Invasive fungal infections (IFIs) have become prominent global health threats, escalating the burden on public health systems. The increasing occurrence of invasive fungal infections is due primarily to the extensive application of chemotherapy, immunosuppressive therapies, and broad-spectrum antifungal agents. At present, therapeutic practices utilize multiple categories of antifungal agents, such as azoles, polyenes, echinocandins, and pyrimidine analogs. Nevertheless, the clinical effectiveness of these treatments is progressively weakened by the emergence of drug resistance, thereby substantially restricting their therapeutic utility. Consequently, there is an imperative need to expedite the discovery of novel antifungal agents. This review seeks to present an exhaustive synthesis of novel antifungal drugs and candidate agents that are either under current clinical investigation or anticipated to progress into clinical evaluation. These emerging compounds exhibit unique benefits concerning their modes of action, antimicrobial spectra, and pharmacokinetic characteristics, potentially leading to improved therapeutic outcomes relative to conventional antifungal regimens. It is anticipated that these novel therapeutic agents will furnish innovative treatment modalities and enhance clinical outcomes in managing invasive fungal infections.

Objective:To investigate the Correlation between ADC combined with serum C-reactive protein (CRP) and delayed encephalopathy after carbon monoxide poisoning (DEACMP), It provides scientific basis for early prediction of DEACMP.Methods:According to the design principle of case-control study, the data of acute carbon monoxide poisoning (ACOP) patients admitted to Shandong Provincial Hospital from December 2017 to December 2021 were retrospectively selected. Among them, patients with DEACMP were selected as the case group, without DEACMP were used as the control group. Univariate and multivariate analyses were performed on the two groups. Receiver operating characteristic curve (ROC) was used to evaluate the diagnostic efficacy of ADC combined with CRP as a combined predictor for disease.Results:A total of 89 patients with ACOP were included, including 33 patients with DEACMP and 56 patients without DEACMP. There were no significant differences in gender, age, smoking, drinking, and underlying diseases (hypertension, coronary heart disease) between groups ( P>0.05). Logistic regression analysis showed that white blood cell count (WBC) ( OR=1.64, 95% CI: 1.19-2.26, P=0.003), CRP ( OR=1.22, 95% CI: 1.03-1.45, P=0.019) and ADC value of central semiovale white matter ( OR=0.99, 95% CI: 0.98-1.00, P=0.010) were associated with DEACMP in patients with ACOP. The ROC curve results showed that the area under the ROC of ADC combined with CRP in the center of semiovale was 0.765 (95% CI: 0.656-0.845), the specificity was 87.9%, the sensitivity was 23.2%, and the cut-off value was 3.5°. Conclusions:WBC, CRP and ADC value of central semiovale are independent factors for DEACMP. ADC value of central semiovale combined with CRP has more clinical value in the early diagnosis of DEACMP. For ACOP patients with DEACMP triggering factors, the diagnosis and treatment awareness of early screening of brain magnetic resonance imaging should be strengthened to avoid DEACMP.

The policy implementation model of G. C. Edwards was used to analyze the public policy health impact assessment in Zhejiang province, and summarize its practice and existing problems in four aspects of policy implementation standards, policy resources, policy executors′ intention and management organization structure, so as to provide reference for promoting the national health impact assessment pilot work. The analysis results showed that Zhejiang province has initially established the public policy health impact assessment mechanism and achieved phased results, but there were still some problems, including the imperfection of policy content and implementation strategy, the inadequacy of leadership decision-making and top-level design, the difference in attitude, understanding and implementation preference of policy implementation subjects, and the ambiguity of the authority and responsibility system of each department in cooperation. In order to further promote the smooth development of public policy health impact assessment, Zhejiang province should actively promote the top-level design to strengthen policy support, integrate and optimize policy resources, gradually establish and improve the health governance mechanism of multiple and overall coordination, and promote the high-quality development of public policy health impact assessment by taking cross departmental cooperation as the path of health co-construction.

Objective:To analyze the satisfaction of referral patients for the medical services provided by the countywide medical community, for reference in further improving its quality and continuity of medical services.Methods:From April to July 2021, a systematic sampling method was adopted to selected the survey subjects from the outpatients from the leading hospitals and three affiliated units of two medical communities, as well as those from two county-level hospitals of non medical communities and five grass-roots medical and health institutions. A total of 660 patients were included in the questionnaire survey. The questionnaire covered key demographic information and 15 satisfaction questions under 4 dimensions. The propensity score matching method was used to reduce confounding factors, factor analysis was used to calculate the satisfaction of referral patients in the medical community group and the non-medical community group, and the systematic dynamics approach was used to analyze the effect of patient satisfaction on referral intention.Results:A total of 641 valid questionnaires were collected. Based on a 1∶2 propensity score matching, 591 patients were finally enrolled, consisting of 102 up-referral cases from the non-community group and 273 such cases from the community group, as well as 76 down-referral cases from the non-community group and 140 such cases from the community group. The overall satisfaction scores by both up and down referral patients were 4.26(1.01)and 4.29(1.14)respectively.The overall satisfaction, medical service satisfaction, technical service quality satisfaction and non-technical service quality satisfaction of up-referral patients, as well as the overall satisfaction, non-technical service quality satisfaction of down-referral patients of the community group were higher than those from the non-community group, with differences statistically significant( P<0.05). The higher satisfaction of patients with their referral in the community, the stronger their referral willingness. Conclusions:The overall satisfaction of refrerral patients in the medical community group is higher than that of the non medical community group. The construction of county medical community has promoted the improvement of satisfaction of referral patients. However, it is still imperative to encourage high-quality medical resources to support primary institutions, to enhance the service level of primary medical and health institutions, to implement differentiated medical insurance reimbursement policies, and to improve the continuity of medical services within the community.

Objective To study the effect of age-related white matter changes (ARWMC) on first symptomatic ischemic stroke events in the oldsters. Methods For the prospective study, a total of 368 eligible oldsters were enrolled in the study from January 2010 to August 2012. The degrees of ARWMC were assessed by ARWMC scale;according to the scores, they were divided into non ARWMC group, mild-moderate ARWMC group and severe ARWMC group. The patients were followed up once every 3 months. The clinical endpoint events and time (first symptomatic ischemic stroke, myocardial infarction and all-cause death) were recorded. Analyses of variance and Chi-square test were used to compare the differences of clinical data among the 3 groups. COX regression was used to assess the risk differences of first symptomatic ischemic stroke in the oldsters of three groups. Results After an average of follow-up for 48.7 months, 50 participants (13.6％) had first symptomatic ischemic stroke;25 (25.8％) were categorized as the severe ARWMC group, 22 (10.9％) were as the mild-medium group, and 3 (4.4％) were as the non ARWMC group. Among the three groups, the differences in age, history of hypertension, systolic blood pressure, incidence of clinical endpoint events and first symptomatic ischemic stroke, and follow-up time of endpoint events were statistically significant (P<0.05); patients from the severe ARWMC group were the oldest, and had the longest history of hypertension, the highest systolic blood pressure, the highest incidence of clinical end events and first symptomatic ischemic stroke, and the shortest follow-up period for clinical end events. COX regression analysis showed that the risk of first symptomatic ischemic stroke in the severe ARWMC group was about 8 times higher than that in the non ARWMC group (hazard ratio=9.012, 95％CI: 2.310-35.154, P=0.002). Conclusion In oldsters, severe ARWMC often accompany hypertension history and poor blood pressure controll, and it is an independent and serious risk factor for long-term first symptomatic ischemic stroke.

Objective To explore the effects of the mouth -muscle strengthening training on the phonetic in-telligibility (PI) of children with functional articulation disorders (FAD) .Methods A total of 80 children of 4 to 7 years old with FAD were randomly divided into the common group (n=40) and comprehensive group (n=40) .Both groups accepted routine speech training ,and the comprehensive group was given mouth muscles training additional-ly .All the children received the assessment of speech before the speech training and 3 months after the training .Re-sults Before the speech training ,the PIs of the common and comprehensive groups were 34 .54％ and 33 .52％ ,re-spectively .The differences between the 2 groups were not statistically significant (P> 0 .05) .After 3 months of speech training ,the PI in the common group increased to 77 .02 ± 4 .21％ from 34 .54 ± 7 .28％ of the baseline ,while in the comprehensive group ,the PI increased to 87 .54 ± 4 .31％ from 33 .52 ± 7 .46％ .In both groups ,the PIs after training were significantly higher than those of before the training respectively .The differences were statistically significant (P<0 .05) .The PIs in the comprehensive group were significantly higher than those of in the common group .The differences were statistically significant (t= -8 .862 ,P<0 .001) .Conclusion Strengthening the mouth muscles is beneficial to improve the PI of children with FAD .

Objective To explore the application and effectiveness of the combination of bilabial /Φ/and inter-dental /θ/to the training of pronouncing fricatives after cleft palate operations .Methods Seventy children aged four to eight years with abnormal fricatives after cleft palate operations over one month were enrolled in the study . They were randomly allocated into the experimental group (35 cases) and the control group (35 cases) .The chil-dren in the experimental group received the combined training of bilabial /Φ/and inter-dental /θ/while those in the control group received routine rehabilitation training .Results After 6 to 10 times of speech training ,the number of erroneous words of the experimental group decreased to 1 .20 ± 0 .35 from 70 .80 ± 0 .52 before the training .The difference was statistically significant (Z= -5 .215 , P= 0 .001) .The number of incorrect words of the control group decreased to 7 .17 ± 0 .45 from 70 .86 ± 0 .50 of the baseline .The difference was statistically significant (Z=-5 .237 ,P=0 .001) .The number of erroneous words of the two groups had no statistical differences before train-ing (t= -0 .079 ,P=0 .937) .The number of wrong words of the experimental group was significantly lower than the control group after training (Z= -7 .023 ,P=0 .001) .Conclusion The application of the combination of bilabi-al /Φ/and inter-dental /θ/to the training of pronouncing fricatives after cleft palate operations can decrease dis-tinctly the number of erroneous words .

Objective To explore the detection trend of vaginal intraepithelial neoplasia(VaIN)of lower genital tract from 2013 to 2015. Methods A retrospective analysis was undertaken of colposcopy-directed biopsy of cervical, vaginal and vulvar intraepithelial neoplasia lesions include cervical intraepithelial neoplasia (CIN), VaIN and vulvar intraepithelial neoplasia (VIN) in Obstetrics and Gynecology Hospital of Fudan University from January 2013 to December 2015. Results (1) Overall data of CIN, VaIN and VIN:a total of 16732 cases were diagnosed of lower genital intraepithelial neoplasia in 3 years, accounting for 23.20% (16732/72128) of total colposcopy-directed biopsy cases. Among them, CIN, VaIN and VIN accounted for 19.48%(14053/72128), 2.67%(1923/72128), 1.05%(756/72128) of total colposcopy-directed biopsy cases of the lower genital tract, 83.99%(14053/16732), 11.49%(1923/16732), 4.52%(756/16732) of total lower genital intraepithelial neoplasia, respectively. (2) Annual data of CIN, VaIN and VIN from 2013 to 2015. The annual proportion of CIN in all intraepithelial neoplasia of lower gential tract was basically stable, consisting of 86.02%(3955/4598),83.25%(4795/5760) and 83.20%(5303/6374), respectively. The annual proportion of VaIN was gradually increasing, consisting of 8.09% (372/4598), 12.45%(717/5760) and 13.08%(834/6374), respectively. The annual proportion of VIN was gradually decreasing, consisting of 5.89% (271/4598), 4.31% (248/5760) and 3.72% (237/6374), respectively. Conclusion The increasing detection of VaIN from 2013 to 2015 might correlate with the increasing attention to inspection of the entire vaginal wall.

Objective To investigate phonological characteristics and rehabilitation training approaches of bilabial consonant articula-tion disorders in patients after repaired cleft palate. Methods From January, 2012 to January, 2016, 51 patients with velopharyngeal incom-petence (VPI) and 57 patients with velopharyngeal competence (VPC) after cleft palate repaire were enrolled. Their phonological character-istics of bilabial consonants articulation disorders were analyzed. They accepted specific rehabilitation training. The correlation between bila-bial consonants articulation disorders and age was analyzed. Results/b/ showed mainly weak pressure in both VPI and VPC patients,/p/showed mainly weak pressure in VPI patients,/p/was mainly substituted by/b/in VPC patients. 46 cases were cured and 2 cases improved in VPI patients after 1-6 weeks of rehabilitation, and the overall cure rate was 90.20%(46/51), and was respectively 100%(13/13), 93.74%(15/16), 77.27%(17/22) in those with mild, moderate and severe disorder. 53 cases were cured and 4 cases improved in VPC patients after 1-5 weeks of rehabilitation, the overall cure rate was 92.98%(53/57), and was respectively 100%(17/17), 90.48%(19/21), 89.47%(17/19) in those with mild, moderate and severe disorder. The number of incorrect words negatively correlated with age in VPC patient (r=-1.000, P<0.001). Conclusion Bilabial consonant articulation disorders occurs mainly on/b/and/p/in patients repaired cleft palate,/b/shows main-ly weak pressure,/p/shows mainly weak pressure and substitution. Specific speech rehabilitation training is significantly effective.

Objective To investigate articulation characteristics and rehabilitation training methods of abnor-mal supradental of patients with dysarthria after lingual frenectomy.Methods A total of 107 patients with dysar-thria after lingual frenectomy were studied for articulation characteristics.Then 32 patients with dysarthria were re-cruited from those 107 patients for further research of the training methods.Results The articulation disorders of/z/and/s/were replaced by/d/when/z/and/s/were combined with/a/,/o/,/e/,/u/or the vowels whose head vowels were them,/z/and/s/were replaced by/j/and/x/when they were combined with/i/.The proportion of these disorders were 32.71%,26.17%,30.84% and 40.19%,respectively.The articulation disorders of/c/was re-placed by/d/or/t/when/c/was combined with/a/,/o/,/e/,/u/or the vowels whose head vowels were them. The proportions were 5.61% and 25.23%,respectively.When/c/was replaced by/q/and/j/.When/c/was com-bined with/i/,the proportions respectively were 42.06% and 14.02%.Then/z/,/c/,/s/were totally replaced to/zh/,/ch/and ,/sh/or lateralization.The proportions of these disorders were 14.02%,15.89%,13.08% and 10.28%,9.35%,11.21%,respectively.After the speech training,the patients made less mistakes about supradental consonant,the number changed from 34.53±6.08 to 7.97±2.52.The differences were statistically significant(t=30.035,P<0.001).Conclusion The main articulation disorders were replacement and lateralization.The training methods that this research has established are significantly effective,and is worth receiving further study and possi-ble clinical application.