Qingguang'an-induced autophagy in TFs inhibits scar formation: A follow-up in vivo mechanistic investigation.

Purpose: To investigate the mechanism by which Qingguang'an inhibits scar formation in rabbits administered glaucoma filtering surgery (GFS). Methods: Combined trabeculectomy was performed in 100 rabbits diagnosed with glaucoma, which were assigned to five groups, including the no surgery, surgery only, mitomycin C (MMC; positive control), Qingguang'an (experimental) and PBS (negative control) groups. The animals were followed up at postoperative days 1-28. Ultrastructure was observed under a transmission electron microscope (TEM). Real-Time Polymerase Chain Reaction (RT-PCR), Western blot, Hematoxylin and Eosin (H&E) staining, Masson's trichrome staining and Immuno-histochemistry (IHC) were performed to assess the harvested blocks. Results: In the Qingguang'an group, intraocular pressure (IOP) on postoperative D28 was significantly lower than values in the no surgery, surgery only and PBS groups (P < 0.05). Its blebs kept better filtering function and less complications in follow-up, which be detected to have less fibroblasts and collagen deposition histologically. Compared with the PBS group, ATG5, Beclin1 and LC3-II mRNA levels were significantly increased while P62 was downregulated in the Qingguang'an group (P < 0.05). Correspondingly, ATG5 and Beclin1 protein amounts in the Qingguang'an group were increased while P62 was downregulated. The LC3-II/Ⅰ ratio tended to rise to the process of autophagy. Abundant autophagosomes were captured under TEM in this condition. Conclusions: Qingguang'an granules can inhibit scar formation in rabbits after GFS and restrain IOP increase by inducing autophagy in TFs.

Association of epidural analgesia during labor and early postpartum urinary incontinence among women delivered vaginally: a propensity score matched retrospective cohort study.

BACKGROUND: Although epidural analgesia is considered the gold standard for pain relief during labor and is safe for maternity and fetus, the association between the epidural analgesia and pelvic floor disorders remains unclear. Thus we estimate the association between epidural analgesia and early postpartum urinary incontinence (UI). METHODS: A propensity score-matched retrospective cohort study was conducted at a university-affiliated hospital in Shanghai, China. Primiparous women with term, singleton, and vaginal delivery between December 2020 and February 2022 were included. UI was self-reported by maternity at 42 to 60 days postpartum and was classified by International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI SF). Using logistic regression models, the associations between epidural analgesia and early postpartum UI were assessed. RESULTS: Among 5190 participants, 3709 (71.5%) choose epidural anesthesia during labor. Analysis of the propensity-matched cohort (including 1447 maternal pairs) showed epidural anesthesia during labor was independently associated with UI in early postpartum period (aOR 1.50, 95% CI 1.24-1.81). This association was mainly contributed to stress UI (aOR 1.38, 95% CI 1.12-1.71) rather than urge UI (aOR 1.45, 95% CI 0.99-2.15) and mixed UI (aOR 1.52, 95% CI 0.95-2.45). Furthermore, we observed that the association between epidural anesthesia and UI was more pronounced among older women (≥ 35 y) and women with macrosomia (infant weight ≥ 4000 g), compared with their counterparts (both P for interaction < 0.01). After further analysis excluding the women with UI during pregnancy, the results remained largely consistent with the main analysis. CONCLUSIONS: The findings support that epidural anesthesia was associated with SUI in the early postpartum period.

Case report: Transvaginal single-port extraperitoneal laparoscopic sacrospinous ligament fixation for apical prolapse: A single-center case series.

Background: Sacrospinous ligament fixation (SSLF) is a minimally invasive and effective procedure for the treatment of apical prolapse. Because intraoperative exposure of the sacrospinous ligament is difficult, SSLF is difficult. The aim of our article is to determine the safety and feasibility of single-port extraperitoneal laparoscopic SSLF for apical prolapse. Methods: This single-center, single-surgeon case series study included 9 patients with pelvic organ prolapse quantification (POP-Q) III or IV apical prolapse who underwent single-port laparoscopic SSLF. Additionally, transobturator tension-free vaginal tap (TVT-O) was performed in 2 patients, and anterior pelvic mesh reconstruction was performed in 1 patient. Results: The operative time ranged from 75 to 105 (mean, 88.9 ± 10.2) min, and blood loss ranged from 25 to 100 (mean, 43.3 ± 22.6) ml. No serious operative complications, blood transfusions, visceral injuries, or postoperative gluteal pain were reported for these patients. After 2-4 months of follow-up, no recurrence of POP, gluteal pain, urinary retention/incontinence, or other complications was observed. Conclusion: Transvaginal single-port SSLF is a safe, effective, and easy-to-master operation for apical prolapse.

Clinicians' practices and attitudes regarding advance care planning in mainland China: A multicenter cross-sectional survey.

OBJECTIVES: This study aims to explore clinicians' practices and attitudes regarding advance care planning (ACP) in mainland China. METHODS: This study was a multicenter cross-sectional survey. Clinicians from tertiary hospitals in Beijing, Guangxi, and Inner Mongolia were invited to participate in the study. A questionnaire was formulated based on related literature to obtain information including demographic characteristics, and practices and attitudes toward ACP. RESULTS: The total number of participants included 285 clinicians. The data response rate was 84.57%. Most of the clinicians had an inadequate understanding of ACP. Only a few clinicians had experience in participating or witnessing an ACP or related end-of-life discussions. Among 285 clinicians, 69.82% of clinicians were willing to introduce ACP to patients. Two hundred and thirty-eight (83.51%) clinicians wanted more education on ACP. Almost all clinicians believed that patients had the right to know about their diagnosis, prognosis, and available care options. Most clinicians (82.11%) regarded that ACP was partially feasible in mainland China. If clinicians had a serious illness, almost everyone was willing to find out their true health status and decide for themselves, and 81.40% wanted to institute an ACP for themselves. The biggest barriers to the use of ACP in mainland China were cultural factors. Statistical analysis revealed that some or good understanding level (P = 0.0052) and practical experience (P = 0.0127) of ACP were associated with the positive willingness. SIGNIFICANCE OF RESULTS: ACP is still in its infancy in mainland China. Clinicians had inadequate understanding and minimal exposure to ACP. Most clinicians recognized the value and significance of ACP and had a positive attitude toward ACP. Clinicians need to be provided with education and training to promote their ACP practices. Culturally appropriate ACP processes and documents need to be developed based on Chinese culture and Chinese needs.

Reduced-dose post-transplant cyclophosphamide plus low-dose post-transplant anti-thymocyte globulin as graft-versus-host disease prophylaxis with fludarabine-busulfan-cytarabine conditioning in haploidentical peripheral blood stem cell transplantation: A multicentre, randomized controlled clinical trial.

Anti-thymocyte globulin (ATG) or post-transplant cyclophosphamide (PTCy)-based regimens are widely used for graft-versus-host disease (GVHD) prophylaxis in haploidentical haematopoietic stem cell transplantation (haplo-HSCT). To improve the effectiveness of GVHD prophylaxis in haploidentical peripheral blood stem cell transplantation (haplo-PBSCT), we conducted a multicentre, randomized clinical trial to determine the efficacy of reduced-dose PTCy (40 mg/kg/d on days 3 and 4) combined with low-dose post-transplant ATG (2.5 mg/kg on day 8)-based GVHD prophylaxis (reduced-dose PTCy/ATG) with fludarabine-busulfan-cytarabine (FBA) conditioning for patients with haematological malignancies. From 2018 to 2022, 122 patients from four institutions were randomly assigned 1:1 to either a reduced-dose PTCy/ATG or a standard-dose ATG group ('Beijing Protocol', ATG: 10 mg/kg). All patients achieved myeloid engraftment. Cumulative incidences of grade II-IV (11.5% vs 39.3%, p = 0.001) and grade III-IV (6.6% vs 24.6%, p = 0.014) acute GVHD at day 100 were significantly reduced in the reduced-dose PTCy/ATG group. Furthermore, two-year overall survival, disease-free survival and GVHD-free/relapse-free survival were significantly improved in the reduced-dose PTCy/ATG group (75.4% vs 54.1%, p = 0.021; 72.7% vs 55.0%, p = 0.044; 61.3% vs 42.3%, p = 0.022 respectively). Our results demonstrate that the addition of low-dose ATG to reduced-dose PTCy with FBA conditioning is a promising strategy in haplo-PBSCT.

Comparing the application of mNGS after combined pneumonia in hematologic patients receiving hematopoietic stem cell transplantation and chemotherapy: A retrospective analysis.

Rapid and accurate pathogen identification is essential for timely and effective treatment of pneumonia. Here, we describe the use of metagenomic next-generation sequencing (mNGS) of bronchoalveolar lavage (BALF) fluid to identify pathogens in patients with hematologic comorbid respiratory symptoms in a retrospective study with 84 patients. In the transplantation group, 8 cases (19.5%) and 47 cases (97.9%) were positive for BALF by conventional method detection and mNGS detection, respectively, and 6 cases (14.0%) and 41 cases (91.1%) in chemotherapy group, respectively. The detection rate of mNGS in both groups was significantly higher than that of conventional detection methods (all P<0.05). Pseudomonas aeruginosa and Streptococcus pneumoniae were the most common bacterial infections in the transplantation and chemotherapy groups, respectively. Aspergillus was the most common fungal infection in both groups. Human betaherpesvirus 5 (HHV-5), torque teno virus and human betaherpesvirus 7 (HHV-7) were the most common pathogen species in both groups. The most common type of infection in patients in the transplantation and chemotherapy groups was the mixed infection of bacteria-virus. Most patients in the transplantation group had mixed infections based on multiple viruses, with 42 cases of viral infections in the transplantation group and 30 cases of viral infections in the chemotherapy group, which were significantly higher in the transplantation group than in the chemotherapy group (χ2 = 5.766, P=0.016). and the mixed infection of virus-virus in the transplantation group was significantly higher than that in the chemotherapy group (27.1% vs 4.4%, P=0.003). The proportion of death due to pulmonary infection was significantly higher in the transplantation group than in the chemotherapy group (76.9% vs 16.7%, χ2 = 9.077, P=0.003). This study demonstrated the value of mNGS of BALF in improving the diagnosis and prognosis of hematologic comorbid pneumonia, helping patients to obtain timely and effective treatment, and giving guidance on the overall treatment plan for patients, with particular benefit for patients with hematologic chemotherapy comorbid pneumonia.

Gynostemma Glycosides Protect Retinal Ganglion Cells in Rats with Chronic High Intraocular Pressure by Regulating the STAT3/JAK2 Signaling Pathway and Inhibiting Astrocyte and Microglia Activation.

Objective: To observe the protective effect of gynostemma glycosides on retinal ganglion cells in rats with chronically high intraocular pressure. Materials and Methods: A total of 60 rats were randomly divided into group A (the blank group, 10 rats) and chronic high IOP model group (50 rats). The IOP model group (IOP above 22 mmHg) was then randomly divided into an additional 5 groups (10 rats per group): group B (negative control group) treated with normal saline; group C treated with gynostemma glycosides 25 mg/(kg-d); group D treated with gynostemma glycosides 50 mg/(kg-d); group E treated with gynostemma glycosides 100 mg/(kg-d); and group F (positive control group) treated with VitB1 and VitB12. The eyes of each rat were monitored from day 1 to 14 (D1-D14). On day 14, rats were euthanized, after which retinal tissue and optic nerve were examined using real-time PCR, western blot, HE staining, LFB staining, and TUNEL assay. Results: Groups A, C, D, E, and F had significantly lower expression of CD11b, GFAP, Brn3α, and more TUNEL cells than in group B (all P < 0.05). Moreover, the relative expression of STAT3 mRNA and JAK2 (mRNA and protein) in groups A, C, D, E, and F was significantly lower than in group B (P < 0.05), while in group E, the expression was lower than in group D (P < 0.05). Conclusion: Gynostemma glycosides protect retinal ganglion cells in rats with chronically high intraocular pressure possibly associated with the STAT3/JAK2 signaling pathway.

Low-dose post-transplant cyclophosphamide with low-dose antithymocyte globulin for prevention of graft-versus-host disease in first complete remission undergoing 10/10 HLA-matched unrelated donor peripheral blood stem cell transplants: a multicentre, randomized controlled trial.

The most widely used regimens of graft-versus-host disease (GVHD) prophylaxis in HLA-matched unrelated donor peripheral blood stem cell transplantation (MUD-PBSCT) are based on anti-thymocyte globulin (ATG) or post-transplant cyclophosphamide (PTCy). To improve the efficiency of GVHD prophylaxis, a novel regimen, composed of low-dose PTCy (20 mg/kg on day +3 and +4) and low-dose ATG (6 mg/kg), was evaluted in patients with hematological malignancies ungoing 10/10 HLA MUD-PBSCT in first remission (CR1). In our prospective, multicenter study, 104 patients were randomly assigned one-to-one to low-dose PTCy-ATG (n = 53) or standard-dose ATG (10 mg/kg, n = 51). Both the cumulative incidences (CIs) of grade II-IV acute GVHD (aGVHD) and chronic GVHD (cGVHD) at 2 years in low-dose PTCy-ATG cohort were significantly reduced (24.5% vs. 47.1%; P = 0.017; 14.1% vs. 33.3%; P = 0.013). The CI of non-relapse-mortality (NRM) was much lower (13.2% vs. 34.5%; P = 0.049) and GVHD-free, relapse-free survival (GRFS) was significantly improved at 2 years in low-dose PTCy-ATG arm (67.3% vs 42.3%; P = 0.032). The low-dose PTCy-ATG based GVHD prophylaxis is a promising strategy for patients in CR1 after 10/10 HLA MUD-PBSCT.

Successful outcomes of second hematopoietic stem cell transplantation for graft failure in pediatric patients with severe aplastic anemia.

Severe aplastic anemia (SAA) is a life-threatening hematological disorder. The major therapies include matched sibling donor (MSD)- hematopoietic stem cell transplantation (HSCT), matched unrelated donor (MUD)-HSCT and immunosuppressive therapy (IST). However, there are many problems that can occur after HSCT, and graft failure (GF) is one of the most serious complications. To find an effective treatment, we analyzed 10 cases of second HSCT to treat SAA pediatric patients who suffered from GF and concluded that second haploidentical family donors HSCT is an effective treatment. Moreover, adding a small dose of busulfan or 2 ~ 3 Gy total body irradiation (TBI) in nonmyeloablative regimens (NMAs) can promote the engraftment. Although the study also showed that PBSCs, as a source of stem cells, can promote the implantation of neutrophil cells, due to small sample size, more research is still needed.

Regulated Exogenous/Endogenous Inflammation via "Inner-Outer" Medicated Electrospun Fibers for Promoting Tissue Reconstruction.

Regenerative medicine aims to provide solutions for structural and functional recovery in conditions where organs suffer from varying degrees of diseases or injuries. However, the exogenous inflammation triggered by implanted biomaterials and endogenous inflammation caused by some disease or tissue destruction has not been solved properly yet. Herein, a functional "inner-outer" medicated core-shell electrospun fibrous membrane is fabricated with RGD surface modification for exogenous inflammation suppression and puerarin loading in the core for long-term endogenous inflammation inhibition through microsol electrospinning technique. The "outer" RGD significantly increases biocompatibility of fibrous membrane through promoting cell viability, adhesion, and proliferation while the "inner" puerarin suppresses inflammatory gene expression via sustained drug release in vitro. Moreover, in a rat abdominal wall hernia model, the functional fibrous membrane successfully reduces exogenous and endogenous inflammation response and promotes wound healing through collagen deposition, smooth muscle formation, and vascularization. In summary, the functional "inner-outer" medicated fibrous membrane holds a great potential for clinical treatment of diseases that needs tissue reconstruction structurally and functionally accompanied by immunoregulation.

Development levels of pediatric palliative care teams and the extent of palliative care understanding and implementation among pediatric oncologists in China.

IMPORTANCE: Pediatric palliative care (PPC) is an interdisciplinary collaboration that focuses on the prevention and relief of patient suffering. PPC has emerged as a critical field of medical expertise and practice. However, no information is available regarding the progress of PPC in the Chinese mainland. OBJECTIVE: This study investigated the geographic distribution, team structure, and services of PPC teams in the Chinese mainland. It also investigated the level of understanding and implementation among pediatric oncologists regarding PPC. METHODS: The PPC subspecialty group of the Pediatrics Society of the Chinese Medical Association included 45 PPC teams. The team structure and services were investigated using questionnaires mailed to the team leader of each PPC team. In addition, we sent questionnaires regarding the level of PPC understanding and implementation of PPC practices to 170 pediatric oncologists in 11 hospitals. RESULTS: The geographical distribution of PPC teams is uneven in China. Most PPC teams are concentrated in the eastern provincial capital of China. Most PPC teams had limited staff and services. The level of PPC understanding was considerably limited across all demographics; most pediatric oncologists reported "some understanding" (n = 71, 41.8%) or "poor understanding" (n = 50, 29.4%). Only 62.9% of pediatric oncologists had experience providing advice to family members regarding PPC matters. INTERPRETATION: China is currently experiencing a critical shortage of PPC resources. Most pediatric oncologists had a limited understanding of PPC and reported limited practical implementation of PPC, which leads to underutilization of PPC resources.

[CLAG Regimen Composed of Continuous Intravenous Infusion of Cladribine in the Treatment of Refractory/Relapsed Acute Myeloid Leukemia].

OBJECTIVE: To study the efficacy and safety of continuous intravenous infusion of 2-Chlorodeoxyadenosine (2-CdA) combined with high-dose cytarabine (Ara-C) and granulocyte colony-stimulating factor (G-CSF) (CLAG regiem) in the treatment of relapsed/refractory acute myeloid leukemia (AML). METHODS: Fifteen patients with refractory/relapsed AML hospitalized in 5 medical units such as Department of Hematology, the Affiliated Tumor Hospital of Zhengzhou University and received one course of CLAG regimen from June 2014 to August 2019 were analyzed retrospectively (specifically: cladribine 5 mg/M2, day 1 to day 5, continuous 24-hour intravenous infusion; Ara-C 2 g/M2, 1 time/day, day 1 to day 5, intravenous infusion; G-CSF 300 mg, 1 time/day, day 0 to day 5, subcutaneous injection). RESULTS: Among the 15 patients with refractory/relapsed AML, 9 males and 6 females, the median age was 35 (13-63) years old. FAB classification: 1 case of M1, 3 cases of M2a, 4 cases of M2b (including 1 case with extramedullary invasion), 1 case of M4 with extramedullary invasion, 5 cases of M5, 1 case of HAL; NCCN classification: 6 cases in intermediate risk group, 9 cases in high risk group; 8 cases refractory, 7 cases relapsed. The median time of pre-chemotherapy was 4 (2-8) (of which NO.15 had received 8 cycles of chemotherapy and received CLL1-CAR-T), and the median white blood cell count before chemotherapy was 12.27 (from 0.78 to 5.29)×109/L. After 1 course of treatment with CLAG regimen, 12 patients achieved complete remission (12/15, 80%), and the median duration of CR was 65 days (0-528) days. IV grade leukopenia and thrombocytopenia was found in all the patients after chemotherapy. The median duration of granulocytosis was 20 (14 to 33) days, and 1 patient died. Seven patients received allogeneic hematopoietic stem cell transplantation. The median EFS and OS time of 15 patients was 85 (19-558) days and 117 (19-558) days, respectively. CONCLUSION: The CLAG regimen consisting of continuous intravenous infusion of cladribine shows high CR in the treatment of AML patients, but the duration of CR is short, myelosuppression is sever, so that infection control is the key. Allogeneic hematopoietic stem cells transplantation should be performed as soon as possible after CR.

[Clinic observation of a levonorgestrel-releasing intrauterine system inserted immediately after artificial abortion].

OBJECTIVE: To compare the contraceptive efficacies and side effects of Mirena (levonorgestrel-releasing intrauterine system, LNG-IUS) inserted immediately after artificial abortion and in the period of regular menstruation. METHODS: A total of 166 female subjects volunteered for the insertion of LNG-IUS. They were divided into 2 groups. Eighty-six female subjects inserted right after artificial abortion were selected as the observation group and 80 female subjects inserted during the period of regular menstruation as the control group. Follow-up was performed at one year after insertion. Contraceptive efficacies and side effects were compared between two groups. RESULTS: No pregnancy was found in both groups. No mirena expulsion occurred in neither groups. The continuation rates were 100%and 95%in the observation and control groups respectively (P > 0.05). The rates of abnormal hemorrhage were 27.5% and 36.2% in observation and control groups respectively during the first three months (P < 0.05). And 22.7% and 23.3% subjects suffered amenorrhea respectively in the first year. No significant difference was found in such side effects as amenorrhea, weight gain, acne and swollen breasts between two groups (P > 0.05). CONCLUSION: Mirena is proved to be an excellent choice for contraception after artificial abortion. Secondary intrauterine surgery may be avoided. And its insertions immediately after artificial abortion or during the period of regular menstruation share the same efficacies.

The influence of early cleavage on embryo developmental potential and IVF/ICSI outcome.

PURPOSE: To observe whether early cleavage can be a predictor of embryo developmental potential, pregnancy and implantation rates. METHODS: A total of 9,544 embryos in 1,095 in vitro fertilization or intracytoplasmic sperm injection cycles were observed with regard to the appearance of early cleavage at 25-29 h post-insemination. RESULTS: A significantly higher proportion of excellent quality embryos were observed in the early cleavage group compared to the late cleavage group (52.5 versus 28.9%, P < 0.01). In the early cleavage group there was also a higher rate of pregnancy per transfer compared with the late cleavage group (38.7 versus 26.3%, P < 0.01). In addition, we found that transfer of only one early cleavage embryo resulted in a high pregnancy rate (38.5%) and a low multiple pregnancy rate (18.0%). CONCLUSION: Early cleavage is a strong indicator of embryo quality, and may be used as an additional criterion in the selection of embryos for transfer to increase pregnancy rate and reduce multiple pregnancy rate.

[Expression of anti-apoptosis livin gene in acute non-lymphocytic leukemia cells and its clinical significance].

To explore the expression of livin gene in acute non-lymphocytic leukemia (ANLL) cells and its clinical significance, the mRNA level of livin gene in 46 ANLL adult patients were measured by using reverse transcription polymerase chain reaction (RT-PCR). Other 10 healthy adults were selected as normal controls (NC), HL-60 cell line was employed as positive control. The results showed that the mRNA level of livin gene in ANLL patients was significantly higher than that in NC, while it decreased in patients with complete remission (CR). In relapsed patients, the level of livin mRNA increased again. In ANLL patients, the CR rate of patients with livin positive was lower than that of patients with livin negative (p<0.05). It is concluded that overexpression of livin gene may play a synergic role in the pathogenesis of ANLL and associates with CR rate in ANLL. It seems that high expression of livin gene may be used as a marker of poor prognosis in acute non-lymphocytic leukemia.