Objective:To evaluate the role of the AMP-activated protein kinase (AMPK)-silent information regulator 1 (SIRT1)-nuclear factor-κB (NF-κB) signaling pathway in reduction of brain injury by panax notoginseng saponins (PNS) in mechanically ventilated rats.Methods:Seventy-two SPF-grade male Sprague-Dawley rats, aged 10 weeks, weighing 357-377 g, were divided into 6 groups ( n=12 each) by a random number table method: sham operation group, model group, PNS low dose group, PNS medium dose group, PNS high dose group, and PNS high dose+ compound C group. PNS 12.5, 25 and 50 mg/kg were intraperitoneally injected in PNS low dose group, PNS medium dose group and PNS high dose group, respectively. In PNS high dose+ compound C group, PNS 50 mg/kg was intraperitoneally injected, and 10 min later compound C 0.2 mg/kg was injected via the tail vein. Normal saline 10 ml/kg was intraperitoneally injected in sham operation group and model group. Drugs or normal saline was injected at 30 min before mechanical ventilation in each group. Mechanical ventilation model: The animals were mechanically ventilated for 6 h, with ventilation frequency 40 times/min, tidal volume 40 ml/kg in model group; The animals were mechanically ventilated for 6 h, with tidal volume 10 ml/kg in sham operation group. Morris water maze test was used to detect the learning and memory function of rats, the concentrations of serum interleukin-1beta (IL-1β), IL-6, tumor necrosis factor-alpha (TNF-α) and dopamine (DA) were detected by enzyme-linked immunosorbent assay, the neuronal counts in the hippocampal CA1 region were determined by Nissl staining, and the expression of P2Y1 purine receptor (P2Y1R), dysbindin-1 and AMPK in hippocampal CA1 region was detected by Western blot. The phosphorylated SIRT1 (p-SIRT1) to SIRT1 ratio and phosphorylated NF-κB p65 (p-NF-κB p65) to NF-κB ratio in hippocampal CA1 region was calculated. Results:Compared with sham operation group, the escape latency was significantly prolonged, the number of crossing the original platform quadrant was reduced, the time of staying at the target platform quadrant was shortened, the serum concentrations of IL-1β, IL-6 and TNF-α were increased, the serum DA concentration was decreased, the nerve count in hippocampal CA1 region was decreased, the expression of P2Y1R and dysbindin-1 was up-regulated, the expression of AMPK was down-regulated, the p-SIRT1/SIRT1 ratio was decreased, and the p-NF-κB p65/NF-κB p65 ratio was increased in model group ( P<0.05). Compared with model group, the escape latency was significantly shortened, the number of crossing the original platform quadrant was increased, the time of staying at the target platform quadrant was prolonged, the serum concentrations of IL-1β, IL-6 and TNF-α were decreased, the serum DA concentration was increased, the nerve count in hippocampal CA1 region was increased, the expression of P2Y1R and dysbindin-1 was down-regulated, the expression of AMPK was up-regulated, the p-SIRT1/SIRT1 ratio was increased, and the p-NF-κB p65/NF-κB p65 ratio was decreased in PNS low dose group, PNS medium dose group and PNS high dose group ( P<0.05). Compared with PNS high dose group, the escape latency was significantly prolonged, the number of crossing the original platform quadrant was reduced, the time of staying at the target platform quadrant was shortened, the serum concentrations of IL-1β, IL-6 and TNF-α were increased, the serum DA concentration was decreased, the nerve count in hippocampal CA1 region was decreased, the expression of P2Y1R and dysbindin-1 was up-regulated, the expression of AMPK was down-regulated, the p-SIRT1/SIRT1 ratio was decreased, and the p-NF-κB p65/NF-κB p65 ratio was increased in PNS high dose+ compound C group ( P<0.05). Conclusions:The mechanism by which PNS reduces brain injury may be related to activation of the AMPK-SIRT1-NF-κB signaling pathway in mechanically ventilated rats.

Objective:To evaluate the efficacy and safety of mitoxantrone hydrochloride liposome injection in the treatment of peripheral T-cell lymphoma (PTCL) in a real-world setting.Methods:This was a real-world ambispective cohort study (MOMENT study) (Chinese clinical trial registry number: ChiCTR2200062067). Clinical data were collected from 198 patients who received mitoxantrone hydrochloride liposome injection as monotherapy or combination therapy at 37 hospitals from January 2022 to January 2023, including 166 patients in the retrospective cohort and 32 patients in the prospective cohort; 10 patients in the treatment-na?ve group and 188 patients in the relapsed/refractory group. Clinical characteristics, efficacy and adverse events were summarized, and the overall survival (OS) and progression-free survival (PFS) were analyzed.Results:All 198 patients were treated with mitoxantrone hydrochloride liposome injection for a median of 3 cycles (range 1-7 cycles); 28 cases were treated with mitoxantrone hydrochloride liposome injection as monotherapy, and 170 cases were treated with the combination regimen. Among 188 relapsed/refractory patients, 45 cases (23.9%) were in complete remission (CR), 82 cases (43.6%) were in partial remission (PR), and 28 cases (14.9%) were in disease stabilization (SD), and 33 cases (17.6%) were in disease progression (PD), with an objective remission rate (ORR) of 67.6% (127/188). Among 10 treatment-na?ve patients, 4 cases (40.0%) were in CR, 5 cases (50.0%) were in PR, and 1 case (10.0%) was in PD, with an ORR of 90.0% (9/10). The median follow-up time was 2.9 months (95% CI 2.4-3.7 months), and the median PFS and OS of patients in relapsed/refractory and treatment-na?ve groups were not reached. In relapsed/refractory patients, the difference in ORR between patients with different number of treatment lines of mitoxantrone hydrochloride liposome injection [ORR of the second-line, the third-line and ≥the forth-line treatment was 74.4% (67/90), 73.9% (34/46) and 50.0% (26/52)] was statistically significant ( P = 0.008). Of the 198 PTCL patients, 182 cases (91.9%) experienced at least 1 time of treatment-related adverse events, and the incidence rate of ≥grade 3 adverse events was 66.7% (132/198), which was mainly characterized by hematologic adverse events. The ≥ grade 3 hematologic adverse events mainly included decreased lymphocyte count, decreased neutrophil count, decreased white blood cell count, and anemia; non-hematologic adverse events were mostly grade 1-2, mainly including pigmentation disorders and upper respiratory tract infection. Conclusions:The use of mitoxantrone hydrochloride liposome injection-containing regimen in the treatment of PTCL has definite efficacy and is well tolerated, and it is a new therapeutic option for PTCL patients.

OBJECTIVE New inhaled formulations that act on the nose, mouth, respiratory tract, and whole body have received increasing attention. Meanwhile, the research and declaration of inhaled drugs have become hot spots amid infectious respiratory pandemic diseases worldwide. Due to the special anatomic structure of the nose, folds, grooves, and special structures may cause the specific uptake and deposition of inhaled substances. There are various epithelial tissues, glands, muscles, and cartilages in the vestibule, respiratory, and olfactory parts of the nose. Inhaled substances can generate irritating and toxic effects on various parts. The pathological diagnosis results from the preclinical safety evaluation of inhaled drugs are considered the gold standard for judging drug toxicology. The nose is composed of many bone components, and decalcification is required for the sectioning of hard bone tissues. Therefore, an efficient and high-quality decalcification method is the crucial pathological technique for evaluating inhaled drugs. METHODS In this study, 10% ethylenediamine tetraacetic acid(EDTA), 10% formic acid, and 5% nitric acid decalcification solutions were selected. Besides, the decalcification time and effect of these decalcification solutions for rat nasal tissues were compared and analyzed under static room temperature and microwave conditions. Moreover, the quality of pathological bone tissue sections prepared through different decalcification methods was comprehensively evaluated. RESULTS Compared with the decalcification method under normal temperature, the decalcification time under the treatment of KOS decreased significantly. The treatment with the EDTA decalcification solution had the longest decalcification time under normal temperature, while the treatment with the nitric acid decalcification solution had the shortest decalcification time under microwaves. During section evaluation, the EDTA decalcification solution had a higher quality score under normal temperature and microwaves, which indicated that the section quality was favorable. The nitric acid decalcification solution had a lower section quality score under microwaves, which indicated that the section quality was unfavorable. There was medium section quality for the formic acid decalcification solution under microwaves and normal temperature and for the nitric acid decalcification solution under normal temperature. The HE staining results suggested that there were incomplete nasal mucosa epithelia, fragmentation, and pink nasal bone tissues in the tissue sections treated by the nitric acid decalcification solution, presenting a peracid state. In the tissue sections treated by the formic acid decalcification solution and the EDTA decalcification solution, the nucleus of epithelial cells was blue-purple, the cytoplasm and interstitial components were pink, and the epithelial tissue structure of nasal mucosa was intact. The MASSON staining results suggested that in the tissue sections treated by the nitric acid decalcification solution, the whole section staining was red, the positive area was not obvious, and the epithelial cell differentiation was not prominent, with a fuzzy structure. In the tissue sections treated by the formic acid decalcification solution, the sections were slightly detached during staining, and slight cracks were observed in submucosa tissues. In the tissue sections treated by the EDTA decalcification solution, the structure of positive regions and epithelial mucosa regions was clear, and the nuclear and interstitial components were clearly distinguished. The immunohistochemical staining (Ki67) results suggested that in the tissue sections treated by the nitric acid decalcification solution, the staining of positive regions was uneven, and there were nonspecific negative reactions in some regions. In addition, local epithelial cells were unstained. In the tissue sections treated by the formic acid decalcification solution, the local regions were not clearly stained, and nonspecific negative and positive reactions appeared in some local regions. In the tissue sections treated by the EDTA decalcification solution, the positive regions were prominent, the boundaries between negative regions and positive ones were clear, and each region of the sections was stained evenly. CONCLUSION Among the three decalcification solutions in this study, the nitric acid decalcification solution had the shortest decalcification time while the poor section and staining quality. The decalcification time of nasal tissues through the EDTA decalcification solution combined with microwaves was significantly shorter than that through the EDTA decalcification solution at normal temperature. Furthermore, this decalcification method achieved favorable section and staining quality.

Objective:To develop a risk prediction model for the recurrence of diabetic foot ulcer (DFU) in diabetic patients and primarily validate its predictive value.Methods:Meta-analysis combined with retrospective cohort study was conducted. The Chinese and English papers on risk factors related to DFU recurrence publicly published in China Biology Medicine disc, China National Knowledge Infrastructure, Wanfang Database, VIP Database, and PubMed, Embase, Cochrane Library, and Web of Science, and the search time was from the establishment date of each database until March 31 st, 2022. The papers were screened and evaluated, the data were extracted, a meta-analysis was performed using RevMan 5.4.1 statistical software to screen risk factors for DFU recurrence, and Egger's linear regression was used to assess the publication bias of the study results. Risk factors for DFU recurrence mentioned in ≥3 studies and with statistically significant differences in the meta-analysis were selected as the independent variables to develop a logistic regression model for risk prediction of DFU recurrence. The medical records of 101 patients with DFU who met the inclusion criteria and were admitted to Affiliated Hospital of Guizhou Medical University from January 2019 to June 2022 were collected. There were 69 males and 32 females, aged (63±14) years. The receiver operating characteristic (ROC) curve of the predictive performance of the above constructed predictive model for DFU recurrence was drawn, and the area under the ROC curve, maximum Youden index, and sensitivity and specificity at the point were calculated. Dataset including data of 8 risk factors for DFU recurrence and the DFU recurrence rates of 10 000 cases was simulated using RStudio software and a scatter plot was drawn to determine two probabilities for risk division of DFU recurrence. Using the β coefficients corresponding to 8 DFU recurrence risk factors ×10 and taking the integer as the score of coefficient weight of each risk factor, the total score was obtained by summing up, and the cutoff scores for risk level division were calculated based on the total score × two probabilities for risk division of DFU recurrence. Results:Finally, 20 papers were included, including 3 case-control studies and 17 cohort studies, with a total of 4 238 cases and DFU recurrence rate of 22.7% to 71.2%. Meta-analysis showed that glycosylated hemoglobin >7.5% and with plantar ulcer, diabetic peripheral neuropathy, diabetic peripheral vascular disease, smoking, osteomyelitis, history of amputation/toe amputation, and multidrug-resistant bacterial infection were risk factors for the recurrence of DFU (with odds ratios of 3.27, 3.66, 4.05, 3.94, 1.98, 7.17, 11.96, 3.61, 95% confidence intervals of 2.79-3.84, 2.06-6.50, 2.50-6.58, 2.65-5.84, 1.65-2.38, 2.29-22.47, 4.60-31.14, 3.13-4.17, respectively, P<0.05). There were no statistically significant differences in publication biases of diabetic peripheral neuropathy, diabetic peripheral vascular disease, glycosylated hemoglobin >7.5%, plantar ulcer, smoking, multidrug-resistant bacterial infection, or osteomyelitis ( P>0.05), but there was a statistically significant difference in the publication bias of amputation/toe amputation ( t=-30.39, P<0.05). The area under the ROC curve of the predictive model was 0.81 (with 95% confidence interval of 0.71-0.91) and the maximum Youden index was 0.59, at which the sensitivity was 72% and the specificity was 86%. Ultimately, 29.0% and 44.8% were identified respectively as the cutoff for dividing the probability of low risk and medium risk, and medium risk and high risk for DFU recurrence, while the corresponding total scores of low, medium, and high risks of DFU recurrence were <37, 37-57, and 58-118, respectively. Conclusions:Eight risk factors for DFU recurrence are screened through meta-analysis and the risk prediction model for DFU recurrence is developed, which has moderate predictive accuracy and can provide guidance for healthcare workers to take interventions for patient with DFU recurrence risk.

Objective:To investigate the clinical characteristics and prognosis of patients with RUNX1-RUNX1T1 fusion gene-positive acute myeloid leukemia (AML) with ASXL2 gene mutation.Methods:The clinical data of 145 newly diagnosed RUNX1-RUNX1T1 fusion gene-positive AML patients treated at the Second Hospital Center of Shanxi Medical University from October 2010 to March 2021 were retrospectively analyzed. Sanger sequencing was used to detect the gene mutation. According to the presence or absence of ASXL2 gene mutation, the patients were divided into mutation group and non-mutation group. The clinical characteristics, gene mutations and prognosis were compared among the two groups.Results:Among 145 AML patients with positive RUNX1-RUNX1T1 fusion gene, we identified recurrent mutations of c-kit, ASXL2, N/KRAS, FLT3, ASXL1, TET2, NPM1 and DNMT3A genes, with mutation rates of 40.7% (59/145), 20.7% (30/145), 15.9% (23/145), 12.4% (18/145), 11.7% (17/145), 11.0% (16/145), 5.5% (8/145), and 2.1% (3/145), respectively. A total of 18 mutation sites were detected in 30 patients with ASXL2 gene mutations including 5 point mutations and 13 frameshift mutations, which mainly occured in the exons 12 and 13. Lactate dehydrogenase (LDH) at initial diagnosis of 30 AML patients with ASXL2 mutation was lower than that of those with ASXL2 non-mutation ( Z = 2.34, P = 0.020), while prothrombin time (PT) of AML patients with ASXL2 mutation was longer than that of those with ASXL2 non-mutation ( Z = 1.99, P = 0.047). A total of 21 (21/30, 70%) patients simultaneously had other gene mutations. The incidence of RAS mutations in patients with ASXL2 mutation was higher than that those with ASXL2 non-mutation, and the difference was statistically significant [30.0% (9/30) vs. 12.1% (14/115), χ2 = 4.41, P = 0.036]. There were no statistically significant differences in complete remission rate [86.7% (26/30) vs. 74.8% (86/115)] and recurrence rate [43.3% (13/30) vs.31.3% (36/115)] of patients with ASXL2 mutation and ASXL2 non-mutation ( χ2 = 0.39, P = 0.534; χ2 = 0.54, P = 0.432). The median overall survival (OS) time was 26 months (1-135 months) and 30 months (1-120 months), respectively in patients with ASXL2 mutation and ASXL2 non-mutation; the median disease-free survival (DFS) time was 14 months (0-60 months) and 13 months (0-94 months), respectively in patients with ASXL2 mutation and ASXL2 non-mutation; and the differences in OS and DFS were not statistically significant of both groups ( χ2 = 0.05, P = 0.822; χ2 = 0.34, P = 0.562). Compared with ASXL1 mutant patients, cases with ASXL2 mutation had higher OS and DFS rates, and the differences were statistically significant ( P = 0.003, P = 0.007). The differences in OS and DFS between patients with ASXL2 mutations and those with positive mutations of c-kit, RAS, FLT3, TET2, NPM1, DNMT3A were not statistically significant (all P > 0.05). Conclusions:RUNX1-RUNX1T1 positive AML patients with ASXL2 mutation tend to have low LDH and high PT, and often coexist with RAS mutations, and their prognosis is better than that in patients with ASXL1 positive mutation.

Objective To analyze the epidemiological characteristics and spatiotemporal clustering of scarlet fever in Jinan, from 2014-2019, and to provide a basis for scarlet fever prevention and control. Methods The case data of scarlet fever in Jinan during 2013-2019 were extracted from the Chinese National Notifiable Infectious Disease Reporting System. Descriptive epidemiology and spatiotemporal rearrangement scanning methods were used to analyze the epidemiological characteristics and spatiotemporal distribution of scarlet fever. The RR values of scarlet fever in different towns (streets) were calculated, and the contour map of RR value was drawn. Results A total of 9 715 cases of scarlet fever were reported in Jinan from 2014 to 2019. During this period, the number of cases and the incidence rate showed a gradual increase, with two seasonal peaks in the winter and spring each year. Spatiotemporal clustering analysis detected a total of eight spatiotemporal aggregation areas, and the strongest one was in Licheng and Lixia Districts, from March 2017 to December 2019 (RR=3.45, LLR=577.88, P<0.001). The relative risk maps in each year from 2014 to 2019 were similar, and the areas with the highest risk were located in the central area of Jinan. Conclusion From 2014 to 2019, scarlet fever is highly prevalent in the central area of Jinan, with obvious spatial and temporal clustering. There are clustering areas in the central, southwest and eastern areas of Jinan, and there was a tendency for the disease to spread to Zhangqiu in the east and Pingyin in the southwest.

Non-coding RNA (ncRNA) have enormous regulatory functions and play important roles in a variety of cellular processes including cell growth, differentiation, survival and apoptosis. Influenza A virus (FluA) is an important pathogen of serious threats to human health and livestock industry. The interaction mechanism between FluA and the host is very complicated. FluA infection can lead to differential expression of hundreds of host ncRNA, which has become a research hotspot in life sciences in recent years. This review summarizes the progress in different host-encoded ncRNA involved in regulating FluA infection, not only to study the interaction between viruses and hosts, but also to discover new antiviral strategies.

The design of research protocol and quality control are the key to ensure the quality of clinical trial. A randomized clinical trial regarding the effects of medication combined with acupuncture on live birth rate in polycystic ovary syndrome (PCOS), which was initially designed as a comparative effectiveness research, then added with an acupuncture control group and finally became a factorial analysis, is taken as an example to explain the protocol design and optimization process, demonstrating the high level of methodology design and international recognization. By a series of measurements, such as unified purchase of acupuncture equipment, multiple trainings and assessments for acupuncturists' knowledge and operation standardization, in-site supervision of local center experts, the standard operation of acupuncture could be ensured and the credibility and scientificity of research results could be improved.

Objective To explore the role of defoamer enema combined with bellym assage on the colonic preparation in elderly patients with constipation. Methods One hundred patients were divided into two groups by random number table method, the experimental group and the control group with 50 cases each. Patients in the control group were told to drink polyethyleneglycolelectrolytesolution 3000 ml. Patients in the experimental group were told to drink polyethyleneglycolelectrolytesolution 2000 ml. After medicinepre paration, the patients of experimental group were given defoamer enema. After that, they were undertaken counterclockwise massage for10 mins, then massageing clockwise until defecation. Results 14 patients with oral catharsis drugs failed to give up check, 46 cases of intervention group and 40 cases of control group finally complete intestinal preparation and colonoscopy. Intervention group patients after bowel preparation before the incidence of abdominal distension, abdominal pain were 6.52% (3/46), 8.70%(4/46), lower than the control group 65.00% (26/40), 25.00% (10/40), the difference was statistically significant (χ2= 32.74, 4.17, P< 0.05). Percent of pass was 65.22%(30/46) for intestinal preparation intervention group, significantly higher than the control group 35.00% (14/40), the difference was statistically significant (χ2= 7.82, P< 0.05). Intervention group intestinal cleanliness ratings of Ottawa total score was 4.00 (4.00), which was lower than the control group 7.00 (4.50), the difference was statistically significant (Z= 3.80, P< 0.05). Endoscopic check process, the intervention group arrived at the terminal ileum and mirror back time were 7.00 (3.00) and 9.00 (1.00) min, were less than 9.00(6.50) and 10.50 (3.00) min in the control group, the difference was statistically significant (Z= 2.09, 4.53, P< 0.05). Intervention group of colons polyps detection rate was 67.39% (31/46), higher than that of control group 30.00% (12/40), the difference was statistically significant (χ2 = 11.97, P< 0.05). Conclusions The bowel preparation with defoamer enema will enhance the intestinal tract cleaness and the detection rate of polyps in elderly patients with constipation.