Objective: To investigate the environmental contamination of norovirus in nurseries and primary/secondary schools, so as to provide a scientific basis for effective prevention and control measures. Methods: A total of 483 external environmental samples were collected from 34 cluster outbreaks of norovirus gastroenteritis in kindergartens and primary/secondary schools in Linhai City from 2021 to 2024. Pathogen detection was conducted using a rapid nucleic acid extraction kit and realtime fluorescence RT-PCR, and the results were analyzed using the χ2 test or Fishers exact test. Results: Among the collected external environmental samples, the total positive rate of surface contamination was 13.66%. The positive rates in kindergartens and primary/secondary schools were 12.20% and 15.82%, respectively. In kindergartens, the five surfaces with the highest detection rates were desks/chairs (23.33%), toilet stool troughs (20.69%), urinal troughs (12.00%), washbasins/sinks (11.11%), and toilet mops (9.38%). In primary/secondary schools, the top five were toilet stool troughs (38.30%), urinal troughs (23.53%), toilet door handles (13.04%), toilet mops (12.50%), and drinking cups (11.11%). The difference in positive detection rates among different external environments in primary/secondary schools was statistically significant (Fishers exact probability test, P<0.01). The positive detection rate in sanitary toilets was higher than that in classroom environments (χ2=17.38), while the positive detection rate in classroom environments of kindergartens was higher than that in primary/secondary schools (χ2=5.42)(P<0.05). Conclusions Norovirus exhibits a high contamination rate in nurseries and schools, particularly in restroom areas. Strengthening sanitation and disinfection in highrisk environments, and improving hygiene awareness among children and staff, are essential for the effective prevent and control of norovirus.

Abstract: It is well-known that crystal form of a drug is a key factor impacting the physicochemical properties of the drug, which in turn affects its in vivo efficacy, safety and stability. The study on crystal forms of solid-state drugs is crucial for drug quality control, selection of production process and evaluation of clinical efficacy. The combination of chemometric and analytical techniques exhibited its great ability to analyze a large amount of multidimensional data, providing the possibility for quantification of trace amount of crystals (< 1%). Meanwhile, using the process analytical technology (PAT) to monitor the crystal content real-time during prescription preparation process can further realize the control on formulation quality and serve as a core technology to support the patent protection of crystalline forms. In this review, the combined application of crystal analytical techniques and chemometric methods for the quantitative analysis of trace crystals were summarized, aiming to provide guidance for the manufacturing of pharmaceutical preparations and their quality control.

Objective:To explore potential predictors of refractory Mycoplasma pneumoniae pneumonia (RMPP) in early stage. Methods:The prospective multicenter study was conducted in Zhejiang, China from May 1 st, 2019 to January 31 st, 2020. A total of 1 428 patients with fever >48 hours to <120 hours were studied. Their clinical data and oral pharyngeal swab samples were collected; Mycoplasma pneumoniae DNA in pharyngeal swab specimens was detected. Patients with positive Mycoplasma pneumoniae DNA results underwent a series of tests, including chest X-ray, complete blood count, C-reactive protein, lactate dehydrogenase (LDH), and procalcitonin. According to the occurrence of RMPP, the patients were divided into two groups, RMPP group and general Mycoplasma pneumoniae pneumonia (GMPP) group. Measurement data between the 2 groups were compared using Mann-Whitney U test. Logistic regression analyses were used to examine the associations between clinical data and RMPP. Receiver operating characteristic (ROC) curves were used to analyse the power of the markers for predicting RMPP. Results:A total of 1 428 patients finished the study, with 801 boys and 627 girls, aged 4.3 (2.7, 6.3) years. Mycoplasma pneumoniae DNA was positive in 534 cases (37.4%), of whom 446 cases (83.5%) were diagnosed with Mycoplasma pneumoniae pneumonia, including 251 boys and 195 girls, aged 5.2 (3.3, 6.9) years. Macrolides-resistant variation was positive in 410 cases (91.9%). Fifty-five cases were with RMPP, 391 cases with GMPP. The peak body temperature before the first visit and LDH levels in RMPP patients were higher than that in GMPP patients (39.6 (39.1, 40.0) vs. 39.2 (38.9, 39.7) ℃, 333 (279, 392) vs. 311 (259, 359) U/L, both P<0.05). Logistic regression showed the prediction probability π=exp (-29.7+0.667×Peak body temperature (℃)+0.004×LDH (U/L))/(1+exp (-29.7+0.667×Peak body temperature (℃)+0.004 × LDH (U/L))), the cut-off value to predict RMPP was 0.12, with a consensus of probability forecast of 0.89, sensitivity of 0.89, and specificity of 0.67; and the area under ROC curve was 0.682 (95% CI 0.593-0.771, P<0.01). Conclusion:In MPP patients with fever over 48 to <120 hours, a prediction probability π of RMPP can be calculated based on the peak body temperature and LDH level before the first visit, which can facilitate early identification of RMPP.

Pharmaceutical excipients, as an indispensable part of drug preparation, play crucial roles as drug carriers, improving drug release, ensuring drug stability, and enhancing patient compliance. Traditional Chinese Medicine (TCM) boasts a rich developmental history. With the modernization of technology, the deep integration of pharmacy, chemistry, and materials science has provided broader opportunities for innovative research in TCM. Simultaneously, the demand for high-quality excipients has become increasingly critical.This paper aims to review current research and applications of excipients in TCM preparations, including pre-mixed and co-processed excipients, modified excipients, and the unification of drugs and excipients, such as flavoring agents, fillers, penetration enhancers, and delivery systems. A meticulous synthesis and analysis of existing research aims to provide a reference for selecting excipients in TCM preparations, stimulate innovation in excipient development for TCM, and advocate for the development of personalized excipients.

Taking the Ligustrum lucidum extract as an example, this study investigated the influence of external mechanical forces under different processing conditions on the crystallographic solid form and the key parameter of drug dissolution rate, so as to provide guidance for the preparation and quality control of traditional Chinese medicine preparations. Under different pulverization and tableting conditions, the change of crystallographic solid form of L. lucidum extract was observed by polarizing light microscope. Meanwhile, the effect of this change on the dissolution rate was investigated, and the mathematical relationship between crystal content and dissolution rate was analyzed. The results showed that the process of ball milling and tableting had a significant impact on the crystallographic solid form of L. lucidum extract. The amorphous extract displayed crystal transformation, which induced a significant decline in dissolution rate. Further studies revealed that there was a negative linear relationship between crystal content and dissolution rate. The results of this study indicated that the crystallographic solid form transformation of traditional Chinese medicine extracts might occur during the preparation process, which may cause potential risks to the quality of traditional Chinese medicine preparations. It is suggested that we should pay attention to and strengthen the investigation of the crystallographic solid form during the preparation process, so as to guarantee the safety, effectiveness, and quality controllability of traditional Chinese medicine preparations.

Objective:To study the localization value of stereoelectroencephalography (SEEG) in refractory epilepsy associated with tuberous sclerosis complex (TSC), and to analyze the prognosis related factors.Methods:A case control study.Data of 66 patients with TSC-related refractory epilepsy who underwent SEEG placement at the Epilepsy Center of Tsinghua University Yu-Quan Hospital from January 2014 to March 2023 were retrospectively analyzed, including medical history, seizure semiology, scalp electroencephalogram (EEG), imaging, and SEEG findings.Patients were divided into a seizure-free group and a seizure group according to the seizures after surgery. t/ χ2 test was used to compare the relationship between age of onset, age of surgery, duration of epilepsy, genetic findings, seizure symptoms, scalp EEG characteristics, SEEG placement protocol and prognosis. Results:A total of 66 patients met the enrollment criteria, of whom 55 patients were seizure-free after surgery (seizure-free group), and 11 patients still had seizures (seizure group).Among the 66 patients, there were 46 males and 20 females; the age of onset was (21.72±30.01) months; the age of SEEG surgery was (6.79±5.12) years; the duration of epilepsy was (4.98±4.11) years.SEEG results showed that seizures started with a single tuber in 43 patients (64.4%), seizures started with 2 or more tubers in one hemisphere in 16 patients, and 7 patients had bilateral multi-tubers or the pathogenic tuber(s) could not be identified.The following factors were found to be associated with prognosis: early age of surgery ( t=-3.463, P<0.01), ictal scalp EEG with a definite lateralization ( χ2=7.876, P<0.05), and the concordance of interictal and ictal EEG ( χ2=6.821, P<0.05).The age of onset, duration of epilepsy, seizure type and symptom, genetic findings, and SEEG placement protocol were not significantly correlated with prognosis.The results of SEEG identified that onset with a single tuber revealed a better postoperative outcome. Conclusions:This study confirms the safety and efficacy of SEEG in TSC-related refractory epilepsy, and also finds that ictal EEG is uniquely valuable in guiding SEEG placement for TSC-related refractory epilepsy, which can help us better select patients with TSC-related refractory epilepsy who are suitable for SEEG placement.

Objective To explore the value of non-contrast CT findings of acute ischemic stroke(AIS)for predicting early prognosis after mechanical thrombectomy.Methods Data of 161 AIS patients from clinical center 1 who underwent mechanical thrombectomy were retrospectively analyzed.The patients were divided into training set(n=113)and internal test set(n=48)at the ratio of 7∶3,while 79 AIS patients who underwent mechanical thrombectomy from clinical center 2 were retrospectively enrolled as external test set.According to the National Institutes of Health stroke scale(NIHSS)scores 7 days after thrombectomy,patients'prognosis were classified as good(＜15 points)or poor(≥15 points).Pre-treatment non-contrast CT images of patients were reviewed,and CT findings were comparatively analyzed.Independent predictors of patients'early prognosis after mechanical thrombectomy were obtained with sequential univariate and multivariate logistic regressions,and a predicting model was established and visualized as a nomogram.The receiver operating characteristic curve was drawn,and the distinction was assessed with the area under the curve(AUC),then calibration was assessed with Hosmer-Lemeshow goodness of fit test,and the net benefit was evaluated with decision curve analysis(DCA).Results Alberta stroke program early CT score(ASPECTS),hyperdense middle cerebral artery sign(HMCAS)and basal ganglia calcification were all independent predictors of early prognosis of AIS after mechanical thrombectomy(all P＜0.05).The predictive model was established combining the above 3 variables and then visualized as a nomogram to predict prognosis of AIS after mechanical thrombectomy,with AUC of 0.776 in internal test set(χ2=6.052,P=0.417)and 0.800 in external test set(χ2=2.269,P=0.811).DCA showed that the nomogram might provide clinical net benefit within certain threshold probability ranges.Conclusion ASPECTS,HMCAS and basal ganglia calcification were all independent predictors of early prognosis of AIS after mechanical thrombectomy.The nomogram originated from predicting model combining the three could be used to somewhat accurately predict poor early prognosis after mechanical thrombectomy.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

In recent years, bio-metal organic frameworks (Bio-MOFs) synthesized with biocompatible ligands have been widely investigated as a potential drug delivery carrier due to their large specific surface area and porosity, rich host-guest intermolecular interactions, and good biocompatibility.In this review, we summarized the design methods of Bio-MOFs including structural and toxic factors, as well as a variety of drug loading methods including click chemistry, with particular focus on recent research advances in Bio-MOFs for pulmonary drug delivery systems, improving pharmaceutical properties of drugs, sustained and controlled drug release, stimulation response and targeted drug delivery systems.Finally, we summarized the bottlenecks that constrain the development of Bio-MOFs in clinical studies of actual pharmaceutical formulations and their future directions for approved formulations, aiming to provide some theoretical reference for promoting the application of Bio-MOFs in drug delivery systems.

In order to guarantee the quality of traditional Chinese medicines (TCMs), the crystallization transformation of complex extracts of TCMs and the influence of solid form on their physicochemical properties were studied.The extract of total flavonoids from Pueraria lobata was taken as a model.Crystallization transformation happened when lofting under different conditions, and the intrinsic dissolution tests were carried out.It was found that humidity was the key factor to induce crystallization of total flavonoids from Pueraria lobata.The greater the wettability was, the more the crystallization was.The dissolution rate of total flavonoids from Pueraria lobata with the most crystallization amount significantly decreased by 96.51% compared to the sample without crystallization.After further simulating the preparation process of total flavonoids from Pueraria lobata, it was found that the wet granulation process with introduced water would also lead to crystallization and reduced dissolution rate.As for all crystallization samples, there was an inversely proportional relationship between the dissolution rates and the amount of crystallization.The risk of crystallization existed both in the storage and preparation process of TCM extracts.Crystallization would significantly affect the dissolution rate, and thus the quality of TCM products.In this study, the crystallization transformation of amorphous complex TCM extracts was discovered, and the effect of the crystallization transformation on its dissolution behavior was systematically studied, which provides a new research idea for assuring the quality of TCM products and promoting the improvement of TCM preparation level.