Given that ovarian stimulation is vital for assisted reproductive technology (ART) and results in elevated serum estrogen levels, exploring the impact of elevated estrogen exposure on oocytes and embryos is necessary. We investigated the effects of various ovarian stimulation treatments on oocyte and embryo morphology and gene expression using a mouse model and estrogen-treated mouse embryonic stem cells (mESCs). Female C57BL/6J mice were subjected to two types of conventional ovarian stimulation and ovarian hyperstimulation; mice treated with only normal saline served as controls. Hyperstimulation resulted in high serum estrogen levels, enlarged ovaries, an increased number of aberrant oocytes, and decreased embryo formation. The messenger RNA (mRNA)‍-sequencing of oocytes revealed the dysregulated expression of lysine-specific demethylase 6b (Kdm6b), which may be a key factor indicating hyperstimulation-induced aberrant oocytes and embryos. In vitro, Kdm6b expression was downregulated in mESCs treated with high-dose estrogen; treatment with an estrogen receptor antagonist could reverse this downregulated expression level. Furthermore, treatment with high-dose estrogen resulted in the upregulated expression of histone H3 lysine 27 trimethylation (H3K27me3) and phosphorylated H2A histone family member X (γ-H2AX). Notably, knockdown of Kdm6b and high estrogen levels hindered the formation of embryoid bodies, with a concomitant increase in the expression of H3K27me3 and γ-H2AX. Collectively, our findings revealed that hyperstimulation-induced high-dose estrogen could impair the demethylation of H3K27me3 by reducing Kdm6b expression. Accordingly, Kdm6b could be a promising marker for clinically predicting ART outcomes in patients with ovarian hyperstimulation syndrome.
Female ; Mice ; Demethylation/drug effects* ; Embryonic Stem Cells ; Estrogens/administration & dosage* ; Gene Expression/drug effects* ; Histones/metabolism* ; Jumonji Domain-Containing Histone Demethylases/metabolism* ; Mice, Inbred C57BL ; Oocytes ; Ovary/drug effects* ; Reproductive Techniques, Assisted ; Animals

Objective:To identify the clinical characteristics and prognosis of patients with hematological disease and neutropenic sepsis in the hematological intensive care unit (HCU).Methods:A retrospective analysis was conducted on patients with hematological disease and sepsis who admitted to HCU, the First Affiliated Hospital of Harbin Medical University from October 2017 to October 2024, to examine the primary therapeutic options, prognosis, cause of death, and infectious features of sepsis.Results:A total of 245 septic patients were included in the study, comprising 88 cases in the neutropenic sepsis group (neutropenic group) and 157 cases in the non-neutropenic sepsis group (non-neutropenic group). Acute leukemia was more prevalent in the neutropenic group [55.68% (49/88) ]. At the time of admission to the HCU, the neutropenic group exhibited unstable vital signs, lower blood cell counts, higher inflammatory markers, elevated Sequential Organ Failure Assessment (SOFA) scores, increased creatinine levels (120.00 μmol/L vs 77.10 μmol/L, P<0.01), higher total bilirubin levels (24.70 μmol/L vs 17.90 μmol/L, P<0.01), and significantly elevated B-type natriuretic peptide levels (567.90 ng/L vs 134.50 ng/L, P<0.01) compared with the non-neutropenic group. Furthermore, septic shock was more common in the neutropenic group [53.40% (47/88) vs 36.94% (58/157), P<0.05]. The mortality rate was also higher in the neutropenic group [46.59% (41/88) ] compared with the non-neutropenic group [32.48% (51/157) ] ( P<0.05), with septic shock accounting for the majority of deaths [70.73% (29/41) ]. Infections caused by gram-negative bacteria [55.68% (49/88) vs 36.30% (57/157), P<0.01] and fungi [14.77% (13/88) vs 6.36% (10/157), P<0.05] were more common in the neutropenic group. However, lung infections were significantly less frequent in the neutropenic group ( P<0.01). Kaplan-Meier survival analysis revealed a substantially worse 28-day overall survival rate for the neutropenic group compared with the non-neutropenic group ( P<0.05) . Conclusion:Patients with hematological diseases and neutropenic sepsis presented with more severe clinical conditions, a higher likelihood of organ failure and septic shock, and significantly increased mortality compared with patients with non-neutropenic sepsis.

Objective:To identify the clinical characteristics and prognosis of patients with hematological disease and neutropenic sepsis in the hematological intensive care unit (HCU).Methods:A retrospective analysis was conducted on patients with hematological disease and sepsis who admitted to HCU, the First Affiliated Hospital of Harbin Medical University from October 2017 to October 2024, to examine the primary therapeutic options, prognosis, cause of death, and infectious features of sepsis.Results:A total of 245 septic patients were included in the study, comprising 88 cases in the neutropenic sepsis group (neutropenic group) and 157 cases in the non-neutropenic sepsis group (non-neutropenic group). Acute leukemia was more prevalent in the neutropenic group [55.68% (49/88) ]. At the time of admission to the HCU, the neutropenic group exhibited unstable vital signs, lower blood cell counts, higher inflammatory markers, elevated Sequential Organ Failure Assessment (SOFA) scores, increased creatinine levels (120.00 μmol/L vs 77.10 μmol/L, P<0.01), higher total bilirubin levels (24.70 μmol/L vs 17.90 μmol/L, P<0.01), and significantly elevated B-type natriuretic peptide levels (567.90 ng/L vs 134.50 ng/L, P<0.01) compared with the non-neutropenic group. Furthermore, septic shock was more common in the neutropenic group [53.40% (47/88) vs 36.94% (58/157), P<0.05]. The mortality rate was also higher in the neutropenic group [46.59% (41/88) ] compared with the non-neutropenic group [32.48% (51/157) ] ( P<0.05), with septic shock accounting for the majority of deaths [70.73% (29/41) ]. Infections caused by gram-negative bacteria [55.68% (49/88) vs 36.30% (57/157), P<0.01] and fungi [14.77% (13/88) vs 6.36% (10/157), P<0.05] were more common in the neutropenic group. However, lung infections were significantly less frequent in the neutropenic group ( P<0.01). Kaplan-Meier survival analysis revealed a substantially worse 28-day overall survival rate for the neutropenic group compared with the non-neutropenic group ( P<0.05) . Conclusion:Patients with hematological diseases and neutropenic sepsis presented with more severe clinical conditions, a higher likelihood of organ failure and septic shock, and significantly increased mortality compared with patients with non-neutropenic sepsis.

Objective:To identify the spatial clustering and its temporal trends among newly reported HIV/AIDS cases in Henan Province during 1995-2020, and to provide evidence for strategies on prevention and control of the disease.Methods:Information about newly reported HIV/AIDS cases in Henan between 1995 and 2020 were obtained from China Information System for Disease Control and Prevention and to describe their demographic characteristics, spatial autocorrelation and changing trends. This program was conducted at county level, using the ArcGIS 10.2.Results:A total of 96 528 HIV/AIDS cases with complete current address information in counties (districts) were newly reported during 1995-2020 in Henan, and the spatial autocorrelation analysis showed that Global Moran's I index was 0.249, Z G value of the Global Getis-Ord G coefficient was 6.472 (all P<0.001), indicating that there was a high clustered positive spatial autocorrelation of HIV/AIDS. The newly reported HIV/AIDS cases from 1995 to 2000, 2001 to 2005, 2006 to 2010, 2011 to 2015, and 2016 to 2020 in Henan Province all exhibited high values of global spatial clustering. Their Moran's I indices were 0.197, 0.103, 0.491, 0.411 and 0.383, respectively. The Z G values of the Global Getis-Ord G coefficient were 4.580, 3.386, 10.246, 8.378 and 8.093, respectively. All of global spatial correlation were statistically significant (all P<0.001). The results of local spatial autocorrelation analysis showed that newly reported HIV/AIDS cases in Henan Province had high-high clustering areas at each time stage mentioned above. The number of high-high clustering counties/districts gradually increased from 6 in 2001-2005 to 21 in 2016-2020, spreading from Zhumadian City and Zhoukou City in southeast Henan to Nanyang City in southwest Henan, Zhengzhou City and its surrounding counties/districts in central Henan. Conclusions:In Henan Province, an increasing trend of clusters appeared on HIV epidemic among newly reported HIV/AIDS cases from 1995 to 2020, and high-high clustering areas gradually expanded from Zhumadian City and Zhoukou City to Nanyang City, Zhengzhou City and its surrounding counties/districts, indicating that it is necessary to strengthen the AIDS prevention and control programs in these areas in Henan.

Objective:To explore the safety and efficacy of Obinutuzumab in the treatment of immune thrombotic thrombocytopenic purpura.Methods:Data from a case of immune thrombotic thrombocytopenic purpura (iTTP) admitted to the Department of haematology of the First Affiliated Hospital of Harbin Medical University were evaluated retrospectively and a literature review was performed.Results:A 66-year-old female patient was admitted to our hospital for thrombocytopenia. On admission, physical examination showed that yellow skin and sclera. The patient was fully conscious but had a decreasing ability to calculate. Laboratory examination revealed a platelet count of 7×10 9/L; liver function: alanine aminotransferase 55.2 U/L, azelaic aminotransferase 117.5 U/L; total bilirubin 142.7 μmol/L, direct bilirubin 64.6 μmol/L, indirect bilirubin 78.1 μmol/L; lactate dehydrogenase: 2362 U/L; creatinine: 260.7 μmol/L; peripheral blood smear showed 4% fragmented erythrocytes; ADAMTS13 activity 2.7% and positive inhibitor (1.12 BU). The patient is treated with plasma exchange and glucocorticoids, but the patient’s symptoms worsened. Rituximab was permanently discontinued for severe infusion reactions. Treatment with Obinutuzumab (1000 mg, qw×2 w) and she achieved a complete remission for 18 months. The treatment was well tolerated with no adverse events related to Obinutuzumab. Conclusion:For iTTP patients with rituximab intolerance, obinutuzumab is a safe and effective alternative treatment option.

Objective:To explore the safety and efficacy of Obinutuzumab in the treatment of immune thrombotic thrombocytopenic purpura.Methods:Data from a case of immune thrombotic thrombocytopenic purpura (iTTP) admitted to the Department of haematology of the First Affiliated Hospital of Harbin Medical University were evaluated retrospectively and a literature review was performed.Results:A 66-year-old female patient was admitted to our hospital for thrombocytopenia. On admission, physical examination showed that yellow skin and sclera. The patient was fully conscious but had a decreasing ability to calculate. Laboratory examination revealed a platelet count of 7×10 9/L; liver function: alanine aminotransferase 55.2 U/L, azelaic aminotransferase 117.5 U/L; total bilirubin 142.7 μmol/L, direct bilirubin 64.6 μmol/L, indirect bilirubin 78.1 μmol/L; lactate dehydrogenase: 2362 U/L; creatinine: 260.7 μmol/L; peripheral blood smear showed 4% fragmented erythrocytes; ADAMTS13 activity 2.7% and positive inhibitor (1.12 BU). The patient is treated with plasma exchange and glucocorticoids, but the patient’s symptoms worsened. Rituximab was permanently discontinued for severe infusion reactions. Treatment with Obinutuzumab (1000 mg, qw×2 w) and she achieved a complete remission for 18 months. The treatment was well tolerated with no adverse events related to Obinutuzumab. Conclusion:For iTTP patients with rituximab intolerance, obinutuzumab is a safe and effective alternative treatment option.

Objective:To investigate the short-term clinical efficacy of Kamikawa anasto-mosis and jejunal interposed double channel anastomosis in laparoscopic proximal gastrectomy.Methods:The retrospective cohort study was conducted. The clinicopathological data of 68 patients with esophagogastric junctional tumors and upper gastric tumors who underwent laparoscopic proximal gastrectomy in two medical centers, including 63 cases in the Changzhi People's Hospital Affiliated to Changzhi Medical College and 5 cases in the Heji Hospital Affiliated to Changzhi Medical College, from March 2018 to December 2020 were collected. There were 57 males and 11 females, aged 62(range, 39?78)years. Of 68 patients, 35 patients undergoing Kamikawa anastomosis in laparoscopic proximal gastrectomy were allocated into Kamikawa group, and 33 patients under-going jejunal interposed double channel anastomosis in laparoscopic proximal gastrectomy were allocated into double channel group. Observation indicators: (1) intraoperative situations; (2) post-operative situations; (3) follow-up. The patients were followed up by outpatient examinations and telephone interview to detect the postoperative score of chew-wun wu special symptoms, post-operative reflux anastomotic esophagitis and anastomotic stenosis up to December 2021. Measure-ment data with normal distri-bution were represented as Mean±SD, and comparison between groups was performed by the t test. Measurement data with skewed distribution were represented as M(range), and comparison between groups was conducted by Mann-Whitney U test. Comparison of ordinal data was performed by nonparametric rank sum test. Count data were expressed as absolute numbers, and comparison between groups was conducted using the chi-square test or Fisher exact probability method. Results:(1) Intraoperative situations. All the 68 patients successfully under-went laparoscopic proximal gastrectomy combined with D 1+ lymph node dissection. The operation time and volume of intraoperative blood loss of the Kamikawa group were (5.15±0.31)hours and (89±11)mL, versus (4.21±0.11)hours and (142±20)mL of the double channel group, respectively, showing significant differences between the two groups ( t=2.81, ?2.34, P<0.05). The digestive tract reconstruction time and the number of lymph node dissection were (1.95±0.13)hours and 30.4±2.4 of the Kamikawa group, versus (1.69±0.76)hours and 28.0±2.4 of the double channel group, respectively, showing no significant difference between the two groups ( t=1.79, 0.73, P>0.05). (2) Postoperative situations. The time to postoperative first flatus, duration of drainage tube placement, duration of postoperative hospital stay were (3.03±0.12)days, (5.46±0.22)days, (13.00±0.50)days of the Kamikawa group, versus (4.42±0.21)days, (9.97±0.76)days, (16.46±0.92)days of the double channel group, showing significant differences in the above indicators between the two groups ( t=?5.80,?5.58, 3.40, P<0.05). Cases with or without drainage tube placement were 32 and 3 of the Kamikawa group, versus 33 and 0 of the double channel group, respectively, showing no significant difference between the two groups ( P>0.05). Cases with grade 1, grade 2, grade 3, grade 4 complica-tions of Clavien-Dindo classification were 31, 0, 4, 0 of the Kamikawa group, versus 27, 3, 1, 2 of the double channel group, respectively, showing a significant difference between the two groups ( Z=?6.28, P<0.05). Postoperative anastomotic stenous, reflux symptoms, anastomotic fistula, pancreatic fistula, pulmonary infection were found in 4, 2, 0, 0, 0 case of the Kamikawa group and 0, 1, 3, 1, 2 cases of the double channel group, respectively. There was no significant difference in the above indicators between the two groups ( P>0.05). There was no complication of incisional infection, abdominal hemorrhage, lymphatic fistula or gastroparesis in either group. Of the 4 patients with perioperative anastomotic stenosis in the Kamikawa group, 2 cases were improved after once gastroscopic balloon dilatation, 2 cases were improved after 4 times of gastro-scopic balloon dilatation. (3) Follow-up. All the 68 patients were followed up at postoperative 3, 6, 12 months. The scores of chew-wun wu special symptoms scale at postopertaive 12 months of the Kamikawa group and double channel group were 16.8±0.7 and 14.6±0.7, respectively, showing a significant difference between the two groups ( t=2.20, P<0.05). There were 2 cases of grade B reflux esophagitis and 1 case of grade B reflux esophagitis, respectively, showing no significant difference between the two groups ( P>0.05). There was no anastomotic stenosis occurred in either group. Conclusions:Laparos-copic proximal gastrectomy with Kamikawa anastomosis or jejunal interposed double channel anastomosis is safe and feasible for esophagogastric junction tumors and upper gastric tumors. The Kamikawa anastomosis has less volume of intraoperative blood loss, shorter time to postoperative first flatus, duration of drainage tube placement and postoperative hospital stay, higher quality of postoperative lfe.

Objective:To analyze the epidemiological characteristics of newly reported HIV-infected cases aged 50 years and above in Henan province during 1995-2020, and to provide evidence for strategies on HIV/AIDS prevention and control.Methods:Information about newly reported HIV-infected cases aged 50 years and above in Henan between 1995 and 2020 were collected from the National Comprehensive HIV/AIDS Information System. The demographic and behavioral characteristics of HIV-infected cases aged ≥50 were analyzed, and the mixed linear model based on CD4 + T lymphocyte (CD4) counts back calculation was used to estimate the years, time and age of the HIV infection. Results:During 1995-2020, a total of 25 038 HIV-infected cases aged 50 years and above were newly reported, accounting for 25.8% (25 038/96 867) of the total number of newly reported HIV-infected cases in Henan. The proportion of newly reported cases over 50-years-old gradually increased from 4.5% (18/396) in 1995-2000 to 35.5% (9 666/27 239) in 2016-2020, with statistically significant difference ( χ2=3 105.53, P<0.001). Among them, the proportion of HIV-infected cases aged 60 years and above were increasing year by year. The proportion of male cases were increasing along with ageing. The proportion of HIV-infected cases detected by medical institutions also showed an upward trend. The newly reported HIV-infected cases aged 50 years and above were mainly transmitted through sexual contact. The proportion of heterosexual transmission increased from 5.5% (1/18) in 1995-2000 to 86.2% (8 334/9 666) in 2016-2020, and the proportion of MSM-behavior-related transmission increased from 0.0% in 1995-2000 to 13.5% (1 304/9 666) in 2016-2020. The majority of cases had extra-marital and/or non-commercial heterosexual behavior (48.1%, 4 007/8 334) and the proportion showed an upward trend. The majority of male cases had commercial heterosexual behavior (54.9%, 3 169/5 775), and with increasing proportion along with the increase of age. The majority of female cases had extra-marital and/or non-commercial heterosexual behavior (62.5%, 1 600/2 559), with increasing proportion of extra-marital and/or non-commercial heterosexual behavior. The proportion of heterosexual behavior with spouse or stable sexual partners showed a downward trend. The estimations based on CD4 counts back calculation model showed that among the newly reported HIV-infected cases aged 50 years and above, the average age being infected was (54.8±10.2) years, with 33.8% (4 263/12 621) infected before 50. The interval between infection and diagnosis was (5.7±6.2) years, of which 52.6% (6 636/12 621) were infected for 5 years or longer and 34.7% (4 384/12 621) were in the last 3 years. There was no linear correlation trend in the composition of infection years among the newly reported HIV-infected cases over 50-years-old. Conclusions:In Henan, from 1995 to 2020, the number of newly reported HIV-infected cases aged 50 years and above was increasing and sexual transmission becoming the main transmission route. The increase of prevalence was mostly seen in 60-years-old men, low education level and detected mainly by medical institutions. For this age group, the focus of HIV/AIDS prevention and control should target on those who were transmitted through extra-marital and/or non-commercial heterosexual, commercial heterosexual and MSM behavior and it is necessary to strengthen the HIV testing and detection in this population and in the elderly floating group.

Currently, titanium alloys are widely used in the field of stomatology; however, owing to long-term exposure to a complex microbial environment, dental plaques easily form on the surface of the materials, affecting the use efficiency and the service life of the materials. The antibacterial titanium alloy is a new kind of titanium alloy with antimicrobials added through surface modification or overall modification. Based on the location of antibacterial agents in titanium alloy materials, antibacterial titanium alloys can be divided into coating and alloy types. The antibacterial effect of coated antibacterial titanium alloy is good, but the disadvantage is that most of the coatings are not wear-resistant. The widely-used antibacterial agent of the alloy type is metal elements, which can be evenly distributed in the alloy, and the antibacterial properties are stable and long-lasting. Based on whether antibacterial agents can be released, antibacterial titanium alloys can be further divided into active antibacterial and passive antibacterial types. Active antibacterial type titanium alloys can release loaded antibacterial agents, and the antibacterial effect is more obvious, but the release duration of antibacterial agents is relatively short. Passive antibacterial titanium alloys exhibit an antibacterial effect by contact sterilization or inhibition of bacterial adhesion instead of releasing antibacterial agents. The antibacterial titanium alloy can inhibit the adhesion of bacteria on the surface of the material and prolong the service life of oral orthodontic appliances, implants and titanium plates. Moreover, the mechanical properties of the titanium alloy after antibacterial modification are not significantly affected, and the addition of antibacterial agents such as hydroxyapatite can increase the osteogenic function of the material. Therefore, the alloy has good application prospects in the fields of dental implant, orthodontic treatment and oral and maxillofacial surgery. However, most of the current studies on antibacterial titanium alloys are in vitro experiments, and their long-term clinical effects and antibacterial mechanisms are still unclear and need further study.

Objective:To analysis the characteristics and trends of non-martial and non-commercial heterosexual transmission of HIV/AIDS cases in Henan province between 2015 and 2020.Methods:Information of newly reported HIV/AIDS through non-martial and non-commercial heterosexual transmission was collected from National Comprehensive HIV/AIDS Information system, using SPSS 22.0 to analyze the characteristics and tend of cases.Results:During 2015-2020, a total of 10 877 HIV/AIDS cases infected by non-martial and non-commercial heterosexual transmission were newly reported in Henan province. This mode of infection increased from 32.6% in 2015 to 35.5% in 2020 (trend χ2=81.880, P<0.01). The male to female ratio was 1.9∶1 (7 105∶3 772). The mean age was (45.5±15.8) years, increasing annually ( F=5.184, P<0.01). For female cases, the proportion of aged 15-50 years group was decreased annually (trend χ2=69.888, P<0.01). Most HIV/AIDS cases were distributed in the early HIV epidemic areas and Zhengzhou city, the same as the cases of the first CD4 +T cells counts (CD4) below 200 cells/μl. The median ( P 25, P 75) first CD4 count was 298 (143, 462) cells/μl. The proportion of the first CD4<200 cells/μl was no significant change annually, while the proportion of the first CD4≥500 cells/μl was decreasing annually (trend χ2=18.961, P<0.01). Conclusions:The reported cases through non-martial and non-commercial heterosexual transmission increased, with most of them were male, married, junior, farmer, migrant laborer, and aged 40-59 years. It is needed to focus on the rural district and the middle-aged population, combined with biological and social factors to control the prevalence of AIDS through comprehensive prevention and control measures.