OBJECTIVES: This study aimed to explore the expression of lysosomal-associated membrane protein 5 (LAMP5) and microRNA (miR)-302a-3p in oral squamous cell carcinoma (OSCC) and their functional mechanism on the invasion and metastasis of OSCC. METHODS: The expression of LAMP5 in OSCC and its sensitivity as a prognostic indicator were analyzed on the basis of The Cancer Genome Atlas database. Western blot, quantitative reverse transcription polymerase chain reaction, and cell immunocytochemistry were used to detect the expression of LAMP5 in OSCC tissues and cells. The effect of LAMP5 on the proliferation, migration, and invasion of OSCC cells was evaluated through cell counting kit-8, immunocytochemistry, migration, and invasion assays, respectively. The miRNA targeting prediction websites were used to predict the miR that regulates LAMP5 and verify the targeted regulatory effect of miR-302a-3p on LAMP5. The effect of LAMP5 knockdown on OSCC tumor growth was evaluated in a nude mouse tumorigenesis model. RESULTS: LAMP5 was highly expressed in OSCC tissues and cells. It showed high sensitivity in the early diagnosis of OSCC. LAMP5 knockdown significantly inhibited the proliferation, migration, and invasion of OSCC cells, whereas LAMP5 overexpression increased these cell activities. The expression of LAMP5 was regulated by miR-302a-3p. In vivo, LAMP5 knockdown significantly inhibited the growth of OSCC tumor. CONCLUSIONS LAMP5 promotes the malignant progression of OSCC by enhancing the proliferation, migration, and invasion of OSCC cells. The expression of LAMP5 is negatively regulated by miR-302a-3p.
MicroRNAs/metabolism* ; Mouth Neoplasms/metabolism* ; Humans ; Animals ; Carcinoma, Squamous Cell/genetics* ; Neoplasm Invasiveness ; Cell Proliferation ; Mice, Nude ; Cell Movement ; Lysosomal Membrane Proteins/genetics* ; Mice ; Cell Line, Tumor ; Neoplasm Metastasis

Objective:To analyze the clinical characteristics and prognosis of patients with myelodysplastic syndrome (MDS) with a bone marrow nucleated erythroid cell proportion of greater than or equal to 50% (MDS-E) .Methods:The clinical characteristics and prognostic factors of patients with MDS-E were retrospectively analyzed by collecting the case data of 1 436 newly treated patients with MDS diagnosed in the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences from May 2014 to June 2023.Results:A total of 1 436 newly diagnosed patients with complete data were included in the study, of which 337 (23.5%) patients with MDS-E had a younger age of onset and lower neutrophil and platelet counts compared with those in patients with an erythroid cell proportion of less than 50% (MDS-NE) (all P<0.05). The proportion of MDS cases with ring sideroblasts (MDS-RS) was higher in the MDS-E group than in the MDS-NE group, and multi-hit TP53 mutations were more enriched in the MDS-E group than in the MDS-NE group (all P<0.05). Among patients with MDS-RS, the frequency of complex karyotypes and the TP53 mutation rate were significantly lower in the MDS-E group than in the MDS-NE group (0 vs 11.9%, P=0.048 and 2.4% vs 15.1%, P=0.053, respectively). Among patients with TP53 mutations, the frequencies of complex karyotypes and multi-hit TP53 mutations were significantly higher in the MDS-E group than in the MDS-NE group (87.5% vs 64.6%, P=0.003 and 84.0% vs 54.2%, P<0.001, respectively). Survival analysis of patients with MDS-RS found that the overall survival (OS) in the MDS-E group was better than that in the MDS-NE group [not reached vs 63 (95% CI 53.3-72.7) months, P=0.029]. Among patients with TP53 mutations and excess blasts, the OS in the MDS-E group was worse than that in the MDS-NE group [6 (95% CI 2.2-9.8) months vs 12 (95% CI 8.9-15.1) months, P=0.022]. Multivariate analysis showed that age of ≥65 years ( HR=2.47, 95% CI 1.43-4.26, P=0.001), mean corpuscular volume (MCV) of ≤100 fl ( HR=2.62, 95% CI 1.54-4.47, P<0.001), and TP53 mutation ( HR=2.31, 95% CI 1.29-4.12, P=0.005) were poor prognostic factors independent of the Revised International Prognostic Scoring System (IPSS-R) prognosis stratification in patients with MDS-E. Conclusion:Among patients with MDS-RS, MDS-E was strongly associated with a lower proportion of complex karyotypes and TP53 mutations, and the OS in the MDS-E group was longer than that in the MDS-NE group. Among patients with TP53 mutations, MDS-E was strongly associated with complex karyotypes and multi-hit TP53 mutations, and among TP53-mutated patients with excess blasts, the OS in the MDS-E group was shorter than that in the MDS-NE group. Age of ≥65 years, MCV of ≤100 fl, and TP53 mutation were independent adverse prognostic factors affecting OS in patients with MDS-E.

Objective To improve the quality of prescriptions and promote the rational drug application of Dingqing Tablets by investigating the outpatient prescriptions in a tertiary A hospital. Methods A total of 4 796 prescriptions of outpatient pharmacy patients from August 1, 2020 to August 1, 2021 were extracted from the hospital information system by the hospital information software, focusing on the analysis of indications, usage and dosage, drug interaction, etc. Results 10 departments including hematology department and geriatrics department were used Dingqing Tablets, and the irrationality was mainly manifested in the superposition of drug flavors and drug interactions. Conclusion Dingqing tablets were widely used in clinic and had remarkable curative effect. However, there are certain risks in the use of Dingqing tablets. It is necessary to add medication education and supervision to promote the safe and rational use of drugs in clinic.

Objective:To explore the impact of completion rates of 3-hour and 6-hour sepsis bundle therapy on prognosis of patients with septic shock in Prefecture-level grade A hospitals, and analyze the risk factors for prognosis.Methods:A retrospective analysis was conducted to patients with septic shock in the intensive care unit (ICU) of Liaocheng People's Hospital, Shandong Province from January 1, 2020 to December 31, 2021. The data of gender, age, acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ), sequential organ failure assessment (SOFA), sites of infection, pathogenic microorganisms, completion rates of 3-hour and 6-hour sepsis bundle therapy, 28-day prognosis were collected. Logistic regression analysis was used to identify risk factors for patients' mortality at 28-day.Results:① Among 159 patients with septic shock, 93 survived and 66 died with 28-day. There were no significant differences in gender and age between the survival group and death group. Compared with the survival group, APACHE Ⅱ score and SOFA score were significantly higher in the death group [APACHE Ⅱ score: 26.85±5.04 vs. 20.67±4.29, SOFA score: 12.86±3.02 vs. 9.37±2.51, both P < 0.05]. ② Sites of infection in the 159 patients: 47 cases were abdominal infection (29.6%), 36 case were bloodstream infection (22.6%), 31 cases were pulmonary infection (19.5%), 16 cases were soft tissue infection (10.1%), 13 cases were urinary tract infection (8.2%), 12 cases were biliary tract infection (7.5%), and 4 cases were other sites infection (2.5%). Pathogens were found in 128 cases and the positive rate was 80.5%, including 90 cases of Gram-negative (G -) bacilli (56.6%), 27 cases of Gram-positive (G +) cocci (17.0%) and 11 cases of fungi (6.9%). The top three pathogenic bacteria were Escherichia coli (49 cases, 30.8%), Klebsiella pneumoniae (21 cases, 13.2%) and Staphylococcus aureus (15 cases, 9.4%). The differences were not statistically significant. ③ Among the 159 patients, 101 cases completed 3-hour sepsis bundle therapy (63.5%), including 67 cases (72.0%) in survival group and 34 cases (51.5%) in death group; 106 cases completed 6-hour sepsis bundle therapy (66.7%), including 70 cases (75.3%) in survival group and 36 cases (54.5%) in death group. The differences between the two groups were statistically significant (all P < 0.05). ④ The factors (APACHE Ⅱ score, SOFA score and completion rate of 3-hour and 6-hour sepsis bundle therapy) affecting the prognosis in the univariate analysis were included in the binary Logistic regression analysis, and the results showed that the APACHE Ⅱ score, SOFA score, completion rate of 3-hour sepsis bundle therapy were independent risk factors affecting mortality within 28-day [odds ratio ( OR) was 1.216, 1.303, 0.402, all P < 0.05]. Conclusions:The higher APACHE Ⅱ score and SOFA score in septic shock, the worse the prognosis. Improving the completion rates of 3-hour and 6-hour bundle therapy especially the completion rate of 3-hour bundle therapy can reduce the mortality of patients and improve the prognosis.

Objective:To provide the basis and direction for the establishment of the database of severe patients by analyizing of the disease composition and outcome of patients in the department of critical care medicine of the 3A hospital.Methods:The clinical data of 3 249 patients admitted to the department of critical care medicine of Liaocheng People's Hospital from January 1, 2019 to December 31, 2021 were retrospectively analyzed, including gender, age, admission time, admission route, diagnosis, acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score 24 hours after admission, outcome and other information.Results:The mean age of 3 249 patients was (61.99±18.29) years old, and the proportion of young and old patients aged 60-74 years accounted the largest (34.01%). There were more males (1 800 cases) than females (1 449 cases). The most patients were admitted in January (119 cases) and the least in March (75 cases). The top eight diseases in the department of critical care medicine were respiratory system diseases (21.88%), multiple injuries (12.65%), cardiovascular system diseases (11.48%), gastrointestinal surgery diseases (9.42%), pathological obstetrics (7.76%), digestive system diseases (7.63%), urinary system diseases (5.69%) and nervous system diseases (5.23%). Among 3 249 critically ill patients, 54.36% (1 766 cases) were transferred to the general ward for treatment after improvement, with APACHE Ⅱ score was 17.99±5.51. 15.91% (517 cases) returned to local hospital for further treatment after improvement, APACHE Ⅱ score was 22.48±6.57. 1.51% (49 cases) were transferred to superior hospitals, APACHE Ⅱ score was 21.71±5.18. 24.22% (787 cases) were discharged automatically, APACHE Ⅱ score was 25.64±5.45. 4.00% (130 cases) died in intensive care unit (ICU), APACHE Ⅱ score was 29.08±8.10. The APACHE Ⅱ score of patients who died in ICU was higher than that of patients who were transferred to another department, another hospital or discharged automatically after their condition improved, and the differences were statistically significant (all P < 0.001). Among 3 249 patients, a total of 1 265 patients were admitted to ICU for sepsis caused by aggravated infection, and 44.43% (562 cases) of the 1 265 patients improved to the general ward after treatment, with APACHE Ⅱ score was 18.99±5.46. 19.21% (243 cases) returned to local hospital after treatment with APACHE Ⅱ score was 22.79±6.74. 1.50% (19 cases) were transferred to superior hospitals for further treatment with APACHE Ⅱ score was 21.21±4.81. 31.54% (399 cases) were discharged automatically with APACHE Ⅱ score was 25.55±4.84; 3.32% (42 cases) died in ICU with APACHE Ⅱ score was 27.69±7.92. The APACHE Ⅱ score of patients who died in ICU was higher than that of patients who were transferred to another department, another hospital or discharged automatically after their condition improved, and the difference was statistically significant (all P < 0.001). Conclusions:Among the patient admitted to ICU 2019-2021 in Liaocheng People's Hospital, respiratory system diseases accounted for the first, multiple injuries accounted for the second place, followed by cardiovascular system diseases, gastrointestinal surgery diseases, pathological obstetrics, etc. Males and elderly patients aged 60-74 years have a higher proportion of severe cases. APACHE Ⅱ scores were associated with patients' prognosis.

Objective To investigate the relieving effect of Yinlian Tongfeng granules on adjuvant arthritis rats. Methods A complete Freund adjuvant model was built for this study. 48 rats were randomly divided into control group, model group, Yinlian Tongfeng granules high, medium and low dose group (15.4g/kg, 7.7g/kg, 3.8g/kg). After the drug intervention, arthritis index, ankle swelling rate, formaldehyde induced pain score were recorded. Elisa method was used to detect IL-4, IL-10 and the content of PK1, PK2. The pathological changes of toe pad in rats were observed. Results Compared with the model control group, Yinlian Tongfeng granules groups significantly inhibited the ankle swelling, reduced the pain reaction caused by formaldehyde (P<0.01), significantly increased the content of anti-inflammatory factors IL-4 and IL-10 (P<0.01), and decreased the content of PK1 and PK2 (P<0.01). Toe edema and lymphocyte infiltration were alleviated. Conclusion Yinlian Tongfeng granules have a significant inhibitory effect on adjuvant arthritis, suggesting that it has a potential therapeutic application for rheumatoid arthritis.

Prokineticin 2 (PK2) is a newly discovered chemokine, which participates in various physiological functions of the body by binding to receptors PKR1 and PKR2. PK signaling pathway is a newly discovered important regulatory pathway for the occurrence and maintenance of pain after tissue injury and nerve injury in recent years. It plays a key role in regulating injury-related nociceptive events and is a potential therapeutic target for many diseases. The activation of PKRs can induce pain sensation and participate in the sensitivity of pain receptors to different stimuli. The PK system (PKs and PKRs) is an important link involved in inflammation and pain transmission in immune cells. PK2 is involved in the regulation of pain perception by activating PKR1 and PKR2 on primary sensory neurons. In rat primary sensory neurons, PK2 also enhances gated ion channel current through the PKC signaling pathway, inhibits GABA-activated currents, and sensitizes purine nucleotide P2 receptor (P2X). This paper reviews the research progress of PK2 in physical pain. We hope to find new drugs for the treatment of inflammatory pain that target the PKs signaling pathway in future studies.

Objective:To evaluate the prognostic value of MIPSS70-plus in Chinese patients with primary myelofibrosis (PMF) .Methods:A total of 113 Chinese patients with PMF were retrospectively analyzed. The Kaplan-Meier method, Log-rank test, and Cox proportional hazard regression model were performed to evaluate the prognostic factors. The likelihood ratio test was used to evaluate the predictive power between MIPSS70-plus and DIPSS systems.Results:The median age of the Chinese patients was 55 (range: 20-70) years, including 71 males and 42 females. According to the standard of MIPSS70-plus system, 99 patients (79.6% ) had a favorable karyotype and 23 patients (20.4% ) had an unfavorable karyotype. JAK2V617F in 55.8% ( n=63) , CALR exon9 in 17.7% (including 15 CALR type 1 and 5 CALR type 2, n=20) , MPLW515 in 4.4% ( n=5) , and triple negative (no detectable JAK2, MPL, and CALR mutations) in 22.1% of patients in our cohort were found by target-specific next-generation sequencing approach. At least one high-molecular risk mutations were presented in 45.1% ( n=51) of patients, with ASXL1 in 38.9% ( n=44) , SRSF2 in 7.1% ( n=8) , IDH1/2 in 4.4% ( n=5) , and EZH2 in 3.5% ( n=4) of patients. A total of 28 patients (26.7% ) were in low risk, 20 (19.0% ) in intermediate risk, 41 (39.0% ) in high risk, and 16 (15.3% ) in very-high risk categories, which were delineated for the MIPSS70-plus model. A 2-year OS was 100% in low risk, 89.7% (95% CI 76.2% -100.0% ) in intermediate risk, 64.8% (95% CI 47.0% -82.6% ) in high risk, and 35.0% (95% CI 10.3% -59.7% ) in very-high risk categories, which had a significant difference ( P<0.001) . A significantly higher predictive power for survival of the MIPSS70-plus group was observed compared with the DIPSS group ( P=0.001, -2 log-likelihood ratios of 86.355 vs 95.990 for the MIPSS70-plus and DIPSS systems, respectively) . Conclusion:The MIPSS70-plus had significantly higher predictive power than the DIPSS.

Objective To evaluate the clinical value of holographic image navigation in urological laparoscopic and robotic surgery.Methods The data of patients were reviewed retrospectively for whom accepted holographic image navigation laparoscopic and robotic surgery from Jan.2019 to Dec.2019 in Beijing United Family Hospital and other 18 medical centers,including 78 cases of renal tumor,2 cases of bladder cancer,2 cases of adrenal gland tumor,1 cases of renal cyst,1 case of prostate cancer,1 case of sweat gland carcinoma with lymph node metastasis,1 case of pelvic metastasis after radical cystectomy.All the patients underwent operations.In the laparoscopic surgery group,there were 27 cases of partial nephrectomy,1 case of radical prostatectomy,2 cases of radical cystectomy and 2 cases of adrenalectomy.In the da Vinci robotic surgery group of 54 cases,there were 51 cases of partial nephrectomy,1 case of retroperitoneal lymph node dissection,1 case of retroperitoneal bilateral renal cyst deroofing and 1 case of resection of pelvic metastasis.There were 41 partial nephrectomy patients with available clinical data for statistic,with a median age of 53.5 years (range 24-76),including 26 males and 15 females.The median R.E.N.A.L score was 7.8 (range 4-11).Before the operation,the engineers established the holographic image based on the contrast CT images and reports.The surgeon applied the holographic image for preoperative planning.During the operation,the navigation was achieved by real time fusing holographic images with the laparoscopic surgery images in the screen.Results All the procedures had been complete uneventfully.The holographic images helped surgeon in understanding the visual three-dimension structure and relation of vessels supplying tumor or resection tissue,lymph nodes and nerves.By manipulating the holographic images extracorporeally,the fused image guide surgeons about location vessel,lymph node and other important structure and then facilitate the delicate dissection.For the 41 cases with available clinical data including 23 cases of robotic-assisted partial nephrectomy and 18 cases of laparoscopic nephrectomy,the median operation time was 140 (range 50-225) min,the median warm ischemia time was 23 (range 14-60) min,the median blood loss was 80(range 5-1 200) ml.In the robotic surgery group,the median operation time was 140 (range 50-215)min,the median warm i schemia time was 21 (range 17-40)min,the median blood loss was 150(range 30-1 200)ml.In the laparoscopic surgery group,the median operation time was 160(range 80-225)min,the median warm ischemia time was 25 (range 14-60)min,the median blood loss was 50 (range 5-1 200) ml.All the patients had no adjacent organ injury during operation.There were 2 cases with Clavien Ⅱ complications.One required transfusion and the other one suffered hematoma post-operation.However,the tumors were located in the renal hilus for these 2 cases and the R.E.N.A.L scores were both 11.Conclusions Holographic image navigation can help location and recognize important anatomic structures during the surgical procedures..This technique will reduce the tissue injury,decrease the complications and improve the success rate of surgery.

Objective:To investigate the clinical effect of "standardized 4 steps" in rheumatic mitral valve repair.Methods:We retrospectively analyze the clinical data of 136 rheumatic mitral valve disease patients undergoing mitral valve repair with "standardized 4 steps" from June 2016 to July 2019 and investigate its clinical outcome. The clinical outcome was compared with those of patients undergoing rheumatic mitral valve replacement.Results:The perioperative mortality was 2.94% in patients with mitral valve repair. Compared with preoperative period, left atrial diameter was significantly reduced and the early diastolic blood flow velocity across mitral valve(E peak) was significantly decreased at 1-week postoperative and follow-up period. The elimination rate of atrial fibrillation was 80.7% during follow-up period. The early clinical outcome and related complications had no difference between mitral repair group and mitral valve replacement group. The main echocardiographic indexes in two groups also had no statistical significance.Conclusion:The early clinical outcome of rheumatic mitral valve repair with "standardized 4 steps" is satisfactory. Rheumatic mitral valve repair with "standardized 4 steps" is feasible, safe and effective.