ObjectiveTo understand the usage of antibiotics in outpatients in a county of Zhejiang Province from 2015 to 2020， so as to provide a basis for further standardizing the clinical application of antibiotics in this region. MethodsOutpatient records and prescription records of 146 public medical institutions from 2015 to 2020 were extracted from the electronic medical record data sharing platform system of medical institutions in a county of Zhejiang Province. The utilization rates and the number of types of antibiotics used in outpatient patients were described. According to the drug anatomy， therapeutic and chemical classification system （ATC）， clinical application classification and dosage form， the use status of different types of antibiotics was observed. The annual percentage change （APC） was used to analyze the time trend of antibiotic use. Among the antibiotic prescriptions in each year， the proportions of prescriptions aimed for different use reasons and patients were compared to analyze the changes in the structures of antibiotic prescriptions. ResultsDuring 2015‒2020， a total of 2 861 438 prescriptions were issued in146 primary public medical institutions in this county， including 314 642 prescriptions for antibiotics， and the overall utilization rate of antibiotics was 11%. The utilization rate of antibiotics showed a decreased trend across the years （from 14.23% in 2015 to 7.59% in 2020，APC=-11.51%， 95%CI=-0.01%‒-21.7%， t=-12.05， P<0.001） and an obvious seasonal variation character （higher in winter and spring， lower in summer and autumn）. Cefoxitin sodium for injection was the most used antibiotic in 2015， and cefuroxime was the most used antibiotic from 2015 to 2020， respectively. The utilization rates of cephalosporins （APC=-11.06%， 95%CI=0‒-20.89%， t=-22.233， P<0.001）， quinolones （APC=-9.74%， 95%CI=0‒-18.53%， t=-7.652， P=0.002）， macrolides （APC=-17.52%， 95%CI=0‒-17.52%， t=-3.626， P=0.022） and lincoamides （APC=-49.01%， 95%CI=0‒-74%， t=-3.35， P=0.029） showed a decreasing trend across the years. There were differences in the distribution of drug use reasons （χ²=9 458.427， P<0.001）， as well as the age （χ²=5 421.709， P<0.001） and sex （χ²=245.322， P<0.001） of patients. During the observation period， 50.69% of antibiotic prescriptions were used to treat respiratory diseases， with the highest proportion of 57.67% in 2015 and the lowest proportion of 34.93% in 2020. 58.37% of patients were aged 50‒70 years， with a decreasing proportion of patients under 50 years （17.83% in 2015， 6.64% in 2020） and an increasing proportion of patients over 70 years （24.1% in 2015， 38.41% in 2020）. ConclusionThe utilization rate of antibiotics used in outpatients from primary public medical institutions in a county of Zhejiang Province shows a decreasing trend across the years， but higher than that of secondary and above hospitals in China， and also higher than that of primary medical institutions in economically-developed areas. The management and monitoring of the clinical use of antibiotics in the county should be actively strengthened.

Standardized reporting is a crucial factor affecting the use of patient guidelines （PGs）， particularly in the reporting and presentation of recommendations. This paper introduced the current status of PG reporting， including the research on PG content and presentation formats， and provided comprehensive recommendations for PG reporting from aspects such as overall framework， recommendations， presentation format， and readability. First， the presentation of PG recommendations should include clearly defined clinical questions， recommendations and their rationale， and guidance on how patients should implement the interventions； for specific content in the PG， such as level of evidence， level of recommendation， it is recommended to explain in text the reasons for giving different levels of recommendation， i.e.， to present the logic behind giving the level of recommendation to the patient； additional information needed in the recommendation framework should be supplemented by tracing references or authoritative textbooks and literature that support the recommendations. Subsequently， the PG text should be written based on the Reporting Checklist for Public Versions of Guidelines （RIGHT-PVG） reporting framework. Finally， to enhance readability and comprehension， it is recommended to refer to the Patient Education Materials Assessment Tool （PEMAT） for translating PG content. To enhance the readability of PGs， it is suggested to present the PG content in a persona-lized and layered manner.

Since the concept of patient versions of guidelines （PVGs） was introduced into China， several PVGs have been published in China， but we found that there is a big difference between the concept of PVG at home and abroad， and the reason for this difference has not been reasonably explained， which has led to ambiguity and even misapplication of the PVG concept by guideline developers. By analyzing the background and purpose of PVGs， and the understanding of the PVG concept by domestic scholars， we proposed the term patient guidelines （PGs）. This refers to guidelines developed under the principles of evidence-based medicine， centered on health issues that concern patients， and based on the best available evidence， intended for patient use. Except for the general attribute of providing information or education， which is typical of common health education materials， PGs also provide recommendations and assist in decision-making， so PGs include both the patient versions of guidelines （PVG） as defined by the Guidelines International Network （GIN） and "patient-directed guidelines"， i.e. clinical practice guidelines resulting from the adaptation or reformulation of recommendations through clinical practice guidelines.

At present， the process and methodology of patient guidelines （PGs） development varies greatly and lacks systematic and standardised guidance. In addition to the interviews with PG developers， we have sorted out the relevant methodology for the adaptation and development of existing clinical practice guideline recommendations and facilitated expert deliberations to achieve a consensus， so as to finally put forward a proposal for guidance on the process and methodology for the development of PGs. The development of PGs can be divided into the preparation stage， the construction stage， and the completion stage in general， but the specific steps vary according to the different modes of development of PGs. The development process of Model 1 is basically the same as the patient version of the guideline development process provided by the International Guidelines Network， i.e.， team formation， screening of recommendations， guideline drafing， user testing and feedback， approval and dissemination. The developer should also first determine the need for and scope of translating the clinical practice guideline into a patient version during the preparation phase. Model 2 adds user experience and feedback to the conventional clinical practice guideline development process （forming a team， determining the scope of the PG， searching， evaluating and integrating evidence， forming recommendations， writing the guideline， and expert review）. Based on the different models， we sort out the process and methods of PG development and introduce the specific methods of PG development， including how to identify the clinical problem and how to form recommendations based on the existing clinical practice guidelines， with a view to providing reference for guideline developers and related researchers.

Objective To investigate the effect of glycine N-methyl transferase (GNMT)on intrauterine adhesion (IUA)fibrosis and its related mechanism.Methods In vivo experiment:A total of 36 healthy female SD rats (SPF grade,6～8 weeks old and weighing from 180～220 g)were subjected in this study.IUA model of SD rats and IUA model of GNMT overexpressed rats were established.RT-qPCR and immunofluorescence assay were applied to detect GNMT expression level in normal uterus and model group.RT-qPCR and Western blotting were used to detect the mRNA and protein levels of fibrosis-related molecules and the activation of TGF-β1/Smad3 signaling pathway in each group.The number of endometrial glands in each group was observed by HE staining.Masson staining was used to analyze the severity of endometrial fibrosis in each group.In vitro experiment:transformed human endometrial stromal cells (THESCs)fibrotic phenotype model was constructed using TGF-β1,and THESCs stably transfected with GNMT overexpression lentvirus were treated with TGF-β1.RT-qPCR and Western blotting were used to detect the mRNA and protein expression of fibrosis-related molecules.The expression of TGF-β1/Smad3 signaling pathway was detected by Western blotting.TGF-β1/Smad3 signaling pathway was activated by TGF-β1/Smad signaling pathway activator (SRI-011381),and the expression of TGF-β1/Smad3 signaling pathway and key molecular proteins of fibrosis phenotype was measured with Western blotting.Results In vivo experiment,the mRNA and protein expression levels of GNMT were significantly decreased in the IUA rats than the control rats (P<0.05).Overexpression of GNMT decreased the mRNA and protein levels of fibrosis related molecules,Collagen Ⅰ,Collagen Ⅲ and FN in the IUA rats (P<0.05),and decreased the phosphorylation levels of TGF-β1 and its downstream Smad3 protein (P<0.05).HE and Masson staining showed that overexpression of GNMT could increase the number of endometrial glands and reduce the severity of fibrosis in the IUA rats (P<0.05).In vitro experiments:overexpression of GNMT decreased the mRNA and protein levels of Collagen Ⅰ,Collagen Ⅲ and FN associated with fibrotic phenotype of THESCs (P<0.05),and reduced the phosphorylation level of Smad3 protein,downstream of TGF-β1 (P<0.05).After activation of TGF-β1/Smad3 signaling pathway,the protein levels of TGF-β1/Smad3 signaling pathway and downstream fibrosis phenotype molecules,Collagen Ⅲ and FN,were significantly decreased in the LV-GNMT+SRI-011381 group.Conclusion Overexpression of GNMT can inhibit endometrial fibrosis by regulating TGF-β1/Smad3 signaling pathway,thus achieving therapeutic effect on IUA.

Objective To retrieve,evaluate and summarize the best evidence on the management of ocular complications in intensive care patients ventilated in prone position,and to provide references for clinical practice.Methods Evidence on management of ocular complications in intensive care patients ventilated in prone position was systemically retrieved in the guideline websites,professional association websites and databases,such as the BMJ Best Practice,UpToDate,Cochrane Library,Joanna Briggs Institute,PubMed,Web of Science,Science Direct,Embase,CNKI,Wanfang and other databases,including guidelines,clinical decisions,evidence summaries,expert consensuses,group standards,systematic reviews and scoping reviews,published from January 2013 to June 2023.The guidelines were individually evaluated by 4 researchers,and the remaining literature was individually evaluated by 2 researchers.The literature that met the criteria was extracted and graded.Results A total of 15 articles were involved,including 6 guidelines,2 clinical decisions,2 evidence summaries,3 systematic reviews,1 scoping review and 1 group standard.Finally,6 evidence topics and 16 pieces of best evidence were formed,including organization and training,risk identification,eye assessment,eye protection,position management and regular observation.Conclusion This study summarized the best evidence on the management of ocular complications in intensive care patients ventilated in prone position.In the application,the best evidence should be selected according to the clinical situation,so as to reduce the incidence of ocular complications and improve the quality of life of patients.

Objective To evaluate the scientificity,transparency and applicability of Chinese guidelines and expert consensuses on nursing published in 2022,in order to improve the quality of guidelines and consensuses.Methods Databases including Medline,Embase,Web of Science,CBM,CNKI,WanFang database,Chinese Medical Journal,and related websites were electronically searched,as well as China Hong Kong,Macao and Taiwan medical journals,to collect Chinese guidelines and expert consensuses on nursing from January to December 2022.STAR tool was used to evaluate the quality of each guidelines and consensuses by 3 assessors independently.Total score,scoring rate of each domain and item were adopted to analyze the outcomes.Results A total of 3 guidelines and 33 expert consensuses were included.The total guidelines and expert consensuses STAR score(33.5±14.3).The quality of guidelines and consensuses was low.The quality of guidelines was moderate with average score of 55.1,and the quality of consensuses was low with average score of 31.5.The included guidelines and consensuses had a highest score rate(52.4％)in the domain of recommendation.Among 39 items of STAR tool,the top 4 items including listing participants and institutions,explaining additional instructions for implementation,describing consensus method,and listing references for recommendations had a high score rate of 100％,83.3％,77.8％,75.0％respectively.However,the items of registration,providing registration information,protocols being searched on public platforms and explaining the role of funding had a low score rate,urgent need for attention and upgrading.Conclusion The overall quality of the Chinese guidelines and expert consensuses on nursing published in 2022 was low.As a medical and nursing practice guidance document,the quality of guidelines and expert consensuses should be improved by encouraging registration,strengthening management of interest conflict,enhancing the rigor of guideline developing process,and expanding the dissemination.

ObjectiveTo explore the mechanism of Dahuang Mudantang in alleviating the intestinal injury in the rat model of acute pancreatitis via the high-mobility group box 1 （HMGB1）/receptor for advanced glycation endproduct （RAGE）/nuclear factor-κB （NF-κB） signaling pathway. MethodOne hundred and twenty SPF-grade Wistar rats received retrograde injection of 5% sodium taurocholate into the biliopancreatic duct for the modeling of intestinal injury in acute pancreatitis. The rats were randomized into blank， model， low-， medium-， and high-dose （3.5， 7， 14 g·kg^-1， administrated by gavage） Dahuang Mudantang， and octreotide （1×10^-5 g·kg^-1， subcutaneous injection） groups （n=20）. The rats in blank and model groups received equal volume of distilled water by gavage. Drugs were administered 1 h before and every 12 h after modeling， and samples were collected 24 h after modeling. The general status of the rats was observed. The biochemical methods were employed to measure the levels of amylase （AMS） and C-reactive protein （CRP） in the serum. The enzyme-linked immunosorbent assay （ELISA） was employed to measure the levels of tumor necrosis factor （TNF）-α， interleukin （IL）-1β， and IL-6 in the colon tissue. The morphological changes of pancreatic and colon tissues were observed by hematoxylin-eosin （HE） staining. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot were employed to measure the expression levels of HMGB1， RAGE， inhibitor of NF-κB kinase （IKK）， and NF-κB suppressor protein α（IκBα）in the colon tissue. ResultThe rats in the model group showed poor general survival， writhing response， reduced frequency of defecation， and dry stool. The symptoms of rats in the model group were mitigated in each treatment group， and the high-dose Dahuang Mudantang showed the most significant effect. Compared with the normal group， the model group had elevated AMS and CRP levels （P<0.05）， which were lowered by Dahuang Mudantang （P<0.05）， especially that at the high dose （P<0.05）. Compared with the normal group， the modeling elevated that levels of TNF-α， IL-1β， and IL-6 （P<0.05）. Such elevations were lowered by Dahuang Mudantang （P<0.05）， and the high-dose group and the octreotide group showed better performance （P<0.05）. The modeling caused necrotic， congested， and destructed pancreatic and colonic tissues， which were ameliorated by the drugs， especially high-dose Dahuang Mudantang. Compared with the normal group， the modeling up-regulated the mRNA levels of HMGB1， RAGE， IKK， IκBα， and NF-κB （P<0.05）. Compared with the model group， Dahuang Mudantang and octreotide down-regulated the mRNA levels of HMGB1， RAGE， IKK， IκBα， and NF-κB （P<0.05）， and the high-dose Dahuang Mudantang demonstrated the best performance （P<0.05）. Western blot results showed a trend consistent with the results of Real-time PCR. ConclusionDahuang Mudantang can improved the general status， reduce inflammation， and alleviate histopathological changes in the pancreatic and colon tissues in the rat model of acute pancreatitis by inhibiting the HMGB1/RAGE/NF-κB signaling pathway.

Enzyme-driven micro/nanomotors consuming in situ chemical fuels have attracted lots of attention for biomedical applications. However, motor systems composed by organism-derived organics that maximize the therapeutic efficacy of enzymatic products remain challenging. Herein, swimming proteomotors based on biocompatible urease and human serum albumin are constructed for enhanced antitumor therapy via active motion and ammonia amplification. By decomposing urea into carbon dioxide and ammonia, the designed proteomotors are endowed with self-propulsive capability, which leads to improved internalization and enhanced penetration in vitro. As a glutamine synthetase inhibitor, the loaded l-methionine sulfoximine further prevents the conversion of toxic ammonia into non-toxic glutamine in both tumor and stromal cells, resulting in local ammonia amplification. After intravesical instillation, the proteomotors achieve longer bladder retention and thus significantly inhibit the growth of orthotopic bladder tumor in vivo without adverse effects. We envision that the as-developed swimming proteomotors with amplification of the product toxicity may be a potential platform for active cancer treatment.

Objective:To investigate the risk factors of post-stroke depression (PSD) in patients with first acute stroke 6 months after onset.Methods:Three hundred and sixty-seven patients with acute stroke who were treated for the first time in the Affiliated Hospital of Xuzhou Medical University were selected retrospectively. After onset for 6 months, the patients were followed up and divided into PSD group and non-PSD group. The clinical data, blood index, imaging data, degree of nerve damage and the patient's stigma level were compared between the two groups.Results:Totally 182 and 185 cases were included in the PSD and non-PSD groups, respectively. The incidence of PSD at 6 months post-stroke was 49.6% (182/367). The results of univariate analysis showed that diseased region, drinking history, monthly income, standard of culture, serum cortisol, total cholesterol (TC), high sensitivity C-reactive protein (hs-CRP), neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), Stigma Scale for Chronic Illness-8 Chronic Disease Stigma Scale-8(SSCI-8) scores, National Institute of Health Stroke Scale (NIHSS) scores and subtype of stroke were risk factors for PSD ( P<0.05). Binary Logistic regression analysis showed that diseased region at frontal lobe ( OR = 3.245, P = 0.011), basal ganglia region ( OR = 2.820, P = 0.007), cerebellar hemisphere ( OR = 4.594, P = 0.010) and serum cortisol ( OR = 1.174, P<0.001), hs-CRP ( OR = 1.057, P<0.001), SSCI-8 scores ( OR = 1.674, P<0.001), NIHSS scores ( OR = 1.283, P<0.001) were independent risk factors for PSD. Conclusions:PSD is a common complication in patients with stroke. Diseased region (at frontal lobe, basal ganglia region, cerebellar hemispheres), hs-CRP, serum cortisol, level of morbidity stigma and degree of neurological impairment are development risk factors for the PSD at 6 months of acute stroke.