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.

Methods: CHB patients and healthy volunteers were enrolled from Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine between August 21, 2018 and December 31, 2020. They were divided into three groups: healthy group, LGDHS group, and latent syndrome (LP) group. Proteomic analysis using isobaric tags for relative and absolute quantitation (iTRAQ) was performed to identify differentially expressed proteins (DEPs). Metabolomic profiling via ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was applied to serum samples to detect differentially regulated metabolites (DMs). Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment were employed to explore dysregulated pathways. Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were utilized to visualize group separation and identify key metabolites and proteins contributing to LGDHS differentiation. Receiver operating characteristic (ROC) curve analysis evaluated the diagnostic performance of key biomarkers, while logistic regression models assessed their predictive accuracy. P values were corrected for multiple tests using the Benjamini-Hochberg method to control the false discovery rate (FDR). Validation of potential biomarkers was conducted using independent microarray data and real-time quantitative polymerase chain reaction (RT-qPCR). Results: A total of 150 participants were enrolled, including healthy group (n = 45), LGDHS group (n = 60), and LP group (n = 45). 254 DEPs from proteomics data and 72 DMs from metabolomic profiling were identified by PCA and OPLS-DA. DEPs were mainly enriched in immune and complement pathways, while DMs involved in amino acid and energy metabolism. The integrated analysis identified seven key biomarkers: α1-acid glycoprotein (ORM1), asparagine synthetase (ASNS), solute carrier family 27 member 5 (SLC27A5), glucosidase II alpha subunit (GANAB), hexokinase 2 (HK2), 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR), and maltase-glucoamylase (MGAM). Microarray validation confirmed the diagnostic potential of these genes, with area under the curve (AUC) values for ROC analysis ranging from 0.536 to 0.759. Among these, ORM1, ASNS, and SLC27A5 showed significant differential ability in differentiating LGDHS patients (P = 0.016, P = 0.035, and P < 0.001, respectively), with corresponding AUC of 0.749, 0.743, and 0.759, respectively. A logistic regression model incorporating these three genes demonstrated an AUC of 0.939, indicating a high discriminatory power for LGDHS. RT-qPCR further validated the differential expression of ORM1 and SLC27A5 between LGDHS and LP groups (P = 0.011 and P = 0.034, respectively), with ASNS showing a consistent trend in expression (P = 0.928). Conclusion This study integrates multi-omics approaches to uncover the molecular mechanisms underlying LGDHS in CHB. The identification of biomarkers ORM1, ASNS, and SLC27A5 offers a solid basis for the objective diagnosis of LGDHS, contributing to the standardization and modernization of TCM diagnostic practices.

Background::Differentiated thyroid cancer (DTC) is commonly diagnosed in women of child-bearing age, but whether pregnancy influences the prognosis of DTC remains controversial. This study aimed to summarize existing evidence regarding the association of pregnancy with recurrence risk in patients previously treated for DTC.Methods::We searched PubMed, Embase, Web of Science, Cochrane, and Scopus based on the prespecified protocol registered at PROSPERO (CRD42022367896). After study selection, two researchers independently extracted data from the included studies. For quantitative data synthesis, we used random-effects meta-analysis models to pool the proportion of recurrence (for pregnant women only) and odds ratio (OR; comparing the risk of recurrence between the pregnancy group and the nonpregnancy group), respectively. Then we conducted subgroup analyses to explore whether risk of recurrence differed by response to therapy status or duration of follow-up time. We also assessed quality of the included studies.Results::A total of ten studies were included. The sample size ranged from 8 to 235, with participants’ age at pregnancy or delivery ranging from 28 to 35 years. The follow-up time varied from 0.1 to 36.0 years. The pooled proportion of recurrence in all pregnant patients was 0.13 (95% confidence intervals [CI]: 0.06-0.25; I2: 0.58). Among six included studies reporting response to therapy status before pregnancy, we observed a trend for increasingly higher risk of recurrence from excellent, indeterminate, and biochemically incomplete to structurally incomplete response to therapy ( Ptrend <0.05). The pooled risk of recurrence in the pregnancy group showed no evidence of a significant difference from that in the nonpregnancy group (OR: 0.75; 95% CI: 0.45-1.23; I2: 0). The difference in follow-up time (below/above five years) was not associated with either the proportion of recurrence in all pregnant patients ( P >0.05) or the OR of recurrence in studies with a comparison group ( P >0.05). Two included studies that focused on patients with distant metastasis also did not show a significant difference in disease recurrence between pregnancy and nonpregnancy groups (OR: 0.51 [95% CI: 0.14-1.87; I2: 59%]). Conclusion::In general, pregnancy appears to have a minimal association with the disease recurrence of DTC with initial treatment. Clinicians should pay more attention to progression of DTC among pregnant women with biochemical and/or structural persistence.Registration::PROSPERO, https://www.crd.york.ac.uk/PROSPERO/; No. CRD42022367896.

Neurodevelopmental disorders(NDDs)are chronic developmental brain disorders that can affect cognition,motor,social adaptation,behavior and so on due to multiple genetic or acquired causes.Natural polysaccharides are synthesized by living organisms,located in the cell wall,inside and between cells,and outside the cells,and are essential components of life activities.Previous studies have found that natural polysaccharides play an important role in neurological diseases,which mainly ameliorate the behavioral abnormalities and clinical symptoms caused by anti-oxidative stress,anti-neuronal apoptosis,anti-neuroinflammation,anti-excitatory amino acid toxicity,and regulation of the brain-gut axis.This review summarizes the intervention role of 17 bioactive polysaccharides from plants and fungi in neurological diseases,aiming to provide new ideas for the research and treatment of NDDs.

Increased intestinal barrier permeability, leaky gut, has been reported in patients with autism. However, its contribution to the development of autism has not been determined. We selected dextran sulfate sodium (DSS) to disrupt and metformin to repair the intestinal barrier in BTBR T⁺tf/J autistic mice to test this hypothesis. DSS treatment resulted in a decreased affinity for social proximity; however, autistic behaviors in mice were improved after the administration of metformin. We found an increased affinity for social proximity/social memory and decreased repetitive and anxiety-related behaviors. The concentration of lipopolysaccharides in blood decreased after the administration of metformin. The expression levels of the key molecules in the toll-like receptor 4 (TLR4)-myeloid differentiation factor 88 (MyD88)-nuclear factor kappa B (NF-κB) pathway and their downstream inflammatory cytokines in the cerebral cortex were both repressed. Thus, "leaky gut" could be a trigger for the development of autism via activation of the lipopolysaccharide-mediated TLR4-MyD88-NF-κB pathway.
Mice ; Animals ; NF-kappa B ; Myeloid Differentiation Factor 88/metabolism* ; Lipopolysaccharides/pharmacology* ; Toll-Like Receptor 4/metabolism* ; Autistic Disorder/metabolism* ; Signal Transduction/physiology*

Objective:To investigate the expression of B7-H3 in diffuse large B-cell lymphoma (DLBCL) and its prognostic significance.Methods:The paraffin-embedded tumor tissues of 103 patients with newly diagnosed DLBCL in Linyi Central Hospital from May 2013 to May 2019 were detected by using immunohistochemistry. The association of the expression of B7-H3 protein with the clinicopathological features, progression-free survival (PFS) and overall survival (OS) of DLBCL patients was analyzed. Cox proportional hazards model was used to analyze the factors affecting PFS and OS.Results:The positive rate of B7-H3 protein in patients with DLBCL was 68.0% (70/103). There were no statistically significant differences in the positive rate of B7-H3 protein among patients with different gender, age, clinical staging, international prognostic index (IPI) score, treatment effect, B symptoms, pathological type and other clinicopathological characteristics (all P > 0.05). The 5-year PFS and 5-year OS rates were 24% and 32% in all patients, the 5-year PFS rates were 47% and 14% in B7-H3 negative and B7-H3 positive patients, respectively ( P < 0.01); and 5-year OS rates were 50% and 24% in B7-H3 negative and B7-H3 positive patients, respectively ( P < 0.001). Multi-factor Cox regression analysis showed that B7-H3 positive was an adverse affecting factor of PFS ( HR = 2.685, 95% CI 1.503 - 4.789, P = 0.001) and OS ( HR = 2.262, 95% CI 1.248 - 4.098, P = 0.007). Conclusions:The moderate and high expression of B7-H3 may be related to the poor prognosis of DLBCL patients.

OBJECTIVE: To investigate the effects of restrictive fluid management in patients with severe traumatic brain injury (sTBI). METHODS: Between January, 2019 and June, 2020, we randomly assigned 51 postoperative patients (stay in the ICU of no less than 7 days) with sTBI into treatment group ( RESULTS: The cumulative fluid balance of the two groups were positive on day 1 and negative on days 3 and 7 after ICU admission; at the same time points, the patients in the treatment group had significantly greater negative fluid balance than those in the control group ( CONCLUSIONS Restrictive fluid management can reduce cerebral edema and improve the prognosis but does not affect the 28-day mortality of patients with sTBI.
Brain Injuries, Traumatic/therapy* ; Fluid Therapy ; Humans ; Prognosis ; Respiration, Artificial ; Treatment Outcome

Objective: To compare the long-term outcomes in ST-elevation myocardial infarction (STEMI) patients who underwent early or late delayed percutaneous coronary intervention (PCI) using drug-eluting stents (DES). Methods: This study was a retrospective, observational and single-center study. Consecutive STEMI patients (n=977), who admitted to Fuwai Hospital in 2013 and underwent successful selective PCI using drug-eluting stents (DES) within 3 to 35 days after symptom onset were enrolled and divided into the early delayed PCI (3-14 d) group (n=495) and the late delayed PCI (15-35 d) group (n=482). General clinical data of the patients and related data of coronary angiography and interventional therapy were collected, and the endpoint events were followed up. The primary endpoint was 2-year major adverse cardiac and cerebrovascular events (MACCE) including cardiac death, recurrent myocardial infarction, definite or probable stent thrombosis and ischemic stroke. The secondary endpoint was 2-year ischemia-driven target vessel revascularization. The incidence of endpoint events of the two groups was compared, and it was compared again after the primary baseline characteristics such as age and gender were matched by the propensity scoring method at a 1∶1 ratio. Results: A total of 910 (93.1%) patients who underwent delayed PCI were transferred from other hospitals, and 292 (29.9%) patients received thrombolysis before PCI. The time interval before PCI was 14 (10, 20) days. The incidence of 2-year MACCE (3.0%(15/495) vs. 2.3%(11/482), P=0.468) and ischemia-driven target vessel revascularization (3.8%(19/495) vs. 5.0%(24/482), P=0.385) were similar between the two groups. The incidence of 2-year MACCE (3.3%(15/453 vs. 2.4%(11/453), P=0.426) and ischemia-driven target vessel revascularization (4.2% (19/453) vs. 4.9%(22/453), P=0.632) were also similar between the two groups after matching propensity score. Conclusion The long-term clinical outcomes after early delayed PCI using DES is statistically equivalent to those of late delayed PCI using DES for STEMI patients who missed the time window for emergency PCI.

Objective To investigate the pathological mechanism of spinal injury by axial compression experiment on animal spine, so as to provide references for the treatment, prevention and research of spinal injury. Methods The biomechanical study of rabbit spine segments was performed by axial segment compression experiment. The compression process was recorded and strain analysis was performed by digital image correlation (DIC) technology. Results From the top to the bottom of the spine, the ultimate load and bearing capacity of the segment increased continuously; the average limit load of the corresponding single vertebral body was significantly larger than the segment; the strain of the intervertebral disc in the horizontal and vertical directions was significantly larger than that of the upper and lower vertebral bodies. Conclusions In the process of spine compression, the bearing capacity of the intervertebral disc should be taken into account and the injury of spinal segments is mainly manifested as abnormality of the intervertebral disc. The research findings contribute to the prevention and treatment of spinal compression fractures, as well as the design of related therapeutic instruments and assistive devices.

Objective To investigate the effect of early intervention with mirror therapy on hemiparetie survivors of ischemic stroke.Methods Thirty-six hemiplegic patients within one month after a stroke were randomly divided into a mirror therapy group (MT group,n=18) and a routine rehabilitation control group (RRC group,n=18).The participants in the MT group received MT for 45 min/d,5 d/wk for 3 weeks in addition to conventional stroke rehabilitation.Those in the RRC group received exercise therapy at the same frequency without the mirror protocol.The Fugl-Meyer assessment (FMA),Wolf motor function test (WMFT),functional ambulation category scale (FAC),Brunnstrom stages of motor recovery,and the modified Ashworth scale (MAS) were used to assess changes in the upper limb,gross hand dexterity and lower limb recovery before and right after the interventions,as well as one and two months after the treatment.Results Significant improvement was observed in the limb function of both groups after the treatment.Compared with the RRC group,there was significantly greater improvement observed in the MT group.This was true of the FMA ratings at all time points,the average WMFT scores one and two months after the intervention,the FAC ratings two months after the intervention,and the Brunnstrom stages at both one and two months after the intervention.However,no significant difference between the two groups in terms of the average MAS scores was observed at any time point.Conclusion Early intervention with MT can significantly accelerate the recovery of a paretic upper limb aud improve walking ability after stroke.Such intervention is worthy of promotion and application in clinical practice.