ObjectiveTo establish a mouse model of rheumatoid arthritis with interstitial lung disease （RA-ILD） in DBA/1 mice using Porphyromonas gingivalis （Pg） infection combined with collagen-induced arthritis （CIA）， and to comprehensively evaluate pathological characteristics in joints， lungs， and serum. MethodsForty DBA/1 mice were randomly divided into four groups， i.e.， Control， Pg infection （Pg）， CIA， and Pg infection combined with CIA （Pg+CIA）， with 10 mice in each group. Arthritis clinical symptoms were evaluated by recording arthritis incidence and clinical scores. Micro-CT scanning was used to assess knee joint pathology. Histopathological changes and collagen deposition in knee joints and lung tissues were analyzed using hematoxylin-eosin （HE） and Masson staining. Immunohistochemistry was performed to detect protein expression of α-smooth muscle actin （α-SMA）， typeⅠ collagen （ColⅠ）， and fibronectin （FN） in lung tissues. Real-time quantitative polymerase chain reaction（Real-time PCR）was used to measure mRNA expression levels of α-SMA， ColⅠ， FN， tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， and IL-1β in lung tissues. Enzyme-linked immunosorbent assay （ELISA） was used to detect serum levels of Pg， cyclic citrullinated peptide （CCP）， and immunoglobulin G （IgG）. ResultsJoint lesions： The CIA and Pg+CIA groups showed 100% arthritis incidence， with evident joint redness， swelling， and deformity. The number of affected limbs was 27 and 28， and clinical scores were 68 and 70， respectively. No obvious clinical symptoms were observed in the Pg group. Histopathological and imaging analyses showed severe joint lesions in the CIA and Pg+CIA groups， with significantly increased histopathological scores， bone mineral density， bone volume fraction， trabecular thickness， and trabecular number compared to the Control group （P<0.01）. No obvious joint pathology was observed in the Pg group. Lung lesions： The Pg+CIA group exhibited marked alveolar inflammation， interstitial inflammatory cell infiltration， and alveolar wall thickening， with pronounced blue staining of collagen fibers. Histopathological scores and collagen area ratios were significantly higher than those of the Control， Pg， and CIA groups （P<0.05）. Lung protein and mRNA expression levels of α-SMA， ColⅠ， and FN were markedly increased， and mRNA levels of IL-6， TNF-α， and IL-1β were significantly elevated compared to the Control group （P<0.05）. Serology： The Pg+CIA group showed significantly higher levels of CCP， Pg， and IgG compared with the Control， Pg， and CIA groups （P<0.05）. ConclusionDBA/1 mice subjected to Pg infection combined with CIA exhibited pronounced symptoms and pathological features of RA-ILD， along with elevated serum anti-CCP antibody levels. This model represents a novel RA-ILD mouse model， providing a valuable experimental tool for investigating RA-ILD pathogenesis and developing new therapeutics， and serves as a basis for establishing anti-cyclic citrullinated peptide antibody （ACPA）-positive RA-ILD animal models.

The randomized controlled trials (RCTs) regarding acupuncture direction published from January 1st, 2013, to November 7th, 2023 were searched in China National Knowledge Infrastructure (CNKI), Wanfang Data Knowledge Service Platform, and VIP Chinese Journal Database. As a result, 21 RCTs were included. The problems identified included conceptual misunderstandings regarding acupuncture direction, incomplete selection strategies, confounding research factors, and inaccuracies in reporting. Based on the findings, four strategic approaches for enhancing therapeutic efficacy through acupuncture direction were summarized: aligning needle direction with the meridian pathway, directing the needle toward the lesion site, orienting the needle toward adjacent acupoints, and targeting special anatomical structures. Two additional strategies were proposed for optimizing the procedure: simplifying acupuncture operations and directing the needle toward safe anatomical sites. Recommendations were made to improve the rationality of research factor settings and the completeness of acupuncture operation reporting. Furthermore, three methods for reporting acupuncture direction were discussed: reporting the tip-pointed position, reporting the insertion angle and orientation, and reporting azimuth and polar angles, aiming to promote greater standardization and completeness in acupuncture practice and reporting.
Acupuncture Therapy/standards* ; Humans ; Acupuncture Points ; Randomized Controlled Trials as Topic ; Meridians

In this study， bibliometric methods were used to systematically investigate the name and origin， the evolution of prescription composition， dose evolution， origin and processing method， decoction method， ancient application， modified application， modern application and other information of Huoxiang Zhengqisan. After research， Huoxiang Zhengqisan， also known as Huoxiang Zhengqitang， was first recorded in Taiping Huimin Hejijufang. The original formula is composed of 41.3 g of Arecae Pericarpium， 41.3 g of Angelicae Dahuricae Radix， 41.3 g of Perilla frutescens（actually Perillae Folium）， 41.3 g of Poria， 82.6 g of Pinelliae Rhizoma， 82.6 g of Atractylodis Macrocephalae Rhizoma， 82.6 g of Citri Reticulatae Pericarpium（actually Citri Exocarpium Rubbum）， 82.6 g of Magnoliae Officinalis Cortex， 82.6 g of Platycodonis Radix， 123.9 g of Pogostemonis Herba， and 103.25 g of Glycyrrhizae Radix et Rhizoma. In this formula， Magnoliae Officinalis Cortex is processed according to the specifications for ginger-processed products， Glycyrrhizae Radix et Rhizoma is processed according to the specifications for stir-fried products， and other herbs are used in their raw products. The botanical sources of the herbs are consistent with the 2020 edition of Pharmacopoeia of the People's Republic of China. The above herbs are ground into a fine powder with a particle size passing through a No. 5 sieve. For each dose， take 8.26 g of the powdered formula， add 300 mL of water， along with 3 g of Zingiberis Rhizoma Recens and 3 g of Jujubae Fructus， and decoct until reduced to 140 mL. The decoction should be administered hot， with three times daily. To induce sweating， the patient should be kept warm under a quilt， and an additional dose should be prepared and taken if needed. This formula is traditionally used to relieve the exterior and resolve dampness， regulate Qi and harmonize the middle， which is mainly used to treat a series of diseases of digestive and respiratory systems. However， potential adverse reactions， including allergies， purpura and disulfiram-like reactions， should be considered during clinical use. Huoxiang Zhengqisan features a rational composition， extensive clinical application， and strong potential for further research and development.

In this study， bibliometric methods were used to systematically investigate the name and origin， the evolution of prescription composition， dose evolution， origin and processing method， decoction method， ancient application， modified application， modern application and other information of Huoxiang Zhengqisan. After research， Huoxiang Zhengqisan， also known as Huoxiang Zhengqitang， was first recorded in Taiping Huimin Hejijufang. The original formula is composed of 41.3 g of Arecae Pericarpium， 41.3 g of Angelicae Dahuricae Radix， 41.3 g of Perilla frutescens（actually Perillae Folium）， 41.3 g of Poria， 82.6 g of Pinelliae Rhizoma， 82.6 g of Atractylodis Macrocephalae Rhizoma， 82.6 g of Citri Reticulatae Pericarpium（actually Citri Exocarpium Rubbum）， 82.6 g of Magnoliae Officinalis Cortex， 82.6 g of Platycodonis Radix， 123.9 g of Pogostemonis Herba， and 103.25 g of Glycyrrhizae Radix et Rhizoma. In this formula， Magnoliae Officinalis Cortex is processed according to the specifications for ginger-processed products， Glycyrrhizae Radix et Rhizoma is processed according to the specifications for stir-fried products， and other herbs are used in their raw products. The botanical sources of the herbs are consistent with the 2020 edition of Pharmacopoeia of the People's Republic of China. The above herbs are ground into a fine powder with a particle size passing through a No. 5 sieve. For each dose， take 8.26 g of the powdered formula， add 300 mL of water， along with 3 g of Zingiberis Rhizoma Recens and 3 g of Jujubae Fructus， and decoct until reduced to 140 mL. The decoction should be administered hot， with three times daily. To induce sweating， the patient should be kept warm under a quilt， and an additional dose should be prepared and taken if needed. This formula is traditionally used to relieve the exterior and resolve dampness， regulate Qi and harmonize the middle， which is mainly used to treat a series of diseases of digestive and respiratory systems. However， potential adverse reactions， including allergies， purpura and disulfiram-like reactions， should be considered during clinical use. Huoxiang Zhengqisan features a rational composition， extensive clinical application， and strong potential for further research and development.

Objective:To explore the clinicopathologic features differences between tall cell variant of papillary thyroid cancer (TCV-PTC) and PTC with tall cell features (PTC-TCF) and the factors influencing efficacy of 131I therapy in patients with TCV-PTC and PTC-TCF. Methods:A retrospective analysis was conducted on 84 patients (28 males, 56 females, age 43.5(35.0, 55.0) years) with pathologically confirmed TCV-PTC or PTC-TCF and who were treated with 131I therapy from January 2018 to June 2023 in the Department of Nuclear Medicine, the Affiliated Hospital of Qingdao University. The patients were divided into structural incomplete response (SIR) group and non-SIR group according to 131I treatment response. Data differences were analyzed by Wilcoxon rank sum test, Fisher exact test, or Mann-Whitney U test. Variables with P<0.1 were enrolled in logistic multivariate regression analysis. The ROC curve was used to obtain the cut-off value of stimulated thyroglobulin (sTg). Results:A total of 37 patients with non-SIR and 6 patients with SIR were found in TCV-PTC group ( n=43), and 33 non-SIR and 8 SIR cases were found in PTC-TCF group ( n=41). Univariate analysis revealed that sTg differed significantly between non-SIR patients and SIR patients in TCV-PTC group ( Z=-2.81, P=0.003), while no significant differences observed for sex, age, multifocality, capsular invasion, T stage, N stage, B-Raf proto-oncogene, serine/threonine-protein kinase (BRAF) V600E mutation, initial recurrence risk, number of metastatic lymph nodes, maximum tumor diameter ( Z values: from -0.74 to -0.11, all P>0.05). In TCV-PTC group, sTg also differed significantly between non-SIR patients and SIR patients ( Z=-4.40, P<0.001), while the other clinical factors above and the proportion of tall cells showed no significant difference ( Z values: from -1.90 to -0.22, all P>0.05). The logistic regression analysis confirmed sTg as an independent risk factor of SIR in both TCV-PTC group (odds ratio ( OR) = 25.156, 95% CI: 2.245-281.812, P=0.009) and PTC-TCF group ( OR=19.214, 95% CI: 2.537-145.502, P=0.004). The ROC curve indicated that the cut-off value of sTg for predicting SIR was 20.75μg/L in TCV-PTC group and 18.55μg/L in PTC-TCF group. Conclusions:sTg is the independent risk factor for predicting the poor prognosis of patients with TCV-PTC (sTg≥20.75μg/L) and PTC-TCF (sTg≥18.55μg/L). However, other clinical characteristics show no statistical difference between TCV-PTC group and PTC-TCF group, suggesting that the invasiveness of PTC-TCF may not be lower than that of TCV-PTC, which close attention should be paid to in clinical practice.

Aeromedical evacuation, a crucial method for casualty transport, significantly enhances survival rates by providing exceptionally rapid transfer and thus gaining valuable treatment time. However, due to the contamination risks during the transport of radioactively contaminated casualties, aeromedical evacuation has not been widely adopted for this specific scenario. This paper reviews the current status of aeromedical evacuation for radioactively contaminated casualties and identifies several challenges. These include incomplete evacuation procedures and regulatory frameworks, difficulties in rapid triage and classification, inadequate evacuation and loading equipment, and the complexity of managing specific injuries during flight. We propose corresponding strategies to address these issues, aiming to provide a reference and guidance for the advancement of aeromedical evacuation for radioactively contaminated casualties.

Objective:To investigate the effects of Xuebijing injection on gut microbiota and intestinal mechanical barrier in mice with lipopolysaccharide (LPS)-induced sepsis, and analyze the potential mechanism by which Xuebijing injection protects gastrointestinal tract.Methods:Twenty-four healthy and clean grade male C57BL/6N mice were divided into four groups, control group, LPS group, LPS+ 5 μl/g Xuebijing injection group (5 μl/g Xuebijing injection group), and LPS+ 10 μl/g Xuebijing injection group (10 μl/g Xuebijing injection group), with six mice in each group. A mouse model of sepsis was established by intraperitoneal injection of mice with 10 μg/g LPS. At 0 and 12 h after successful modeling, the mice were intraperitoneally injected with 5 or 10 μl/g Xuebijing injection. Blood, ileum, and colon fecal samples were collected 12 h after the second administration. ELISA was used to detect the levels of diamine oxidase (DAO), D-blood lactic acid (D-Lac), TNF-α, and IL-6. HE staining was used to observe the local ileum damage, and Chiu′s score was used to evaluate the degree of intestinal tissue damage. Immunohistochemical staining and Western blot were used to detect the expression of Claudin-1, Occludin, and zona occludins-1(ZO-1) in ileum tissues, followed by semi quantitative analysis. One-way analysis of variance was used for intergroup comparisons, and LSD or Tamhane′s T2 test was used for pairwise comparisons based on the homogeneity of variance. The diversity and species composition of mouse fecal microbiota, and the differences among groups were analyzed using 16S rRNA sequencing.Results:The levels of DAO, D-Lac, TNF-α, and IL-6 in the LPS group were higher than those in the control group (all P<0.000 1). After the intervention with Xuebijing injection, the levels of DAO, D-Lac, TNF-α, and IL-6 decreased (all P<0.05) and showed no significant differences with those in the control group (all P>0.05). Besides, 10 μl/g Xuebijing injection was more effective than 5 μl/g Xuebijing injection in reducing the concentrations (all P<0.05). Chiu′s score was higher in the LPS group than in the control group and the 10 μl/g Xuebijing injection group (both P<0.05). Western blot showed that the expression levels of Occludin, Claudin-1, and ZO-1 in the LPS group were lower than those in the control group (all P<0.01), and Xuebijing injection intervention significantly increased the expression levels of these proteins in a dose-dependent manner as compared with the LPS group (all P<0.000 1). Apart from the expression level of ZO-1, which showed no significant difference between the two Xuebijing injection groups ( P>0.05), the results of immunohistochemical staining were consistent with those of Western blot. The 16S rRNA sequencing results showed that there were differences in the Alpha and Beta diversity indices, and the composition and structure of gut microbiota among the four groups. The structure of gut microbiota in the mice treated with Xuebijing injection was similar to that in the mice of the control group and it was in a dose-dependent manner. Wilcoxon rank sum test showed that there were statistically significant differences in six gut microbiota groups at the phylum level, and 32 gut microbiota groups at the genus level among the mice of four groups (all P<0.05). Conclusions:Xuebijing injection can provide protective effects on the gastrointestinal tract by protecting the structure of gut microbiota and intestinal barrier function, and the protective effect is somewhat correlated with the drug dosage.

OBJECTIVE: To evaluate the risks and benefits of different resuscitation fluids in patients with early sepsis and septic shock by observing and comparing clinical indicators, clinical outcomes, and the concentration changes of glycocalyx biomarkers, and to determine how to appropriately select suitable resuscitation fluids for sepsis patients to aid fluid therapy. METHODS: A single center, prospective, randomized controlled trial was conducted. Patients with early sepsis and septic shock who have required fluid resuscitation after capacity status assessment admitted to the department of critical care medicine of Fourth Hospital of Hebei Medical University from April to October 2023 were enrolled. Patients were randomly assigned to either the experimental group (balanced crystalloid solution+albumin) or the control group (balanced crystalloid solution) by a random number table method. Clinical data of both groups of patients before and after resuscitation at 3, 8, and 24 hours were monitored, and blood samples were collected, enzyme-linked immunosorbent assay (ELISA) was used to measure the concentration of plasma glycocalyx biomarker syndecan-1. The 28-day and 90-day survival rates and complications were also assessed. RESULTS: A total of 66 patients were enrolled, including 44 in the experimental group and 22 in the control group. The baseline data of two groups were balanced and comparable. There was no statistically significant difference in the plasma concentration of syndecan-1 between the experimental group and the control group before and after resuscitation, and both showed a trend of first increasing and then decreasing. However, the plasma syndecan-1 level in the control group at 8 hours and 24 hours after resuscitation were significantly higher than the baseline level before resuscitation [ng/L: 19.02 (14.41, 27.80), 18.95 (12.40, 22.50) vs. 14.67 (11.57, 21.14), both P < 0.05], while there was no statistically significant difference at any time point within the experimental group. The correlation analysis between plasma syndecan-1 level and lactic acid, albumin, and sequential organ failure assessment (SOFA) in all patients showed that a positive correlation between syndecan-1 level and SOFA score before resuscitation (r = 0.247, P = 0.046), and a negative correlation between syndecan-1 level and albumin level at 24 hours after resuscitation (r = -0.308, P = 0.012). There were no statistically significant differences in 28-day and 90-day mortality, length of hospital stay, length of intensive care unit (ICU) stay, duration of mechanical ventilation, blood purification time, number of organ injuries, and complications between the two groups. However, the baseline albumin level in the experimental group was significantly lower than that in the control group (g/L: 28.7±4.5 vs. 31.6±4.2, P < 0.05). Analysis of clinical treatment data showed that compared with the control group, the experimental group had lower absolute lactate level at 8 hours and 24 hours after resuscitation [mmol/L: 8 hours was 1.30 (1.00, 1.88) vs. 1.60 (1.30, 3.05), 24 hours was 1.15 (0.80, 1.78) vs. 1.55 (1.08, 2.05), both P < 0.05], and higher lactate clearance rate [8 hours was 45% (27%, 56%) vs. 20% (-4%, 46%), 24 hours was 55% (34%, 70%) vs. 34% (-14%, 59%), both P < 0.05]. However, there were no statistically significant differences in the amount of fluid resuscitation, use of vasoactive drugs, and oxygenation index between the two groups during the resuscitation process. Multivariate Logistic regression analysis showed that body mass index (BMI) was independently correlated with 90-day mortality [odds ratio (OR) = 1.991, 95% confidence interval (95%CI) was 1.023-3.387, P = 0.043]. CONCLUSIONS There are no significant difference in plasma syndecan-1 level during fluid resuscitation of early sepsis and septic shock patients using balanced crystalloid fluid and balanced crystalloid fluid combined with albumin resuscitation, and there are no statistically significant differences in the impact on 28-day and 90-day prognosis, length of hospital stay, complications, and other aspects of the patients. However, compared to balanced crystalloid fluid, the combination of balanced crystalloid fluid and albumin for fluid resuscitation in sepsis patients has lower lactate level and better lactate clearance effect, but further validation is still needed through large-scale randomized controlled trials.
Humans ; Clinical Relevance ; Crystalloid Solutions/administration & dosage* ; Fluid Therapy/methods* ; Glycocalyx/metabolism* ; Isotonic Solutions/administration & dosage* ; Prospective Studies ; Resuscitation/methods* ; Sepsis/therapy* ; Shock, Septic/therapy* ; Syndecan-1/blood*

Penicillin G acylases (PGAs) are industrially important enzymes primarily used for the synthesis of first- and second-generation cephalosporins or penicillins. This study aims to establish a high-efficiency biosynthetic system for cefradine on the purpose of significantly enhancing its catalytic efficiency in cefradine synthesis and developing its potentials for industrial application. In this study, we identified and engineered penicillin G acylase and obtained a highly active mutant KsPGA M7(M168F/F313G) for the synthesis of cefradine. The mutant achieved a conversion rate over 95% in the scaled-up reaction. To validate its industrial applicability, we immobilized both the wild-type and mutant enzymes and applied them in continuous flow reactions, which achieved a space-time yield of 2 800 g/(L·d). This study lays a foundation for the future applications of penicillin G acylases in the industrial synthesis of cefradine.
Penicillin Amidase/biosynthesis* ; Protein Engineering/methods* ; Cephradine/metabolism* ; Escherichia coli/metabolism* ; Enzymes, Immobilized/metabolism* ; Recombinant Proteins/biosynthesis*

Objective:To explore the clinical efficacy of autologous platelet-rich plasma (PRP) in the treatment of acute injury to the anterior talofibular ligament (ATFL).Methods:A retrospective study was conducted to analyze the data of 96 patients who had been admitted to Department of Orthopedic Trauma Repair, The Nanhua Hospital Affiliated to Hengyang Medical School for acute ATFL injuries of grades Ⅰ & Ⅱ from January 2022 to December 2023. They were divided into 2 groups according to their different treatments. In the PRP group subjected to local PRP injection combined with conservative treatment, there were 49 patients (28 males and 21 females), with an age of (32.5±6.5) years. In the conservative group subjected to traditional conservative treatment, there were 47 patients (24 males and 23 females), with an age of (30.5±5.3) years. The 2 groups were compared in terms of visual analog scale (VAS) pain scores, talar anterior translations, Karlsson scores, American Orthopaedic Foot & Ankle Society (AOFAS) ankle-hindfoot scores before and 6 months after treatment.Results:No statistically significant differences were observed in the baseline characteristics between the 2 groups before treatment, indicating comparability ( P>0.05). All patients were followed up for (9.1±1.7) months. In both groups, the VAS pain scores significantly decreased after treatment than the pre-treatment ones, the talar anterior translations significantly reduced after treatment than the pre-treatment ones, and the AOFAS and Karlsson scores significantly increased after treatment than the pre-treatment ones ( P < 0.05). After 6 months of treatment, the talar translation distance [(2.5±0.4) mm], AOFAS ankle hind foot score [(91.7 ± 4.0) points], and Karlsson score [(93.0±3.5) points] in the PRP group were significantly better than those in the conservative group [(6.1±0.9) mm, (87.1±4.3) points, (89.0±4.0) points]( P < 0.05). Conclusion:In the treatment of acute ATFL injury, PRP therapy demonstrates good clinical efficacy, for it can significantly reduce pain, promote functional recovery, and improve joint stability.