Objective To explore the efficacy of a compound nutrition preparation on wound healing after acute trauma and investigate the underlying mechanism primarily.Methods After skin wound model was successfully constructed on totally 60 male SD rats surgically,they were randomly divided into control group(CON group),whey protein group(WP group)and low-and high-dose nutritional formula groups(LDF and HDF groups),with 15 animals in per group.From the next day after surgery,the rats in each group were given corresponding nutritional interventions for 2 weeks.During the intervention,the wound conditions were observed and recorded,and the wound area was measured.The samples were collected on the 3rd,7th and 14th days after surgery,respectively.Serum albumin(ALB),prealbumin(PA),total protein(TP),inflammatory factors(TNF-α,IL-1β,IL-6 and IL-10),immunoglobulins(IgA,IgG and IgM)and hydroxyproline(Hyp)were detected by the corresponding reagent kits.The histopathologic changes of wound were observed with HE staining.Masson staining was used to observe the collagen fiber deposition in wound tissue.The angiogenesis of wound tissue was evaluated by immunohistochemical staining.Results Compared with the CON group,the wound healing speed,collagen synthesis and angiogenesis speed were significantly accelerated in the WP group,LDF group and HDF group(P＜0.05),and the effects were the most obvious in the HDF group.On the 3rd day after surgery,in the WP,LDF and HDF groups,the serum ALB,PA and TP levels were significantly increased(P＜0.05),serum TNF-α and IL-1β levels were obviously decreased(P＜0.05),and serum IL-10 level was notably increased(except WP group)when compared with the CON group.The serum IgG and IgM levels were significantly increased in the LDF group and HDF group(P＜0.05)and significant increment of IgA was only observed in the HDF group(P＜0.05).On the 7th day after modeling,the levels of ALB,PA and TP were significantly increased(P＜0.05),the levels of TNF-α,IL-1β and IL-6 were obviously decreased(P＜0.05),and the levels of IL-10 were remarkably increased(P＜0.05)in the HDF group than the CON group;The LDF group and HDF group had significantly elevated serum IgG and IgM levels(P＜0.05),but only the former group had statistically increased serum IgA level(P＜0.05).On the 14th day after modeling,the HDF group had significantly increased levels of ALB and TP(P＜0.05),decreased levels of IL-1β(P＜0.05),and raised levels of IgG and IgM when compared with the CON group(P＜0.05).Conclusion Our compound nutrition preparation promotes wound healing in rat model of acute trauma,which might be related to its improving the nutritional status,promoting collagen synthesis,and thus alleviating inflammatory response and enhancing immune function.

Objective To analyze the clinical data and head imaging features of perioperative acute ischemic stroke(POAIS)with non-small cell lung cancer(NSCLC)and to explore the possible risk factors and pathogeneses of it,and to provide evidence for the prevention and treatment of POAIS.Methods Data of patients with primary NSCLC who underwent lung resection and had POAIS was retrospectively collected,and the clinical data of patients with cerebral infarction of large artery atherosclerosis(LAA)and stroke of undetermined etiology(SUE)was compared.Results There were 25 NSCLC patients with POAIS,some of whom had no history of cardiovascular and cerebrovascular diseases,and the proportion was higher in SUE.The most common excision site was left upper lobe,especially in SUE.The pathological stage and type were mainly early stage and adenocarcinoma.Most patients developed POAIS within 7 days after surgery,and mainly mild to moderate.Middle cerebral artery was the main responsible vessel and most patients'cerebral infarction locations≥3.SUE was the most common type of Trial of Org 10172 in Acute Stroke Treatment(TOAST),followed by LAA type.Compared with SUE,more patients had a history of type 2 diabetes(P=0.006)and higher preoperative fasting glucose level(P=0.013)with LAA type.Conclusion Attention should be paid to the prevention of LAA type cerebral infarction in NSCLC patients with type 2 diabetes or preoperative high fasting glucose level,and antithrombotic regimen is selected according to different etiological mechanisms of POAIS.The formation of pulmonary vein thrombosis after lung resection should be prevented and paid attention to.

AIM:This study aim to investigate the effects of lipopolysaccharide(LPS)-induced inflammation on the aging phenotype of hematopoietic stem/progenitor cells(HSPCs)in the bone marrow(BM)and spleen of mice.METHODS:(1)Young(2-month old)wild-type(WT)mice were treated with LPS to establish an actue inflammation model.The percentage of HSPCs in the BM and spleen of mice after LPS stimulation,as well as the ratio of mature cells in peripheral blood(PB)and spleen,were analyzed using flow cytometry.The proliferation of HSPCs in the BM and spleen was evaluated by examining the expression of the proliferation marker Ki67.In addition,changes in CD45 expression on HSPCs in the spleen of mice following LPS exposure were investigated by flow cytometry.(2)The percentage of HSPCs in BM and mature cells in PB and spleen of both young(2-month old)and old(24-month old)WT mice were analyzed by flow cytometry.(3)The transcriptome changes of hematopoietic stem cells(HSCs)after LPS stimulation was performed by an in silico analysis.RESULTS:(1)Mice exposed to LPS exhibited a significant increase in the percentage of HSPCs in BM and a marked elevation in the percentages of myeloid cells in PB and spleen compared to the mice in control group(P<0.05).(2)LPS exposure resulted in increased spleen weight and cell counts(P<0.05),along with a higher per-centage of HSPCs in the spleen compared to controls(P<0.05).(3)LPS stimulation promoted the proliferation of HSPCs in the BM and spleen(P<0.05).(4)The expression of CD45 was reduced on HSPCs from spleen of mice after LPS stimu-lation(P<0.01).(5)In comparison to young mice,aged mice showed an increase in spleen weight and a higher percent-age of HSPCs in the spleen(P<0.05).(6)Aged mice,in comparison to young mice,demonstrated a significantly higher percentage of HSPCs in the BM and myeloid skewing in the PB and spleen(P<0.01).(7)The silico analysis revealed up-regualtion of reactive oxygen species(ROS)and apoptosis signaling in HSPCs following LPS stimulation.CONCLU-SION:Young HSPCs stimulated by LPS exhibited an increase in cell number,a bias towards myeloid differentiation,en-hanced extramedullary hematopoiesis,and elevated levels of ROS and apoptosis,all of which collectively manifested the aging phenotype of HSPCs.

Objective To investigate the influence of sodium bicarbonate Ringer's solution and compound Ringer's solution on patients'acid-base balance and liver and kidney function during controlled low central venous pressure(CLCVP)hepatectomy.Methods A total of 60 patients with primary liver cancer who underwent CLCVP hepatectomy in the Affiliated Cancer Hospital of Zhengzhou University from June 2020 to June 2022 were selected and randomly divided into the sodium bicarbonate Ringer's solution group and compound Ringer's solution group,with 30 patients in each group.Patients in the sodium bicarbonate Ringer's solution group were infused with sodium bicarbonate Ringer's solution,while patients in the compound Ringer's solution group were infused with compound Ringer's solution after anesthesia induction and before liver parenchymal disconnection.The pH value,base excess(BE)and blood lactic acid(Lac)levels were detected using the blood gas analyzer in the two groups before anesthesia induction(T,),at the beginning of surgery(T2),2 h during surgery(T3),4 h during surgery(T4),and at the end of surgery(T5),respectively.The levels of serum alanine aminotransferase(ALT),aspartate aminotransferase(AST),blood urea nitrogen(BUN),and serum creatinine(Scr)were detected using the automatic biochemical analyzer 24 h before and 24 h after surgery,respectively.The body mass,surgical time,intraoperative infusion volume,urine volume,changes in body acid-base balance during surgery,and changes in liver and kidney function before and after surgery between the two groups were compared.Results There was no statistically significant difference in body mass,surgical time,intraoperative infusion volume,and urine volume between the two groups of patients(P＞0.05).At T,,there was no statistically significant difference in pH value,BE and Lac levels between the two groups of patients(P＞0.05).Compared to T,,the pH value in the compound Ringer's solution group increased at T2 and decreased at T3,T4 and T5,while BE and Lac levels from T2 to T5 showed an increasing trend(P＜0.05);compared to T,,the pH value in the sodium bicarbonate Ringer's solution group increased at T2 and decreased at T3,BE and Lac levels increased at T2 and T3(P＜0.05),and there was no statistically significant difference in pH value,BE and Lac levels at T4 and T5 compared to T1(P＞0.05).At T5,the pH value in the sodium bicarbonate Ringer's solution group was significantly higher than that in the compound Ringer's solution group,while the BE and Lac levels were significantly lower than those in the compound Ringer's solution group(P＜0.05).There was no statisti-cally significant difference in the levels of ALT,AST,BUN and Scr 24 hours before surgery between the two groups of patients(P＞0.05);compared to 24 hours before surgery,there was no significant change in the levels of ALT,AST,BUN and Scr 24 hours after surgery(P＞0.05);there was no statistically significant difference in the levels of ALT,AST,BUN and Scr 24 hours after surgery between the two groups(P＞0.05).Conclusion Compared to compound Ringer's solution,sodium bicarbonate Ringer's solution has a smaller impact on the internal environment of the body during the CLCVP hepatectomy and can effectively maintain the stability of the body's acid-base balance.Both the two solutions have no significant impact on the patient's liver and kidney function.

Objective To construct a model of Fat-1/APPPS1 transgenic mice and a cellular model of microglia and explore the improvement effect and underlying mechanism of n-3 polyunsaturated fatty acids(n-3 PUFAs)on the learning and memory abilities of APPPS1 mice by regulating microglial activation and polarization.Methods After the male mice with heterozygous Fat-1 genotype were mated with the female ones with heterozygous APPPS1 genotype,genetic identification was used to screen the male offspring with Fat-1/APPPS1 genotype.Then after the male wild-type(WT)mice and those with Fat-1,Fat-1/APPPS1,and APPPS1 genotypes were bred until 9 months old,their learning and memory abilities were evaluated with Morris water maze(MWM)test.In addition,gas chromatography-mass spectrometry(GC-MS)was performed to detect the concentration of PUFAs in the brain,and immunohistochemistry(IHC)was applied to detect the deposition of β-amyloid protein(Aβ)in the hippocampal regions.Moreover,immunofluorescence assay,qRT-PCR,and enzyme-linked immunosorbent assays(ELISA)were conducted to measure inflammation,and transcription and expression of Iba-1(indicating the microglial activation)and CD86 and CD206(indicating microglial polarization)in central nervous system(CNS).After pretreated with DHA+EPA(25 pmol/mL∶25 μmol/mL),microglial model of inflammatory injury was established in immortalized mouse BV2 cells induced by LPS(1 μg/mL).Afterwards,immunofluorescence assay,qRT-PCR and Western blotting were used to detect inflammation and microglial activation and polarization.Results Compared with the APPPS1 mice,endogenous n-3 PUFAs effectively improved the learning and memory disorders in Fat-1/APPPS1 ones(P＜0.05),remarkably alleviated Aβ deposition in the hippocampal regions(P＜0.05),evidently reduced CNS inflammation and microglial activation(P＜0.05)and transformed the activated microglia from M1 to M2(P＜0.05).Furthermore,BV2 cells with DHA+EPA pretreatment obviously resisted LPS-induced cellular inflammation and induced activated ones from M1 to M2(P＜0.05).Conclusion n-3 PUFAs inhibit the microglial activation,regulate the microglial polarization from M1 to M2,reduce CNS inflammation,and thus alleviate learning and memory disorders in APPPS1 mice.

Background::Although overnight fasting is recommended prior to endoscopic retrograde cholangiopancreatography (ERCP), the benefits and safety of high-carbohydrate fluid diet (CFD) intake 2 h before ERCP remain unclear. This study aimed to analyze whether high-CFD intake 2 h before ERCP can be safe and accelerate patients’ recovery.Methods::This prospective, multicenter, randomized controlled trial involved 15 tertiary ERCP centers. A total of 1330 patients were randomized into CFD group ( n = 665) and fasting group ( n = 665). The CFD group received 400 mL of maltodextrin orally 2 h before ERCP, while the control group abstained from food/water overnight (>6 h) before ERCP. All ERCP procedures were performed using deep sedation with intravenous propofol. The investigators were blinded but not the patients. The primary outcomes included postoperative fatigue and abdominal pain score, and the secondary outcomes included complications and changes in metabolic indicators. The outcomes were analyzed according to a modified intention-to-treat principle. Results::The post-ERCP fatigue scores were significantly lower at 4 h (4.1 ± 2.6 vs. 4.8 ± 2.8, t = 4.23, P <0.001) and 20 h (2.4 ± 2.1 vs. 3.4 ± 2.4, t= 7.94, P <0.001) in the CFD group, with least-squares mean differences of 0.48 (95% confidence interval [CI]: 0.26–0.71, P <0.001) and 0.76 (95% CI: 0.57–0.95, P <0.001), respectively. The 4-h pain scores (2.1 ± 1.7 vs. 2.2 ± 1.7, t = 2.60, P = 0.009, with a least-squares mean difference of 0.21 [95% CI: 0.05–0.37]) and positive urine ketone levels (7.7% [39/509] vs. 15.4% [82/533], χ2 = 15.13, P <0.001) were lower in the CFD group. The CFD group had significantly less cholangitis (2.1% [13/634] vs. 4.0% [26/658], χ2 = 3.99, P = 0.046) but not pancreatitis (5.5% [35/634] vs. 6.5% [43/658], χ2 = 0.59, P = 0.444). Subgroup analysis revealed that CFD reduced the incidence of complications in patients with native papilla (odds ratio [OR]: 0.61, 95% CI: 0.39–0.95, P = 0.028) in the multivariable models. Conclusion::Ingesting 400 mL of CFD 2 h before ERCP is safe, with a reduction in post-ERCP fatigue, abdominal pain, and cholangitis during recovery.Trail Registration::ClinicalTrials.gov, No. NCT03075280.

Objective:To evaluate the impact of self-crosslinked hyaluronic acid (SCH) gel on endometrium recovery after artificial abortion.Methods:A multicenter, prospective randomized controlled trial was conducted across 18 hospitals from December 2021 to February 2023, involving 382 women who underwent artificial abortion. Participants were randomly allocated to receive either treatment with SCH gel (SCH group) or no treatment (control group) in a 1∶1 ratio. The primary outcome was endometrium thickness in 14 to 18 days after the first postoperative menstruation. Secondary outcomes included changes in menstrual volume during the first postoperative menstruation, menstruation resumption within 6 postoperative weeks, time to menstruation resumption, duration of the first postoperative menstruation, and incidence of dysmenorrhea.Results:Baseline characteristics of participants were comparable between the two groups (all P>0.05), with 95.3% (182/191) in SCH group and 92.7% (177/191) in the control group completed the study. The postoperative endometrial thickness in SCH group was significantly greater than that in the control group [(9.78±3.15) vs (8.95±2.32) mm; P=0.005]. SCH group also had significantly fewer participants with reduced menstrual volume [23 cases (12.6%, 23/182) vs 31 cases (17.5%, 31/177); P=0.038]. Although SCH group experienced less dysmenorrhea during the first postoperative menstrual period, this difference was not statistically significant [28.5% (51/179) vs 37.1% (65/175); P=0.083]. Outcomes were similar between SCH group and the control group regarding the proportion of participants who resumed menstruation within 6 weeks postoperatively, time to menstruation resumption, and duration of the first postoperative menstruation ( P=0.792, 0.485, and 0.254, respectively). No serious adverse events were observed during the study period, and no adverse events were attributed to SCH gel treatment. Conclusion:The application of SCH gel after artificial abortion is safe and might aid in the recovery of the endometrium.

Objective:To explore the effects of G protein-coupled receptor 55 (GPR55) antagonist CID16020046 on renal fibrosis in mice, and provide a new method and idea for the treatment of renal fibrosis.Methods:(1) GPR55 overexpression and GPR55 antagonist CID16020046 were used in renal fibroblasts (NRK-49F) of rats, respectively. Meanwhile,transforming growth factor-β1 (TGF-β1) was applied in the NRK-49F cells to observe the expression of fibrosis-related factors and inflammatory factors. (2) A mouse model of renal fibrosis with unilateral ureteral obstruction (UUO) was established in vivo. Eight-week-old male C57BL/6J mice (20-25 g) were randomly divided into three groups according to the random number table method: sham group ( n=6), model group (UUO group, n=7), model + CID16020046 drug (UUO+CID group, n=8). The drug CID16020046 (10 mg/kg) was intraperitoneally injected 1 day before modeling, on the day of modeling and every day after surgery in UUO+CID group, and the corresponding dose of 0.9% normal saline was injected intraperitoneally in sham and UUO groups.The mice were sacrificed for sampling 7 days after UUO surgery, and their renal function indicators, liver transaminase, and cardiac markers were examined. Western blotting and quantitative real-time PCR were used to detect the expression of renal fibrosis-related factors and inflammatory factors. Immunohistochemistry staining, Sirius red staining and Masson trichrome staining were used to detect the pathological changes of renal tissues. Results:(1) After NRK-49F cells were stimulated by TGF-β1, the mRNA and protein expression levels of GPR55 were significantly increased (both P<0.05). There was no statistically significant difference in the mRNA expression of fibrosis-related factors fibronectin and collagen Ⅰ, and inflammatory factors interleukin-1β and tumor necrosis factor-α between TGF-β1 group and TGF-β1 + GPR55 overexpression group (all P>0.05). Compared with the TGF-β1 group, the protein expression levels of fibrosis-related factors alpha-smooth muscle actin (α-SMA) and vimentin, and the mRNA expression levels of collagen Ⅰ and α-SMA were lower in the TGF-β1 + CID group (all P<0.05). (2) Compared with sham group, the mRNA and protein expression levels of GPR55 in UUO group were higher (both P<0.05). The serum creatinine in the UUO+CID group was lower compared to the UUO group ( P<0.05). There was no statistically significant difference in blood urea nitrogen, alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase and creatine kinase isoenzyme between UUO group and UUO+CID group (all P>0.05). Compared with the UUO group, the protein expression levels of renal fibrosis-related factors fibronectin, collagen Ⅰ and vimentin, and the mRNA expression levels of fibronectin, collagen Ⅰ, collagen Ⅲ and α-SMA were lower in the UUO+CID group (all P<0.05). The degree of renal tubular dilation and interstitial collagen fiber deposition in the UUO+CID group was significantly reduced compared to the UUO group (all P<0.05). Conclusions:CID16020046 can reduce serum creatinine in UUO mice, protect renal function, and simultaneously decrease the expression of fibrosis-related factors in renal fibroblasts and mouse kidney tissues, thereby alleviating renal fibrosis.

Objective To investigate the-75 G/A single-nucleotide polymorphism in the promoter region of apolipoprotein A1 gene(apoA1)and its association with gestational diabetes mellitus(GDM)in pregnant women and to provide references for the exploration in the molecular genetic basis of GDM.Methods A total of 626 GDM patients and 1022 normal pregnant women,ie,the controls,were included in the study.The genotyping of apoA1-75 G/A polymorphism was performed by polymerase chain reaction and restriction fragment length polymorphism(PCR-RFLP)analysis.Total cholesterol(TC),triglycerides(TG),high-density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol(LDL-C),and glucose(Glu)were measured by enzymatic methods.Plasma insulin(INS)was measured by chemiluminescence immunoassay.The protein levels of apoA1 and apoB were measured by the turbidimetric immunoassay.Results Allele frequencies of G and A were 0.718 and 0.282 in the GDM group and 0.713 and 0.287 in the control group,respectively.Distribution of the genotype frequencies was found to be in Hardy-Weinberg equilibrium in both the GDM and control groups.There was no significant difference in the frequencies of alleles G and A and the genotypes of apoA1-75 G/A polymorphism between the GDM and the control group(P>0.05).In the GDM group,the carriers with the genotype AA were associated with significantly higher levels of TC,HDL-C,and apoA1 than those with genotypes GG and GA did(all P<0.05).After the GDM patients were divided into obese and non-obese subgroups,the genotype-related apoA1 variation was observed only in obese patients,while the genotype-related TC and HDL-C variations were evident in non-obese patients(P<0.05).In the control group,carriers of genotypes AA and GA had higher systolic blood pressure(SBP)and HDL-C than the carriers of genotype GG did(all P<0.05).Carriers of genotypes AA had significantly lower Glu levels than carriers of genotypes GG and GA did(P<0.05).The control subjects were further divided into subgroups according to their body mass index(BMI).Analysis of the subgroups showed that AA carriers were associated with higher SBP levels in the obese control women only,while lower Glu levels were evident in both obese and non-obese control women.Conclusion These results suggest that-75 G/A polymorphism in the apoA1 gene is not associated with GDM.However,the genetic variation is closed associated with the plasma apoA1,HDL-C,and TC levels in GDM patients and plasma HDL-C,Glu,and SBP levels in the control subjects.The apoA1 variant-associated lipids and SBP variation is BMI dependent in both groups.

Objective: To understand the current status of diagnosis and treatment of chronic lymphocytic leukemia (CLL) /small lymphocytic lymphoma (SLL) among hematologists, oncologists, and lymphoma physicians from hospitals of different levels in China. Methods: This multicenter questionnaire survey was conducted from March 2021 to July 2021 and included 1,000 eligible physicians. A combination of face-to-face interviews and online questionnaire surveys was used. A standardized questionnaire regarding the composition of patients treated for CLL/SLL, disease diagnosis and prognosis evaluation, concomitant diseases, organ function evaluation, treatment selection, and Bruton tyrosine kinase (BTK) inhibitor was used. Results: ①The interviewed physicians stated that the proportion of male patients treated for CLL/SLL is higher than that of females, and the age is mainly concentrated in 61-70 years old. ②Most of the interviewed physicians conducted tests, such as bone marrow biopsies and immunohistochemistry, for patient diagnosis, in addition to the blood test. ③Only 13.7% of the interviewed physicians fully grasped the initial treatment indications recommended by the existing guidelines. ④In terms of cognition of high-risk prognostic factors, physicians' knowledge of unmutated immunoglobulin heavy-chain variable and 11q- is far inferior to that of TP53 mutation and complex karyotype, which are two high-risk prognostic factors, and only 17.1% of the interviewed physicians fully mastered CLL International Prognostic Index scoring system. ⑤Among the first-line treatment strategy, BTK inhibitors are used for different types of patients, and physicians have formed a certain understanding that BTK inhibitors should be preferentially used in patients with high-risk factors and elderly patients, but the actual use of BTK inhibitors in different types of patients is not high (31.6%-46.0%). ⑥BTK inhibitors at a reduced dose in actual clinical treatment were used by 69.0% of the physicians, and 66.8% of the physicians had interrupted the BTK inhibitor for >12 days in actual clinical treatment. The use of BTK inhibitors is reduced or interrupted mainly because of adverse reactions, such as atrial fibrillation, severe bone marrow suppression, hemorrhage, and pulmonary infection, as well as patients' payment capacity and effective disease progression control. ⑦Some differences were found in the perceptions and behaviors of hematologists and oncologists regarding the prognostic assessment of CLL/SLL, the choice of treatment options, the clinical use of BTK inhibitors, etc. Conclusion: At present, a gap remains between the diagnosis and treatment of CLL/SLL among Chinese physicians compared with the recommendations in the guidelines regarding the diagnostic criteria, treatment indications, prognosis assessment, accompanying disease assessment, treatment strategy selection, and rational BTK inhibitor use, especially the proportion of dose reduction or BTK inhibitor discontinuation due to high adverse events.
Female ; Humans ; Male ; Aged ; Middle Aged ; Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy* ; Prognosis ; Lymphoma, B-Cell ; Immunohistochemistry ; Immunoglobulin Heavy Chains/therapeutic use*