Objective:As medical demands rose rapidly and innovative pharmaceuticals continuously launched onto the market,the National Essential Medicines List(NEML)confronted a novel challenge whether or not to include new medicines.The practice of WHO including new medicines in the WHO Essential Medicines List(WHO EML)was analyzed to provide references for the adjustment of NEML.Methods:Based on the theory of the right to life and health,it explored the theoretical basis of WHO incorporating new medicines into WHO EML.The cancer medicines were taken as the examples to investigate evaluation criteria.Results:For the selection of new medicines,WHO refined multi-dimensional evaluation criteria and took targeted measures to improve selection process and management system.Conclusion:When China attempted to include new drugs in the NEML,it was necessary to adjust selection concept,optimize selection process,improve NEML structure and content,improve selection criteria and strengthen the construction of selection and management guarantee system.

Objective:To investigate the role of the Smad3 signaling pathway in the process of silica-induced epithelial-mesenchymal transition (EMT) .Methods:In September 2022, lung epithelial cells (BEAS-2B) were exposed to different concentrations of silica suspension (0, 50, 100, and 150 μg/ml) for 6 and 12 hours. Additionally, SIS3, a specific inhibitor of phosphorylated Smad3 (p-Smad3) , was utilized to establish the p-Smad3 inhibition model. The cells were divided into four groups: blank control gruop, silica group, SIS3 intervention group, and SIS3 +silica group. Cell morphology was observed using an inverted fluorescence microscope, while cell viability was assessed using a Cell Counting Kit-8 (CCK-8) . The mRNA and protein expression levels of E-cadherin (E-Cad) , N-cadherin (N-Cad) , Vimentin, Smad3, and p-Smad3 were analyzed by Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting, respectively. Differences between two groups were compared using Student's t-test, and multiple group comparisons were analyzed using a one-way analysis of variance with the Student-Newman-Keuls test.Results:Compared with the blank control group, the morphology of BEAS-2B cells shifted from epithelial to mesenchymal cell-like following silica exposure, and the cell viability of BEAS-2B cells declined after exposure to 150 μg/ml silica for 6 and 12 hours. Furthermore, silica exposure led to significant reductions in mRNA and protein expression levels of the epithelial cellular marker (E-Cad) in BEAS-2B cells, accompanied by increased expressions of interstitial cellular markers (N-Cad and Vimentin) . Importantly, the level of p-Smad3/Smad3 expression levels was also elevated in silica-treated cells ( P<0.05) . Compared to the blank control group, the level of p-Smad3/Smad3 expression levels was significantty reduced. Moreover, compared to the silica group, the protein expression levels of N-Cad and Vimentin in the cell of the SIS3+silica group were significantly reduced, while the E-Cad expression was increased ( P<0.05) . Conclusion:Silica exposure can prmote the epithelial mesenchymaol transformotion process by activating smod3 signa ling pathuay, and in hibiting smad3 signa ling pathuay can effctively alleviate the occurrence of epithelial mesenchymal transformation process.

Objective:As medical demands rose rapidly and innovative pharmaceuticals continuously launched onto the market,the National Essential Medicines List(NEML)confronted a novel challenge whether or not to include new medicines.The practice of WHO including new medicines in the WHO Essential Medicines List(WHO EML)was analyzed to provide references for the adjustment of NEML.Methods:Based on the theory of the right to life and health,it explored the theoretical basis of WHO incorporating new medicines into WHO EML.The cancer medicines were taken as the examples to investigate evaluation criteria.Results:For the selection of new medicines,WHO refined multi-dimensional evaluation criteria and took targeted measures to improve selection process and management system.Conclusion:When China attempted to include new drugs in the NEML,it was necessary to adjust selection concept,optimize selection process,improve NEML structure and content,improve selection criteria and strengthen the construction of selection and management guarantee system.

Objective:To investigate the role of the Smad3 signaling pathway in the process of silica-induced epithelial-mesenchymal transition (EMT) .Methods:In September 2022, lung epithelial cells (BEAS-2B) were exposed to different concentrations of silica suspension (0, 50, 100, and 150 μg/ml) for 6 and 12 hours. Additionally, SIS3, a specific inhibitor of phosphorylated Smad3 (p-Smad3) , was utilized to establish the p-Smad3 inhibition model. The cells were divided into four groups: blank control gruop, silica group, SIS3 intervention group, and SIS3 +silica group. Cell morphology was observed using an inverted fluorescence microscope, while cell viability was assessed using a Cell Counting Kit-8 (CCK-8) . The mRNA and protein expression levels of E-cadherin (E-Cad) , N-cadherin (N-Cad) , Vimentin, Smad3, and p-Smad3 were analyzed by Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting, respectively. Differences between two groups were compared using Student's t-test, and multiple group comparisons were analyzed using a one-way analysis of variance with the Student-Newman-Keuls test.Results:Compared with the blank control group, the morphology of BEAS-2B cells shifted from epithelial to mesenchymal cell-like following silica exposure, and the cell viability of BEAS-2B cells declined after exposure to 150 μg/ml silica for 6 and 12 hours. Furthermore, silica exposure led to significant reductions in mRNA and protein expression levels of the epithelial cellular marker (E-Cad) in BEAS-2B cells, accompanied by increased expressions of interstitial cellular markers (N-Cad and Vimentin) . Importantly, the level of p-Smad3/Smad3 expression levels was also elevated in silica-treated cells ( P<0.05) . Compared to the blank control group, the level of p-Smad3/Smad3 expression levels was significantty reduced. Moreover, compared to the silica group, the protein expression levels of N-Cad and Vimentin in the cell of the SIS3+silica group were significantly reduced, while the E-Cad expression was increased ( P<0.05) . Conclusion:Silica exposure can prmote the epithelial mesenchymaol transformotion process by activating smod3 signa ling pathuay, and in hibiting smad3 signa ling pathuay can effctively alleviate the occurrence of epithelial mesenchymal transformation process.

COVID-19 has brought huge damage and impact to the economy, society and healthy systems of China and the world. As a blood product prepared from healthy human blood, human intravenous immunoglobulin have played an active role in the fight against the epidemic. This article summarized the treatment plans, expert consensus and clinical reports in China concerning immunoglobulin in the treatment of COVID-19, and discussed the related possible mechanism of action, aiming at providing references for the drugs screening of COVID-19.

Objective To investigate the expression of endoplasmic reticulum stress - related factors, glucose - regulated protein 78(GRP78)and growth arrest and DNA damage - inducible protein 34( GADD34)and neuronal apoptosis in the brain of zebrafish larvae after hypoxia/ reoxygenation brain injury,and the neuroprotective role of Taurine. Methods The 5 day post - fertilization zebrafish larvae were randomly assigned to 3 groups:control group, hypoxia/ reoxygenation model group(model group)and Taurine treatment group(Taurine group). According to the dif-ferent time points for observation,each group was subdivided into 5 subgroups(1 h,3 h,6 h,24 h,48 h)with 100 ze-brafish larvae each. The pathological changes in the brain tissues and cell apoptosis were detected by fluorescence ter-minal deoxynucleotidyltransferase - mediated dUTP nick end - labeling( TUNEL). The expression of GRP78 and GADD34 mRNA in the brain of zebrafish larvae were detected by real - time quantitative reverse transcription PCR (qRT - PCR). The changes in GRP78 and GADD34 protein were detected by Western blot. Results (1)TUNEL:apoptosis index(AI)was increased after hypoxia/ reoxygenation,and reached the peak at 3 h in model group,the AI in Taurine group was decreased compared with that in the model group at the same time point(1 h:22. 83 ± 1. 80 vs 30. 18 ± 1. 81,3 h:23. 22 ± 2. 46 vs 42. 97 ± 4. 01,6 h:16. 80 ± 1. 69 vs 22. 97 ± 1. 91,all P ﹤ 0. 05).(2)qRT -PCR:the expression of GRP78 and GADD34 mRNA was increased at 1 h after hypoxia/ reoxygenation,and reached the peak at 3 h in the model group,the expression in Taurine group was decreased compared with that in the model group at the same time point(GRP78 mRNA:1 h:2. 35 ± 0. 13 vs 5. 36 ± 0. 35,3 h:3. 08 ± 0. 33 vs 4. 27 ± 0. 52,6 h:1. 57 ± 0. 12 vs 3. 00 ± 0. 13,all P ﹤ 0. 05;GADD34 mRNA:1 h:5. 14 ± 0. 55 vs 7. 45 ± 0. 67,3 h:2. 79 ± 0. 58 vs 5. 83 ± 0. 51,6 h:1. 79 ± 0. 22 vs 3. 67 ± 0. 30,all P ﹤ 0. 05).(3)Western blot:the expression of GRP78 and GADD34 pro-tein was increased at 1 h,reached the peak at 6 h,but it was decreased in Taurine group(GRP78 protein:1 h:1. 12 ± 0. 11 vs 1. 37 ± 0. 13,3 h:0. 79 ± 0. 11 vs 1. 25 ± 0. 10,6 h:0. 55 ± 0. 10 vs 1. 52 ± 0. 14,all P ﹤ 0. 05;GADD34 pro-tein:1 h:0. 92 ± 0. 11 vs 1. 11 ± 0. 13,3 h:0. 96 ± 0. 11 vs 1. 52 ± 0. 09,6 h:0. 76 ± 0. 05 vs 1. 89 ± 0. 06,all P ﹤0. 05).(4)The expression of GRP78 and GADD34 protein was positively correlated with AI in the model group(r =0. 53,0. 56 respectively,all P ﹤ 0. 05). Conclusion One of neuroprotective mechanisms of Taurine against hypoxia/reoxygenation brain injury may down - regulate GRP78 and GADD34 expression.

Objective To explore the effect of the posterior condylar offset (PCO) on clinical results after total knee arthroplasty (TKA) using a high-flex posterior-stabilized (PS) fixed-bearing prosthesis.Methods Clinical and radiographic materials of 107 consecutive female patients (107 knees),who had undergone primary TKAs for end-stage osteoarthritis was prospectively analyzed.All operations were performed by using the same operative technique.Based on the corrected PCO change,all cases were divided into two groups:66 knees in which the corrected PCO change ≥0 mm (aged 48-73 years,with an average of 61.4 years) and 41 knees in which the corrected PCO change ＜ 0 mm (aged 52-75 years,with an average of 62.2 years).One-year postoperatively,clinical and radiographic variables from the two groups were compared by independent t-test.The associations between the corrected PCO changes and the improvements of clinical variables in all patients were analyzed by Pearson linear correlation.Results The corrected PCO change was 2.49±1.71 mm in the PCO change ≥0 mm group and-1.28±1.41 mm in the PCO change ＜ 0 mm group.One-year postoperatively,the Knee Society scores,the Western Ontario and McMaster Universities Osteoarthritis Index,non-weight-bearing active and passive range of knee flexion,flexion contracture,and their improvements had no statistical differences between the two groups.The corrected PCO change was not significantly correlated with the improvement of any clinical variable.While the PCO change ≥0 mm group (130.40°± 11.63°) demonstrated greater flexion than the PCO change ＜ 0 mm group (123.80°±13.12°) during active weight-bearing one year after TKA,which was significantly different between the two groups (t=2.11,P=0.0401).Conclusion Restoration of PCO plays an important role in the optimization of active knee flexion during weight-bearing conditions after posterior-stabilized TKA,while it had no benefit to non-weight-bearing knee flexion and any other clinical result.

ObjectivesTo investigate the expression of glucose regulated protein 78 (GRP78), CCAAT/enhancer binding protein homologous protein (CHOP) and cysteine asparate protease-12 (caspase-12) and neuronal apoptosis in the brain of zebraifsh larvae after hypoxia reperfusion, and the neuroprotective effect of taurine.Methods Five day old post-fertilization zebraifsh larvae were randomly assigned into 3 groups, control group, hypoxia reperfusion group (model group) and taurine group, and the taurine group was further divided into 3 subgroups according to different concentrations (1 mmol/L, 5 mmol/L, 10 mmol/L) with 100 zebraifsh larvae each. The behavior, recovery time and median survival time of those zebraifsh larvae after hypoxia with 1h reperfusion were observed and recorded. The pathological changes and apoptosis of neurons were detected by Nissl staining and terminal deoxynucleotidyltransferase-mediated dUTP nick end-labeling. The expression of GRP78, CHOP and caspase-12 in the brain of zebrafish larvae were detected by Western blot.Results Compared with the model group, the recovery time was shortened, the median survival time was extended, the Nissl stained neurons was increased and the apoptotic neurons were decreased in the taurine groups. GRP78, CHOP and caspase-12 were expressed in model group and taurine group. The expression of GRP78, CHOP and caspase-12 was much lower in taurine group than in model group.Conclusions Hypoxia reperfusion may induce endoplasmic reticulum stress and taurine may be neuroprotective against hypoxia reperfusion by down-regulating GRP78, CHOP and caspase-12.

OBJECTIVE: To analyze the related factors of difficult laryngeal exposure under retaining laryngoscope. METHOD: We did a retrospective analysis of 287 retaining laryngoscope surgery patients' clinical datas to observe the relationship between difficult glottis exposure and patients' gender, degree of mouth opening, BMI, neck circumference, head and neck flexion, TMD, HMD and SMD. RESULT: By ROC curve analysis, we determine the optimal threshold for TMD was 7.35 cm, HMD was 6.33 cm, SMD was 14.75 cm. Univariate analysis showed that gender, and glottis exposure had no significant correlation with difficult laryngeal exposure under retaining laryngoscope. Degree of mouth opening, BMI, neck circumference, head and neck flexion, TMD, HMD and SMD had correlation with difficult laryngeal exposure. Multivariate analysis showed that neck circumference, head and neck flexion, TMD, SMD were independent factors of difficult laryngeal exposure under retaining laryngoscope. CONCLUSION Measurement of neck circumference, head and neck flexion, TMD, SMD before the operation is important for the prediction of difficult laryngeal exposure under retaining laryngoscope.
Glottis ; Head ; Humans ; Laryngoscopes ; Laryngoscopy ; adverse effects ; methods ; Larynx ; Neck ; Posture ; ROC Curve ; Retrospective Studies

OBJECTIVE: To analyze the correlated factors of cervical lymphatic metastasis of T3 and T4 glottic carcinoma. METHOD: We did a retrospective analysis of 91 glottic carcinoma patients' clinical data to analyze cervical lymph node metastasis on different T stage, pathologic degree and the tumor sites. RESULT: The cervical lymph node metastasis rate of 91 cases of T3 and T4 glottic carcinoma was 21.98%. T3 group's metastasis rate was 18.06% (13/72), T4 group's metastasis rate was 36.84% (7/19), P > 0.05. Grouped according to the degree of pathological differentiation, well-differentiated squamous cell carcinoma metastasis rate is 13.89% (5/36), middle-differentiated squamous cell carcinoma metastasis rate is 26.00% (13/50), and poorly-differentiated squamous cell carcinoma metastasis rate is 40.00% (2/5), P > 0.05. Cervical lymph node metastasis rate was 16.22%, when the tumor invading supraglottic region. Cervical lymph node metastasis rate was 15.38%, when the tumor invading subraglottic region. Cervical lymph node metastasis rate was 46.15%, when the tumor invading supraglottic and subraglottic region (P < 0.01). CONCLUSION Cervical lymph node metastasis in cN0 patient with supraglottic carcinoma is effected by T classification, cervical lymphatic metastasis of T3 and T4 glottic carcinoma is not entirely effected by T stage and pathologic degree. When the tumor invades supraglottic and subraglottic region, cervical lymph node metastasis is significantly higher. Therefore, the area of tumor invasion is an important factor for lymph node metastasis.
Humans ; Laryngeal Neoplasms ; pathology ; Lymph Nodes ; Lymphatic Metastasis ; Lymphatic Vessels ; Neck ; Neck Dissection ; Neoplasm Staging ; Retrospective Studies