Association of serum 25-hydroxyvitamin D with cardiovascular mortality and kidney outcome in patients with early stages of CKD.

PURPOSE: While serum 25-hydroxyvitamin D (25[OH]D) deficiency is prevalent in chronic kidney disease (CKD), the effects of 25(OH)D deficiency on cardiovascular mortality and kidney outcomes in patients with early-stage CKD remain incompletely understood. METHODS: This multicenter retrospective cohort study included adult patients with stages 1-3 CKD from 19 medical centers across China between January 2000 and May 2021. The primary outcome was cardiovascular mortality. The secondary study outcome included CKD progression (defined as a sustained > 40% eGFR decrease from baseline or progress to end-stage kidney disease), and annual percentage change of eGFR. RESULTS: Of 9229 adults with stages 1-3 CKD, 27.0% and 38.9% had severe (< 10 ng/mL) and moderate (10 to < 20 ng/mL) serum 25(OH)D deficiency, respectively. Compared with patients having 25(OH)D ≥ 20 ng/mL, a significantly higher risk of cardiovascular mortality (hazard ratio [HR] 1.90, 95% CI 1.37-2.63), CKD progression (HR 2.20, 95% CI 1.68-2.88), and a steeper annual decline in eGFR (estimate - 7.87%; 95% CI - 10.24% to - 5.51% per year) was found in those with serum 25(OH)D < 10 ng/mL. Similar results were obtained in subgroups and by sensitivity analyses. CONCLUSIONS: 25(OH)D deficiency is associated with increased risks of cardiovascular mortality and CKD progression in patients with early-stage CKD. Studies are needed to determine whether early intervention for 25(OH)D deficiency could improve the prognosis of patients with early-stage CKD.

Fabrication and evaluation of porous coatings doped with bioactive elements on titanium surfaces.

OBJECTIVE: Although pure titanium (PT) and its alloys exhibit excellent mechanical properties, they lack biological activity as implants. The purpose of this study was to improve the biological activity of titanium implants through surface modification. MATERIALS AND METHODS: Titanium was processed into titanium discs, where the titanium discs served as anodes and stainless steel served as cathodes, and a copper- and cobalt-doped porous coating [pure titanium model (PTM)] was prepared on the surface of titanium via plasma electrolytic oxidation. The surface characteristics of the coating were evaluated using field emission scanning electron microscopy (FE-SEM), energy dispersive X-ray spectroscopy (EDS), X-ray photoelectron spectroscopy (XPS), atomic force microscopy (AFM), and profilometry. The corrosion resistance of PTM was evaluated with an electrochemical workstation. The biocompatibility and bioactivity of coated bone marrow mesenchymal stem cells (BMSCs) were evaluated through in vitro cell experiments. RESULTS: A copper- and cobalt-doped porous coating was successfully prepared on the surface of titanium, and the doping of copper and cobalt did not change the surface topography of the coating. The porous coating increased the surface roughness of titanium and improved its resistance to corrosion. In addition, the porous coating doped with copper and cobalt promoted the adhesion and spreading of BMSCs. CONCLUSIONS: A porous coating doped with copper and cobalt was prepared on the surface of titanium through plasma electrolytic oxidation. The coating not only improved the roughness and corrosion resistance of titanium but also exhibited good biological activity.

[Clinical features and death risk factors of pneumocystis jirovecii pneumonia in kidney disease patients with immunosuppressive therapy].

To investigate the clinical features and death risk factors of pneumocystis jirovecii pneumonia (PJP) in kidney disease patients with immunosuppressive patients. A Retrospective case series study was performed in 52 PJP patients with kidney disease who received immunosuppressive therapy in Nephrology or Respiratory department of Peking University First Hospital from January 1, 2006 to August 31, 2021. Patients were divided into survival group (36 cases) and death group (16 cases) according to their clinical outcomes. Univariate analysis was performed to compare the differences of clinical features between the two groups. Multivariate logistic regression model was used to analyze the death risk factors. The results showed that the median serum creatinine was 192.5 (109.8, 293.7) µmol/L, and the incidence of acute kidney injury was 63.5% (33/52). Univariate analysis showed that age (t=1.197,P=0.030), C-reactive protein level (t=2.378,P=0.022), time from onset to diagnosis (χ2=6.62,P=0.010), PJP severity (χ2=5.482,P=0.019), complicated with septic shock (χ2=3.997,P=0.046), mechanical ventilation (χ2=11.755,P=0.001), and blood purification therapy (χ2=4.748,P=0.029) were statistically significant. There were no statistically significant differences between the two groups in gender, duration and dosage of hormone therapy before PJP onset, intravenous methylprednisolone pulse therapy, immunosuppressant use, and serum creatinine level before and after hospitalization for anti-PJP treatment (all P>0.05). Multivariate analysis showed that the time from onset to diagnosis of PJP was >10 days (OR=40.945, 95%CI: 1.738-451.214; P=0.021) and severe PJP (OR=25.502, 95%CI: 1.426-74.806; P=0.028) was an independent death risk factor for kidney disease complicated with PJP of immunosuppressive therapy. In conclusion, the time from onset to diagnosis of PJP and PJP severity are independent death risk factors in patients with kidney disease complicated with PJP of immunosuppressive therapy. Close attention should be paid to oxygenation condition and early diagnosis can prevent the aggravation of PJP and improve the prognosis.

METTL3 Modulates Ctsk+ Lineage Supporting Cranial Osteogenesis via Hedgehog.

N6-methyladenosine (m6A) modification, a eukaryotic messenger RNA modification catalyzed by methyltransferase-like 3 (METTL3), plays a pivotal role in stem cell fate determination. Calvarial bone development and maintenance are orchestrated by the cranial sutures. Cathepsin K (CTSK)-positive calvarial stem cells (CSCs) contribute to mice calvarial ossification. However, the role of m6A modification in regulating Ctsk+ lineage cells during calvarial development remains elusive. Here, we showed that METTL3 was colocalized with cranial nonosteoclastic Ctsk+ lineage cells, which were also associated with GLI1 expression. During neonatal development, depletion of Mettl3 in the Ctsk+ lineage cells delayed suture formation and decreased mineralization. During adulthood maintenance, loss of Mettl3 in the Ctsk+ lineage cells impaired calvarial bone formation, which was featured by the increased bone porosity, enhanced bone marrow cavity, and decreased number of osteocytes with the less-developed cellular outline. The analysis of methylated RNA immunoprecipitation sequencing and RNA sequencing data indicated that loss of METTL3 reduced Hedgehog (Hh) signaling pathway. Restoration of Hh signaling pathway by crossing Sufufl/+ alleles or by local administration of SAG21 partially rescued the abnormity. Our data indicate that METTL3 modulates Ctsk+ lineage cells supporting calvarial bone formation by regulating the Hh signaling pathway, providing new insights for clinical treatment of skull vault osseous diseases.

[Efficacy of navel application of Jianpiwenyang Gel for chronic diarrhea of spleen and stomach weakness type: a randomized controlled trial and analysis of the mechanism].

OBJECTIVE: To investigate the efficacy of Jianpiwenyang Gel (SSWYG) for treating chronic diarrhea and explore its therapeutic mechanism. METHODS: Eighty patients with chronic diarrhea of spleen and stomach weakness type were randomized into two groups for interventions with lifestyle adjustment and treatment with bifid triple viable capsules (control group, n=40) or naval application with SSWYG (treatment group, n=40) for one week, after which symptoms of chronic diarrhea were evaluated. The Chinese medicine system pharmacology analysis platform (TCMSP), GeneCards, NCBI, OMIM database and GEO database (GSE14841) were used to obtain the active ingredients and target proteins of SSWYG and chronic diarrhea-related targets. The key targets were obtained by topological analysis for Gene Ontology (GO) and KEGG analyses. The affinity and binding characteristics of SSWYG for specific targets were verified by molecular docking using AutoDock software. RESULTS: In both groups, gastrointestinal symptom rating scale (GSRS), Bristol Scale and TCM syndrome scores significantly improved after the treatments (P < 0.05), and better effects were observed in the treatment group (P < 0.05). Sixtyeight targets of SSWYG in treating chronic diarrhea were obtained, and 33 most probable ones were screened out by topological analysis. GO and KEGG analyses identified several chronic diarrhea-related pathways including the TNF and IL-17 pathways. Molecular docking study showed good affinity of the core components of SSWYG for the key targets CASP3, JNK, IL1B, IL6, and AKT1. JUN and CASP3 had the lowest binding energy and the highest stable binding energy with multiple major active ingredients of SSWYG. CONCLUSION: SSWYG can significantly improve clinical symptoms of chronic diarrhea possibly by regulating the TNF and IL-17 as well as other pathways via CASP3 and JUN, suggesting a complex therapeutic mechanism of SSWYG involving multiple ingredients and targets and coordinated regulation of multiple pathways.

Olfaction in the Anthropocene: NO3 negatively affects floral scent and nocturnal pollination.

There is growing concern about sensory pollutants affecting ecological communities. Anthropogenically enhanced oxidants [ozone (O3) and nitrate radicals (NO3)] rapidly degrade floral scents, potentially reducing pollinator attraction to flowers. However, the physiological and behavioral impacts on pollinators and plant fitness are unknown. Using a nocturnal flower-moth system, we found that atmospherically relevant concentrations of NO3 eliminate flower visitation by moths, and the reaction of NO3 with a subset of monoterpenes is what reduces the scent's attractiveness. Global atmospheric models of floral scent oxidation reveal that pollinators in certain urban areas may have a reduced ability to perceive and navigate to flowers. These results illustrate the impact of anthropogenic pollutants on an animal's olfactory ability and indicate that such pollutants may be critical regulators of global pollination.

Higher Cognitive Reserve Is Beneficial for Cognitive Performance Via Various Locus Coeruleus Functional Pathways in the Pre-Dementia Stage of Alzheimer's Disease.

BACKGROUND: Cognitive reserve (CR) shows protective effects on cognitive function in older adult and in Alzheimer's disease (AD). However, the brain mechanisms underlying the CR effect on the non-dementia AD spectrum (subjective cognitive decline (SCD) and mild cognitive impairment (MCI)) are unknown. The aim of this study was to investigate the potential moderate effect of CR on brain functional networks associated with cognitive performance. METHODS: We selected 200 participants, including 48 cognitively normal (CN) and 56 SCD, and 96 patients with MCI from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Seed-based locus coeruleus functional connectivity (LC FC) was conducted to detect early brain functional changes in the non-dementia AD spectrum. CR was assessed via years of education and intelligence (IQ). The ANDI composite executive function scores (ADNI-EF) and ADNI composite memory scores (ANDI-MEM) at baseline and 24-month follow-up were used to assess cognitive performance. RESULTS: Compared to the CN group, the SCD group showed abnormal LC FC with the executive control network (dorsolateral prefrontal cortex, DLPFC), salience network, sensorimotor network, reward network, and hippocampus, while these alterations were inverted at the MCI stage. The LC-hippocampus FC was correlated with ADNI-MEM at baseline and follow-up, and these relationships were moderated by education. The LC-DLPFC FC was correlated with ADNI-EF at baseline, and this association was moderated by IQ. CONCLUSION: Our results manifested that higher levels of CR would confer protective effects on SCD and MCI. Furthermore, IQ and education could moderate the relationship between LC FC and cognition through different pathways.

[Arterial spin labeling in assessment of interstitial fibrosis in renal allografts].

Objective: To explore the feasibility and application value of arterial spin labeling (ASL) in evaluating the degree of renal fibrosis after kidney transplantation. Methods: This is a cross-sectional study. Renal transplant recipients who received treatment at the First Affiliated Hospital of Soochow University from December 2021 to December 2022 were enrolled. All participants underwent ASL scan, and the values of renal cortical renal blood flow (RBF) were measured through post-processing software. The participants were divided into different groups according to the Banff interstitial fibrosis score (ci score) of the transplanted kidneys, and then relevant indicators were compared. One-way analysis of variance was conducted to compare the differences in renal cortical RBF among the groups. Spearman correlation analysis was employed to investigate the association between renal cortical RBF and ci score of the transplanted kidney. Receiver operating characteristic curve was used to analyze the diagnostic effectiveness of renal cortical RBF and laboratory indicators for distinguishing varying degrees of fibrosis in transplanted kidneys. The Delong test was utilized to compare the area under the curve (AUC). Results: A total of 60 patients (42 males and 18 females) were included in the study, with a mean age of (44.6±10.8) years. All patients were divided into 4 groups: ci0 group (ci score=0, 11 cases), ci1 group (ci score=1, 21 cases), ci2 group (ci score=2, 20 cases), and ci3 group (ci score=3, 8 cases). With an increase in the degree of fibrosis in the transplanted kidney, there was a corresponding decrease in the renal cortical RBF value. The differences in renal cortical RBF values among the 4 groups were statistically significant[ci0 group: (214.9±28.5) ml·(100 g)-1·min-1; ci1 group: (181.7±29.3) ml·(100 g)-1·min-1; ci2 group: (158.8±39.2) ml·(100 g)-1·min-1; ci3 group: (123.1±27.2) ml·(100 g)-1·min-1; F=14.02, P<0.001]. The renal cortical RBF was moderately negatively correlated with the ci score (r=-0.644, P<0.001). The AUC for discriminating between ci0 and ci1-3 of renal cortical RBF and 24-hour urine protein was 0.881 (95%CI: 0.772-0.950) and 0.680 (95%CI: 0.547-0.795), respectively. The AUC for renal cortical RBF was significantly higher than that for 24-hour urine protein (P=0.047). The renal cortical RBF can distinguish between ci0-1 and ci2-3, as well as ci0-2 and ci3, with the corresponding AUC value of 0.796 (95%CI: 0.673-0.889) and 0.900 (95%CI: 0.795-0.963), respectively. Conclusion: ASL can quantitatively assess renal blood perfusion in transplanted kidneys and demonstrates high operational efficacy in distinguishing varying degrees of fibrosis in the transplanted kidneys.

[Updates on immunotherapy of gastrointestinal cancers and practical challenges].

Gastrointestinal (GI) cancers are the most common tumors of the digestive system, and their high morbidity and cancer-related mortality dramatically threaten the health of the population. With the researching progress of immunotherapy, its use in the treatment of GI cancers in the perioperative and advanced stages is becoming more and more important. Currently, immunotherapy has become the standard first-line treatment for MSI-H late-stage colorectal cancer, while in the first-line treatment of late-stage gastric cancer, immunotherapy combined with chemotherapy and HER2-targeted drugs (in HER2-positive patients) has also achieved significant efficacy and long-term survival benefits. Advances in immunotherapy in the neoadjuvant and adjuvant treatment and in the second- and later-line treatment of late-stage GI cancers have demonstrated its promising therapeutic potential. However, there is still an urgent need for future studies to explore more immunotherapy combination strategies for patients with GI cancers, especially with MSS colorectal cancers.

Rationale and Design of a Phase II Trial of Combined Serplulimab and Chemotherapy in Patients with Histologically Transformed Small Cell Lung Cancer: a Prospective, Single-arm and Multicentre Study.

AIMS: Transformed small cell lung cancer (T-SCLC) is a highly aggressive clinical disease with a notably poor prognosis. It most often arises from epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) following treatment. To date, no standard treatment has been established for T-SCLC. Platinum-etoposide was the most commonly used regimen, but progression-free survival remains unsatisfactory. Therefore, there is an urgent unmet need to develop novel and effective strategies for this population. Our study, a multicentre, open-label, single-arm phase II clinical trial (NCT05957510), aims to evaluate the efficacy and safety of serplulimab plus chemotherapy in untreated T-SCLC patients after histological transformation. MATERIALS AND METHODS: In total, 36 eligible participants experiencing SCLC transformation from EGFR-mutant NSCLC will be enrolled to receive combination therapy of serplulimab, etoposide and carboplatin for four to six cycles, followed by maintenance therapy with serplulimab for up to 2 years. The primary endpoint is progression-free survival; secondary endpoints include objective response rate, overall survival and safety. RESULTS: Enrolment started in July 2023 and is ongoing, with an estimated completion date of December 2025. CONCLUSIONS: This study aims to provide valuable insights into the efficacy and safety of combining serplulimab with chemotherapy for treating patients with T-SCLC originating from EGFR-mutant NSCLC.

[Femtosecond laser assisted cataract surgery in a complicated cataract patient with reverse implantable collamer len: a case report].

The patient is a 33-year-old female who, 11 years ago, underwent bilateral posterior chamber phakic intraocular lens (pIOL) implantation due to myopia. She presented with a 2-year history of declining vision in her right eye and sought medical attention. She received femtosecond laser-assisted cataract surgery combined with pIOL extraction. Anterior segment optical coherence tomography and ultrasound biomicroscopy both showed an inverted pIOL in the right eye. Good visual results were achieved, and there were no complications during the six-month follow-up.

[The predictive values of platelet mitochondrial mass and quantity during the perioperative period in elderly patients on the occurrence of postoperative delirium].

Objective: To investigate the changes of platelet mitochondrial mass and quantity during perioperative period in elderly patients, and assess their predictive values on the occurrence of postoperative delirium (POD). Methods: In this prospective study, 162 elderly patients scheduled for abdominal surgery under general anesthesia were enrolled from November 2021 to January 2022 in Nanjing Drum Tower Hospital Affiliated to Nanjing University Medical School. Among them, 20 patients [10 males, 10 females, aged (71.4±6.8) years] developed POD within 3 days after surgery (POD group), and another 20 patients[12 males, 8 females, aged (67.7±5.3) years] who did not develope POD were selected as controls (control group) using propensity score matching method. Blood samples were collected preoperatively, at the end of surgery and on the first postoperative day. Platelets were extracted and mitochondrial mass was detected with flow cytometry. Transmission electron microscopy was used to determine mitochondrial quantity. The receiver operating characteristic (ROC) curve was drawn to analyze the value of mitochondrial mass and quantity in predicting the occurrence of POD. Results: The mean fluorescence intensities of platelet mitochondrial mass were 193±46, 236±61, 264±53 preoperatively, at the end of surgery and on the first postoperative day in the POD group, respectively. The corresponding values were 209±61, 191±67 and 201±56 in the control group. The platelet mitochondrial mass of patients in the POD group was significantly increased on the first postoperative day compared to preoperative levels (P<0.001). In contrast, there was no significant difference in the control group (P=0.410). Patients in the POD group had higher platelet mitochondrial mass than patients in the control group on the first postoperative day(P=0.002). Meanwhile, platelets from patients in the POD group showed significantly higher number of mitochondria than platelets from patients in the control group [3 (2, 4) vs 2 (1, 2), P<0.001]. According to the ROC curve of platelet on the first postoperative day, at a mitochondrial mass cut-off value of>275.35, the sensitivity, specificity and area under the ROC curve to detect the occurrence of POD were 55%, 90% and 0.800 (95%CI: 0.666-0.934, P<0.001). At a mitochondrial quantity cut-off value of>2, the sensitivity, specificity and area under the ROC curve to detect the occurrence of POD were 53%, 78% and 0.680 (95%CI: 0.584-0.776, P<0.001). Conclusions: Patients who developed POD show higher platelet mitochondrial mass after surgery compared to preoperative levels. The mitochondrial mass of platelets on the first postoperative day has good predictive value on the occurrence of POD.

Norovirus outbreaks in hospitals in China: a systematic review.

BACKGROUND: Norovirus outbreaks in hospitals can potentially impair patient care and result in significant financial expenses. There is currently limited information on hospital norovirus outbreaks in the Chinese mainland. AIM: To systematically review the published literature to describe the characteristics of norovirus outbreaks in Chinese mainland hospitals to facilitate prompt identification and control of outbreaks. METHODS: A systematic review was performed according to the Preferred Reporting Items for Systematic Review and Meta-Analysis standards. Databases including PubMed, Web of Science, and Chinese Journals Online databases (China National Knowledge Infrastructure (CNKI), Chinese Wan Fang digital database (WANFANG) were searched from inception to July 18th, 2022. FINDINGS: A total of 41 norovirus Chinese hospital outbreaks occurring before July 18th, 2022 were reported in 32 articles. Most reported outbreaks were from Shanghai and Beijing, and occurred in December and January. Cases were mainly adults. The male:female ratio was 1.22:1. The majority of cases in norovirus outbreaks were hospitalized patients (56.82%); medical staff were affected in 15 outbreaks. Norovirus outbreaks occurred in both private and public hospitals, and in secondary and tertiary care centres, and occurred mainly in internal medicine and geriatric departments. Person-to-person transmission was the primary transmission mode and GII was more prevalent. CONCLUSION: Norovirus outbreaks in hospitals can affect both patients and healthcare workers, sometimes causing serious financial losses. In order to have a more complete understanding of the disease burden caused by norovirus outbreaks, surveillance needs to be established in hospitals.

[Research advances in the treatment of keloid with glucocorticoids].

As a first-line classical drug, glucocorticoids are used in most combination treatment regimens of keloid. However, there are issues such as poor treatment efficacy and recurrence of keloid after keloid was treated with glucocorticoids, which seriously affect the therapeutic effect. In recent years, many studies have explored the factors influencing the efficacy of glucocorticoids in treating keloid and the action mechanism of glucocorticoids from different perspectives. Based on this, this paper reviews the mechanism and the factors influencing the efficacy of glucocorticoids in treating keloid, and explores ways to improve the treatment efficacy of glucocorticoids, aiming to provide thoughts for improving glucocorticoid-related diagnostic and therapeutic strategies.

[Screening for asymptomatic atrial fibrillation in elder community populations in Dalian: a single center study].

Objective: We aimed to determine the epidemiological characteristics of asymptomatic AF in elder community population (≥65 years old) to analyze the detection rate of different screening methods. Methods: The study was a prospective cohort study. The elder (≥65 years old) residents who voluntarily participated in free physical examination in Dalian community were selected. The participants were randomly divided into screening group (including intensive screening group and single screening group) and control group. The control group received interrogation, medical history collection and routine 12-lead electrocardiogram (ECG) examination. Screening group received an additional single-lead ambulatory ECG equipment worn for 5-7 days. Intensive screening group received two equal-length wearings in 2020 and 2021 respectively, while one screening group only wore once in 2020. Results: Finally 3 340 residents ((70.7±5.0) years old) which consisted of 1 488 males (44.55%) were enrolled. There were 1 945 residents in screening group, including 859 in intensive screening group and 1 086 in one-time screening group. The control group included 1 395 people. Detection rate of asymptomatic AF was significantly higher in screening group than control group (79(4.06%) vs. 24(1.72%), P<0.001). Higher detection rate was found in screening group than control group in AF risk factors (1 or 2-3) subgroups and CHA2DS2-VASc score (2-3 or≥4) subgroups (P<0.05). Additionally, no difference was found between intensive screening group and single screening group (42(4.89%) vs. 37(3.41%), P=0.100). Intensive screening increased detection rate (7(6.93%) vs. 1(0.58%), P=0.009) only in residents those with low thrombosis risk (CHA2DS2-VaSc<2). Conclusions: Screening in elderly (≥65 years old) can significantly improve the detection rate of asymptomatic AF by wearing single lead dynamic ECG device. The rate increased significantly with the increase of risk factors associated with AF by single screening. In addition, repeat screening of the same method may only improve detection rates in the group with low risk thrombotic scores and non-combination of AF risk factors.Screening methods that are appropriate for different populations may require further exploration.

[Efficacy, prognosis and influencing factors of transcatheter arterial embolization in the treatment of neuroendocrine neoplasm liver metastases].

Objective: To evaluate the efficacy of transcatheter arterial embolization (TAE) in the treatment of neuroendocrine neoplasm liver metastases (NENLM), analyze the prognosis and related factors. Methods: Clinical data of NENLM patients treated with TAE in the First Affiliated Hospital of Nanjing Medical University from January 2018 to March 2022 were retrospectively analyzed. Objective response rate (ORR), disease control rate (DCR), and adverse event rate after TAE were evaluated according to the Response Evaluation Criteria In Solid Tumors and the Common Terminology Criteria for Adverse Events. The prognosis was evaluated by median overall survival (mOS) and median progression-free survival (mPFS). The survival curve was plotted by Kaplan-Meier method. Multivariate Cox regression was used to analyze prognostic factors. Results: A total of 39 NENLM patients were included in this study, aged (53.3±10.3) (23-74) years old, including 23 males and 16 females. Among them, 9 cases had functional neuroendocrine neoplasms. There were 31 cases with primary sites locating in the digestive system, 32 cases with WHO G1 and G2 primary sites, 27 cases with abundant blood supply for liver metastases and 13 cases with liver tumor load >50%. Thirty patients received treatment of long-acting somatostatin analogue(SSA). A total of 123 TAE were performed in 39 cases, with an ORR of 38.5% (15/39) and a DCR of 76.9% (30/39). There were no serious adverse events of level 4-5 during the perioperative period. The median follow-up was 38.7 (95%CI: 31.3-46.1) months, with mOS of 37.3(95%CI: 27.0-47.5) months and mPFS of 12.6 (95%CI: 7.1-18.1) months. Multivariate Cox regression analysis found that the combination of long-term SSA treatment was an influencing factor for overall survival of patients (HR=0.207, 95%CI: 0.076-0.567, P=0.002). Conclusions: TAE can effectively reduce the load of liver metastases in patients with NENLM, and the combination of long-term SSA treatment can improve the ovreall survival of patients.

[Efficacy and safety of TBI+rATG-based conditioning regimen for haploidentical allogeneic hematopoietic stem cell transplantation in 11 cases of chemotherapy-resistant advanced peripheral T-cell lymphoma].

Objective: To evaluate the clinical outcomes and safety of haploidentical hematopoietic stem cell transplantation (haplo-HSCT) using a conditioning regimen based on total body irradiation (TBI) and rabbit anti-human thymocyte globulin (rATG) in the management of chemotherapy-resistant advanced peripheral T-cell lymphoma (PTCL) . Methods: Clinical data of 11 patients with chemotherapy-resistant advanced PTCL who underwent haplo-HSCT with a TBI+rATG-based conditioning regimen at the Department of Hematology, Shanghai Liquan Hospital and Shanghai Zhaxin Integrated Traditional Chinese and Western Medicine Hospital, from September 2019 to December 2022 were retrospectively analyzed. Results: ①Among the 11 patients (six males and five females), with a median age of 40 years (range: 22-58 years), there were six cases of PTCL, not otherwise specified (PTCL-NOS), three cases of angioimmunoblastic T-cell lymphoma (AITL), one case of large-cell transformation of mycosis fungoides (MF-LCT), and one case of T-cell large granular lymphocytic leukemia (T-LGLL). According to the Lugano staging system, all patients were in stage Ⅲ or Ⅳ, and eight patients had B symptoms. Before transplantation, the median number of prior lines of chemotherapy was 4 (range: 2-10), and all patients had progressive disease (PD). The median time from diagnosis to transplantation was 17 months (range: 6-36 months). ②The conditioning regimen consisted of a TBI dose of 10 Gy, administered at 2 Gy on day -8 and 4 Gy from day -7 to day -6, rATG was administered at a daily dose of 2.5 mg/kg from day -5 to day -2. Etoposide (VP-16) was given at a dose of 15 mg/kg/d from day -5 to day -4, while cyclophosphamide (CTX) was administered at a dose of 50 mg/kg/d from day -3 to day -2. In patients with central nervous system involvement, etoposide and cyclophosphamide were replaced with thiotepa (TT) at a dose of 5 mg/kg/d from day -5 to day -4. Additionally, cytarabine (Ara-C) was added at a dose of 2.0 g/m(2) twice a day from day -3 to day -2 into the conditioning. ③Successful engraftment was achieved in all patients, with a median time to neutrophil engraftment of 14.5 d (range: 11-16 d) and a median time to platelet engraftment of 13 days (range: 8-18 days). Acute graft-versus-host disease (aGVHD) occurred in one patient (grade Ⅰ-Ⅱ), and another patient experienced grade Ⅲ-Ⅳ aGVHD. Among the eight survivors, four developed chronic GVHD (cGVHD). ④Post-transplantation, nine patients achieved complete response (CR). ⑤Hematopoietic suppression occurred in all patients after conditioning, with three experiencing diarrhea, four developing mucositis, three exhibiting elevated transaminase/bilirubin levels, and seven developing infectious complications. These non-hematologic adverse events were effectively managed. ⑥At one year post-transplantation, the non-relapse mortality (NRM) was (22.5±14.0) %, the cumulative incidence of relapse (CIR) was (20.2±12.7) %, and overall survival (OS) rate was (72.7±13.4) %, and disease-free survival (DFS) rate was (63.6±14.5) % . Conclusion: TBI+rATG-based conditioning regimen for haplo-HSCT is an effective and safe treatment approach for patients with chemotherapy-resistant advanced PTCL.

Effects of lactic acid bacteria-fermented formula milk supplementation on colonic microbiota and mucosal transcriptome profile of weaned piglets.

Supplemental probiotic fermented milk as a gut modulator can improve growth performance for weaned piglets by promoting the development of the small intestine in digestion and immune function. The effect on colon health might also play a considerable part in the favourable role of probiotic fermented milk in the growth performance improvement of weaned piglets; however, it has yet to be reported. This study aimed to investigate the effects of supplementation with lactic acid bacteria-fermented formula milk (LFM) on colonic morphology, microbiota composition, and mucosal transcriptome profile in weaned piglets. A total of 24 male weaned piglets were randomly divided into two groups: a control (CON) treatment or the LFM-supplemented treatment. Each group consisted of six replicates (cages) with two piglets per cage, and each piglet in the LFM group was supplemented with 80 mL LFM three times a day for 21 d, while the CON group was treated with the same amount of drinking water. Results showed that supplementation of LFM reduced the colonic histological damage scores and significantly increased the number of goblet cells per crypt. Furthermore, LFM consumption decreased the levels of pro-inflammation cytokines in the colonic mucosa. LFM downregulated the expression of inflammatory genes (CXCL9 and CXCL10) involving Toll-like receptor signalling pathway, immune response, and response to bacterium, and up-regulated two active genes (S100A8 and S100A9) involving the IL-17 signalling pathway and Toll-like receptor 4 binding. In addition, LFM could increase the potential probiotic genera containing Lachnospira and Anaerorhabdus furcosa group, which were positively related to short-chain fatty acid (SCFA) production. Correspondingly, LFM-fed piglets had higher total bacterial load and total SCFA concentration in the colonic digesta compared with the CON group. These novel findings support the benefits of LFM in enhancing intestinal homoeostasis and ameliorating weaning stress for weaned piglets, which is associated with the modulation of gut microbiota composition and immune-related genes.