned HPV negative within six months all had normal vaginal microecology when enrollment (5/5). While those who turned negative six months later had a higher proportion of vaginal clutter bacteria (2/3), a poor grade of Lactobacillus (2/3) and a higher proportion of vaginal dysbiosis (2/3). Conclusions:(1) Interferon therapy could shorten the negative turning time of hrHPV. (2) Women with normal vaginal microecology have the ability to naturally clear hrHPV. (3) The vaginal microecological Gram-stain test has limited value in predicting hrHPV clearance, perhaps due to its inability to detect Lactobacillus subtypes.

Objective:To establish a rat model of vulvovaginal candidiasis (VVC) and to directly observe the histopathological and ultrastructural characteristics of vaginal mucosal barrier after Candida albicans infection and treatment with Lactobacillus crispatus.Methods:Female unmated SD rats were used to establish the VVC model and divided into three groups (normal group, VVC group, and Lactobacillus group; n=6 per group). Lactobacillus group received intravaginal administration of Lactobacillus crispatus suspension, while rats in VVC group and normal group were infused with phosphate buffered solution instead. Vaginal tissues were collected on day 4 post-treatment for HE staining and transmission electron microscopy (to observe ultrastructural pathological changes). Results:The results of HE staining revealed the disruption and desquamation of vaginal epithelium, necrotic epithelial tissues, neutrophil infiltration in Candida albicans-infected rats. Lactobacillus crispatus intervention restored the damaged vaginal mucosal structure (mucosal layers and thickness) to normal levels, mucosal layers of Lactobacillus group and normal group were 9.50±1.38 vs 10.67±1.03 ( P=0.226), mucosal thickness of Lactobacillus group and normal group were (116.50±12.14) vs (130.33±13.91) μm ( P=0.211). The results of transmission electron microscopy revealed intercellular desmosome rupture, loss of microvilli and glycocalyx on superficial cells, and mitochondrial swelling in Candida albicans-infected rats. Lactobacillus crispatus intervention restored the damaged vaginal mucosal ultrastructures (mitochondria and intercellular connections, etc.) to normal levels. Conclusions:Fungal infection severely disrupte the vaginal mucosal barrier in rats. Lactobacillus crispatus could restore the vaginal mucosal barrier and epithelial ultrastructures.

Objective:To retrospectively analyze the viral levels and associated factors in patients with hepatitis B virus (HBV)-related primary liver cancer (PHC) in real-world settings and further explore the correlation between low viral load (LVL) and/or low-level viremia (LLV) and PHC.Methods:Five hundred twenty-four cases with HBV-related PHC with complete pathologically confirmed data from 2013 to 2020 were included. Percentages (%) were used to express their viral load, antiviral (oral) status, patient compliance, presence or absence of cirrhosis, family history of liver cancer, and others. LVL definition: After excluding detection errors by PCR method, serum HBV DNA <50-2 000 IU/ml, and those who had received antiviral drug treatment were called LLV. Antiviral treatment (AVT) rate definition: As of the confirmed diagnosis of PHC, those who had been regularly treated using oral antiviral drugs for six months or more (≥6 months).Results:General situation: The ratio of male to female enrolled patients was 15.90:1 (493/31). Patients aged >40 years accounted for 91.98% (482 cases). Hepatitis B surface antigen (HBsAg) positivity condition: The ratio of HBsAg-positive to HBsAg-negative/anti-HBc-positive (HBsAg-/anti-HBc+) PHC patients was 5.89:1 (448/76). Among the 76 HBsAg-/anti-HBc+patients, the ratio of HBsAg-/anti-HBs+/anti-HBc+ to HBsAg-/anti-HBs-/anti-HBc+ patients was 0.95:1 (37/39). Hepatitis B e antigen (HBeA) positivity condition: The ratio of HBeAg-negative to HBeAg-positive cases was 3.23:1 (400/124). HBV DNA level condition: The medical history records of 75.00% of patients (393/524) had traceable HBV DNA test reports. Out of 393 patients, 45.04% (177/393) accounted for undetectable HBV DNA, 13.49% (53/393) accounted for LVL, 41.48% (163/393) accounted for HBV DNA exceeding the upper limit of LVL, and 4.07% (16/393) accounted for LLV. Among HBsAg-positive and HBsAg-/anti-HBc+ patients, the HBV DNA positivity rates were 59.12% (214/362) and 6.45% (2/31), respectively. Antiviral treatment condition: Among the 448 HBsAg-positive PHC patients, the total AVT rate was 18.08% (81/448), of which seven patients did not have their HBV DNA results traced back. Among them, the AVT rate of 148 patients with HBV DNA lower than the lowest detection value was 41.22% (61/148); the AVT rate of 53 patients with LVL was 18.87% (10/53); and the AVT rate of 163 patients with HBV DNA≥LVL upper limit was 1.84% (3/163). Liver cirrhosis and family history condition: 348 patients (66.41%) had liver cirrhosis. 67 patients (12.79%) had a distinct family history of HBV-related liver cirrhosis and liver cancer. Alpha-fetoprotein (AFP) condition: 514 patients underwent AFP testing, with 30.93% of the patients had normal AFP levels, and 69.07% had AFP levels exceeding the upper limit of normal values (355/514). Among them, 10 μg/L400 μg/L accounted for 34.44% (177/514) and 34.63% (178/514), respectively. Tissue typing condition: 99.05% (519/524) were hepatocellular carcinoma, and well-differentiated and moderately differentiated cases accounted for only 8.59%.Conclusions:In the real world, comprehensive, timely screening, standardized, and effective antiviral treatment have not yet been achieved for patients with chronic hepatitis B, resulting in the persistence of HBsAg and/or HBV DNA positivity (especially LVL and/or LLV). Although LVL does not account for a high proportion among all HBV-related PHC populations, the vast majority of LVL populations have not received any antiviral treatment. In addition, some PHC populations with HBV DNA>2 000 IU/ml have not received standard antiviral treatment before the onset of the disease, which should be paid attention to. At the same time, HBsAg-/anti-HBc+ populations may have latent HBV infection and may even progress to PHC. Notably, PHC may still occur after HBeAg seronegative conversion.

Objective:To understand the current status of anemia, iron deficiency, and iron-deficiency anemia among preschool children in China.Methods:A cross-sectional study was conducted with a multi-stage stratified sampling method to select 150 streets or townships from 10 Chinese provinces, autonomous regions, or municipalities (East: Jiangsu, Zhejiang, Shandong, and Hainan; Central: Henan; West: Chongqing, Shaanxi, Guizhou, and Xinjiang; Northeast: Liaoning). From May 2022 to April 2023, a total of 21 470 children, including community-based children aged 0.5 to<3.0 years receiving child health care and kindergarten-based children aged 3.0 to<7.0 years, were surveyed. They were divided into 3 age groups: infants (0.5 to<1.0 year), toddlers (1.0 to<3.0 years), and preschoolers (3.0 to<7.0 years). Basic information such as sex and date of birth of the children was collected, and peripheral blood samples were obtained for routine blood tests and serum ferritin measurement. The prevalence rates of anemia, iron deficiency, and iron-deficiency anemia were analyzed, and the prevalence rate differences were compared among different ages, sex, urban and rural areas, and regions using the chi-square test.Results:A total of 21 460 valid responses were collected, including 10 780 boys (50.2%). The number of infants, toddlers, and preschoolers were 2 645 (12.3%), 6 244 (29.1%), and 12 571 (58.6%), respectively. The hemoglobin level was (126.7±14.8) g/L, and the serum ferritin level was 32.3 (18.5, 50.1) μg/L. The overall rates of anemia, iron deficiency, and iron-deficiency anemia were 10.4% (2 230/21 460), 28.3% (6 070/21 460), and 3.9% (845/21 460), respectively. The prevalence rate of anemia was higher for boys than for girls (10.9% (1 173/10 780) vs. 9.9% (1 057/10 680), χ2=5.58, P=0.018), with statistically significant differences in the rates for infants, toddlers and preschoolers (18.0% (475/2 645), 10.6% (662/6 244), and 8.7% (1 093/12 571), respectively, χ2=201.81, P<0.01), and the rate was significantly higher for children in rural than that in urban area (11.8% (1 516/12 883) vs. 8.3% (714/8 577), χ2=65.54, P<0.01), with statistically significant differences in the rates by region ( χ2=126.60, P<0.01), with the highest rate of 15.8% (343/2 173) for children in Central region, and the lowest rate of 5.3% (108/2 053) in Northeastern region. The prevalence rates of iron deficiency were 33.8% (895/2 645), 32.2% (2 011/6 244), and 25.2% (3 164/12 571) in infants, toddlers, and preschoolers, respectively, and 30.0% (3 229/10 780) in boys vs. 26.6% (2 841/10 680) in girls, 21.7% (1 913/8 821), 40.0% (870/2 173), 27.1% (2 283/8 413), 48.9% (1 004/2 053) in Eastern, Central, Western, and Northeastern regions, respectively, and each between-group showed a significant statistical difference ( χ2=147.71, 29.73, 773.02, all P<0.01). The prevalence rate of iron-deficiency anemia showed a significant statistical difference between urban and rural areas, 2.9% (251/8 577) vs. 4.6% (594/12 883) ( χ2=38.62, P<0.01), while the difference in iron deficiency prevalence was not significant ( χ2=0.51, P=0.476). Conclusions:There has been a notable improvement in iron deficiency and iron-deficiency anemia among preschool children in China, but the situation remains concerning. Particular attention should be paid to the prevention and control of iron deficiency and iron-deficiency anemia, especially among infants and children in the Central, Western, and Northeastern regions of China.

Objective:To analyze the vaginal microecological status of vaginitis population and non-vaginitis population of gynecological female outpatients.Methods:A total of 30 265 women who visited the gynecological outpatient clinic of Beijing Obstetrics and Gynecology Hospital from December 2018 to December 2020 completed vaginal microecological examination. After removing the follow-up patients, 23 181 women were divided into group with symptoms and signs of vaginitis (6 697 cases) and group without symptoms and signs of vaginitis (16 484 cases), according to whether the women with symptoms and signs of vaginitis or not. And the vaginal microecological status of the two groups was compared and analyzed.Results:(1) The total detection rate of vaginitis in the initial women was 34.87% (8 083/23 181), of which 46.10% (3 087/6 697) in group with symptoms and signs of vaginitis and 30.31% (4 996/16 484) in group without symptoms and signs of vaginitis, nearly 1/3 of the gynecological outpatients without signs and symptoms of vaginitis had vaginitis. (2) Among the types of simple vaginitis, vulvovaginal candidiasis (VVC) was the most frequent in group with symptoms and signs of vaginitis (16.01%, 1 072/6 697), followed by aerobic vaginitis (AV; 12.83%, 859/6 697), with significant differences compared with group without symptoms and signs of vaginitis (all P<0.001). There were no statistical differences between the two groups of bacterial vaginosis (BV) and trichomonal vaginitis (TV), indicating that BV and TV were more likely to be neglected (all P>0.05). (3) The proportion of various combinations of vaginitis among 2 632 cases of mixed vaginitis were, in descending order: BV+AV, VVC+AV, BV+AV+VVC, AV+TV, AV+TV+BV, BV+VVC. (4) Microecological analysis of 15 098 cases diagnosed with non-vaginitis had normal flora (including those with normal flora and those with normal flora but decreased function) in 14 013 cases (92.81%, 14 013/15 098), abnormal flora in 429 cases (2.84%, 429/15 098) and the BV intermediate in 656 cases (4.34%, 656/15 098); this indicated that the vast majority of the microecological tests were normal in the vaginal microbiota of those without vaginitis. Conclusions:Microecological examination could diagnose multiple pathogenic infections at once, and is especially important as a guide for the definitive diagnosis of mixed vaginitis and vaginitis with atypical clinical symptoms. Vaginal infections such as BV and TV that are easily overlooked should be concerned.

Objective:To explore the influencing factors and effectiveness of community follow-up in patients with cardiac implantable electronic device (CIED) implantation.Method:A total of 132 patients who received CIED implantation in the Department of Cardiology of Tongren Hospital, Shanghai Jiao Tong University School of Medicine from February 2021 to February 2022 were enrolled in this prospective cohort study. Among them 33 patients were followed up in community health service centers associated with Tongren Hospital (community follow-up group) and 99 matched patients were followed up in the CIED outpatient clinic of the hospital (outpatient follow-up group) with a ratio of 1∶3. The clinical data of the selected patients were collected through a questionnaire survey; the follow-up data were extracted through the CarelinkExpress electronic follow-up platform and the CIED outpatient information system of Tongren Hospital. Adjustment of the treatment protocol or CIED parameters at follow-up, and the referral from the community health service centers were defined as visit with-an-action (VWA). The endpoint of follow-up was the occurrence of major adverse events. The multivariate logistic regression model was used to analyze the factors influencing patient selection for community follow-up.Results:The univariate analysis showed that the frequency of visits to community health service centers and the service contracting rate in community follow-up group were higher than those of outpatient follow-up group ( P<0.05). The multivariate logistic regression analysis showed that the contracted community physician service was an independent influencing factor of patient choosing community follow-up ( OR=2.143, 95% CI: 1.103-4.166, P=0.025). A total of 469 visits of followed up occurred in 132 patients, including 45 community visits and 424 outpatient visits. VWA accounted for 22.2% (10/45) in the community follow-up group, and 17.2% (73/424) in the outpatient follow-up group ( P>0.05). There was no significant difference in the safety and effectiveness indicators (VWA, major adverse events, and unplanned follow-up) between the two groups ( P>0.05). More patients in the community follow-up group walked to the hospital than the outpatient follow-up group ( P<0.05);and the main transportation for the later was by bus or taxi(42(42.4%)or 41(41.4%)). The average waiting time in the community follow-up group was significantly shorter than that in outpatient follow-up group ( P<0.05). The total time required for a single follow-up in the community follow-up group was 50.0 (45.0, 59.5) minutes, which was significantly shorter than that in the routine outpatient follow-up group (107.0 (90.0, 135.0) minutes, P<0.05). Conclusions:The contracting with community physicians is an independent influencing factor for CIED implanted patients to choose community follow-up. The safety and effectiveness of community follow-up are comparable to routine outpatient follow-up, and community follow-up is more convenient.