With the rapid advancement of synthetic biology, CRISPR-Cas systems have emerged as a powerful tool for gene editing, demonstrating significant potential in various fields, including medicine, agriculture, and industrial biotechnology. This review comprehensively summarizes the significant progress in applying artificial intelligence (AI) technologies to the design, mining, and modification of CRISPR-Cas systems. AI technologies, especially machine learning, have revolutionized sgRNA design by analyzing high-throughput sequencing data, thereby improving the editing efficiency and predicting off-target effects with high accuracy. Furthermore, this paper explores the role of AI in sgRNA design and evaluation, highlighting its contributions to the annotation and mining of CRISPR arrays and Cas proteins, as well as its potential for modifying key proteins involved in gene editing. These advancements have not only improved the efficiency and precision of gene editing but also expanded the horizons of genome engineering, paving the way for intelligent and precise genome editing.
CRISPR-Cas Systems/genetics* ; Artificial Intelligence ; Gene Editing/methods* ; RNA, Guide, CRISPR-Cas Systems/genetics* ; Machine Learning ; Humans ; Genetic Engineering/methods* ; Synthetic Biology

Objective: To investigate the epidemilogical characteristics of pulmonary tuberculosis in Huzhou City, Zhejiang Province from 2014 to 2023, so as to provide the basis for formulating prevention and control measures for the construction of "TB-free city". Methods: The data of pulmonary tuberculosis cases in Huzhou City from 2014 to 2023 was collected through the Infectious Disease Reporting Management System of Chinese Disease Prevention and Control Information System. The onset time, region, and population distribution characteristics of the cases were described. Results: A total of 11 598 cases of pulmonary tuberculosis were reported in Huzhou City from 2014 to 2023, with an average annual incidence of 37.42/105. The reported incidence decreased from 47.50/105 in 2014 to 28.36/105 in 2023 (P<0.05), with an annual decline rate of 5.57%. There were 6 304 etiological positive cases, accounting for 54.35%. The peak season for pulmonary tuberculosis cases was from March to September, with the highest seasonal ratio of 112.48% in May. The average annual reported incidence rates in Anji County and Changxing County were relatively high (46.14/105 and 41.15/105). The reported incidence rate of pulmonary tuberculosis in Huzhou City increased with age (P<0.05), peaking at 97.36/105 in the group aged 75 to <80 years. There were 7 991 male pulmonary tuberculosis cases and 3 607 female cases, with a male-to-female ratio of 2.22∶1. The average annual incidence rates of pulmonary tuberculosis was higher in males than in females (50.39/105 vs. 23.87/105). Farmers were the primary occupation affected, with 6 350 cases accounting for 54.75%. Conclusions The reported incidence rate of pulmonary tuberculosis in Huzhou City decreased from 2014 to 2023, with a high incidence in spring and summer. The incidence rates in Anji County and Changxing County were higher than Huzhou City's average. Male, elderly residents and farmers were the key populations for pulmonary tuberculosis prevention and control.

Objective:To improve the ability of aviation physicians and physical examiners in differential diagnosis of primary angiitis of the central nervous system (PACNS) and the level of aeromedical assessment by exploring the diagnosis and treatment of PACNS.Methods:The clinical diagnosis and treatment of a pilot with PACNS were reported and the related literatures were reviewed.Results:The clinical manifestation of the fighter trainer pilot was numbness of the left finger, and then gradually appeared numbness and weakness of the left face and left upper limb more than 1 month. The initial diagnosis was viral encephalitis and acute disseminated encephalomyelitis and the hormonal shock treatment was ineffective. The final diagnosis was PACNS. The patient′s condition was improved by cyclophosphamide shock treatment. Aeromedical assessment concluded that the pilot was temporarily grounded.Conclusions:Pilot with PACNS is rarely reported and easy to be misdiagnosed due to the clinical and imaging findings are lack of specificity. The aeromedical assessment of PACNS pilots should be individualized according to the severity of illness, type of aircraft and flight duties.

Shift handover is a process of transferring power and responsibility between medical staff,and it is also a basic part of medical activities.Intensive care unit(ICU)is the core area for the treatment of critically ill patients,with complex patient conditions and fine and diverse treatment.If clinical information cannot be shared accurately and in time,it will lead to the delay of the patient's condition,diagnosis and treatment plan.At the same time,the omission of handover information and communication problems can easily lead to safety risks,prolonged hospital stay and increased number of readmissions.Therefore,as one of the important links in ICU diagnosis and treatment and nursing work,accurate,complete and effective handover can ensure the rapid and accurate transmission of patient information and promote the smooth development of diagnosis and treatment and nursing work.This paper reviews the application scope of ICU shift handover model,analyzes the main characteristics,application status and application effects of ICU shift model,and discusses the problems and shortcomings of the existing ICU shift model,in order to provide a reference for further optimizing the quality of ICU shift.PRISMA extension for scoping reviews(PRISMA-ScR)as methodological guidance,we conducted a systematic search across major databases including PubMed,Web of Science,Embase,Cumulative Index to Nursing and Allied Health Literature(CINAHL),and Chinese databases(Wanfang,CNKI,Chinese Medical Association,CBM)using both subject headings and free-text terms).The search time limit was from the establishment of the database to July 18,2024.The preliminary retrieved literature bibliographer was imported into Endnote 20.0 software,and the obtained literature was selected and screened by two researchers.A total of 14 articles were included,of which 10 were from China and 4 were from the United States,and all were published between 2012 and 2022.The analysis showed that the ICU shift mode mainly included improved shift mode,group system shift mode,anti-shift mode,checklist type shift sheet mode and electronic information ICU shift.The shift mode showed diversified characteristics,optimized staffing to a certain extent,standardized the specific content and process of shift,and improved the quality of shift.Significant advances have been made in information delivery and quality of care.However,domestic research is mostly focused on the improvement of the shift mode,which faces the shortcomings of increasing workload,coordination and communication challenges,and the scientification and standardization of tools.Electronic information technology makes up for the shortcomings of information omission in the traditional shift process through the advantages of automatic data collection and information collection,and shows positive results in the process of shift.Future research needs to further explore the basis of not increasing the load of ICU clinical medical staff,ensuring the efficiency of shift and normal work flow.Pay attention to the intelligent,standardized and personalized construction of ICU shift,improve the quality of diagnosis and treatment and nursing,and ensure the safety of patients.

Shift handover is a process of transferring power and responsibility between medical staff,and it is also a basic part of medical activities.Intensive care unit(ICU)is the core area for the treatment of critically ill patients,with complex patient conditions and fine and diverse treatment.If clinical information cannot be shared accurately and in time,it will lead to the delay of the patient's condition,diagnosis and treatment plan.At the same time,the omission of handover information and communication problems can easily lead to safety risks,prolonged hospital stay and increased number of readmissions.Therefore,as one of the important links in ICU diagnosis and treatment and nursing work,accurate,complete and effective handover can ensure the rapid and accurate transmission of patient information and promote the smooth development of diagnosis and treatment and nursing work.This paper reviews the application scope of ICU shift handover model,analyzes the main characteristics,application status and application effects of ICU shift model,and discusses the problems and shortcomings of the existing ICU shift model,in order to provide a reference for further optimizing the quality of ICU shift.PRISMA extension for scoping reviews(PRISMA-ScR)as methodological guidance,we conducted a systematic search across major databases including PubMed,Web of Science,Embase,Cumulative Index to Nursing and Allied Health Literature(CINAHL),and Chinese databases(Wanfang,CNKI,Chinese Medical Association,CBM)using both subject headings and free-text terms).The search time limit was from the establishment of the database to July 18,2024.The preliminary retrieved literature bibliographer was imported into Endnote 20.0 software,and the obtained literature was selected and screened by two researchers.A total of 14 articles were included,of which 10 were from China and 4 were from the United States,and all were published between 2012 and 2022.The analysis showed that the ICU shift mode mainly included improved shift mode,group system shift mode,anti-shift mode,checklist type shift sheet mode and electronic information ICU shift.The shift mode showed diversified characteristics,optimized staffing to a certain extent,standardized the specific content and process of shift,and improved the quality of shift.Significant advances have been made in information delivery and quality of care.However,domestic research is mostly focused on the improvement of the shift mode,which faces the shortcomings of increasing workload,coordination and communication challenges,and the scientification and standardization of tools.Electronic information technology makes up for the shortcomings of information omission in the traditional shift process through the advantages of automatic data collection and information collection,and shows positive results in the process of shift.Future research needs to further explore the basis of not increasing the load of ICU clinical medical staff,ensuring the efficiency of shift and normal work flow.Pay attention to the intelligent,standardized and personalized construction of ICU shift,improve the quality of diagnosis and treatment and nursing,and ensure the safety of patients.

Objective:To improve the ability of aviation physicians and physical examiners in differential diagnosis of primary angiitis of the central nervous system (PACNS) and the level of aeromedical assessment by exploring the diagnosis and treatment of PACNS.Methods:The clinical diagnosis and treatment of a pilot with PACNS were reported and the related literatures were reviewed.Results:The clinical manifestation of the fighter trainer pilot was numbness of the left finger, and then gradually appeared numbness and weakness of the left face and left upper limb more than 1 month. The initial diagnosis was viral encephalitis and acute disseminated encephalomyelitis and the hormonal shock treatment was ineffective. The final diagnosis was PACNS. The patient′s condition was improved by cyclophosphamide shock treatment. Aeromedical assessment concluded that the pilot was temporarily grounded.Conclusions:Pilot with PACNS is rarely reported and easy to be misdiagnosed due to the clinical and imaging findings are lack of specificity. The aeromedical assessment of PACNS pilots should be individualized according to the severity of illness, type of aircraft and flight duties.

ObjectiveTo explore the pharmacodynamic effects of total flavonoids of Paeonia suffruticosa flower （TFPFs） on rats with hyperuricemia and provide scientific data support for the research and development of therapeutic drugs for hyperuricemia. MethodThe hyperuricemia model was induced by adenine combined with ethambutol in rats. The rats were randomly divided into a blank control group， a model group， two positive control groups （allopurinol at 42 mg·kg^-1 and Tongfengshu tablets at 600 mg·kg^-1）， and high-， medium-， and low-dose TFPFs groups （260， 130， and 65 mg·kg^-1）. The general conditions of rats were observed and recorded， and the body weight was recorded once every 5 days. The 24-hour urine volume， water intake， uric acid （UA）， and urinary protein of rats were determined after the last administration. The kidney index was calculated. The pathological changes in thymus and spleen tissues of rats were observed by hematoxylin-eosin （HE） staining. The serum activities of UA， creatinine （Cr）， blood urea nitrogen （BUN）， malondialdehyde （MDA）， superoxide dismutase （SOD）， and total antioxidant capacity （T-AOC） of rats were determined. The xanthine oxidase （XOD） and adenosine deaminase （ADA） activities in the liver were detected. The content of uric acid transporter 1 （URAT1）， organic anion transporter 1 （OAT1）， and glucose transporter 9 （GLUT9） in the kidney was detected by enzyme-linked immunosorbent assay （ELISA）. ResultCompared with the results in the model group， TFPFs could improve the mental state of rats， increase the body weight（P<0.01）， promote UA excretion（P<0.01）， reduce the content of urinary protein（P<0.05）， relieve renal glomerular atrophy， renal tubular epithelial cell status， and urate crystal deposition in renal tubules， dwindle 24-hour urine volume， water intake， kidney index（P<0.05）， serum levels of UA， Cr， BUN， and MDA（P<0.05，P<0.01）， inhibit the activities of XOD（P<0.05） and ADA（P<0.05，P<0.01）in the liver， diminish the expression of GLUT9 in the renal homogenate（P<0.05）， and increase serum SOD and T-AOC activities as well as OAT1 expression（P<0.01） in the kidney. The pathological changes of thymus and spleen were improved. ConclusionTFPFs possess a protective effect on the kidney of rats with hyperuricemia， which is achieved by promoting uric acid excretion， inhibiting oxidation and the activity of key enzymes in uric acid synthesis， and regulating the expression of uric acid transporters.

Objective:To explore the application effect of global trigger tool (GTT) in detecting adverse events in ICU patients.Methods:According to contents of triggers in the GTT white paper, combined with the scope of domestic adverse event reporting and some ICU indexes, 16 triggers were established. A total of 1 683 medical records were collected from ICU of the Second People's Hospital of Liaocheng in Shandong Province from July 2018 to June 2019. According to the inclusion/exclusion criteria, 421 medical records of discharged patients were randomly selected according to the number of sampling intervals and 420 medical records were reviewed after eliminating repeated medical records. GTT method was used for retrospective analysis.Results:Of the 420 medical records actually used for review, 14 of the 16 triggers were positive, and the positive frequency of triggers was 128 cases, involving 62 patients. Adverse events were identified 51 times, involving 43 patients, with a detection rate of 10.24% (43/420) . Among the 51 cases of adverse events, 37 cases (72.55%) were Grade E, 13 cases (25.49%) were Grade F, and 1 case (1.96%) was Grade H. No Grade G or I was found. In the same year, 18 cases of adverse events were reported voluntarily in ICU, the reporting rate was 1.07% (18/1 683) .Conclusions:GTT can be effectively applied to the detection of adverse events in ICU patients, and a properly designed trigger can improve the detection rate.

Objective To explore the short-term hemodynamic change of fluid challenge (FC) with crystalloid or colloid and define fluid responsiveness at the optimal time in patients with septic shock. Methods A prospective observational study was conducted. Septic shock patients monitored with pulmonary catheters admitted to medical intensive care unit (ICU) of the Peking Union Medical College Hospital from July 2016 to December 2018 were enrolled. All included patients received FC and were divided into two groups according to the type of fluid used, i.e. crystalloid group (normal saline for 500 mL) and colloid group (4% succinyl gelatin for 500 mL). The choice of fluid type was decided by the attending physician. Hemodynamic variables were measured at baseline, and 0 (immediately), 10, 30, 45, 60, 90, 120 minutes after FC, included cardiac index (CI), heart rate (HR), mean artery pressure (MAP), central venous pressure (CVP) and pulmonary arterial wedge pressure (PAWP). Fluid responsiveness was defined as CI increased by more than 10% after FC. The data were analyzed by repeated measurements of variance between the two groups as well as responders and nonresponders. Results Forty patients were included, 20 cases each in colloid group and crystalloid group; of whom 26 were fluid responders with 12 of colloid group and 14 of crystalloid group. Of the 14 nonresponders, 8 were of colloid group and 6 of crystalloid group. ① Compared with before FC, CI (mL·s-1·m-2) was significantly increased in crystalloid and colloid groups after FC (71.7±16.7 vs. 65.0±16.7, 68.3±25.0 vs. 63.3±23.3, both P < 0.05). In the colloid group, volume expansion increased the CI to maximum (76.7±18.3) at 30 minutes after FC, at 120 minutes after FC, a significantly higher CI (70.0±16.7) was also observed (P < 0.05), an increased in CI≥10% was observed at 60 minutes after FC. In the crystalloid group, CI was increased to maximum at 10 minutes (73.3±28.3) and decreased to baseline at 60 minutes, an increased in CI≥10% was also observed at 10 minutes after FC. In addition, there was no significant difference in CI changes between colloidal group and crystalloid group at different time points after FC. ② CI did not change over time in nonresponders groups, whereas in responders CI increased parallelly to that in both crystalloid and colloid groups over time. However, an increased in CI≥10% was observed through the 120 minutes after FC in responders of colloid group compared with that of at 30 minutes after FC in crystalloid group. There was significant difference in CI changes between colloidal group and crystalloid group at 30, 45, 60, 90 minutes after FC (mL·s-1·m-2: 18.3±3.3 vs. 8.3±1.7, 18.3±3.3 vs. 5.0±1.7, 13.3±1.7 vs. 3.3±1.7, 11.7±3.3 vs. 3.3±1.7, all P <0.05). ③ The maximal values of CVP and PAWP were observed at the end of FC. In colloid group, both the two variables were notably higher than that before FC over 120 minutes compared with that of only at 10 minutes in crystalloid group. The MAP in colloid increased to maximum immediately at the end of FC and decreased to baseline at 45 minutes, however, the MAP in crystalloid group and HR of both groups showed no differences over 120 minutes. Conclusions Hemodynamic changes were significantly different between crystalloid and colloid after FC in patients with septic shock. Therefore, the timing of fluid responsiveness assessment should be different individually. The assessment time of colloid group may be prolonged to 30 minutes after FC while that of crystal group can be at 10 minute after FC.

Objective To evaluate the accuracy of central venous-to-arterial carbon dioxide partial pressure difference (Pcv-aCO2) before and after rapid rehydration test (fluid challenge) in predicting the fluid responsiveness in patients with septic shock. Methods A prospective observation was conducted. Forty septic shock patients admitted to medical intensive care unit (ICU) of Peking Union Medical College Hospital from October 2015 to June 2017 were enrolled. All of the patients received fluid challenge in the presence of invasive hemodynamic monitoring. Heart rate (HR), blood pressure, cardiac index (CI), Pcv-aCO2 and other physiological variables were recorded at 10 minutes before and immediately after fluid challenge. Fluid responsiveness was defined as an increase in CI greater than 10% after fluid challenge, whereas fluid non-responsiveness was defined as no increase or increase in CI less than 10%. The correlation between Pcv-aCO2 and CI was explored by Pearson correlation analysis. Receiver operating characteristic (ROC) curves were established to evaluate the discriminatory abilities of baseline and the changes after fluid challenge in Pcv-aCO2 and other physiological variables to define the fluid responsiveness. The patients were separated into two groups according to the initial value of Pcv-aCO2. The cut-off value of 6 mmHg (1 mmHg = 0.133 kPa) was chosen according to previous studies. The discriminatory abilities of baseline and the change in Pcv-aCO2(ΔPcv-aCO2) were assessed in each group. Results A total of 40 patients were finally included in this study. Twenty-two patients responded to the fluid challenge (responders). Eighteen patients were fluid non-responders. There was no significant difference in baseline physiological variable between the two groups. Fluid challenge could increase CI and blood pressure significantly, decrease HR notably and had no effect on Pcv-aCO2 in fluid responders. In non-responders, blood pressure was increased significantly and CI, HR, Pcv-aCO2 showed no change after fluid challenge. Pcv-aCO2 was comparable in responders and non-responders. In 40 patients, CI and Pcv-aCO2 was inversely correlated before fluid challenge (r = -0.391, P = 0.012) and the correlation between them weakened after fluid challenge (r = -0.301, P = 0.059). There was no significant correlation between the changes in CI and Pcv-aCO2 after fluid challenge (r = -0.164, P = 0.312). The baseline Pcv-aCO2 and ΔPcv-aCO2 could not discriminate between responders and non-responders, with the area under ROC curve (AUC) of 0.50 [95% confidence interval (95%CI) =0.32-0.69] and 0.51 (95%CI = 0.33-0.70), respectively. HR and blood pressure before fluid challenge and their changes after fluid challenge showed very poor discriminative performances. Before fluid challenge, 16 patients had a Pcv-aCO2 > 6 mmHg. Their mean CI was significantly lower and Pcv-aCO2 was significantly higher than that in 24 patients whose Pcv-aCO2 ≤6 mmHg [n = 24; CI (mL·s-1·m-2): 48.3±11.7 vs. 65.0±18.3, P < 0.01; Pcv-aCO2 (mmHg): 8.4±1.9 vs. 2.9±2.8, P < 0.01]. Pcv-aCO2was decreased significantly after fluid challenge in patients with an initial Pcv-aCO2 > 6 mmHg and their ΔPcv-aCO2 was notably different as compared with the patients whose baseline Pcv-aCO2≤6 mmHg (mmHg: -3.8±3.4 vs. 0.9±2.9, P < 0.01). 68.8% (11/16) patients responded to the fluid challenge in patients with an initial Pcv-aCO2 > 6 mmHg. The AUC of the baseline Pcv-aCO2 and ΔPcv-aCO2 to define fluid responsiveness was 0.85 (95%CI = 0.66-1.00) and 0.84 (95%CI = 0.63-1.00), respectively, and the positive predictive value was 1 when the cut-off value was 8.0 mmHg and -4.2 mmHg, respectively. 45.8% (11/24) patients responded to the fluid challenge in patients whose baseline Pcv-aCO2≤6 mmHg. There was no predictive value of baseline Pcv-aCO2 and ΔPcv-aCO2 on fluid responsiveness. Conclusion Pcv-aCO2 and its change cannot serve as a surrogate of the change in cardiac output to define the response to fluid challenge in septic shock patients whose baseline Pcv-aCO2≤6 mmHg, while the predictive values of baseline Pcv-aCO2and the change in Pcv-aCO2 are presented in patients with the initial value of Pcv-aCO2 > 6 mmHg. Clinical Trial Registration Clinical Trials, NCT01941472.