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Study procedure
A participant’s intravenous cannula was inserted into a vein in the right arm (dose escalation group) or a vein catheter (dose expansion group) for administration or top-up of the study drug. Only patients in the ciprofol group required an open vein in the left arm for blood collection for PK analysis. A simultaneous a...
PMC10147789
End points
SECONDARY
The primary end-point was the success rate of induction of general anesthesia produced by the initial bolus dose, i.e. the percentage of patients who achieved successful induction after the initial bolus dose, without requiring a top-up dose.The secondary end-points were: (1) the time to reach a MOAA/S ≤ 1, defined as ...
PMC10147789
Measurements
DBP and mean arterial blood pressure, pain
The pain associated with a ciprofol or propofol injection was assessed approximately 15 s after initiation of the bolus injection. MOAA/S scores were recorded every 1 min and the eyelash reflex every 30 s.Hemodynamic parameters including HR, SBP, DBP and mean arterial blood pressure (MAP) were recorded at intervals of ...
PMC10147789
Emergence time
Once surgery was completed, the MOAA/S score was assessed every 2 min until patients’ MOAA/S scores reached 5.
PMC10147789
Drugs
PMC10147789
Investigational drugs
Ciprofol emulsion (20 mL: 200 mg in part 1, and 20 mL: 50 mg in part 2 (Liaoning Haisco Pharmaceutical Group Co., Ltd., China) and Diprivan® (20 mL: 200 mg, AstraZeneca, UK).Midazolam (Jiangsu Nhwa Pharmaceutical Co., Ltd., China), sufentanil (Yichang Humanwell Pharmaceutical Co., Ltd., China) and rocuronium bromide (E...
PMC10147789
Statistical analysis
Wilson’s
IBM SPSS (ver. 25) was used for all statistical analyses. The demographic characteristics were analyzed using analysis of variance (ANOVA), chi-square, Fisher or Kruskal–Wallis tests. The primary outcome was also analyzed using Wilson’s and/or Fisher tests. Time to MOAA/S ≤ 1 and loss of the eyelash reflex were evaluat...
PMC10147789
Results
PMC10147789
Demographic characteristics of patients in the dose escalation and dose expansion groups
From December 2016 to July 2018, a total of 109 patients for inclusion in both part 1 and part 2 were enrolled and the flow chart is shown in Fig. Flow chart of patient enrollment
PMC10147789
Efficacy
PMC10147789
Primary outcome
The success rates of anesthesia induction in patients who received one initial bolus dose of ciprofol-0.5 mg/kg, propofol-2.0 and 2.5 mg/kg were all 100%. However, 1 patient in the ciprofol-0.4 mg/kg group (part I) and one in the ciprofol-0.3 mg/kg group (part II) required one top-up dose and then achieved successful i...
PMC10147789
Secondary outcomes
All of the patients who received an initial bolus reached MOAA/S scores ≤ 1 at the end of the first min of administration except for 2 patients (1 in the 0.4 mg/kg ciprofol group and the other in the 2.0 mg/kg propofol group), who achieved MOAA/S scores ≤ 1 at the end of the second min of drug administration).As shown ...
PMC10147789
Discussion
pain
Propofol has been reported to have a narrow therapeutic index and the guidelines recommend usage only by experienced anesthesiologists, with close monitoring and individual dose adjustments [The main finding of the present study was that the success rates of induction with ciprofol-0.5 mg/kg as an i.v. bolus was compar...
PMC10147789
Conclusion
The efficacy and safety of a single i.v. bolus dose of 0.5 mg/kg ciprofol for the induction of general anesthesia in patients undergoing selective surgery was comparable to propofol administered at a dose of 2.0 mg/kg. Lower doses of ciprofol, 0.3 mg/kg or 0.4 mg/kg, could also achieve the same efficacy but occasionall...
PMC10147789
Acknowledgements
We would like to thank other investigators Yuan Zeng, Tingting Jiang, ZhaoTing Meng, Rufeng Zeng, Huacheng Liu, Dingxin Kang, Li Yang, Yunxia Hu, Weixiang Min, Lu Jiang, Qiang Xu, Qingping Wu, Zhenghua Zhao, Yanling Jin, Fang Wang, Lili Wang, Saiying Wang, Huan Chang, and Kaiming Duan for their great assistance with th...
PMC10147789
Funding
This work was supported by the Sichuan Haisco Pharmaceutical Group Co., Ltd. The funder had no role in the design of the study, collection, analysis or interpretation of the data or in writing the manuscript.
PMC10147789
Conflicts of interest
The authors have no relevant financial or non-financial interests to disclose.
PMC10147789
References
PMC10147789
Background
NKTL, PTCL, Natural killer/T-cell lymphoma, peripheral T-cell lymphoma, NHL
PERIPHERAL T-CELL LYMPHOMA, NHL
Natural killer/T-cell lymphoma (NKTL) is a rare type of aggressive and heterogeneous non-Hodgkin's lymphoma (NHL) with a poor prognosis and limited therapeutic options. Therefore, there is an urgent need to exploit potential novel therapeutic targets for the treatment of NKTL. Histone deacetylase (HDAC) inhibitor chida...
PMC9900953
Methods
NKTL, tumors
TUMORS
We performed a phase II clinical trial to evaluate the efficacy of chidamide in 28 relapsed/refractory NKTL patients. Integrative transcriptomic, chromatin profiling analysis and functional studies were performed to identify potential predictive biomarkers and unravel the mechanisms of resistance to chidamide. Immunohi...
PMC9900953
Results
NKTL, hyperactivity
We demonstrated that chidamide is effective in treating relapsed/refractory NKTL patients, achieving an overall response and complete response rate of 39 and 18%, respectively. In vitro studies showed that hyperactivity of JAK-STAT signaling in NKTL cell lines was associated with the resistance to chidamide. Mechanisti...
PMC9900953
Supplementary Information
The online version contains supplementary material available at 10.1186/s13148-023-01436-6.
PMC9900953
Keywords
PMC9900953
Introduction
Natural killer/T-cell lymphoma, NKTL, Barr virus-associated T-cell lymphoma
EPSTEIN
Natural killer/T-cell lymphoma (NKTL) is an aggressive Epstein–Barr virus-associated T-cell lymphoma (TCL) that accounts for 10% of all TCLs [Histone acetylation is an important mode of epigenetic regulation controlled by the antagonistic actions of two classes of enzymes: histone acetyltransferases (HATs) and histone ...
PMC9900953
Methods
PMC9900953
Patients and cell lines
NKTL, tumor, Cancer
MYCOPLASMA, MYCOPLASMA, TUMOR, CANCER
A phase II clinical trial to evaluate chidamide monotherapy in relapsed/refractory NKTL was conducted at Sun Yat-sen University Cancer Center (SYSUCC). The study was approved by the institutional review board of SYSUCC in accordance with the Declaration of Helsinki, and applicable regulations according to Good Clinical...
PMC9900953
Drugs
ALDRICH
Chidamide was provided by Shenzhen Chipscreen Biosciences Ltd. SAHA was obtained from Sigma–Aldrich. Trichostatin A (TSA), belinostat and tofacitinib were purchased from Selleckchem. Romidepsin was obtained from MedChemExpress. Ruxolitinib and Stattic were purchased from Axon Medchem and Millipore, respectively.
PMC9900953
Cell viability assays
Tecan
PROLIFERATION
A total of 2000 cells were seeded in 96-well plates in triplicate and treated with the indicated drugs at various concentrations or not treated for 96 h. Cell viability was measured by the CellTiter-Glo Luminescent Cell Viability Assay (Promega) according to the manufacturer’s instructions, and luminescence was read us...
PMC9900953
Calculation of the combination index (CI)
CI values were determined by the inhibition rate of the cells treated with drugs and computed using CalcuSyn [
PMC9900953
Cell cycle assays
2 × 10
PMC9900953
Cell apoptosis assay
2 × 10
PMC9900953
H&E staining and immunohistochemistry (IHC)
NKTL
EPSTEIN
H&E staining, IHC for TNFRSF8 (CD30) and Epstein–Barr encoding region in situ hybridization (EBER ISH) were performed with formalin-fixed, paraffin-embedded (FFPE) tissues from NKTL patients using standard procedures [
PMC9900953
ChIP-qPCR, ChIP-seq and ChIP-seq data analyses
The primer sequences used for ChIP-qPCR are listed in Additional File
PMC9900953
Real-time RT–qPCR, RNA-seq and RNA-seq data analyses
The primer sequences used for RT–qPCR are listed in Additional File
PMC9900953
In vivo studies
In vivo studies were conducted in compliance with animal protocols approved by the SingHealth Institutional Animal Care and Use Committee. Five- to eight-week-old female NOD/SCID/IL2rγnull (NSG) mice were kept under standard laboratory conditions according to the National Advisory Committee for Laboratory Animal Resear...
PMC9900953
Statistical analysis
SD
Graphs include results that are expressed as the mean ± SD of three independent experiments. Statistical differences between the two groups were evaluated by a two-tailed Student’s 
PMC9900953
Results
PMC9900953
Clinical efficacy of chidamide, a novel HDAC inhibitor, in relapsed/refractory NKTL patients
NKTL
DISEASE PROGRESSION
To evaluate the efficacy of chidamide, a single-arm, phase II clinical trial was performed in 28 NKTL patients who relapsed after or were refractory to chemoradiotherapy and/or autologous stem cell transplantation (ASCT). The patients were treated with chidamide until disease progression or intolerance. The demographic...
PMC9900953
Characterization of NKTL cell line sensitivity to chidamide in vitro
NKTL, death
PROLIFERATION
To assess the in vitro efficacy of chidamide in NKTL, we evaluated the IC50 of the drug in 11 NKTL cell lines (Fig. Chidamide inhibits cell proliferation and selectively induces the death of NKTL cells.
PMC9900953
Enhancer landscapes in chidamide-resistant and chidamide-sensitive cells
NKTL
To investigate the underlying mechanism of resistance to chidamide in NKTL cells, we performed chromatin immunoprecipitation sequencing (ChIP-seq) for H3K27ac and H3K4me3 in two resistant cell lines (HANK1 and SNK6) and two sensitive cell lines (KHYG1 and MEC04). Epigenetic changes in H3K27ac and H3K4me3, which are ass...
PMC9900953
Aberrant activation of the JAK-STAT pathway in NKTL
NKTL
As the JAK-STAT pathway was found to be implicated in resistance to chidamide, we examined the activity of its effector molecules, STAT3 and STAT5 in both sensitive and resistant NKTL cell lines. High levels of phospho-STAT3 and STAT5 were detected in resistant cell lines compared to sensitive cell lines (Fig. The JAK-...
PMC9900953
Pharmacologically targeting the JAK-STAT pathway overcomes resistance to chidamide in NKTL
NKTL
We hypothesized that targeting the JAK-STAT pathway could reverse chidamide resistance in NKTL cell lines. To test this hypothesis, we treated the chidamide-resistant NKTL cell lines (HANK1 and SNK6) with tofacitinib (JAK inhibitor), chidamide or a combination of both drugs for 96 h and determined the combination index...
PMC9900953
The JAK inhibitors tofacitinib/ruxolitinib induce chromatin remodeling at JAK-STAT genes
NKTL
To understand how JAK inhibitors reverse chidamide resistance in NKTL cells, we performed RNA-seq of HANK1 cells treated with DMSO, tofacitinib or ruxolitinib. Compared to the control treatment, tofacitinib and ruxolitinib treatment remarkably upregulated 131 common genes and downregulated 141 common genes in HANK1 cel...
PMC9900953
Clinical efficacy of JAK-STAT inhibition and chidamide in chidamide-resistant NKTL
NKTL, death
EPSTEIN, VIRUS, DISEASE
We next assessed whether JAK-STAT inhibition could be a potential therapeutic strategy to overcome resistance to chidamide in the clinic. A 48-year-old Chinese male patient who was initially diagnosed with stage IIA extranodal NKTL of the nasal type was recruited. He was refractory to first-line asparaginase-based chem...
PMC9900953
Discussion
NKTL, tumor, H3Y41, PTCL
DISORDER, REGRESSION, DISEASE, TUMOR
In the current management of NKTL, a substantial proportion of patients still experience treatment failures, and salvage options are severely limited. Increasing evidence suggests that PTCL is characteristically an epigenetic disorder, with several HDAC inhibitors receiving regulatory approvals for the treatment of rel...
PMC9900953
Conclusions
NKTL
In summary, our study shows favorable clinical outcomes of chidamide in treating relapsed/refractory NKTL patients. JAK-STAT inhibitors may further expand the clinical utility of HDAC inhibitors, including chidamide, romidepsin and belinostat, by remodeling the resistant enhancer landscape toward a sensitive state. The...
PMC9900953
Acknowledgements
We thank Shenzhen Chipscreen Biosciences Ltd. for providing us with chidamide for our work. We thank Dr. Yoshitoyo Kagami, Dr. C. Clayberger, Dr. Norio Shimizu, Dr. Paul Coppo and Dr. Philippe Gaulard for kindly providing the cell lines used in this study.
PMC9900953
Author contributions
PD
PATHOLOGY
JC, HH, CKO and JT conceived, designed and supervised the study; JC, YG, ZL, YW and KXYC performed the experiments; JC, ZZ, YG, XY, PG, ZL, JH, PD, JYC, JL, BKHC, HH, CKO and JT analyzed and interpreted the data; YG, XL and HH provided samples; XY, JH, DC, JWP, JK, DH, HH, YS, LL, SL, XW, HY, NFG, JB, TK, STL and BTT p...
PMC9900953
Funding
Cancer
CANCER
This work was supported by the National Natural Science Foundation of China (81970176, 81972596 and 81772963), Guangdong Innovative and Entrepreneurial Research Team Program (2016ZT06S638 and 2016ZT06S252), Sci-Tech Project Foundation of Guangzhou City (201707020039), Medical Scientific Research Foundation of Guangdong...
PMC9900953
Availability of data and materials
The datasets supporting the conclusions of this article are available at GEO under accession number GSE152185.
PMC9900953
Declarations
PMC9900953
Ethics approval and consent to participate
tumor
TUMOR
The study was approved by the institutional review board of SYSUCC in accordance with the Declaration of Helsinki, and applicable regulations according to Good Clinical Practice guidelines. Written informed consent was obtained from all patients before enrollment in the trial. This trial was registered at ClinicalTrial...
PMC9900953
Consent for publication
All authors have agreed to publish this manuscript.
PMC9900953
Competing interests
The authors declare that they have no competing interests.
PMC9900953
References
PMC9900953
Background
HGP1705, acid-related disorders
EROSIVE ESOPHAGITIS
Proton-pump inhibitors (PPIs) are the most effective drugs for treating acid-related disorders. However, once-daily dosing with conventional PPIs fail to fully control acid secretion over 24 h. This study aimed to compare the efficacy and safety of HIP1601 (dual delayed-release esomeprazole) and HGP1705 (delayed-releas...
PMC10729464
Methods
treatment-emergent adverse, HGP1705, GERD-related
We enrolled 213 patients with EE randomized in a 1:1 ratio to receive 40 mg HIP1601 (n = 107) or HGP1705 (n = 106) once daily for 4 or 8 weeks. The primary endpoint was the EE healing rate, confirmed by endoscopy up to week 8. GERD-related symptoms and treatment-emergent adverse events were compared between both groups...
PMC10729464
Results
HGP1705
By week 8, the estimated healing rates of EE were 97.8% and 96.8% in the HIP1601 and HGP1705 groups, respectively, with a 95% confidence interval of -4.7 to 7.2. After 4 or 8 weeks of treatment, the EE healing rate at week 4, complete resolution rate of symptoms, time to sustained resolution of symptoms, and number of ...
PMC10729464
Conclusions
HGP1705
GERD
The efficacy and safety of HIP1601 40 mg were comparable to those of HGP1705 40 mg for the treatment of EE and symptomatic improvement of GERD.
PMC10729464
Trial registration
NCT04080726 (
PMC10729464
Supplementary Information
The online version contains supplementary material available at 10.1186/s12876-023-03087-6.
PMC10729464
Keywords
PMC10729464
Background
chronic disorder, heartburn, GERD, acid regurgitation, Barrett’s esophagus [HIP1601, esophagitis, Barrett’s esophagus, reflux of gastric
CHRONIC DISORDER, ESOPHAGEAL STRICTURE, GERD, ESOPHAGITIS, GASTROESOPHAGEAL REFLUX DISEASE (GERD), COMPLICATIONS
Gastroesophageal reflux disease (GERD) is a chronic disorder caused by the reflux of gastric contents, resulting in symptoms such as heartburn and acid regurgitation as well as potential complications such as esophagitis and Barrett’s esophagus [Proton pump inhibitors (PPIs) are the most commonly prescribed class of me...
PMC10729464
Materials and methods
PMC10729464
Study design
treatment-emergent adverse, HGP1705, GERD-related
EROSIVE ESOPHAGITIS, HEART
This study was designed as a multicenter, double-blind, randomized controlled, non-inferiority trial involving patients with erosive esophagitis (EE). Patients with EE were randomly assigned to receive either HIP1601 40 mg or HGP1705 40 mg for 4 or 8 weeks. Complete EE healing rates, GERD-related symptoms, and treatmen...
PMC10729464
Study subject
primary esophageal motility disorders, heartburn, malignancy, acid regurgitation, active gastric or, Zollinger-Ellison syndrome, Barrett’s esophagus, duodenal ulcer
ESOPHAGEAL DYSPLASIA, GASTROINTESTINAL BLEEDING, ZOLLINGER-ELLISON SYNDROME, INFLAMMATORY BOWEL DISEASE
Male and female patients aged 19–75 years were eligible for inclusion if they had endoscopically confirmed EE based on the Los Angeles (LA) Classification (grades A–D). Additionally, patients had to experience symptoms of acid regurgitation and/or heartburn 7 days prior to the screening visit.The exclusion criteria for...
PMC10729464
Study protocol
Figure  Randomization protocol and patient disposition
PMC10729464
Efficacy and safety assessment
GERD, death, TEAEs, disability
ADVERSE EVENTS, ADVERSE EVENT, GERD, REMISSION, ADVERSE EVENT
The primary endpoint of the study was the complete healing rate of EE confirmed endoscopically up to week 8 in the per-protocol set (PPS) population. The complete healing of EE was defined as the LA Classification criterion “Not Present” in endoscopy after administration of the clinical trial drug [Patients were instru...
PMC10729464
Statistical analyses
HGP1705
For estimating the necessary number of subjects, the complete healing rate of EE by week 8 was assumed to be 93.7% in the HGP1705 40 mg group [Safety analysis was conducted among those who took at least one dose of the clinical trial drugs after random assignment, for whom data on safety assessments could be obtained. ...
PMC10729464
Results
PMC10729464
Study population and baseline characteristics
GASTROESOPHAGEAL REFLUX DISEASE
In total, 213 patients were enrolled in this clinical trial (Fig. Table  Baseline patient demographics and characteristics according to treatment groupGERD, Gastroesophageal reflux disease; LA, Los Angeles; SD, standard deviation
PMC10729464
Primary endpoint
HGP1705
EROSIVE ESOPHAGITIS
Based on the PPS analysis by week 8, the complete healing rate of EE in the HIP1601 group was 97.8% (91/93), which was higher than the rate of 96.8% (91/94) in the HGP1705 group (Table  Healing rate of erosive esophagitis by weeks 8 and 4EE, erosive esophagitis; CI, confidence interval; FAS, full analysis set; PPS, per...
PMC10729464
Secondary endpoints
PMC10729464
Healing rate of erosive esophagitis at week 4
HGP1705
In PPS analysis at week 4, the complete healing rate of EE in the HIP1601 and HGP1705 groups were 91.4% (85/93) and 92.6% (87/94), respectively, and the 95% CI of the difference between the two groups ranged from − 8.9 to 6.6 (Table 
PMC10729464
Complete resolution rate of GERD symptoms at week 4 or 8
dysphagia, HGP1705, heartburn, GERD, acid regurgitation, pain
DYSPHAGIA, GERD
After 4 weeks of treatment, the complete resolution rate of overall GERD symptoms, including heartburn, acid regurgitation, dysphagia, and epigastric pain, was 49.5% (46/93) in the HIP1601 group and 48.9% (46/94) in the HGP1705 group (Table  Complete resolution rate of symptoms after treatment (per protocol set)46(49.5...
PMC10729464
Proportion of heartburn- and acid regurgitation-free days and nights by week 1, 2, 4, 8 (per protocol set)
HGP1705
The proportions of heartburn- and acid regurgitation-free days by week 4 were 68.1% and 68.7% in HIP1601 group, and 71.9% and 69.3% in HGP1705 group, respectively (Fig.  The proportion of symptoms-free days and nights after 1, 2, 4 weeks of treatment (per protocol set). A, the proportion of heartburn-free days after 1,...
PMC10729464
Time to sustained resolution of heartburn and acid regurgitation (per protocol set)
HGP1705, heartburn
The median time to sustained resolution of heartburn was 7 days (95% CI: 3.0–16.0) in the HIP1601 group and 8 days (95% CI: 5.0–11.0) in the HGP1705 group (Supplementary Table The proportion of patients who achieved sustained resolution of nocturnal heartburn and nocturnal acid regurgitation was 87.2% (34/39) and 81.8%...
PMC10729464
Number of rescue medication use
HGP1705
The mean number of rescue medications administered in the HIP1601 (7.8 per subject) was lower than that (9.3 per subject) in the HGP1705 group. However, there was no significant difference between the two groups (
PMC10729464
Tolerability and safety
HGP1705, TEAEs
ADVERSE EVENTS, EVENTS, ADVERSE EVENT
The incidence of TEAEs was 14.3% (15/105; 22 events) in the HIP1601 group and 14.2% (15/106; 20 events) in the HGP1705 group (Table  Summary of treatment-emergent adverse events (safety analysis set)TEAE: treatment-emergent adverse events*TEAEs: Adverse events with start date on or after administration of the study dru...
PMC10729464
Discussion
GERD, fracture, TEAEs, erosions, hypomagnesemia, reflux disease, NERD, community-acquired pneumonia, Barrett’s esophagus, esophageal and extraesophageal symptoms, gastric acid
ADVERSE EVENTS, GERD, HYPOMAGNESEMIA, CLOSTRIDIUM DIFFICILE INFECTION, COMMUNITY-ACQUIRED PNEUMONIA, COMPLICATIONS
The goal of GERD treatment is to alleviate symptoms and prevent complications. Although currently approved delayed-release PPIs have shown benefits in the treatment of GERD, unmet needs remain [Although a new class of drugs, such as potassium-competitive acid blockers (P-CABs), has recently been developed, PPIs remain ...
PMC10729464
Conclusions
GERD, HGP1705
GERD
In conclusion, the findings of this study support the efficacy and safety of HIP1601 40 mg as a treatment option for EE healing and alleviating GERD symptoms. The results indicate that HIP1601 is not inferior to HGP1705 40 mg in terms of both efficacy and safety, as demonstrated by comparable healing rates and tolerabi...
PMC10729464
CONSORT guidelines
The study adheres to the CONSORT guidelines and a completed CONSORT has been submitted separately.
PMC10729464
Electronic supplementary material
Below is the link to the electronic supplementary material. Supplementary Material 1
PMC10729464
Acknowledgements
Not applicable.
PMC10729464
Author contributions
Hwoon-Yong Jung: Study concept and design, study supervision, acquisition of data, revision of the manuscript, statistical analysis, interpretation of data, verified the underlying data. Hyun Lim: Acquisition of data, drafting of the manuscript, revision of the manuscript, interpretation of data,. Jae Myung Park, Jong ...
PMC10729464
Funding
This work was supported by Hanmi Pharmaceuticals Co., Ltd., Seoul, Republic of Korea (HM-ESOM-301).
PMC10729464
Data availability
Relevant data have been presented in the main manuscript. The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.
PMC10729464
Declarations
PMC10729464
Ethics approval and consent to participate
The study protocol was approved by the ethics committees of all participating hospitals.
PMC10729464
Consent for publication
Informed consent was obtained from all individual participants included in the study.
PMC10729464
Competing interests
The authors declare no competing interests.
PMC10729464
References
PMC10729464
Background
fibrosis, IUA
INTRAUTERINE ADHESIONS, FIBROSIS
Intrauterine adhesion (IUA) is a frequent acquired endometrial condition, for which there is no effective preventive or treatment. Previous studies have found that vaginal microbiota dysregulation is closely related to endometrial fibrosis and IUA. Therefore, we wondered whether restoration of vaginal microbiota by vag...
PMC10032012
Results
IUA
First, we created a mechanically injured mouse model of IUA and restored the mice’s vaginal microbiota by the addition of
PMC10032012
Conclusions
This study confirmed that
PMC10032012
Clinical trial registration
:
PMC10032012
Supplementary Information
The online version contains supplementary material available at 10.1186/s12866-023-02823-y.
PMC10032012
Keywords
PMC10032012
Results
PMC10032012
Discussion
TGF-β1, inflammation, fibrosis, intrauterine inflammation, infection, IUA, endometrial basal layer damage
ENDOMETRITIS, INTRAUTERINE ADHESION, INFLAMMATION, FIBROSIS, INFECTION
Finally, 10 vaginal secretion samples were selected in the group C, I, E and L, a total of 40 samples were used for high-throughput sequencing. In α-diversity, there are significant differences in Shannon (P < 0.01) and Simpson (P < 0.005) (Fig.  The effect of We allow visitors to reproduce images with permission and/...
PMC10032012