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.

Humans ; Asthma/drug therapy* ; Biological Therapy

Objective:To systematically evaluate the effect of pars plana vitrectomy (PPV) combined total peeling of internal limiting membrane (ILM) versus fovea-sparing peeling of ILM for myopic foveoschisis.Methods:A evidence-based medicine study. Chinese and English as search terms for myopic foveoschisis, vitrectomy, and peeling of internal limiting membrane were used to search literature in China National Knowledge Infrastructure, Wanfang database, VIP database, PubMed of National Library of Medicine, Medline, Embase, and Cochrane Library. The high myopic macular schisis was selected as the research object, the intervention method was PPV combined with complete ILM peeling and combined with foveal preservation ILM peeling surgery clinical control study between Jan 1, 2010, and Jun 31, 2021. Incomplete or irrelevant literature and review literature were excluded. The method of Newcastle-Ottawa Scale system was used to evaluate the included literature. The literature was meta-analyzed by RevMan5.3 software. The mean difference ( MD) and a confidence interval ( CI) of 95% were used to describe the effect sizes of continuous data, fixed effects model was performed. The data including the best corrected visual acuity (BCVA), central fovea thickness (CFT), and postoperative macular hole (MH) were analyzed. Results:In those databases, 232 articles based search stratery were totally retrieved, and 10 articles (417 eyes) were finally included for meta-analysis with 245 eyes for PPV combined total peeling of ILM and 172 eyes for PPV combined fovea-sparing peeling of ILM. Meta-analysis results showed there was no significant difference in BCVA and CFT between the two groups (BCVA: MD=0.05, 95% CI 0.00-0.11; P>0.05; CFT: MD=-4.79, 95% CI -18.69-9.11, P>0.05). It was compared with the incidence of MH, the difference was statistically significant (odds ratio=5.70, 95% CI 2.22-14.61, P<0.05). Conclusion:BCVA and CFT could be improved by PPV combined total and fovea-sparing peeling of ILM for myopic foveoschisis; compared with complete ILM peeling, the incidence of MH was lower after foveal-sparing ILM peeling.

Objective To investigate and analyze the cause of the abnormal results in the individual dose monitoring conducted by this laboratory from 2014 to 2017. Methods Radiologic workers wear personal thermoluminescent dosimeters to monitor the individual dose equivalent H_P(10). A statistical analysis is conducted on the results above the investigation level. Results During the time when our individual dose monitoring was conducted from 2014 to 2017, this laboratory had detected 69 person-time abnormal results in 40 workplaces, of which 83% occurred in the profession of diagnostic roentgenology. 54% of the dose level range from 1.25 to 5.00 mSv. The main causes of the abnormal results include improper wearing of personal dosimeters (67%), unknown causes (20%), increased workload (10%) and equipment maintenance (3.0%)etc. Conclusion Radiation workplaces should enhance the management of radiologic workers, improve their trainings on radiation protection and raise their protection awareness.

Objective To investigate the influence of Joint Commission International (JCI) accreditation on nursing practice.Methods Totally 30 medical institutions which had passed the JCI accreditation were investigated to compare the scores of nursing practice before and after JCI accreditation.Results Before JCI accreditation,the average standardized score of governance,leadership and management dimension was 81.20,but the scores of other dimensions were below 80.After the JCI accreditation,the quality improvement and patient safety(QPS) dimension scored 81.10,and scores of other dimensions were all above 90.The differences of all dimensions were statistically significant (P＜0.001) before and after the JCI accreditation,the scores were all much greater than those before the accreditation,and improvement of AOP(77.37％)and IPSG(69.86％)was most obvious with statistical significance (P＜0.001).Conclusion JCI accreditation plays a certain role in promoting nursing practice,making nursing process more systematic and comprehensive and the safety of nursing guaranteed.

Objective To observe the evolution of astrocytes,GDNF,BDNF and Jak-STAT signal pathway after spinal cord ischemia-reperfusion injury in rabbits.Methods Spinal cord ischemia was induced by means of balloon occlusion of the infrarenal aorta for 22 minutes in 54 male New Zealand white rabbits.We assigned rabbits to 9 groups (n =6),one sham group,eight operation groups.The operation process in the sham group was the same as the operation group except the ischemia reperfusion of the spinal cord.At 0 h,1 h,2 h,3 h,8 h,24 h,48 h and 72 h after reperfusion,animals were sarcrificed and the spinal cord was removed for histologic,immunohistochemical study and western blotting.Results Normal neurons were decreased with the extension of reperfusion time.Levels of GFAP increased at 3 h and reached a peak at 48 h after reperfusion.GDNF was increased reaching two peaks after injury,the first peak was at 3 h,the second was at 72 h.BDNF level was increased and peaked at 24 h after reperfusion.The expression of p-STAT3 showed a biphasic pattern which peaked at 1h and 48 h.GFAP,GDNF,BDNF were rare and the level of p-STAT3 could be neglected in sham group.Conclusion Spinal cord ischemia-reperfusion injury could induce the activation of astrocytes,the expression of GDNF,BDNF and the activation of JakSTAT signal pathway.They showed different expression rules in this study.

Objective: To observe the activation of microglia and the changing rule of inflammatory cytokine as IL-6, IL-10 and nuclear factor-κB (NF-κB) in experimental rabbits after spinal cord ischemia reperfusion (SCIR) injury in order to provide theoretical basis for post-conditioning time. Methods: Rabbit SCIR injury model was established by thoracic aorta balloon occlusion. 54 New Zealand male adult white rabbits were divided into 9 groups: Sham group (the animals received balloon implantation without occlusion), SCIR-0h group (reperfusion was conducted at 0 hour of spinal cord ischemia), SCIR-1h, -2h, -3h, -8h, -24h,-48h and -72h groups. n=6 in each group. The number of normal and apoptosis neurons, the levels of Iba-1, IL-6, IL-10 and NF-κB in spinal tissue were examined and compared among different groups respectively. Results: The number of normal neuron was decreasing with the extended reperfusion time, TUNEL-positive neuron began to increasing in SCIR-8h group and the peak was reached in SCIR-24h group. The expression of Iba-1 began to elevating in SCIR-2h group and the peak was obtained in SCIR-8h group; NF-κB began to rising in SCIR-3h group and the peak was observed in SCIR-8h group; both IL-6 and IL-10 arrived the peak in SCIR-24h group. The expressions of NF-κB, IL-6 and IL-10 were positively related to Iba-1 level. Conclusion: Microglia activation had dynamic changes in experimental SCIR rabbits and the expression levels of NF-κB, IL-6 and IL-10 were positively to microglia activation; post-conditioning time at front and back to microglia activation may reduce neuron injury.

OBJECTIVETo explore the clinical characteristics and significance of RET proto-oncogene screening in multiple endocrine neoplasia type 2A (MEN2A).

METHODSComprehensive medical history was obtained for 5 members from a 3-generation family from southern China. Clinical investigations have included biochemical testing, imaging, and screening of germline RET proto-oncogene mutations.

RESULTSGenetic screening has revealed a missense mutation at codon 618(TGC>CGC) of exon 10 in 3 patients(p.C618R), which was consistent with their clinical manifestations. For the 3 individuals, the age at diagnosis was 21, 26 and 36 yr, and the maximum diameter of medullary thyroid carcinoma was 22, 25 and 39 cm, respectively. The 36-year-old female patient initially underwent right total thyroidectomy plus right neck lymph node dissection. Four years later, she again underwent left adrenal tumorectomy and left total thyroidectomy plus left neck lymph node dissection. The 21-year-old male patient underwent right total thyroidectomy plus right modified neck dissection. The follow-up was respectively 146 and 26 months following the initial operation. Two patients still presented elevated calcitonin and had bilateral neck lymph node masses and/or left thyroid masses on imaging examination. The 26-year-old female patient, who presented bilateral thyroid masses and elevated calcitonin, has refused thyroidectomy.

CONCLUSIONCombined family survey and RET gene screening can facilitate early diagnosis and surgical treatment to improve the prognosis.

Adult ; Asian Continental Ancestry Group ; genetics ; Base Sequence ; Carcinoma, Neuroendocrine ; Exons ; Female ; Humans ; Male ; Molecular Sequence Data ; Multiple Endocrine Neoplasia Type 2a ; enzymology ; genetics ; Mutation, Missense ; Pedigree ; Proto-Oncogene Proteins c-ret ; genetics ; Thyroid Neoplasms ; enzymology ; genetics ; Young Adult

Objective To explore the clinical significance of integrated screening of RET in a Chinese multiple endocrine neoplasia type 2A(MEN 2A)family and to evaluate the feasibility and effectiveness of prophy-lactic total thyroidectomy to MEN 2A-related medullary thyroid carcinoma ( MTC).Methods Medical history was obtained from 10 family members in a 3-generation south China family .Systemic investigations including bio-chemical tests, imaging examinations and germline RET screening were performed .3 asymptomatic mutation car-riers underwent prophylactic total thyroidectomy .Results RET screening showed a heterozygous missense muta-tion of TGC to CGC at codon 634 on exon 11 in 6 members(p.C634R), which was completely consistent with the clinical manifestations.There were 4 males and 2 females.The initial mean diagnostic age of 33.5 years(ranging from 19 years to 65 years) and the mean maximum diameter of MTC was 2.3 cm(ranging from 0.7 cm to 5.2 cm). Among them 3 members had palpable neck masses (1 case with diarrhea).Right total thyroidectomy +right level Ⅵlymph-node dissection with modified right neck dissection in one case , and bilateral total thyroidectomy +bilat-eral level Ⅵlymph-node dissection in 2 were performed .In other 3 asymptomatic mutation carriers , prophylactic total thyroidectomy +bilateral level Ⅵ lymph-node dissection were also performed .Among them, 1 case of a-symptomatic pheochromocytom ( PHEO) underwent cortical-sparing adrenalectomy before MTC .After the first op-eration, 4 patients still presented a high value of calcitonin , among whom 1 patient( T3N 1bM 0-1) underwent re-operation for 3 times after the initial operation and presented metastasis to bone after 130 months, taking vandet-anib orally up to now;2 patients underwent reoperation at 6 and 7 months after initial operation respectively (T1N 1bM0 and T2N 1bM0), and the other one patient was closely monitored and followed up for 22 months(T2N 1b M0).Moreover, The calcitonin levels dropped to normal in the other 2 asymptomatic cases(T1N0M0) who were followed up for 20 months.Conclusions Pedigree screening can work up an early diagnosis and improve the prognosis of MEN 2A.Integrated screening of RET and pre-operative calcitonin level measurement and prophylac-tic thyroidectomy for asymptomatic RET mutation carriers are reasonable and effective .