Natural products (NPs) are an important source of new drugs for the treatment of stroke. Identifying cellular targets for bioactive molecules is a major challenge and critical issue in the development of new drugs for stroke. Small-molecule probes play a unique role in target discovery. However, drawbacks to these probes include non-specificity, unstable activity, and difficulty in synthesis. Small-molecule probes based on NPs at least partially compensate for these shortcomings. NPs feature rich chemical and structural diversity, biocompatibility, and unique biological activities. These features could be exploited to provide new ideas and tools for target discovery. Small-molecule probes based on NPs provide a precise and direct search for interacting protein targets of NPs-active small molecules. This review explores the properties of small-molecule probes based on NPs and their applications in mechanistic studies of stroke and other diseases. We hope that this review will bring new perspectives to the mechanistic study of NPs-active small molecules and accelerate the translation of these ingredients into drug candidates for the treatment of stroke.

Objective:To analyze the changing trends of the epidemic characteristics of human brucellosis in Hangzhou City, and to provide a basis for further formulating prevention and control measures.Methods:The epidemic data of brucellosis in Hangzhou City from 2004 to 2021 were collected from the "China Disease Control and Prevention Information System" and the annual reports, compilations and summaries of prevention and control work of brucellosis in Hangzhou City, and the epidemiological characteristics and trends of brucellosis cases in Hangzhou City from 2004 to 2009, 2010 to 2015, and 2016 to 2021 were compared and analyzed.Results:A total of 186 cases of brucellosis were diagnosed in Hangzhou City from 2004 to 2021, with an average annual incidence rate of 0.151/100 000, ranging from 0.016/100 000 to 0.286/100 000. The incidence rate showed a stage-by-stage upward trend from 2004 to 2009, 2010 to 2015, and 2016 to 2021 ( Z = 3.15, P = 0.002). The age of onset of brucellosis cases was predominantly 18 - 60 years old, accounting for 78.49% (146/186). The male-to-female ratio was 2.10∶1.00 (126∶60). The occupational and non-occupational populations accounted for 62.90% (117/186) and 37.10% (69/186), respectively, with the proportion of non-occupational cases in the three stages being 28.57%, 23.29% and 51.76%, showing an increasing trend (χ 2trend = 9.85, P = 0.002). The regional distribution was dominated by Yuhang District, accounting for 55.91% (104/186), followed by Jianggan District (9.14%, 17/186) and Fuyang District (7.53%, 14/186). The number of brucellosis epidemic counties (cities, districts) increased from 6 to 9. The seasonal analysis showed that the proportion of cases from January to June decreased from 84.93% (23/28) from 2004 to 2009 to 54.12% (46/85) from 2016 to 2021. The proportion of infection from outside the province in the three stages was 0, 10.96% and 27.38%, respectively, showing an upward trend (χ 2trend = 18.16, P < 0.001), the main infected areas were Henan Province, Heilongjiang Province, and Inner Mongolia Autonomous Region. In clinical symptoms and signs, the incidence of muscle and joint pain and low back pain increased from 60.71% (17/28) and 10.71% (3/28) from 2004 to 2009, respectively, to 83.53% (71/85) and 25.88% (22/85) from 2016 to 2021, both showing an upward trend (χ 2trend = 9.92, 4.67, P = 0.002, 0.031). Conclusions:The incidence of human brucellosis in Hangzhou City is on the rise, and the number of cases of non-occupational population has increased significantly in recent years. The sheep breeding places have gradually become the high incidence areas of brucellosis in Hangzhou City. It is recommended to strengthen the promotion and education of knowledge on brucellosis prevention among the general public, and focus on actively monitoring human brucellosis in high-risk areas.

Objective:To investigate the iodine nutritional status of pregnant women in Hangzhou City and analyze its influencing factors, in order to provide a basis for guiding pregnant women in Hangzhou City to supplement iodine scientifically.Methods:A stratified random sampling method was used to conduct a questionnaire survey on 1 400 pregnant women in Hangzhou City from March to October 2018. Random urine samples and household salt samples from pregnant women were collected, and the levels of urine iodine and salt iodine were measured using arsenic cerium catalytic spectrophotometry and direct titration, respectively. The iodine nutritional status of pregnant women with different basic characteristics and dietary levels were analyzed and compared (Kruskal-Wallis test), and the main influencing factors affecting the urinary iodine concentration level of pregnant women were identified (the ordinal multiple classification logistic regression analysis).Results:The median urinary iodine of pregnant women was 135.00 μg/L, and the qualified iodized salt consumption rate of pregnant women was 83.36% (1 167/1 400). In terms of basic characteristics, there were statistically significant differences in the distribution level of urine iodine among pregnant women with different pregnancy frequency, delivery frequency, and natural abortion frequency ( P < 0.05). In terms of diet, the frequency of consuming milk, yogurt, meat, and whether pregnant women consumed cabbage and cauliflower showed statistically significant differences in urinary iodine distribution levels ( P < 0.05). Ordinal multiple classification logistic regression analysis showed that the urine iodine levels of pregnant women who were pregnant twice were higher than those who were pregnant ≥3 times ( OR = 1.64, P = 0.003). Pregnant women who never or occasionally consumed yogurt had lower urine iodine levels than or equal to those who consumed 2 bottles of yogurt per day ( OR = 0.53, P = 0.044). Pregnant women who never or occasionally consumed meat and those who consumed meat once a week had higher urinary iodine levels than that who consumed meat ≥2 times per week ( OR = 1.40, 1.47, P < 0.05). Conclusions:The overall iodine nutrition of pregnant women in Hangzhou City is at an deficiency level. Pregnancy experience and dietary level are influencing factors on iodine nutrition of pregnant women. It is necessary to carry out in-depth health education for pregnant women, improve the dietary structure during pregnancy, and improve the abnormal iodine nutrition of pregnant women.

OBJECTIVE: To investigate the clinical efficacy and advantages of Tianji orthopedic robot assisted cannulated screw internal fixation for femoral neck fracture. METHODS: The clinical data of 41 patients with femoral neck fracture who underwent internal fixation with cannulated screws from January 2019 to January 2022 were retrospectively analyzed. According to different surgical methods, they were divided into Tianji robot group and traditional cannulated screw fixation group (traditional operation group). Among them, there were 18 patients in Tianji robot group including 8 males and 10 females with age of (56.00±4.22) years old, Garden typeⅠ (4 cases), type Ⅱ (11 cases), type Ⅲ (2 cases), and type Ⅳ (1 case). There were 23 patients in the traditional operation group, including 10 males and 13 females, aged (54.87±4.81) years old;there were 5 cases of Garden typeⅠ, 14 cases of type Ⅱ, 3 cases of type Ⅲ and 1 case of type Ⅳ. The operation time, intraoperative blood loss, fluoroscopy times, guide needle placement times, operation costs and other indicators were observed and compared between two groups. Harris score was used to evaluate hip joint function 12 months after operation. RESULTS: The wounds of all patients healed in Grade A without complications. There were significant differences between two groups in terms of operation time, times of intraoperative fluoroscopy, times of guide needle placement, amount of intraoperative bleeding, and operation cost (P<0.05). All 41 patients were followed up for at least 12 months. The fractures of both groups were healed. There was no infection, screw loosening, fracture displacement and femoral head necrosis in Tianji robot group during follow-up;Screw loosening occurred in 2 patients in the traditional operation group during follow-up. At 12 months after operation, Harris hip joint function score of Tianji robot group was higher than that of traditional operation group in daily activity, lameness, joint activity score and total score (P<0.05). CONCLUSION Tianji robot assisted nail placement is a better method for the treatment of femoral neck fracture, which improves the surgical efficiency, is more accurate, has higher success rate of one-time nail placement, shorter operation time, less radiation, and has better hip joint function recovery after surgery.
Male ; Female ; Humans ; Middle Aged ; Robotics ; Retrospective Studies ; Femoral Neck Fractures/surgery* ; Bone Screws ; Fracture Fixation, Internal/methods* ; Treatment Outcome

Objective: To investigate the epidemiological characteristics of malaria in Hangzhou City from 2004 to 2021, so as to provide the evidence for formulating the post-elimination control strategy for malaria in Hangzhou City. Methods: The epidemic situation of malaria in Hangzhou City from 2004 to 2021 were collected from the National Information System for Disease Control and Prevention in China, and the temporal, spatial and human distributions of malaria cases and the source of malaria infections were analyzed in Hangzhou City during the pre-elimination stage (2004 to 2009), the elimination stage (2010 to 2015) and the post-elimination stage (2016 to 2021). Results: Totally 602 malaria cases were reported in Hangzhou City from 2004 to 2021,and the annual mean incidence of malaria was 0.22/105, 0.20/105 and 0.18/105 during the pre-elimination, elimination and post-elimination stages, appearing a tendency towards a decline. Men accounted for 63.96%, 85.07% and 93.75% of all malaria cases and there were 67.86%, 82.84% and 80.00% of cases at ages of 18 to 50 years during the pre-elimination, elimination and post-elimination stages, both appearing a tendency towards a decline (χ2trend=56.748, P<0.001; χ2trend=39.971, P<0.001). The predominant occupation of malaria cases shifted from farmers or migrant workers to multiple occupations, and the proportion of commercial servants increased from 4.87% during the pre-elimination stage to 24.38% during the post-elimination stage (χ2trend=73.308, P<0.001). The proportion of Plasmodium vivax malaria cases reduced from 96.43% during the pre-elimination stage to 7.50% during the post-elimination stage, and the proportion of P. falciparum malaria cases increased from 3.57% to 71.25%, while P. ovale, P. malariae and mixed infections were identified since 2010. There was a significant season-specific incidence of P. vivax malaria during the pre-elimination stage, and the period between May and October was an epidemic season; however, there was no season-specific incidence of P. vivax malaria during the elimination and post-elimination stages. The regional distribution of malaria cases presented a tendency towards a shift from suburb and rural areas to urban areas (χ2trend=74.229, P<0.001). No local cases were detected in Hangzhou City since 2010, and 94.22% of malaria cases were overseas imported cases after malaria elimination, including 90.61% from Africa. Conclusions oung and middle-aged men were high-risk populations for malaria in Hangzhou City from 2004 to 2021, and overseas commercial servants gradually became the predominant source of malaria infections, with malaria parasite species tending to be diverse. Improving the management of overseas imported cases and timely identification and treatment of cases are major interventions to consolidate malaria elimination achievements in Hangzhou City.

Compliance is directly related to the patient’s understanding and implementation degree of treatment plans, and is closely related to treatment outcomes. But previous studies have shown that the compliance of cancer patients is generally low. Foreign countries have rich practical experience in improving the compliance of cancer patients. Therefore, this paper started with the concept of compliance, expounded the classification of compliance, analyzed the current situation and gaps of compliance of cancer patients at home and abroad, introduced experience of foreign cancer patients’ compliance improvement strategies from the three aspects of policy, doctors and patients, and put forward localized recommendations for improving the compliance of cancer patients in combination with the national conditions.

Objective:To understand the epidemiological characteristics of brucellosis in non-occupational population reported in Hangzhou, and provide basis for diagnosis and further prevention and control of brucellosis in non-occupational population.Methods:The basic information, epidemiological characteristics, clinical characteristics and laboratory test data of brucellosis patients reported in Hangzhou from 2008 to 2019 were collected retrospectively. The data were obtained from the case questionnaire of confirmed brucellosis and annual report of brucellosis prevention and control work of Hangzhou Center for Disease Control and Prevention over the years. The epidemiological characteristics, clinical characteristics and diagnosis of brucellosis in non-occupational population were analyzed.Results:From 2008 to 2019, 76 cases of brucellosis in non-occupational population were reported in Hangzhou, accounting for 34.23% (76/222) of the total reported brucellosis cases. In the 76 cases of brucellosis in non-occupational population, there were 47 males and 29 females, the ratio of male to female was 1.62∶1.00; the age was (47.37 ± 16.04) years old, ranging from 6 to 84 years old. The peak incidence of brucellosis in non-occupational population was from March to May, accounting for 59.21% (45/76); the main routes of infection were direct contact and digestive tract, accounting for 80.26% (61/76). The main clinical symptoms were fever (100.00%, 76/76), hyperhidrosis (73.68%, 56/76) and muscle and joint pain (69.74%, 53/76); the diagnosis time was 27 (14, 49) d, and the longest diagnosis time was 190 d. Among them, 39 cases were misdiagnosed, accounting for 51.32% (39/76). Sixty suspected Brucella strains were identified by routine culture of automatic blood culture apparatus in hospital laboratory, and 54 strains of Brucella melitensis were identified by typing, with a coincidence rate of 90.00%. The blood culture rate of patients from 2015 to 2019 (88.46%, 46/52) was significantly higher than that from 2008 to 2014 (58.33%, 14/24), the difference was statistically significant (χ 2=8.968, P < 0.05). Conclusions:From 2008 to 2019, the onset of brucellosis in non-occupational population is seasonal in Hangzhou, the infection mode is diverse, the clinical symptoms are not typical, and it is easy to be misdiagnosed. Blood culture for suspected brucellosis patients in high incidence season is conducive to the early diagnosis of brucellosis.

Objective:To understand the iodine deficiency disorders (IDD) knowledge, attitude and practice (KAP) among population in and near salts marketing areas of Hangzhou urban areas, so as to provide the evidence for making effective health education and health promotion models.Methods:A face to face KAP questionnaire investigation was conducted in 5 salts marketing survey points of 5 urban areas according to the north, south, east, west and center locations in 2018. The survey included basic information, awareness of the harm of iodine deficiency disorders (IDD), ways to acquire knowledge of IDD prevention and control, knowledge of IDD prevention, and attitudes towards iodized salt and iodine-free salt. The survey results were analyzed.Results:Totally 991 people completed the investigation; and 80.8% (801/991) of the population surveyed knew that iodine deficiency will cause endemic goiter, and 41.7% (413/991) of them knew that IDD could lead to varying degrees of mental impairment; 62.1% (615/991) obtained IDD prevention knowledge from TV, radio, Internet and newspaper; 76.8% (761/991) knew that IDD can be prevented by taking iodized salt. However, 8.9% (88/991) thought eating seafood was the best way to prevent IDD; 50.9% (504/991) thought iodized salt may not cause excessive iodine intake, but 56.5% (560/991) considered that there was a correlation between iodized salt and thyroid nodules. 56.2% (557/991) believed that the supply of iodized salt should be opened.Conclusions:The population in and near salts marketing areas of Hangzhou urban areas remains relatively lack of knowledge on IDD and salt iodization. The routes people obtaining IDD knowledge are very limited and the health education should be highlighted.

Objective To investigate the effects of administrative region changes on prevention and control of fluorosis,in order to provide a scientific basis for evaluation and improvement of prevention and control measures.Methods An investigation was conducted in all drinking water-born endemic fluorosis areas in Hangzhou in 2017,to evaluate the status quo of water-improving defluoridation projects,measure the water fluoride content with "the Standard Detection Methods for Domestic Drinking Water" (GB/T 5750.7-2006),detect the dental fluorosis with Dean method and the urinary fluoride content by fluoride selective electrode method in children aged 8 to 12 years old.Results The historical endemic fluorosis areas in Hangzhou now involved 38 natural villages of 22 administrativevillages in 8 townships of 5 counties (cities and districts).All villages had completed water-improving projects which were running well as the fluoride contents of drinking water were less than 1.00 mg/L.The detection rate of dental fluorosis was 1.13％ (9/795) among children aged 8-12 years.A total of 198 urine samples were tested,the urinary fluoride content varied from 0.12 to 2.90 mg/L,and the geometric mean was 0.77 mg/L.Conclusion Administrative region changes do not influence the effect of water-improving defluoridation projects,but management and monitoring of the water-improving projects still should be strengthened.

Objective To establish a normal reference range of thyroid-related indicators of early pregnant women in Hangzhou,and investigate the prevalence of thyroid disease among them after the implementation of a new standard of salt iodine content, in order to provide reference for monitoring of thyroid disease in pregnant women.Methods A total of 582 women in early pregnancy(0 - 13 weeks of gestation) in Hangzhou were selected via the stratified random sampling method as the subjects of the study and for detection of serology thyroid function. The levels of serum thyroid stimulating hormone (TSH), free thyroxine (FT4), thyroid peroxidase antibody(TPOAb) and thyroglobulin antibody (TgAb) were measured by chemiluminescence method. According to the standard American Academy of Clinical Biochemistry (NACB), 359 women in early pregnancy were strictly screened to establish the normal reference value of TSH, FT4, and the reference range using the 95% confidence interval (95%CI). At the same time, the newly establish reference interval was used to evaluate the thyroid function of 582 early pregnant women. Results The reference interval of TSH in early pregnant women of Hangzhou was 0.048 -3.354 mU/L.The reference interval of FT4was(13.023 ± 3.316) pmol/L, and the tenth percentile of FT4was 11.030 pmol/L. Eighty-four persons' thyroid function was abnormal in 582 and the rate of abnormal was 14.4% (84/582), in which the rates of abnormal in clinical hypothyroidism, subclinical hypothyroidism, subclinical hyperthyroidism and hypothyroxinemia were 0.2% (1/582), 3.4% (20/582), 1.9% (11/582) and 8.9% (52/582), respectively. The case with clinical hyperthyroidism was not detected. The positive rate of TPOAb and TgAb were 10.8% (63/582) and 11.7%(68/582). The abnormal rate of hypothyroxinemia and the positive rate of TPOAb in early pregnant women in the city(11.4%,13.5%)were significantly higher than that in the rural areas(6.3%,8.1%,χ2=4.708,4.309, P < 0.05). Conclusions The normal reference value of thyroid hormones in early pregnant women in Hangzhou is established, and it is found that the incidence of thyroid disease is higher in pregnant women in Hangzhou after the implementation of the new standard of salt iodine content, therefore, it is imperative to carry out monitoring (or screening)of thyroid function in early pregnant women.