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.

Recently, diffusion models have emerged as a promising paradigm for molecular design and optimization. However, most diffusion-based molecular generative models focus on modeling 2D graphs or 3D geometries, with limited research on molecular sequence diffusion models. The International Union of Pure and Applied Chemistry (IUPAC) names are more akin to chemical natural language than the Simplified Molecular Input Line Entry System (SMILES) for organic compounds. In this work, we apply an IUPAC-guided conditional diffusion model to facilitate molecular editing from chemical natural language to chemical language (SMILES) and explore whether the pre-trained generative performance of diffusion models can be transferred to chemical natural language. We propose DiffIUPAC, a controllable molecular editing diffusion model that converts IUPAC names to SMILES strings. Evaluation results demonstrate that our model outperforms existing methods and successfully captures the semantic rules of both chemical languages. Chemical space and scaffold analysis show that the model can generate similar compounds with diverse scaffolds within the specified constraints. Additionally, to illustrate the model's applicability in drug design, we conducted case studies in functional group editing, analogue design and linker design.

Objective:To preliminarily explore the association of pregnancy factors with cow's milk protein allergy in infants.Methods:This study was based on data from a subcohort of a study called ge-netic susceptibility to cow's milk allergy in Chinese children,including infants born in Peking University People's Hospital between March 1,2020,and December 31,2020.The infants were divided into a cow's milk protein allergy(CMPA)group and a control group according to whether they had developed cow's milk protein allergy at the age of 1 year.We retrospectively collected the clinical data of infants and their mothers before and during pregnancy,and analyzed the association of multiple factors during pregnancy with cow's milk protein allergy in infants.Results:A total of 278 infants were enrolled in this study,including 52 infants with CMPA and 226 infants without CMPA.Among them,there were 143 boys and 135 girls.The proportion of male infants in the CMPA group(69.2％)was higher than that in the control group(47.3％),and the difference was statistically significant(P=0.004).There were no significant differences in the distribution of birth weight,gestational age at birth,low-birth-weight in-fants,premature,umbilical cord entangle neck,and neonatal asphyxia between the CMPA group and the control group(P＞0.05).The proportion of mothers complicated with autoimmune diseases,anemia or antibiotics exposure during pregnancy in the CMPA group was higher than that in the control group,and there were statistical differences between the two groups(P＜0.05).There was no significant difference in the distribution of other pregnancy complications between the two groups(P＞0.05),such as eclamp-sia/preeclampsia,chronic hypertension/gestational hypertension,diabetes/gestational diabetes,thyroid diseases,and so on.There was no significant difference in the overall distribution of some blood routine indexes during pregnancy between the CMPA group and the control group(P＞0.05).Multivariate Lo-gistic regression analysis showed that male infant,mothers complicated with autoimmune diseases or ane-mia,antibiotic exposure during pregnancy were independent risk factors for cow's milk protein allergy.Conclusion:Male infant,mothers complicated with autoimmune diseases or anemia,antibiotic exposure during pregnancy were independent risk factors for cow's milk protein allergy.

Objective:Based on the forgetting curve principle to construct a model for the popularization of cardiopulmonary resuscitation among college students and validate its effectiveness, providing reference for the promotion of cardiopulmonary resuscitation.Methods:A randomized controlled trial was conducted. In October 2021, a multistage random sampling method was used to select 262 freshmen and sophomores from the School of Mathematics and Physics at Leshan Normal University as the control group, and 262 freshmen and sophomores from the School of Electronic Information and Artificial Intelligence as the experimental group.The control group received conventional training, while the experimental group, in addition to conventional training, received cardiopulmonary resuscitation retraining based on the Ebbinghaus forgetting curve at three time intervals: within 1 week, within 1 month, and within 1 to 6 months after training. The retraining included online self-learning, on-site observation reinforcement, and social practice sublimation. The cardiopulmonary resuscitation knowledge awareness rate and cardiopulmonary resuscitation skill assessment of the two groups were compared before training, immediately after training, and 6 months after training.Results:The final number of participants was 256 in the control group (126 males and 130 females) and 224 in the experimental group (110 males and 114 females). There were no statistically significant differences in cardiopulmonary resuscitation knowledge awareness rate and cardiopulmonary resuscitation skill scores between the two groups before and immediately after training (both P>0.05). Immediately after training, the average cardiopulmonary resuscitation knowledge awareness rate in the experimental and control groups were 91% (1 626/1 792) and 88% (1 806/2 048), respectively, which were significantly higher than the pre-training rates of 55% (989/1 792) and 55% (1 129/2 048) ( χ2=8.46, 7.30, both P<0.01). The cardiopulmonary resuscitation skill scores were (42.00 ± 3.55) and (41.68 ± 3.40), respectively, higher than the pre-training scores of (15.41 ± 4.85) and (15.92 ± 4.66) ( t=84.47, 45.56, both P<0.05). Six months after training, the awareness rates of determination of consciousness and cardiac arrest judgment, cardiopulmonary resuscitation steps, chest compression location, frequency, depth, and the ratio of chest compressions to artificial ventilation in the experimental group in college students were 90% (201/224), 93% (208/224), 92% (206/224), 93% (208/224), 89% (200/224), and 94% (210/224), respectively, higher than those in the control group, which were 62% (158/256), 71% (182/256), 77% (198/256), 73% (186/256), 70% (178/256), and 69% (176/256) ( χ2 values were 4.21-7.03, all P<0.01). The cardiopulmonary resuscitation skill score in the experimental group was (49.77 ± 3.68), higher than the control group′s (34.95 ± 4.79) ( t=38.25, P<0.01). The proportion of students confident in using cardiopulmonary resuscitation to save others was 92% (206/224) in the experimental group, higher than 58% (148/256) in the control group ( χ2=7.68, P<0.01). Six months after training, the cardiopulmonary resuscitation skill score in the experimental group was (49.77 ± 3.68), higher than the immediate post-training score of (42.00 ± 3.55), whereas the control group's cardiopulmonary resuscitation skill score was (34.95 ± 4.79), lower than the immediate post-training score of (41.68 ± 3.40) ( t=22.74, 18.33, both P<0.01). Conclusions:The cardiopulmonary resuscitation popularization model for college students based on the forgetting curve is conducive to mastering cardiopulmonary resuscitation knowledge and skills among trained college students, enhancing their confidence in using cardiopulmonary resuscitation techniques to rescue others. Moreover, it helps save the human, financial, and material resources required for cardiopulmonary resuscitation training to a certain extent and is worthy of promotion.

Objective To compile nursing guidelines for diabetic patients undergoing ultrasound-guided islet transplantation through percutaneous portal vein puncture and catheterisation,providing valuable insights for the care of such patients during the surgical procedure.Methods Between December 2017 to September 2023,a total of 27 patients underwent 44 surgical procedures for ultrasound-guided islet transplantation via percutaneous portal vein puncture and catheterisation at our hospital.Nursing assistance was provided preoperatively,intraoperatively and postoperatively for all the procedures.Results All 27 patients who had undergone 44 surgical procedures successfully went through the ultrasound-guided islet transplantation via percutaneous portal vein puncture and catheterisation.Among the 44 surgical procedures,3(6.8%)resulted in upper abdominal and liver area pain,nausea and vomiting during surgery,8(18.2%)had transient increase of portal vein pressure during transplantation,and 6(13.6%)encountered active bleeding following the removal of the portal vein catheters.None of the patients developed delayed portal vein bleeding or complication such as portal vein thrombosis after the surgery.Conclusions Nursing interventions play a crucial role in ensuring the successful outcomes of ultrasound-guided islet transplantation.Following measures are the keys and they play an important roles in ensuring the smooth completion of ultrasound-guided islet transplantation:preoperatively,carefully assess the condition of recipients and provide them with psychological supports and patient education.Intraoperatively,closely monitor the vital signs,portal vein pressure and blood glucose as well as to prevent complications.Postoperatively,implement the nursing measures to prevent the recipients from postoperative bleeding of portal vein.

Objective:To investigate the relationship between gestational weight gain (GWG) in twin pregnancies and adverse perinatal outcomes.Methods:This retrospective study included twin pregnant women with live births at≥25 weeks of gestation and their offspring, who delivered at Peking University People's Hospital from January 2012 to October 2022. Total GWG was standardized according to gestational age and categorized into three groups based on the 2009 Institute of Medicine (IOM) guidelines: insufficient GWG (GWG below IOM recommendations), appropriate GWG (GWG within IOM recommendations), and excessive GWG (GWG above IOM recommendations). Comparisons between data of the three groups used analysis of variance, Kruskal-Wallis test or Bonferroni correction or Chi-square partitions. Multivariable logistic regression models and generalized estimating equations with logistic regression models were used to analyze the independent effects of GWG on maternal and neonatal outcomes. Results:A total of 794 twin pregnant women and their 1 588 live-born neonates were included in the study. There were 360 women (45.3%) with appropriate GWG, 356 (44.8%) with insufficient GWG, and 78 (9.8%) with excessive GWG. Both insufficient and excessive GWG were associated with an increased risk of preterm birth [adjusted ORs of 1.39 (95% CI: 1.04-1.88) and 1.70 (95% CI: 1.05-2.78), respectively]. Insufficient GWG was associated with an increased risk of gestational diabetes mellitus (adjusted OR=1.42, 95% CI: 1.00-2.01) and low birth weight infants (adjusted OR=2.04, 95% CI: 1.57-2.66). Insufficient GWG was also associated with a reduced risk of eclampsia or preeclampsia (adjusted OR=0.50, 95% CI: 0.33-0.75), cesarean section (adjusted OR=0.48, 95% CI: 0.30-0.77), discordant twin growth (adjusted OR=0.56, 95% CI: 0.37-0.85), and large for gestational age infants (adjusted OR=0.46, 95% CI: 0.35-0.61). Excessive GWG was associated with an increased risk of eclampsia or preeclampsia (adjusted OR=2.85, 95% CI: 1.65-4.91), and large for gestational age infants (adjusted OR=2.49, 95% CI: 1.60-3.86), while with a decreased risk of low birth weight infants (adjusted OR=0.42, 95% CI: 0.27-0.65). Conclusions:More than half of the twin pregnancies have GWG outside the recommended range of the IOM guidelines. Both insufficient and excessive GWG are associated with adverse perinatal outcomes, particularly an increased risk of preterm birth.

Objective:To analyze the maternal and neonatal outcomes of pregnant women with leukemia.Methods:This retrospective study analyzed the clinical data of singleton pregnant women with leukemia and their neonates at the Obstetrics Department of Peking University People's Hospital from June 2009 to May 2021. Statistical analysis was performed using a two-sample t-test, the Wilcoxon Mann-Whitney rank sum test, and the Chi-square test (or Fisher's exact test). Results:(1) Ninety-one pregnant women were enrolled in this study, accounting for 2.8‰ of all deliveries during the same period. Among them, there were 15 (16.5%) with acute lymphoblastic leukemia, 38 (41.8%) with acute myeloid leukemia, and 38 (41.8%) with chronic myelogenous leukemia. Twenty-nine of the 91 pregnancies (31.9%) were terminated in the second or third trimester, and 62 babies (68.1%) were born through spontaneous delivery or cesarean section. The 62 parturients were (30.1±5.0) years old, of whom two died of complications of leukemia within 7 d after delivery, and five were transferred to the intensive care unit after delivery. Of the 62 cases, 18 (29.0%) received a blood transfusion and 12 (19.3%) received chemotherapy during pregnancy. (2) The proportion of patients with unremitted leukemia during pregnancy or newly developed leukemia was higher in women with terminated pregnancy than in those who continued the pregnancy [96.6% (28/29) vs 54.8% (34/62), χ2=15.83, P<0.001]. (3) The gestational age of the 62 newborns was (37.7±2.7) weeks. Premature, low birth weight and small-for-gestational-age infants accounted for 29.0% (18/62), 25.8% (16/62), and 12.9% (8/62), respectively. Hyperbilirubinemia occurred in 10 neonates (16.1%) and hypoglycemia in two (3.2%). Perinatal anoxia and asphyxia were reported in 13 cases (21.0%). Appearance, organ malformations, or chromosomal abnormalities were found in four neonates (6.4%) whose mothers did not receive chemotherapy during pregnancy. Fifty-nine infants underwent routine blood tests within 3 d after birth. The results showed that the mean white blood cell count, hemoglobin concentration, and platelet count were (16.1±7.0)×10 9/L, (181.5±20.0) g/L and (266.2±63.7)×10 9/L, respectively, and no juvenile cells were detected in their peripheral blood samples. Twenty children were followed up to 4 years and 4 months (9 months to 10 years and 3 months). No abnormalities in physical or mental development, motor function, or hematological system were reported. Conclusions:Pregnancy complicated by leukemia is rare and dangerous, which requires an individualized management strategy besides therapy for leukemia. A good prognosis is still expected with appropriate treatment.

Objective:To investigate the status of knowledge, attitude, and behavior of enteral nutrition implemented by nurses in burn intensive care unit (BICU) and analyze its influencing factors.Methods:A multi-center cross-sectional survey research method was used. On May 8 th, 2022, 107 BICU nurses who met the inclusion criteria were selected from the burn departments of the First Affiliated Hospital of Army Medical University (the Third Military Medical University), Guangdong Provincial People's Hospital, the First Affiliated Hospital of Guangxi Medical University, the Affiliated Hospital of Qinghai University, the Second Affiliated Hospital of Air Force Medical University, the Affiliated Hospital of Nantong University, Guiyang Steel Factory Staff Hospital, and the Second Affiliated Hospital of Kunming Medical University. The self-made nurses' enteral nutrition nursing knowledge-attitude-behavior questionnaire for severely burned patients was used to investigate the nurses' gender, age, working years, professional title, position, highest educational background, and whether they received systematic training in knowledge of enteral nutrition, the scores of each factor, and the total scores of knowledge, attitude, and behavior dimensions of enteral nutrition in nurses. The nurses were classified according to the general data, and the total scores of their knowledge, attitude, and behavior of enteral nutrition were calculated. Data were statistically analyzed with independent sample t test, one-way analysis of variance, Mann-Whitney U test, and Kruskal-Wallis H test. According to the results of univariate analysis and combined with clinical experience and significance, the generalized linear model analysis was carried out to screen the independent influencing factors of the total scores of knowledge, attitude, and behavior of enteral nutrition in BICU nurses. Results:A total of 107 nurses were surveyed, and 107 valid questionnaires were collected, with an effective recovery rate of 100%. In the BICU nurses' enteral nutrition knowledge-attitude-behavior questionnaire, the total scores of knowledge, attitude, and behavior were 44±13, 87±15, and 70±19, respectively. Most of the BICU nurses in this survey were female, aged 22-48 (31±6) years, and the number of nurses worked for 1-5, 6-10, and ≥11 years was evenly distributed. The majority of the professional titles of nurses were nurses, positions were responsible nurses, and the highest educational background was undergraduate. Forty-four nurses received systematic training in knowledge of enteral nutrition. There were statistically significant differences in the total scores of knowledge of enteral nutrition among BICU nurses with different ages, working years, professional titles, positions, highest educational background, and whether they received systematic training in knowledge of enteral nutrition (with H values of 27.36, 15.27, and 10.19, respectively, Z values of -3.33, -2.59, and -6.46, respectively, P<0.05). There were no statistically significant differences in the total scores of attitude and behavior of enteral nutrition among BICU nurses with different gender, ages, working years, professional titles, positions, highest educational background, and whether they received systematic training in knowledge of enteral nutrition ( P>0.05). Age (26-30, 31-35, and ≥36 years old), highest educational background (undergraduate), and the systematic training received in enteral nutrition knowledge were the independent influencing factors for the total score of knowledge of enteral nutrition in BICU nurses (with 95% confidence intervals of 0.12-0.36, 0-0.30, 0.03-0.31, 0.01-0.32, and 0.19-0.40, respectively, standardized regression coefficients of 0.24, 0.15, 0.17, 0.17, and 0.29, respectively, P<0.05). There were no independent influencing factors for the total scores of enteral nutrition attitude and behavior of BICU nurses in different characteristics ( P>0.05). Conclusions:The BICU nurses have low cognitive level in the implementation of enteral nutrition, their concept needs to be updated in time, and their behavior needs to be further standardized. Age (26-30, 31-35, and ≥36 years old), highest educational background (undergraduate), and the systematic training received in enteral nutrition knowledge were the independent influencing factors for the knowledge of enteral nutrition in BICU nurses.

Objective:To explore the clinical effect of X-N advancement flap in repairing pressure ulcer on the buttock or back.Methods:From June 2018 to June 2019, 20 patients with grade Ⅳ pressure ulcers on the buttock or back were hospitalized and treated in the Department of Traumatology, Burns and Plastic Surgery of Fourth Affiliated Hospital of Guangxi Medical University, including 15 males and 5 females, aged 48-89 years. The area of the patient′s wound was 8 cm×5 cm-15 cm×12 cm after debridement, and all were repaired with the X-N advancement flap designed by the author. The flap was designed according to the direction of skin relaxation on both sides of the wound, and the skin was incised in X-shape and sutured in N-shape. The width and advancement distance of the flap were recorded, and the ratio of the advancement distance to the width of the flap was calculated. The flap survival, complication, and follow-up were observed and recorded.Results:The width of the flap was (5.9±1.2) cm, the advancement distance of the flap was (10.3±2.5) cm, and the ratio of the advancement distance to the width of the flap was 1.8±0.4. All the flaps survived, and none of the flaps had blood flow disorder. Local dehiscence occurred in the flap of one patient 1 week after surgery, which was healed after laying on the floating bed, strengthened care, and wound dressing change. The flap of one patient developed infection 5 days after surgery, which was healed after partial suture removal, smooth drainage, and replacement with sensitive antibiotics. The wounds of the remaining 18 patients were all cured. After 3 months of follow-up, the flaps survived well with good elasticity and texture.Conclusions:The X-N advancement flap can make the skin and soft tissue move forward effectively. It is simple and effective to repair pressure ulcers on the back or buttock of patients with this flap, which is worthy of clinical promotion and application.

Objective To provide helpful continued medical education (CME) for physicians and improve gout treatment,we conducted a questionnaire survey to investigate physicians' knowledge in nine districts of Beijing.Methods A questionnaire survey including ten gout-related questions was conducted among 298 physicians in Beijing.Demographic data and previous gout CME experience were collected.Chi-square test or Student's t test,univariate analysis and logistic regression analysis were used to evaluate the relevant factors of physicians' knowledge level.Results A total of 250 valid copies were collected including 127 from community service centers (CSC),123 from tertiary hospitals.The correct answer rate of gout etiology,pathogenesis and attack symptoms were over 70％ in both groups.45.5％ (56/123) CSC doctors and 57.4％ (66/115) tertiary doctors answered right drugs to control acute gout attack (P=0.067).Only 42.3％ (52/123) in CSC and 53.4％ (63/118) in hospitals chose allopurinol as a urate-lowering drug (ULT),while 46.3％ (57/123) and 32.2％ (38/118) doctors considered colchicine as a ULT drug (P=0.084) respectively.Near half doctors considered that gout patients should take long-term ULT [40.5％ (51/126) vs.57.6％ (68/118)respectively,P=0.007].Univariate analysis showed that CME training could improve gout-related knowledge in CRC doctors.Conclusion Most CSC doctors generally understand basic knowledge of gout,while confusion of treatment is still significant.CME especially including standard gout treatment should be performed by doctors in tertiary hospitals.