OBJECTIVE To standardize the main processes and related technical links of the clinical comprehensive evaluation of drugs， and provide guidance and reference for improving the quality of comprehensive evaluation evidence and its transformation and application value. METHODS The construction of Guideline for the Workflow of Clinical Comprehensive Evaluation of Drugs was based on the standard guideline formulation method of the World Health Organization （WHO）， strictly followed the latest definition of guidelines by the Institute of Medicine of the National Academy of Sciences of the United States， and conformed to the six major areas of the Guideline Research and Evaluation Tool Ⅱ. Delphi method was adopted to construct the research questions； research evidence was established by applying the research methods of evidence-based medicine. The evidence quality classification system of the Chinese Evidence-Based Medicine Center was adopted for evidence classification and evaluation. The recommendation strength was determined by the recommendation strength classification standard formulated by the Oxford University Evidence-Based Medicine Center， and the recommendation opinions were formed through the expert consensus method. RESULTS & CONCLUSIONS The Guideline for the Workflow of Clinical Comprehensive Evaluation of Drugs covers 4 major categories of research questions， including topic selection， evaluation implementation， evidence evaluation， and application and transformation of results. The formulation of this guideline has standardized the technical links of the entire process of clinical comprehensive evaluation of drugs， which can effectively guide the high-quality and high-efficient development of this work， enhance the standardized output and transformation application value of evaluation evidence， and provide high-quality evidence support for the scientific decision-making of health and the rationalization of clinical medication.

Single-cell sequencing(SCS)has great potential in oral squamous cell carcinoma(OSCC)research.With the development of SCS technology,its sensitivity and accuracy are gradually increasing,while its cost is gradually decreasing.SCS is poised to become a crucial technological tool in cancer research.SCS technology provides significant assistance in the discovery of new cell-specific markers and cell types by identifying differential gene expression and epigenetic information alterations caused by genomic mutations at the resolution of a single cell.In OSCC studies,SCS not only helps unveil the heterogeneity of cancer cells and provides more accurate understanding of the tumor microenvironment,but also facilitates a deeper exploration of the interactions between OSCC cells,immune cells and stromal cells.This sheds light on their mutual influences and roles in tumor initiation and progression.Utilizing SCS to classify immune cells in tumors and comprehend immune escape mechanisms is pivotal for the effective development of immunotherapy.This comprehensive review outlined the current status of SCS technology development and discussed its latest research advancements and prospective applications in the field of OSCC.

Objective:To investigate the accuracy and reproducibility of diaphragmatic excursion (DE) measurements through hepato-renal/spleno-renal section as a novel method for assessing diaphragmatic function.Methods:Twelve healthy participants were recruited. Each participant underwent DE measurements performed by four operators with varying levels of experience using traditional methods (liver/spleen section) and novel methods (hepato-renal/spleno-renal section), respectively. Among them, two experienced operators were critical care clinicians, and diaphragmatic ultrasound was performed in more than 50 cases. The other two inexperienced operators were respiratory therapists, with less than 10 cases of diaphragmatic ultrasound operations, who received a 2-hour theoretical and operational training before the study. Operators initially used the conventional method with a 1.5-6.0 MHz convex probe in M-mode, placing the sampling line perpendicular to the diaphragm at the point of maximum excursion, and the liver/spleen section DE was determined during normal breathing of participant. Then, they used the novel method with a 1.6-4.5 MHz phased array probe to observe diaphragmatic movement cranio-caudally along the mid-axillary line, employing anatomic M-mode with the sampling line placed perpendicular to the diaphragm at the level of the renal midpoint, and the DE of the hepato-renal/spleno-renal section was measured during normal breathing. The liver and hepato-renal sections were used to assess the right diaphragm, and spleen and spleno-renal sections were used to assess the left diaphragm. Correlation analysis of DE measurements from different sections was conducted using the Deming method, while consistency was assessed using the Bland-Altman method. The consistency of clinical acceptability was defined as the absence of fixed and proportional bias, with a difference of two standard deviations less than 40% of the mean measurement value. Percentage consistency limit = two standard deviations of the differences between measurements/mean measurement value×100%.Results:Four operators performed image scans of DE in all four sections for each of the twelve subjects, with a high DE acquisition rate of 100% (48/48) for hepato-renal and spleno-renal sections, followed by the liver section [91.7% (44/48)] and the spleen section [66.7% (32/48)], particularly for the left diaphragm assessment, where the DE acquisition rate of spleno-renal section was significantly higher than that of traditional spleen section ( P < 0.01). The overall measurement results showed that no significant difference was found in DE determined via the hepato-renal and spleno-renal sections using the novel method (cm: 1.64±0.10 vs. 1.55±0.14, P > 0.05), and they were significantly higher than those determined via the conventional liver and spleen sections (cm: hepato-renal section vs. liver section was 1.64±0.10 vs. 1.44±0.09, spleno-renal section vs. spleen section was 1.55±0.14 vs. 1.09±0.14, both P < 0.01). Correlation analysis revealed good correlations of DE between hepato-renal section and spleno-renal section, between liver section and hepato-renal section, between liver section and spleno-renal section ( r values were 0.62, 0.59, and 0.42, all P < 0.01). Consistency analysis showed that the consistency in DE between hepato-renal section and spleno-renal section, as well as between liver section and hepato-renal section was good (both % consistency limits < 40%). However, the DE measured in the spleen section were not correlated with the other three sections, and there was no inconsistency (all % consistency limits > 40%). There was no statistically significant difference in DE measured by the four operators in the liver, spleen, hepato-renal, and spleno-renal sections (cm: 1.49±0.34, 1.44±0.37, 1.43±0.30, and 1.40±0.27 in liver section; 1.10±0.36, 1.05±0.18, 1.09±0.22, and 1.06±0.26 in spleen section; 1.67±0.43, 1.57±0.34, 1.63±0.32, and 1.66±0.36 in hepato-renal section; 1.45±0.33, 1.48±0.34, 1.50±0.24, and 1.65±0.26 in spleno-renal section; all P > 0.05). According to the clinically acceptable range of consistency limits, the DE measured by the four operators in all four sections showed good consistency (all % consistency limits < 40%). Conclusion:The novel method of measuring DE through hepato-renal/spleno-renal sections is accurate, highly reproducible, and has a high acquisition rate, serving as a viable alternative to the conventional method involving the liver/spleen section.

Objective:To investigate the prognostic value of early serum lactate, albumin, and lactate/albumin ratio (L/A) on the 28-day prognosis of adult patients with sepsis.Methods:A retrospective cohort study was conducted among adult patients with sepsis admitted to the First Affiliated Hospital of Xinjiang Medical University from January to December in 2020. Gender, age, comorbidities, lactate within 24 hours of admission, albumin, L/A, interleukin-6 (IL-6), procalcitonin (PCT), C-reactive protein (CRP) and 28-day prognosis were recorded. The receiver operator characteristic curve (ROC curve) was drawn to analyze the predictive value of lactate, albumin and L/A for 28-day mortality in patients with sepsis. Subgroup analysis of patients was performed according to the best cut-off value, Kaplan-Meier survival curves were drawn, and the 28-day cumulative survival of patients with sepsis was analyzed.Results:A total of 274 patients with sepsis were included, and 122 patients died at 28 days, with a 28-day mortality of 44.53%. Compared with the survival group, the age, the proportion of pulmonary infection, the proportion of shock, lactate, L/A and IL-6 in the death group were significantly increased, and albumin was significantly decreased [age (years): 65 (51, 79) vs. 57 (48, 73), pulmonary infection: 75.4% vs. 53.3%, shock: 37.7% vs. 15.1%, lactate (mmol/L): 4.76 (2.95, 9.23) vs. 2.21 (1.44, 3.19), L/A: 0.18 (0.10, 0.35) vs. 0.08 (0.05, 0.11), IL-6 (ng/L): 337.00 (97.73, 2 318.50) vs. 55.88 (25.26, 150.65), albumin (g/L): 27.68 (21.02, 33.03) vs. 29.62 (25.25, 34.23), all P < 0.05]. The area under the ROC curve (AUC) and 95% confidence interval (95% CI) of lactate, albumin, and L/A were 0.794 (95% CI was 0.741-0.840), 0.589 (95% CI was 0.528-0.647), 0.807 (95% CI was 0.755-0.852) for predicting 28-day mortality in sepsis patients. The optimal diagnostic cut-off value of lactate was 4.07 mmol/L, the sensitivity was 57.38%, the specificity was 92.76%. The optimal diagnostic cut-off value of albumin was 22.28 g/L, the sensitivity was 31.15%, the specificity was 92.76%. The optimal diagnostic cut-off of L/A was 0.16, the sensitivity was 54.92%, and the specificity was 95.39%. Subgroup analysis showed that the 28-day mortality of sepsis patients in the L/A > 0.16 group was significantly higher than that in the L/A ≤ 0.16 group [90.5% (67/74) vs. 27.5% (55/200), P < 0.001]. The 28-day mortality of sepsis patients in the albumin ≤ 22.28 g/L group was significantly higher than that in the albumin > 22.28 g/L group [77.6% (38/49) vs. 37.3% (84/225), P < 0.001]. The 28-day mortality in the group with lactate > 4.07 mmol/L was significantly higher than that in the group with lactate ≤ 4.07 mmol/L [86.4% (70/81) vs. 26.9% (52/193), P < 0.001]. The three were consistent with the analysis results of Kaplan-Meier survival curve. Conclusion:The early serum lactate, albumin, and L/A were all valuable in predicting the 28-day prognosis of patients with sepsis, and L/A was better than lactate and albumin.

Polymyxin B, which is a last-line antibiotic for extensively drug-resistant Gram-negative bacterial infections, became available in China in Dec. 2017. As dose adjustments are based solely on clinical experience of risk toxicity, treatment failure, and emergence of resistance, there is an urgent clinical need to perform therapeutic drug monitoring (TDM) to optimize the use of polymyxin B. It is thus necessary to standardize operating procedures to ensure the accuracy of TDM and provide evidence for their rational use. We report a consensus on TDM guidelines for polymyxin B, as endorsed by the Infection and Chemotherapy Committee of the Shanghai Medical Association and the Therapeutic Drug Monitoring Committee of the Chinese Pharmacological Society. The consensus panel was composed of clinicians, pharmacists, and microbiologists from different provinces in China and Australia who made recommendations regarding target concentrations, sample collection, reporting, and explanation of TDM results. The guidelines provide the first-ever consensus on conducting TDM of polymyxin B, and are intended to guide optimal clinical use.
Humans ; Anti-Bacterial Agents/therapeutic use* ; China ; Drug Monitoring/methods* ; Polymyxin B ; Practice Guidelines as Topic

OBJECTIVE To explore the mechanism of Kuaisong yin in the prevention and treatment of constipation. METHODS Slow transit constipation （STC） model was established with Compound difenoxylate tablet in mice and rats. Two batches of mice were divided into blank group， model group， positive control group （Maren soft capsule， 0.64 g/kg）， Kuaisong yin low-dose， medium-dose and high-dose groups （3.2， 6.4， 12.8 g/kg）， with 10 mice in each group. The effect of Kuaisong yin on constipation in mice was evaluated by intestinal propulsion experiment and defecation experiment. Rats were divided into blank group， model group， positive control group （Maren soft capsule，0.36 g/kg）， Kuaisong yin low-dose and high-dose groups （2.4， 4.8 g/kg）， with 7 or 8 rats in each group. They were given relevant medicine once a day for 1 week. The metabonomics of serum and urine of rats were analyzed by UPLC-Q-TOF-MS/MS technology. RESULTS Compared with model group， the ink propulsion rate and 5 h defecation volume of mice in Kuaisong yin high-dose group were significantly increased （P＜0.05）； the first defecation time of mice in Kuaisong yin medium-dose and high-dose groups was significantly shortened， and the quality of defecation was significantly reduced within 5 h （P＜0.05 or P＜0.01）. Serum metabonomics screened 16 compounds （such as proline， propionylcarnitine， hemolytic phosphatidylcholine， etc.） and 6 metabolic pathways （such as sphingomyelin metabolism， arginine and proline metabolism， sphingolipid biosynthesis-lactose and neolactone series）. Urine metabonomics screened 20 different metabolites （such as prostaglandin A2， L-valine， phosphatidylcholine， sphingomyelin， etc.） and 8 metabolic pathways （such as valine， leucine and isoleucine biosynthesis， sphingomyelin metabolism， pyruvate metabolism， etc.）. CONCLUSIONS Kuaisong yin can play a role in improving constipation by regulating different metabolites such as hemolytic phosphatidylcholine， phosphatidylcholine， prostaglandin A2， L-valine， proline， and regulating metabolic pathways such as multiple amino acid metabolism， sphingomyelin metabolism， etc.

OBJECTIVE To study the mechanism of Compound zaoren granule in improving insomnia. METHODS Forty-nine mice were divided into blank group， model group， positive control group 1 （Estazolam tablets 0.5 mg/kg），control group 2 （Shumian capsule 0.6 g/kg）， Compound zaoren granule low-dose， medium-dose and high-dose groups （2.5， 5， 10 g/kg）， with 7 mice in each group. The insomnia model was established by chronic unpredictable mild stress combined with 4-chloro-DL- phenylacetic acid. The behavioral changes of mice were investigated through open field test and pentobarbital sodium synergistic hypnosis experiment， as well as the pathomorphology of mice hypothalamus tissue was observed by HE staining. The metabonomics analysis and multivariate statistical analysis of serum in mice were performed by UHPLC-Q-TOF-MS/MS， and the differential metabolites were screened out； the metabolic pathway analysis was conducted based on MetaboAnalyst 5.0 database. RESULTS Compared with blank group， the total travelling distance， the number of entering the central region and the moving distance in the central region of the model group were significantly reduced （P＜0.05）， the proportion of total rest time was significantly increased （P＜0.05）， the sleep duration of mice was significantly shortened （P＜0.05）， and hypothalamic nerve cells damaged and severely vacuolated. Compared with model group， the total travelling distance of Compound zaoren granule low-dose and medium-dose groups were increased significantly and the proportions of total rest time of those groups were decreased significantly （P＜0.05）， and the sleep duration of mice in Compound zaoren granule high-dose group was prolonged significantly （P＜0.05）； the hypothalamic nerve cells of mice in each administration group recovered to varying degrees， and the hypothalamus histiocytes of mice in the Compound zaoren granules high-dose group were closer to those in the blank group. A total of 18 differential metabolites （such as phenylalanine， taurine， norvaline， methionine） and 4 important amino acid metabolic pathways （L-phenylalanine， tyrosine and tryptophan biosynthesis； taurine and hypotaurine metabolism； L-phenylalanine metabolism； cysteine and methionine metabolism） were identified through metabolomics analysis. CONCLUSIONS Compound zaoren granules can normalize the disordered metabolism in vivo by regulating differential metabolites such as phenylalanine， taurine， and four amino acid metabolic pathways， so as to improve insomnia.

Objective: To explore the association between dietary inflammatory index (DII) and metabolic syndrome (MetS) and its components among children aged 6-14 years in Beijing, so as to provide a reference for preventing MetS. Methods: A cross sectional study was carried out in 2 086 records of 1 832 children from the 2017 and 2019 Nutrition and Health Surveillance in Primary and Secondary school students of Beijing (NHSPSB). Three day consecutive 24 hour dietary recalls combined with weighing household cooking oils and condiments were used to collect dietary intake and calculate DII. MetS was diagnosed according to "Definition and Suggestion on the Metabolic Syndrome of Chinese Children and Adolescent". The Generalized estimating equations (GEEs) models were used to analyze the association between DII and the presence of MetS and its components (abdominal obesity, high triglyceride, low high density lipoprotein cholesterol, hypertension, and hyperglycemia). Results: The mean DII score was (1.64±1.07) for the included children. No significant association was found between DII scores and the likelihood of MetS (per 1 point increment: OR =1.16, 95% CI =0.92-1.48, P >0.05). In terms of the components of MetS, DII scores were positively associated with the odds of high triglyceride (per 1 point increment: OR =1.17, 95% CI =1.01-1.36, P <0.05). There was no statistically significant difference in the association among different age groups ( P >0.05). No significant associations were observed between DII and other MetS components( P >0.05). Conclusion DII scores may not be correlated with the risk of MetS, but proinflammatory diet might increase the risk of high triglyceride. DII score in childhood should be emphasized to identify and prevent MetS as soon as possible.

Model informed precision dosing for warfarin is to provide individualized dosing by integrating information related to patient characteristics, disease status and pharmacokinetics /pharmacodynamics of warfarin, through mathematical modeling and simulation techniques based on the quantitative pharmacology. Compared with empirical dosing, it can improve the safety, effectiveness, economy, and adherence of pharmacotherapy of warfarin. This consensus report describes the commonly used modeling and simulation techniques for warfarin, their application in developing and adjusting dosing regimens, medication adherence and economy. Moreover, this consensus also elaborates the detailed procedures for the implementation in the warfarin pharmacy service pathway to facilitate the development and application of model informed precision dosing for warfarin.

Objective: To evaluate the therapeutic efficacy of acupuncture plus Dang Gui Bu Xue Qu Feng Tang for benign essential blepharospasm (BEB). Methods: A prospective randomized controlled trial was performed. A total of 105 participants were randomized 1:1:1 into an acupuncture group, a herbal medicine group and an acupuncture plus herbal medicine group. Participants in the acupuncture group received manual acupuncture treatment, twice a week. Participants in the herbal medicine group received Dang Gui Bu Xue Qu Feng Tang, oral administration, once a day. Participants in the acupuncture plus herbal medicine group received both treatments. The therapeutic effects of the three groups were evaluated after four weeks of treatment. The primary outcome was the Jankovic rating scale (JRS) score, and the secondary outcome was the blepharospasm disability index (BSDI) score. Results: After four weeks of treatment, the JRS total scores significantly decreased in all three groups versus baseline (P<0.05). A greater reduction in the JRS total score was reported in participants in the acupuncture plus herbal medicine group (P<0.05), but there was no significant difference between the acupuncture group and the herbal medicine group (P>0.05). The acupuncture plus herbal medicine group had a greater decrease in the JRS severity score than the herbal medicine group (P<0.05). The reduction in the JRS frequency score was not significantly different among the three groups (P>0.05). The BSDI scores significantly decreased in all three groups versus baseline (P<0.05), but the reduction in the BSDI score was insignificantly different among the three groups (P>0.05). Conclusion: It is effective in the treatment of BEB either to use acupuncture and Dang Gui Bu Xue Qu Feng Tang alone or in combination. The combination therapy shows a more significant effect than either of the treatment alone.