Alzheimer disease is a progressive neurodegenerative disorder which has emerged as a major public health concern with the global population aging, and the development of effective therapeutic agents has become increasingly urgent due to its rapid increase in prevalence. There is some progress in drug development, however, the majority of new drugs have failed to demonstrate sustained clinical efficacy in large-scale trials. In addition, high costs, severe side effects have further hindered the widespread application of these therapies. This article reviews recent progress in the development of pharmacological treatments for Alzheimer disease, focusing on disease-modifying therapies targeting amyloid-β and tau proteins, also analyzes the results of phase 2 and phase 3 clinical trials of traditional and novel drugs. Future research efforts should continue to explore novel therapeutic targets and strategies to offer more effective treatment options for patients with Alzheimer disease.

Objective To perform on-site calibration of high-pressure ionization chambers and NaI(Tl) γ spectrometers in state-controlled atmospheric radiation environment automatic continuous monitoring stations and verify the reliability of the online radiation environment monitoring system. Methods ¹³⁷Cs, ⁶⁰Co, and ²⁴¹Am were used as γ reference radiation sources to measure the metrological performance of high-pressure ionization chambers in nine state-controlled atmospheric radiation environment automatic monitoring stations in Hubei Province, China. The performance metrics included background radiation, response, and repeatability. Additionally, the correlation between dose rate and humidity was analyzed, and the energy resolution and activity response of NaI(Tl) γ spectrometers were measured. Results Among the nine state-controlled atmospheric radiation environment automatic monitoring stations, the background radiation of high-pressure ionization chambers ranged from 58.2 nGy/h to 82.6 nGy/h. The response of the high-pressure ionization chambers ranged from 0.94 to 1.08, fulfilling the requirement of 1.0 ± 0.2. The repeatability of high-pressure ionization chambers ranged from 0.43% to 3.80%, satisfying the requirement of not exceeding 10%. A significant correlation was observed between dose rate and humidity, with a correlation coefficient of 0.4476. For NaI(Tl) γ spectrometers, the energy resolution ranged from 6.8% to 7.9%, fulfilling the requirement of not exceeding 9% for the 661.7 keV energy peak of ¹³⁷Cs. The NaI(Tl) γ spectrometers showed 1.4% to 1.8% s⁻¹·Bq⁻¹ activity response to ²⁴¹Am and 6.6‰ to 8.4‰ s⁻¹·Bq⁻¹ activity response to ⁶⁰Co. Conclusion The online monitoring systems in the nine state-controlled atmospheric radiation environment automatic monitoring stations are stable and reliable, providing accurate radiation environment monitoring data for public awareness.

Objective To evaluate the efficacy,safety and patient compliance of a quadruple therapy containing minocycline compared with the traditional quadruple therapy in the treatment of Helicobacter(H.)pylori.Methods This study included 200 H.pylori positive patients,with 100 assigned to the minocycline-containing bismuth quadruple therapy group(LBMC group)and the other 100 to the amoxicillin-containing bismuth quadruple therapy group(LBAC group).After matching the two groups of patients using the propensity score matching(PSM)method,there were 86 cases in each group.Telephone follow-up was conducted on the 14th day after the start of treatment to record patient medication compliance and adverse drug reactions.A 13C urea breath test was performed for re-examination at least one month after completing the treatment plan and discontinuing medication.The intention-to-treat(ITT)and per-protocol(PP)analyses were used to compare the H.pylori eradication rates between the two groups,and Chi-square test and t-test were used for intergroup comparison.Results In the ITT analysis,the eradication rates of the LBMC group and the LBAC group were 89.5%(77/86,95%CI:82.9%～96.1%)and 82.6%(71/86,95%CI:74.4%～90.7%),respectively.In the PP analysis,the eradication rates were 92.6%(75/81,95%CI:86.8%～98.4%)and 88.8%(71/80,95%CI:81.7%～95.8%),respectively.The adverse reaction rate of the LBMC group was 27.9%(24/86),and that of the LBAC group 31.4%(27/86),showing no statistically significant difference(P>0.05).In terms of compliance,the LBMC group was 94.2%(81/86),and the LBAC group 93.0%(80/86),revealing no statistically significant difference(P>0.05).Conclusion As a first-line treatment for eradicating H.pylori,regimens containing minocycline demonstrate equivalent eradication rates to those containing amoxicillin,with similar safety and compliance.They can be used as an alternative treatment for patients allergic to penicillin.

Objective To evaluate the efficacy,safety and patient compliance of a quadruple therapy containing minocycline compared with the traditional quadruple therapy in the treatment of Helicobacter(H.)pylori.Methods This study included 200 H.pylori positive patients,with 100 assigned to the minocycline-containing bismuth quadruple therapy group(LBMC group)and the other 100 to the amoxicillin-containing bismuth quadruple therapy group(LBAC group).After matching the two groups of patients using the propensity score matching(PSM)method,there were 86 cases in each group.Telephone follow-up was conducted on the 14th day after the start of treatment to record patient medication compliance and adverse drug reactions.A 13C urea breath test was performed for re-examination at least one month after completing the treatment plan and discontinuing medication.The intention-to-treat(ITT)and per-protocol(PP)analyses were used to compare the H.pylori eradication rates between the two groups,and Chi-square test and t-test were used for intergroup comparison.Results In the ITT analysis,the eradication rates of the LBMC group and the LBAC group were 89.5%(77/86,95%CI:82.9%～96.1%)and 82.6%(71/86,95%CI:74.4%～90.7%),respectively.In the PP analysis,the eradication rates were 92.6%(75/81,95%CI:86.8%～98.4%)and 88.8%(71/80,95%CI:81.7%～95.8%),respectively.The adverse reaction rate of the LBMC group was 27.9%(24/86),and that of the LBAC group 31.4%(27/86),showing no statistically significant difference(P>0.05).In terms of compliance,the LBMC group was 94.2%(81/86),and the LBAC group 93.0%(80/86),revealing no statistically significant difference(P>0.05).Conclusion As a first-line treatment for eradicating H.pylori,regimens containing minocycline demonstrate equivalent eradication rates to those containing amoxicillin,with similar safety and compliance.They can be used as an alternative treatment for patients allergic to penicillin.

Alzheimer disease is a progressive neurodegenerative disorder which has emerged as a major public health concern with the global population aging, and the development of effective therapeutic agents has become increasingly urgent due to its rapid increase in prevalence. There is some progress in drug development, however, the majority of new drugs have failed to demonstrate sustained clinical efficacy in large-scale trials. In addition, high costs, severe side effects have further hindered the widespread application of these therapies. This article reviews recent progress in the development of pharmacological treatments for Alzheimer disease, focusing on disease-modifying therapies targeting amyloid-β and tau proteins, also analyzes the results of phase 2 and phase 3 clinical trials of traditional and novel drugs. Future research efforts should continue to explore novel therapeutic targets and strategies to offer more effective treatment options for patients with Alzheimer disease.

A 69-year-old female patient received immunotherapy with intravenous infusion of sintilimab 200 mg once per 21 days because of recurrence of left lung adenocarcinoma after operation. The patient had no history of diabetes mellitus and blood sugar level was normal before treatment. Three days after the first intravenous infusion of sintilimab, the patient felt dry mouth and fatigue, 10 days later her symptoms were worsened, accompanied by nausea. Laboratory examination showed random blood glucose 27.0 mmol/L and hypoglycemic treatment was given. On the 29th day of intravenous infusion of sintilimab, oral glucose tolerance test showed that fasting, 1, 2 and 3 hours postprandial blood glucose levels were higher than those of the upper reference value, C-peptide and insulin were lower than those of the lower reference value, urine routine showed ketone bodies (±) and glucose (++++). Autoimmune diabetes mellitus caused by sintilimab was considered. After several adjustments, the hypoglycemic regimen was finally determined as recombinant human insulin injection 12 units subcutaneously before morning and evening meals, 14 units before lunch; albumin biosynthesis human insulin injection 12 units subcutaneously at bedtime. Five days later, the patient′s symptoms such as dry mouth, fatigue, and nausea disappeared, with fasting glucose 4.8-5.8 mmol/L and postprandial glucose 7.8-8.7 mmol/L. Urine routine examination showed negative ketone body and glucose.

A 69-year-old female patient received immunotherapy with intravenous infusion of sintilimab 200 mg once per 21 days because of recurrence of left lung adenocarcinoma after operation. The patient had no history of diabetes mellitus and blood sugar level was normal before treatment. Three days after the first intravenous infusion of sintilimab, the patient felt dry mouth and fatigue, 10 days later her symptoms were worsened, accompanied by nausea. Laboratory examination showed random blood glucose 27.0 mmol/L and hypoglycemic treatment was given. On the 29th day of intravenous infusion of sintilimab, oral glucose tolerance test showed that fasting, 1, 2 and 3 hours postprandial blood glucose levels were higher than those of the upper reference value, C-peptide and insulin were lower than those of the lower reference value, urine routine showed ketone bodies (±) and glucose (++++). Autoimmune diabetes mellitus caused by sintilimab was considered. After several adjustments, the hypoglycemic regimen was finally determined as recombinant human insulin injection 12 units subcutaneously before morning and evening meals, 14 units before lunch; albumin biosynthesis human insulin injection 12 units subcutaneously at bedtime. Five days later, the patient′s symptoms such as dry mouth, fatigue, and nausea disappeared, with fasting glucose 4.8-5.8 mmol/L and postprandial glucose 7.8-8.7 mmol/L. Urine routine examination showed negative ketone body and glucose.

Objective To determine the optimal electron beam energy at different field size through a Monte Carlo-based simulation of the therapy head of Varian X 6 MV linear accelerator so as to study the influence of radial intensity on depth dose.Methods Firstly,keeping the radial intensity unchanged for the field of interest while changing electron beam energy,compassion was carried out of calculated percentage depth doses between measured values.Thus,the optimal energy was identified for this field size.Then,the obtained energy was set the optimal value to study the radial intensity influence on the depth doses.Results The optimal electron energy for 4 cm ×4 cm,10 cm × 10 cm,20 cm × 20 cm and 30 cm × 30 cm field sizes was 5.9,6.0,6.3 and 6.4 MeV respectively.Changes in radial intensities resulted in negligible changes in percentage depth doses for4 cm ×4-cm and 10 cm × 10 cm fields,but led to observable discrepancy for 20 cm × 20 cm and 30 cm × 30 cm fields.Conclusions The optimal electron energies for different field sizes are slightly different.Change in radial intensity distribution has significant influence on the depth dose for large field.To improve simulation accuracy,the field size needs to be taken into consideration in determining the electron beam energy and radial intensity distribution.

Objective To understand tobacco use rate and explore the factors associated with tobacco use in middle school students in China.Methods A self-administered questionnaire survey was conducted among 155 117 eligible middle students selected through multi-stage stratified cluster sampling from 31 provinces of China.The questionnaire consists of the following topics:tobacco use and cessation,passive smoking,access to tobacco products,tobacco control and tobacco advertisement,and knowledge about and attitudes to tobacco.Software SAS 9.3 was used for sample weighting and data analysis.Results Current tobacco use rate was 6.9％ in middle school students in China.The rate was higher in boys (11.2％) than in girls (2.2％),and in rural area (7.8％) than in urban area (4.8％).Students in western area had the highest tobacco use rate (10.3％),followed by the students in middle area (6.4％),and the rate in students in eastern area was lowest (4.5％).Parent smoking (especially mother smoking),friend smoking,teacher smoking,pocket money for a week ＞ 20 yuan,tobacco advertisement or promotion,passive smoking,misconception of tobacco addiction,active attitude to smoking behavior were the risk factors for tobacco use.Conclusions Smoking rate in boys in China was higher than the average global level.A comprehensive intervention strategy by Framework Convention on Tobacco Control should be used to reduce tobacco use in adolescents,including health education,increasing cigarette price,banning tobacco advertisement and promotion,and smoke-free legislation.

BACKGROUND:It is crucial for us to find an objective and sensitive means for the assessment ofthe severitv and development of dementia,so as to make instant diagnosis and examination of therapeutic effect on patientswith vascular dementias(VD).Event related potential endogenetic eomponent P300 is proved closely correlated with the cognitive management of examinees but not with stimulus property,thereby considered as one of the most valuable and objective index for brain superior psychological activity.OBJECTIVE:To study the role and significance of events related potential P300,providing objective basis for clinical diagnosis and therapeutic assessment for patients with VD.DESIGN:Non-randomized simultaneous controlled explorative study based on patients. SETTING:Neurological department and electromyography department in aprovincial hospital and neurological department in a medical college hospital.PARTICIPANTS:Between February 2000 and June 2001,64 patients were of VD at neurological clinic and ward ofthe Second Affiliated Hospital of Chongqing Medical College,including 38 males and 26 females with theaverage age of(66.0±4.6)years(VD group).Culturallevel:19 cases re-ceiyed over senior school education,31 cases of junior school education and14 cases of illiteracy.Meanwhile 60 inpatients without VD were enrolled(non-VD group)including 35 males and 25 females withthe average age of(68.0±3.7)years.Culturallevel:senior school or above,15 cases,junior school, 29 cases and illiteracy,16 cases.METHODS:Mental sate of both VD and non-VD groups were assessed with mini-mental state examination(MMSE),and tested with P300 potential observing the variability of latency and amplitude of P300 in patients.Both methods were compared between VD group and non-VD group, moreover relationship between P300 latency and MMSE scores was also explored.MAIN OUTCOME MEASURES:Variability of P300 latency and amplitude Relationship between P300 latency and MMSE scores.RESULTS:P300 latency was found prolonged in 74% and 7% of VD group and non-VD group respectively,with obvious significance between them,meanwhile prolonged P300 latency was proved closely correlated with the MMSE scores(r=0.609 6,P＜0.05).CONCLUSION:P300 latency can be considered as an obiective predictor for the earlier diagnosis and the assessment of therapeutic effects in patients with VD.