OBJECTIVE: To explore the safety and efficacy of high-dose etoposide (VP-16) combined with recombinant human granulocyte colony-stimulating factor (rhG-CSF) as salvage mobilization for peripheral blood stem cells (PBSC) in newly diagnosed multiple myeloma (NDMM) patients. METHODS: From April 2021 to May 2023, eight NDMM patients who had failed to yield sufficient PBSC during initial mobilization with high-dose cyclophosphamide (CTX) combined with rhG-CSF underwent salvage mobilization with 1.2 g/m2 etoposide combined with rhG-CSF 10 μg/(kg·d). The effects and adverse reactions of initial mobilization and salvage mobilization were analyzed. RESULTS: For salvage mobilization and initial mobilization, the numbers of PBSC collections were 16 and 18, respectively. The mean value of total collected CD34⁺ cells were (11.90±5.75)×10⁶/kg and (1.67±0.75)×10⁶/kg (P =0.0010) in salvage mobilization group and initial mobilization group, respectively. The proportion of patients with a total collection of CD34⁺ cell count≥2×10⁶/kg were 100% and 37.5% (P =0.0625), and the proportion of patients with a total collection of CD34⁺ cell count≥5×10⁶/kg were 87.5% and 0% (P =0.0156) in salvage mobilization group and initial mobilization group, respectively. For five patients who underwent high-dose CTX initial mobilization but had a total CD34⁺ cell count < 2×10⁶/kg, successful collection was achieved through salvage mobilization with high-dose VP-16. Salvage mobilization with high-dose VP-16 was scheduled 2-3 weeks after failure of CTX mobilization. Adverse reactions of high-dose VP-16 mobilization did not increase compared to the initial mobilization with high-dose CTX. CONCLUSION As a salvage mobilization regimen, VP-16 1.2 g/m² combined with rhG-CSF is safe and highly effective in NDMM patients who failed to initial mobilization with high-dose CTX combined with rhG-CSF.
Humans ; Multiple Myeloma/therapy* ; Etoposide/therapeutic use* ; Hematopoietic Stem Cell Mobilization/methods* ; Cyclophosphamide/therapeutic use* ; Granulocyte Colony-Stimulating Factor ; Salvage Therapy ; Peripheral Blood Stem Cells ; Male ; Middle Aged ; Female ; Peripheral Blood Stem Cell Transplantation

Objective To explore the effect of rehmanniae radix extract(RRE)on chondrocyte apoptosis in the rabbit model of knee osteoarthritis(KOA)by regulating the miR-485-5p/heat shock protein 90 beta family member 1(Hsp90b1)axis.Methods New Zealand rabbits were randomly assigned into control,KOA,low-dose RRE,medium-dose RRE,high-dose RRE,celecoxib,high-dose RRE+antagonist control,and high-dose RRE+miR-485-5p antagonist groups,with 12 rabbits in each group.Rabbits in other groups except the control group were modeled for KOA with the improved Hulth method.After modeling for 8 weeks,the rabbits were administrated with corresponding agents for 4 weeks.The changes in the activity rating of rabbits were recorded.ELISA was employed to measure the levels of tumor necrosis factor-α(TNF-α)and interleukin(IL)-6 in the serum.Safranine O-fast green staining was conducted to reveal the pathological changes in the cartilage tissue and Mankin scoring was performed.TUNEL was employed to detect chondrocyte apoptosis.Real-time fluorescence quantitative PCR was performed to determine the expression of miR-485-5p in the cartilage tissue.Western blot was employed to determine the protein levels of Hsp90b1,cleaved cysteinyl aspartate-specific proteinase-3(Caspase-3),and Bcl2-associated-X(Bax)in the cartilage tissue.The dual-luciferase reporter assay was employed to examine the relationship between miR-485-5p and Hsp90b1.Results Compared with the control group,the KOA group showed down-regulated expression of miR-485-5p,elevated levels of TNF-α and IL-6 in the serum,cartilage erosion and losses,and increases in activity rating,Mankin score,chondrocyte apoptosis rate,and protein levels of Hsp90b1,cleaved Caspase-3,and Bax(all P<0.001).Compared with the KOA group,RRE at low,medium,and high doses,and celecoxib up-regulated the expression of miR-485-5p,lowered the levels of TNF-α and IL-6 in the serum,alleviated the pathological damage to the cartilage tissue,and decreased the activity rating,Mankin score,chondrocyte apoptosis rate,and protein levels of Hsp90b1,cleaved Caspase-3,and Bax(all P<0.05).Compared with the high-dose RRE group and the high-dose RRE+antagonist control group,high-dose RRE+miR-485-5p antagonist down-regulated the expression of miR-485-5p,elevated the levels of TNF-α and IL-6 in the serum,exacerbated the pathological damage to the cartilage tissue,and increased the activity rating,Mankin score,chondrocyte apoptosis rate,and protein levels of Hsp90b1,cleaved Caspase-3,and Bax(all P<0.05).The results indicated that there was a targeted regulatory relationship between miR-485-5p and Hsp90b1.Conclusion RRE may inhibit the expression of Hsp90b1 by up-regulating miR-485-5p,thereby inhibiting chondrocyte apoptosis in the rabbit model of KOA.
Animals ; Rabbits ; Apoptosis/drug effects* ; Chondrocytes/pathology* ; Osteoarthritis, Knee/drug therapy* ; MicroRNAs/metabolism* ; Rehmannia/chemistry* ; Disease Models, Animal ; Tumor Necrosis Factor-alpha/blood* ; Plant Extracts/pharmacology* ; Interleukin-6/blood* ; HSP90 Heat-Shock Proteins/metabolism* ; Male ; Drugs, Chinese Herbal/pharmacology*

Objective To investigate the effects of parecoxib sodium injection combined with dexmedetomidine hydrochloride injection on postoperative cognitive function and stress response in patients with osteoporotic compression fractures.Methods The patients with osteoporotic compression fractures were divided into treatment group and control group according to the treatment plan.The control group was given intravenous injection of dexmedetomidine hydrochloride injection 0.2 μg·kg-1load dose,then micro pump injection 0.2 μg·kg-1·min-1 maintenance dose,until 30 min before the end of the operation;patients in the treatment group were intravenously injected with parecoxib sodium injection 20 mg before local anesthesia and 30 min before the end of operation on the basis of the control group.The pain,sedation,hemodynamics[mean arterial pressure(MAP),heart rate(HR)],cognitive function and safety evaluation were compared between the two groups before operation(T0),2 h after operation(T1),6 h after operation(T2),12 h after operation(T3)and 24 h after operation(T4).Results There were 39 cases in the treatment group and 41 cases in the control group.Visual analogue scale(VAS)scores in treatment group and control group were(3.09±0.55)and(3.41±0.62)scores at T1;VAS scores were(3.02±0.57)and(3.35±0.48)scores at T2;VAS scores were(2.64±0.44)and(2.90±0.46)scores at T3;VAS scores were(2.02±0.41)and(2.35±0.47)scores at T4;MMSE scores were(25.28±1.57)and(24.33±1.42)scores at T2;MMSE scores were(28.16±1.01)and(27.25±0.89)scores at T4;MoCA scores were(24.63±1.60)and(23.59±1.25)scores at T2;MoCA scores were(27.20±0.97)and(26.48±0.83)scores at T4.There were statistically significant differences in the above indexes between the treatment group and the control group(all P＜0.05).Adverse drug reactions in the treatment group included bradycardia,hypotension,nausea vomiting and hypokalemia;adverse drug reactions in the control group included bradycardia,hypotension and nausea vomiting.The total incidence rates of adverse drug reactions were 12.82％and 9.76％,without statistically significant difference(P＞0.05).Conclusion Compared with using dexmedetomidine alone,parecoxib sodium combined with dexmedetomidine is beneficial for relieving postoperative pain in patients with osteoporotic compression fractures,improving postoperative cognitive function.

To investigate the intervention effect and mechanism of Zhenwu Decoction on diabetic nephropathy(DN) mice of spleen-kidney Yang deficiency syndrome based on the Rho-associated coiled-coil kinase(ROCK)/IκB kinase(IKK)/nuclear factor-κB(NF-κB) pathway. Ninety-five 7-week-old db/db male mice and 25 7-week-old db/m male mice were fed adaptively for one week. The DN model of spleen-kidney Yang deficiency syndrome was induced by Dahuang Decoction combined with hydrocortisone by gavage, and then the model was evaluated. After modeling, they were randomly divided into a model group, high-dose, medium-dose, and low-dose Zhenwu Decoction groups(33.8, 16.9, and 8.45 g·kg~(-1)·d~(-1)), and an irbesartan group(25 mg·kg~(-1)·d~(-1)), with at least 15 animals in each group. The intervention lasted for eight weeks. After the intervention, body weight and food intake were measured. Serum crea-tinine(Scr), blood urea nitrogen(BUN), fasting blood glucose(FBG), urinary albumin(uALb), and urine creatinine(Ucr) were determined. The uALb/Ucr ratio(ACR) and 24 h urinary protein(UTP) were calculated. Renal pathological morphology was evaluated by HE staining and Masson staining. The levels of key molecular proteins in the ROCK/IKK/NF-κB pathway were detected by Western blot. Enzyme-linked immunosorbent assay(ELISA) was used to detect interleukin-1β(IL-1β), interleukin-6(IL-6), interleukin-8(IL-8), interleukin-10(IL-10), and tumor necrosis factor-α(TNF-α). Compared with the blank group, the model group showed increased content of BUN, uALb, and SCr, increased values of 24 h UTP and ACR, decreased content of Ucr(P<0.05), enlarged glomeruli, thickened basement membrane, mesangial matrix proliferation, inflammatory cell infiltration, and collagen fiber deposition. The protein expression of ROCK1, ROCK2, IKK, NF-κB, phosphorylated IKK(p-IKK), phosphorylated NF-κB(p-NF-κB), and phosphorylated inhibitor of NF-κB(p-IκB) increased(P<0.05), while the protein expression of inhibitor of NF-κB(IκB) decreased(P<0.05). The levels of inflammatory factors IL-1β, IL-6, IL-8, and TNF-α increased(P<0.05), while the level of IL-10 decreased(P<0.05). Compared with the model group, the groups with drug treatment showed decreased levels of BUN, uALb, SCr, 24 h UTP, and ACR, increased level of Ucr(P<0.05), and improved renal pathological status to varying degrees. The high-and medium-dose Zhenwu Decoction groups and the irbesartan group showed reduced protein expression of ROCK1, ROCK2, IKK, NF-κB, p-IKK, p-NF-κB, and p-IκB in the kidneys(P<0.05), increased protein expression of IκB(P<0.05), decreased levels of serum inflammatory factors IL-1β, IL-6, IL-8, and TNF-α(P<0.05), and increased level of IL-10(P<0.05). Zhenwu Decoction can significantly improve renal function and renal pathological damage in DN mice of spleen-kidney Yang deficiency syndrome, and its specific mechanism may be related to the inhibition of inflammatory response by down-regulating the expression of key molecules in the ROCK/IKK/NF-κB pathway in the kidney.
Mice ; Male ; Animals ; NF-kappa B/metabolism* ; Interleukin-8 ; Interleukin-10 ; Tumor Necrosis Factor-alpha/metabolism* ; Interleukin-6 ; I-kappa B Kinase ; Spleen ; Irbesartan ; Uridine Triphosphate ; Yang Deficiency/drug therapy* ; Kidney/pathology*

The emergence of regular short repetitive palindromic sequence clusters (CRISPR) and CRISPR- associated proteins 9 (Cas9) gene editing technology has greatly promoted the wide application of genetically modified pigs. Efficient single guide RNA (sgRNA) is the key to the success of gene editing using CRISPR/Cas9 technology. For large animals with a long reproductive cycle, such as pigs, it is necessary to screen out efficient sgRNA
Animals ; CRISPR-Cas Systems/genetics* ; Clustered Regularly Interspaced Short Palindromic Repeats/genetics* ; Gene Editing ; RNA, Guide/genetics* ; Swine

Objective:To study the soil physical and chemical properties， microorganisms， and metabolites in different culture environments of Gastrodia elata， so as to provide scientific basis for subsequent cultivation of G. elata in multiple environments. Method:The tubersphere soil of G. elata cultured in different environments was collected for analyzing the soil nutrients， microbial numbers， and metabolite differences using the agrochemical method， plate-count method， and gas chromatography-time-of-flight mass spectrometry （GC-TOF-MS）-based non-targeted metabonomic approach. Result:The analysis of soil physical and chemical properties revealed the highest soil moisture， pH， available potassium， and available phosphorus in the spinney and the highest electrical conductivity， total nitrogen， alkali-hydrolyzable nitrogen， and organic matter in the pinewood. As demonstrated by the quantitative analysis of soil microorganisms， the cultivable microorganisms were bacteria， actinomycetes， and fungi， with the bacterial population and total microbial biomass in the spinney and the number of fungi and actinomycetes in the barren slope detected to be the largest. The ratio of bacteria to fungi （B/F value） in the pinewood was the highest， while that in the barren slope was the lowest. The results of metabonomic research demonstrated that the compositions and quantities of soil metabolites in the spinney （Z group）， pinewood （S group）， and barren slope （HD group） varied. Through comparisons between S and Z groups， between HD and Z groups， as well as between HD and S groups by orthogonal partial least squares discriminant analysis （OPLS-DA）， 18， 35， and 24 differential metabolites were separately screened out， and the Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis yielded 5， 9， and 13 metabolic pathways. There existed a significant causal relationship of the soil physical and chemical properties and microbial numbers with the metabolites. Conclusion:The soil physical and chemical properties， microbial numbers， and metabolite changes differed significantly in different culture environments of G. elata， which were sorted by the suitability in a descending order as follows： spinney > pinewood >barren slope. The soil physical and chemical properties and microbial numbers are the crucial factors driving changes in soil metabolites， suggesting that regulating the soil physical and chemical characteristics and microbial characteristics in the culture environment is an important mechanism for maintaining the G. elata-soil-microbial symbiotic system.

Seabuckthorn contains flavonoids, tannins, terpenoids, polysaccharides, and vitamins, which have anti-inflammation,anti-oxidation, liver protection, anti-cardiovascular disease, anti-aging, immune enhancing, anti-tumor, and anti-bacterial activities.We reviewed the papers focusing on the chemical constituents, pharmacological activities, and utilization of seabuckthorn. The quality markers(Q-markers) of seabuckthorn were predicted and analyzed based on original plant phylogeny, chemical composition correlation, traditional medicinal properties, pharmacodynamic correlation, traditional and extended efficacy, pharmacokinetics, metabolic processes, and measurable components. With this review, we aim to provide theoretical reference for the quality control and quality standard establishment of seabuckthorn, so as to promote the rational exploitation and utilization of seabuckthorn resources, and improve the healthy and sustainable development of seabuckthorn industry.
Anti-Inflammatory Agents ; Biomarkers ; Drugs, Chinese Herbal ; Flavonoids ; Hippophae

COVID-19 ; Humans ; RNA, Viral ; Risk Factors ; SARS-CoV-2

Objective: Endoscopic submucosal dissection (ESD) of undifferentiated early gastric cancer (UD-EGC) remains controversial due to high positive rate of horizontal and vertical resection margins and the risk of lymph node metastasis. The purpose of this study was to compare long-term outcomes of patients with UD-EGC undergoing ESD versus surgery. Methods: This study was a retrospective cohort study. Inclusion criteria: (1) patients with early gastric cancer undergoing ESD or surgical resection; (2) histological types included poorly differentiated adenocarcinoma, poorly differentiated adenocarcima with signet ring cell carcinoma, and signet ring cell carcinoma; (3) no lymph node metastasis or distant metastasis was confirmed by preoperative CT and endoscopic ultrasonography. Exclusion criteria: (1) previous surgical treatment for gastric cancer; (2) synchronous tumors; (3) death with unknown cause; (4) additional surgical treatment was performed within 1 month after ESD. According to the above criteria, clinical data of patients with UD-EGC who received ESD or surgery treatment in Cancer Hospital of Chinese Academy of Medical Sciences from January 2009 to December 2016 were collected. After further comparing the clinical outcomes between the two groups by 1:1 propensity score matching, 61 patients in the ESD group and 61 patients in the surgery group were finally included in this study. The disease-free and overall survivals were analyzed by Kaplan-Meier method. Results: All patients in the two groups completed operations successfully. In the ESD group, the median operation time was 46.3 (26.5, 102.3) minutes, 61 cases (100%) were en-bloc resection, and 57 cases (93.4%) were complete resection. Positive margin was found in 4 (6.6%) patients, of whom 2 were positive in horizontal margin and 2 were positive both in horizontal and vertical margins. In the surgery group, only 1 case had positive horizontal margin and no positive vertical margin was observed. There was no significant difference in the positive rate of margin between the two groups (P>0.05). Median follow-up time was 59.8 (3.0, 131.5) months. The follow-up rate of ESD group and surgery group was 82.0% (50/61) and 95.1% (58/61), respectively. The 5-year disease-free survival rate in ESD group and surgery group was 98.2% and 96.7%, respectively (P=0.641), and the 5-year overall survival rate was 98.2% and 96.6%, respectively (P=0.680). In the ESD group, 1 patient (1.6%) had lymph node recurrence, without local recurrence or distant metastasis. In the surgery group, 1 case (1.6%) had anastomotic recurrence and 1 (1.6%) had distant metastasis. Conclusion: ESD has a sinilar long-term efficacy to surgery in the treatment of UD-EGC.
Endoscopic Mucosal Resection ; Gastric Mucosa ; Humans ; Neoplasm Recurrence, Local ; Retrospective Studies ; Stomach Neoplasms/surgery* ; Treatment Outcome

OBJECTIVE: To explore the epidemiologic characteristics of acupuncturists who are sensitive to stimulation of moxa smoke, which could provide further direction for safety protection of exerting moxibustion and to further verify the feasibility of internet survey. METHODS: A self-made questionnaire regarding body response to moxa smoke was established, which was used to conduct a face-to-face survey among acupuncturists who had performed long-term moxibustion. The Logistic regression model was used to analyze the factors affecting the stimulation response of acupuncturists and the epidemiological characteristics of acupuncturists was obtained. RESULTS: A total of 733 valid data was obtained. The multivariate Logistic regression analysis showed that the history of chronic respiratory disease was the main risk factor of stimulus response including cough, phlegm in the throat, asthma, dyspnea, shortness of breath and nasal dryness after exposure to moxa smoke (<0.05, <0.01). The risk of stimulus response such as cough, tearing and nasal dryness was higher in women than in men (<0.05, <0.01). The risk of dry eyes and eyes pain in smokers was higher than those in non-smokers (<0.05). The risk of shortness of breath in those who were exposed to second-hand smoke was higher than those who were not exposed to second-hand smoke (<0.05). The analysis of index trend line showed that the results of internet survey were similar to those of face-to-face survey. CONCLUSION The stimulus response of acupuncturist after long-term exposure to moxa smoke is related to the history of chronic respiratory disease, being female, smoking or exposure of second-hand smoke, therefore more attention should be paid to those populations. In addition, the internet survey can be used for the epidemiological investigation of safety of moxa smoke.
Cough ; Female ; Humans ; Male ; Moxibustion ; Mucus ; Smoke ; Surveys and Questionnaires