Objective:To investigate the clinical efficacy and safety of ixazomib-containing regimens in the treatment of patients with multiple myeloma(MM).Methods:A retrospective analysis was performed on the clinical efficacy and adverse reactions of 32 MM patients treated with a combined regimen containing ixazomib in the Hematology Department of the First People's Hospital of Lianyungang from January 2020 to February 2022.Among the 32 patients,15 patients were relapsed and refractory multiple myeloma(R/RMM)(R/RMM group),17 patients who responded to bortezomib induction therapy but converted to ixazomib-containing regimen due to adverse events(AE)or other reasons(conversion treatment group).The treatment included IPD regimen(ixazomib+pomalidomide+dexamethasone),IRD regimen(ixazomib+lenalidomide+dexamethasone),ICD regimen(ixazomib+cyclophosphamide+dexamethasone),ID regimen(ixazomib+dexamethasone).Results:Of 15 R/RMM patients,overall response rate(ORR)was 53.3％(8/15),among them,1 achieved complete response(CR),2 achieved very good partial response(VGPR)and 5 achieved partial response(PR).The ORR of the IPD,IRD,ICD and ID regimen group were 100％(3/3),42.9％(3/7),33.3％(1/3),50％(1/2),respectively,there was no statistically significant difference in ORR between four groups(x2=3.375,P=0.452).The ORR of patients was 50％after first-line therapy,42.9％after second line therapy,60％after third line therapy or more,with no statistically significant difference among them(x2=2.164,P=0.730).In conversion treatment group,ORR was 88.2％(15/17),among them,6 patients achieved CR,5 patients achieved VGPR and 4 patients achieved PR.There was no statistically significant difference in ORR between the IPD(100％,3/3),IRD(100％,6/6),ICD(100％,3/3)and ID(60％,3/5)regimen groups(x2=3.737,P=0.184).The median progression-free survival(PFS)time of R/RMM patients was 9 months(95％CI:6.6-11.4 months),the median overall survival(OS)time was 18 months(95％CI:11.8-24.4 months).The median PFS time of conversion treatment group was 15 months(95％CI:7.3-22.7 months),the median OS time not reached.A total of 10 patients suffered grade 3-4 adverse event(AE).The common hematological toxicities were leukocytopenia,anemia,thrombocytopenia.The common non-hematological toxicities were gastrointestinal symptoms(diarrhea,nausea and vomit),peripheral neuropathy,fatigue and infections.Grade 1-2 peripheral neurotoxicity occurred in 7 patients.Conclusion:The ixazomib-based chemotherapy regimens are safe and effective in R/RMM therapy,particularly for conversion patients who are effective for bortezomib therapy.The AE was manageable and safe.

Objective To investigate the inhibitory effects of Wumeiwan on oxidative stress injury of ulcerative colitis mice induced by dextran sulfate sodium(DSS)by regulating Kelch-like ECH related protein 1(Keap-1)-nuclear factor E2 related factor 2(Nrf2)/heme oxygenase-1(HO-1)signaling pathwayand.Methods Forty C57BL/6 mice were randomly divided into five groups:normal group,model group,positive control group,experimental-L,-H groups.UC mice model were induced by free access to 2％DSS water.Mice in normal and model group were orally administered with 0.9％NaCl,mice in positive control group were orally treated with Mesalazine solution(0.005 g·10 g-1·d-1),while mice in experimental groups were orally administered with Wumeiwan decoction at the dose of 0.13 and 0.26 g·10 g-1·d-1,respectively.All the drugs were administered for consecutive 7 days,1 times a day.The levels of disease activity index(DAI)and the colon length were scored.The levels of superoxide dismutase(SOD),catalase(CAT),cyclooxygenase-2(COX-2)and inducible nitric oxide synthase(iNOS)in colon tissue of mice were determined by real-time fluorescence quantitative polymerase chain reaction(qRT-PCR)method.The level of Keap-1,Nrf2,HO-1 proteins in colon tissue were determined by Western blot method.Results The levels of DAI of seventh day in normal group,positive control group,experimental-L,-H groups were 0、(2.62±0.33),(1.87±0.35),(1.87±0.35)and(1.58±0.35);the colon lengths were(8.16±0.47)、(5.98±0.24),(7.58±0.38),(7.33±0.24)and(7.48±0.51)cm;the SOD mRNA were 1.01±0.16、0.40±0.01,1.43±0.45,0.65±0.01 and 0.83±0.02;the CAT mRNA were 1.01±0.20、0.45±0.01,0.84±0.02,0.68±0.07 and 0.87±0.05;the COX-2 mRNA were 1.03±0.33、16.65±0.60,4.78±0.25,14.07±0.60 and 7.39±0.15;the iNOS mRNA were 1.04±0.40、20.71±0.66,8.09±0.93,15.44±0.68 and 11.66±0.06;the levels of Keap-1 were 1.22±0.16、1.10±0.05,1.18±0.05,1.94±0.08 and 1.17±0.08;the levels of Nrf2 were 1.12±0.16、0.76±0.15,0.65±0.13,0.70±0.16 and 0.82±0.18;the levels of HO-1 were 1.34±0.15、1.00±0.12,0.89±0.10,1.50±0.18 and 1.40±0.13,respectively.Significant difference was found between normal group and model group(P＜0.01,P＜0.05);significant difference was also found between the experimental-L,-H groups and model group(P＜0.01,P＜0.05).Conclusion Wumeiwan can inhibit oxidative stress in mice with UC,the mechanisms may be related to adjusted the expression of Keap-1-Nrf2/HO-1 signaling pathway protein in colon.

Objective To explore the current status of H.pylori infection in the natural population of Sanya City,analyze its influencing factors,and provide a reference basis for the prevention and control of H.pylori infection.Methods A total of 677 residents from four districts of Sanya City were selected by overall stratified random sampling method,and were subjected to urea 14C breath test and questionnaire survey to calculate the positive rate of H.pylori in the natural population and analyze the influencing factors of H.pylori infection.Results A total of 606 residents were included,and the number of H.pylori positive detections was 261,with a positive detection rate of 38.5％.Among them,different ethnicity,marital status,smoking,eating vegetables and fruits,and literacy level were associated with H.pylori infection(P＜0.05);gender,age,BMI,alcohol consumption,drinking water source,betel quid chewing,and the number of cohabitants were not significantly associated with H.pylori infection(P＞0.05).Family infection was an independent risk factor for H.pylori infection in the natural population of Sanya City,and Li ethnicity,frequent consumption of fruits and vegetables,and college and higher education level were independent protective factors for H.pylori infection in the natural population of Sanya City.Conclusion The rate of H.pylori infection in the natural population of Sanya City is lower than the national average.Consuming more fruits and vegetables and improving the awareness of hygiene protection are conducive to the prevention of H.pylori infection;and the promotion of the family and related members with the same examination and treatment is important to avoid aggregation of infection within the family.

The hypoxic microenvironment and inflammatory state of residual tumors caused by insufficient radio-frequency ablation(iRFA)are major reasons for rapid tumor progression and pose challenges for immu-notherapy.We retrospectively analyzed the clinical data of patients with hepatocellular carcinoma(HCC)treated with RFA and observed that iRFA was associated with poor survival outcomes and progression-free survival.Using an orthotopic HCC mouse model and a colorectal liver metastasis model,we observed that treatment with melatonin after iRFA reduced tumor growth and metastasis and achieved the best out-comes when combined with anti-programmed death-ligand 1(anti-PD-L1)therapy.In mechanism,melatonin inhibited the expression of epithelial-mesenchymal transitions,hypoxia-inducible factor(HIF)-1 α,and PD-L1 in tumor cells after iRFA.Flow cytometry revealed that melatonin reduced the proportion of myeloid-derived suppressor cells and increased the proportion of CD8+T cells.Transcriptomic analysis revealed an upregulation of immune-activated function-related genes in residual tumors.These findings demonstrated that melatonin can reverse hypoxia and iRFA-induced inflammation,thereby overcoming the immunosuppressive tumor microenvironment(TME)and enhancing the efficacy of immunotherapy.

Objective:We aimed to develop a novel visualized model based on nomogram to predict postoperative overall survival.Methods:This was a multicenter, retrospective, observational cohort study, including participants with histologically confirmed gastric and colorectal cancer who underwent radical surgery from 11 medical centers in China from August 1, 2015 to June 30, 2018. Baseline characteristics, histopathological data and nutritional status, as assessed using Nutrition Risk Screening 2002 (NRS 2002) score and the scored Patient-Generated Subjective Global Assessment, were collected. The least absolute shrinkage and selection operator regression and Cox regression were used to identify variables to be included in the predictive model. Internal and external validations were performed.Results:There were 681 and 127 patients in the training and validation cohorts, respectively. A total of 188 deaths were observed over a median follow-up period of 59 (range: 58 to 60) months. Two independent predictors of NRS 2002 and Tumor-Node-Metastasis (TNM) stage were identified and incorporated into the prediction nomogram model together with the factor of age. The model's concordance index for 1-, 3- and 5-year overall survival was 0.696, 0.724, and 0.738 in the training cohort and 0.801, 0.812, and 0.793 in the validation cohort, respectively.Conclusions:In this study, a new nomogram prediction model based on NRS 2002 score was developed and validated for predicting the overall postoperative survival of patients with gastric colorectal cancer. This model has good differentiation, calibration and clinical practicability in predicting the long-term survival rate of patients with gastrointestinal cancer after radical surgery.

Objective To investigate the effect of injection volume on clinical efficacy after minimally invasive puncture and drainage in the treatment of moderate basal ganglia cerebral hemorrhage underlying controlling the dosage of drugs in the elderly.Methods After successfully inserting the puncture needle into the center point in the largest layer long axis,the liquid hematoma was aspirated,and 40,000 units urokinase was injected into the hematoma cavity twice a day(2 mL in the small volume Group(SG),and 4 mL in the large volume group(LG),respectively).The needle were then adjusted and removed according to the hematoma clearance.The clearance rate of hematoma,intracranial pressure,edema volume,mortality,incidence of complications,neurological deficit score(NDS)and activities of daily living(ADL)were compared and analyzed.Results There were no significant differences in the first hematoma clearance rate,postoperative ICP and mortality between the two groups(P>0.05).Comparing to the SG,there was a relative higher postoperative hematoma clearance rate and lower volume of perihematoma edema in the LG(P<0.05).Meanwhile,the needle retention time,urokinase usage and cumulative complications at 28 days after operation were lower than in the SG(P<0.05).For two parameters representing long-term outcome,the NDS and ADL scores were much better in LG than in SG(P<0.05).Conclusion Large volume injection can effectively drain the hematoma,shorten the needle retention time,reduce the usage of urokinase,decrease the incidence of postoperative complications and improve the prognosis of patients,thereby providing effective and safe method in treating moderate basal ganglia cerebral hemorrhage in the elderly.

Objective:To explore the effect of pentraxin 3 (PTX3) on memory improvement and Aβ expression in Alzheimer's disease (AD) model mice.Methods:(1) Ten 5-month-old 5×FAD mice were randomly divided into PTX3 group and model group ( n=5); 5 C57BL/6 wild-type mice at the same age were selected as control group; mice in the PTX3 group and control group were stereotactically injected 4 μL 0.5 g/L PTX3 or same dose of phosphate buffered saline (PBS); Morris water maze test was used to detect the learning and memory abilities, Y maze test was used to detect the short-term memory, and ELISA was used to obsevre the contents of Aβ 40 and Aβ 42 in the brain hemisphere. (2) Twenty-five 3-month-old 5×FAD mice were randomly divided into model group, 2 μg/kg PTX3 group, 4 μg/kg PTX3 group, 8 μg/kg PTX3 group, and 16 μg/kg PTX3 group ( n=5); 5 C57BL/6 wild-type mice at the same age were selected as control group; mice in the PTX3 groups were intranasally injected 2, 4, 8, and 16 μg/kg PTX3, respectively; those in the model group and control group were intranasally injected same dose of PBS; injection was given once every 96 h for a total of 7 times. Morris water maze test was used to detect the learning and memory abilities, Y maze test was used to detect the short-term memory, and ELISA was used to obsevre the contents of Aβ 40 and Aβ 42 in the hippocampus. Results:(1) Compared with the model group, the PTX3 group had significantly shorter platform latency, higher percentage of exploration time and higher percentage of spontaneous alternations ( P<0.05). Compared with those in model group ([63.38±21.42] pg/mL, [29.77±6.11] pg/mL), the concentrations of Aβ 40 and Aβ 42 in the brain tissues of PTX3 group ([15.87±2.11] pg/mL, [16.55±1.95] pg/mL) were statistically lower ( P<0.05). (2) Compared with the model group, the 16 μg/kg PTX3 group had significantly shorter escape latency and higher percentage of exploration time ( P<0.05); compared with the model group, the 2 μg/kg PTX3 group and 16 μg/kg PTX3 group had significantly higher percentage of spontaneous alternations ( P<0.05). The contents of Aβ 40 and Aβ 42 in the hippocampus of 8 μg/kg PTX3 group and 16 μg/kg PTX3 group were statistically lower compared with those in the model group ( P<0.05). Conclusion:PTX3 may attenuate cognitive deficits and decrease Aβ expression in the brain or hippocampus tissues of 5×FAD mice with AD.

This study explored the growth-promoting effect and mechanism of the endophytic bacterium Kocuria rosea on Rehmannia glutinosa, aiming to provide a scientific basis for the development of green bacterial fertilizer. R. glutinosa 'Jinjiu' was treated with K. rosea, and the shoot parameters including leaf length, leaf width, plant width, and stem diameter were measured every 15 days. After 120 days, the shoots and roots were harvested. The root indicators(root number, root length, root diameter, root fresh weight, root dry weight, root volume, and root vitality) and secondary metabolites(catalpol, rehmannioside A, rehmannioside D, verbascoside, and leonuride) were determined. The R. glutinosa growth-promoting mechanism of K. rosea was discussed from the effect of K. rosea on the nutrient element content in R. glutinosa and rhizosphere soil and the genome information of this plant. After application of K. rosea, the maximum increases in leaf length, leaf width, plant width, and stem diameter were 35.67%(60 d), 25.39%(45 d), 40.17%(60 d), and 113.85%(45 d), respectively. The root number, root length, root diameter, root volume, root fresh weight, root dry weight, and root viability increased by 41.71%, 45.10%, 48.61%, 94.34%, 101.55%, 147.61%, and 42.08%, respectively. In addition, the content of rehmannioside A and verbascoside in the root of R. glutinosa increased by 76.67% and 69.54%, respectively. K. rosea promoted the transformation of nitrogen(N), phosphorus(P), and potassium(K) in the rhizosphere soil into the available state. Compared with that in the control, the content of available N(54.60 mg·kg~(-1)), available P(1.83 μmol·g~(-1)), and available K(83.75 mg·kg~(-1)) in the treatment with K. rosea increased by 138.78%, 44.89%, and 14.34%, respectively. The content of N, P, and K in the treatment group increased by 293.22%, 202.63%, and 23.80% in the roots and by 23.60%, 107.23%, and 134.53% in the leaves of R. glutinosa, respectively. K. rosea carried the genes related to colonization(rbsB, efp, bcsA, and gmhC), N, P, and K metabolism(narG, narH, narI, nasA, nasB, GDH2, pyk, aceB, ackA, CS, ppa, ppk, ppk2, pstS, pstA, pstB, and pstC), and indole-3-acetic acid and zeatin synthesis(iaaH and miaA). Further studies showed that K. rosea could colonize the roots of R. glutinosa and secrete indole-3-acetic acid(3.85 μg·mL~(-1)) and zeatin(0.10 μg·mL~(-1)). In summary, K. rosea promotes the growth of R.ehmannia glutinosa by enhancing the nutrient uptake, which provides a theoretical basis for the development of plant growth-promoting microbial products.
Rehmannia/metabolism* ; Endophytes/metabolism* ; Plant Roots/growth & development* ; Micrococcaceae/genetics* ; Data Mining ; Plant Leaves/metabolism* ; Genomics ; Rhizosphere

The modernization and development of traditional Chinese medicine has led to higher standards for the quality of traditional Chinese medicine products. The extraction process is a crucial component of traditional Chinese medicine production, and it directly impacts the final quality of the product. However, the currently relied upon methods for quality assurance of the extraction process, such as simple wet chemical analysis, have several limitations, including time consumption and labor intensity, and do not offer precise control of the extraction process. As a result, there is significant value in incorporating near-infrared spectroscopy (NIRS) in the production process of traditional Chinese medicine to improve the quality control of the final products. In this study, we focused on the extraction process of Xiao'er Xiaoji Zhike oral liquid (XXZOL), using near-infrared spectra collected by both a Fourier transform near-infrared spectrometer and a portable near-infrared spectrometer. We used the concentration of synephrine, a quality control index component specified by the pharmacopoeia, to achieve rapid and accurate detection in the extraction process. Moreover, we developed a model transfer method to facilitate the transfer of models between the two types of near-infrared spectrometers (analytical grade and portable), thus resolving the low resolution, poor performance, and insufficient prediction accuracy issues of portable instruments. Our findings enable the rapid screening and quality analysis of XXZOL onsite, which is significant for quality monitoring during the traditional Chinese medicine production process.

Objective:To explore the clinical manifestations and genetic characteristics of Wolf-Hirschhorn syndrome (WHS) to improve the ability of diagnosis and differential diagnosis of the disease.Methods:The clinical features and auxiliary examinations and treatment of a proband with WHS caused by microdeletion of 4p16.3 segment who admitted to the Third Affiliated Hospital of Zhengzhou University in December 2021 were recorded, and whole exome sequencing (WES) of the family was performed. The prognosis was followed up.Results:The female proband, 11 months old, presented with convulsions at the age of 8 months, with the characteristics of heat sensitivity and cluster seizures, and her identical twin sister had a similar medical history. Physical examination found malnutrition, retarded development, special face, prominent forehead, wide nasal bridge, small jaw, precordial murmur and grade 3/6 murmur in the whole period, hyperactivity of P2, and low limb muscle tone. The whole exon and copy number variation (CNV) test of the family revealed that the proband had a 1.99 Mb heterozygous deletion in the chromosome 4p16.3 segment, including WHSC1 (NSD2), WHSC2 (NEFLA) and other genes. Copy number variation sequencing (CNV-Seq) of the proband and her sister showed 1.97 and 1.92 Mb heterozygous deletion of chromosome 4p16.3, respectively. Genealogical analysis by quantitative polymerase chain reaction revealed that the CNV was de novo, and it was determined to be a pathogenic variant according to the American College of Medical Genetics and Genomics guidelines. The proband took sodium valproate orally, and her sister took oral sodium valproate, zonisamide, and levetiracetam successively, and at the same time they received family rehabilitation training. The age at the last follow-up was 1 year and 8 months. Neither of them had convulsions again in the past 3 months, but the developmental delay was obvious. Conclusion:WHS patients may present with growth retardation, epilepsy, Greek warrior helmet-like special face, and congenital heart disease, and may have microdeletions in the chromosome 4p16.3 segment.