BACKGROUND:The treatment of early knee osteoarthritis can be achieved through two knee preservation treatments:Unicondylar knee arthroplasty and high tibial osteotomy.However,further exploration is needed to determine whether there are differences in knee joint recovery between the two knee preservation surgeries at different stages after surgery. OBJECTIVE:To compare the efficacy and related complications of unicondylar knee arthroplasty and high tibial osteotomy in the treatment of varus osteoarthropathy of the knee,and to provide a reference for clinical decision. METHODS:A total of 103 patients with varus osteoarthritis of the knee underwent surgical treatment in the Affiliated Hospital of Nantong University from September 2018 to September 2022 were selected.Among them,86 patients were followed up for more than 1 year.According to different surgical methods,the patients were divided into unicondylar knee arthroplasty group(49 cases)and high tibial osteotomy group(37 cases).Knee function,pain,and line of force correction were evaluated before surgery,4 weeks,3 months,6 months,and 1 year after surgery in both groups.Hospital for special surgery knee score,functional score of Western Ontario and McMaster Universities Osteoarthritis Index,changes of lateral space of the knee joint,range of motion,proprioception(position sense),and postoperative activity recovery speed were evaluated comprehensively. RESULTS AND CONCLUSION:(1)There were no significant differences in preoperative hospital for special surgery knee score,Western Ontario and McMaster Universities Osteoarthritis Index score and lateral knee compartment size between the two groups.(2)The hospital for special surgery knee score of patients undergoing unicondylar knee arthroplasty was better than that of patients undergoing high tibial osteotomy within 4 weeks after surgery(P<0.05).At 3 and 6 months after surgery,compared with the improvement of the two groups,the hospital for special surgery knee score in the unicondylar knee arthroplasty group was lower than that in the high tibial osteotomy group,and the difference was significant(P<0.05).The range of motion flexion value and position perception of patients undergoing high tibial osteotomy were significantly better than those undergoing unicondylar knee arthroplasty 6 months after surgery(P<0.05).(3)The unicondylar knee arthroplasty group was better than the high tibial osteotomy group in terms of the speed of knee movement recovery(P<0.05).(4)However,there was no significant difference between the two groups in the change of hospital for special surgery knee score,range of motion,and the width of lateral knee space during 1-year follow-up.(5)All patients were followed up for more than 1 year,and no adverse complications were found during the follow-up.(6)It is indicated that the short-term effect of knee functional recovery in patients with high tibial osteotomy is better than that in patients with unicondylar knee arthroplasty,but there is no significant difference in medium-and long-term efficacy between the two kinds of surgery for medial knee arthritis.

In order to explore the possible role and molecular mechanism of the combined action of leech and bear bile in liver and gallbladder diseases, this study first used network pharmacology methods to screen the components and targets of leech and bear bile, as well as the related target genes of liver and gallbladder diseases. The selected key genes were subjected to interaction network and GO/KEGG enrichment analysis. Then, using sodium oleate induced HepG2 cell lipid deposition model and DL-ethionine induced mouse fatty liver model, the activity of leech and bear bile alone and in combination in reducing liver fat was evaluated in vitro and in vivo, and the expression of key pathway related proteins suggested by network pharmacology was detected by Western blot. The results of network pharmacology analysis showed that the active ingredients of leech and bear bile have 295 intersecting targets with liver and gallbladder related diseases, involving more than 200 signaling pathways, including the PI3K/Akt signaling pathway and phospholipase D signaling pathway closely related to glucose and lipid metabolism. The results of in vitro validation experiments showed that both leech and bear bile, alone and in combination, can significantly inhibit the lipid deposition induced by sodium oleate in human liver cells, reduce the triacylglycerol level in cell culture supernatant, and inhibit the lipid content in liver cells. The observation results of Nile red staining confocal microscopy showed that the combination of leech and bear bile had better activity in reducing lipid deposition in liver cells compared to using them alone. In a mouse fatty liver model, the combination of leech and bear bile can better reduce elevated organ indices, blood lipids, and liver lipid levels, as well as lower the levels of serum liver injury biomarkers. The animals used in this experiment and related disposal meet the requirements of animal welfare. Before the experiment, it was reviewed and approved by IACUC, Institute of Materia Medica, Chinese Academy of Medical Sciences. The Western blot experiment results showed that the combination of leech and bear bile can significantly upregulate the expression levels of p-PI3K and p-Akt proteins, and increase the p-PI3K/PI3K and p-Akt/Akt ratios, which is consistent with the predicted results of network pharmacology. The combination of leech and bear bile has great potential for treating fatty liver disease, and activating the PI3K/Akt pathway may be one of the important mechanisms for reducing lipid deposition in liver cells.

ObjectiveTo investigate the immunomodulatory effect of polysaccharides from Astragali Radix-Angelicae Sinensis Radix herb pair（Qi-gui polysaccharides） on lipopolysaccharide（LPS）-induced RAW264.7 macrophages and to characterize the structure of the active component Qi-gui homogeneous polysaccharide（AAPS-4a）， and evaluate its protective effect on ulcerative colitis（UC）. MethodsThe effects of six Qi-gui polysaccharides（0.01-100 mg·L^-1） on the proliferation of RAW264.7 cells were assessed by cell proliferation and activity assay（CCK-8）， and enzyme-linked immunosorbent assay（ELISA） was used to investigate the effects of the six polysaccharides（3， 10 mg·L^-1） on the secretion levels of tumor necrosis factor（TNF）-α， interferon（IFN）-β， and nitric oxide（NO） in LPS-induced RAW264.7 cells. After screening for active polysaccharides， high-performance size-exclusion chromatography（HPSEC） was used to determine its homogeneity and relative molecular weight， then its characteristic functional groups were identified by Fourier transform infrared spectroscopy（FT-IR）， monosaccharide composition was analyzed by high performance liquid chromatography（HPLC）， methylation analysis combined with gas chromatography-mass spectrometry（GC-MS） was performed to determine the types and linkage modes of sugar residues， and one- and two-dimensional nuclear magnetic resonance（NMR） were used to identify the sugar residue composition and configuration of the active polysaccharide. Finally， experimental animals were divided into the normal group， model group， AAPS-4a low-dose group（50 mg·kg^-1）， AAPS-4a high-dose group（100 mg·kg^-1）， and sulfasalazine（SASP） group （75 mg·kg^-1）. Except for the normal group， the acute UC mouse model was induced using 3.5% dextran sulfate sodium salt（DSS）. Each treatment group was administered the corresponding dose via oral gavage for 7 days， and changes in body weight were recorded. After treatment， the spleen index and disease activity index（DAI） score were calculated， TNF-α and interleukin-6（IL-6） levels in the serum were detected by ELISA， and histopathological changes in colon tissue were observed by hematoxylin-eosin（HE） staining. ResultsAt the cellular level， AAPS-4a exhibited a dose-dependent inhibition of LPS-induced increases in TNF-α， IFN-β， and NO levels（P<0.01）. Structural characterization of AAPS-4a revealed that it was a homogeneous polysaccharide with a relative molecular weight of 7.6×10³ Da， consisting of mannose（Man）， glucose（Glc）， and galactose（Gal） in a molar ratio of 1.3∶23.9∶1.0. It was primarily composed of five sugar residues of 1，6-α-D-Glcp， T-α-D-Glcp， 1，3-β-D-Galp， 1，4-α-D-Manp， and 1，2-α-D-Galp. In vivo experiments showed that compared with the normal group， the model group demonstrated markedly increased DAI score and spleen index， significantly reduced colon length， and significantly elevated levels of TNF-α and IL-6（P<0.01）. Compared with the model group， the AAPS-4a high-dose group significantly reduced the DAI score and spleen index， as well as TNF-α and IL-6 levels， and improved colonic atrophy（P<0.05， P<0.01）. Pathological observations showed that AAPS-4a significantly inhibited inflammatory cell infiltration in colon tissue and alleviated pathological damage. ConclusionAAPS-4a， a neutral homogeneous polysaccharide composed of 1，6-α-D-Glcp， T-α-D-Glcp， 1，3-β-D-Galp， 1，4-α-D-Manp and 1，2-α-D-Galp， is identified as a key bioactive component contributing to the anti-UC effect of the Qi-gui herb pair. Its immunoregulatory and anti-UC properties suggest its potential as a therapeutic agent for UC.

Male infertility can result from impaired sperm motility caused by multiple morphological abnormalities of the flagella (MMAF). Distinct projections encircling the central microtubules of the spermatozoal axoneme play pivotal roles in flagellar bending and spermatozoal movement. Mammalian sperm-associated antigen 17 ( SPAG17 ) encodes a conserved axonemal protein of cilia and flagella, forming part of the C1a projection of the central apparatus, with functions related to ciliary/flagellar motility, skeletal growth, and male fertility. This study investigated two novel homozygous SPAG17 mutations (M1: NM_206996.2, c.829+1G>T, p.Asp212_Glu276del; and M2: c.2120del, p.Leu707*) identified in four infertile patients from two consanguineous Pakistani families. These patients displayed the MMAF phenotype confirmed by Papanicolaou staining and scanning electron microscopy assays of spermatozoa. Quantitative real-time polymerase chain reaction (PCR) of patients' spermatozoa also revealed a significant decrease in SPAG17 mRNA expression, and immunofluorescence staining showed the absence of SPAG17 protein signals along the flagella. However, no apparent ciliary-related symptoms or skeletal malformations were observed in the chest X-rays of any of the patients. Transmission electron microscopy of axoneme cross-sections from the patients showed incomplete C1a projection and a higher frequency of missing microtubule doublets 1 and 9 compared with those from fertile controls. Immunofluorescence staining and Western blot analyses of spermatogenesis-associated protein 17 (SPATA17), a component of the C1a projection, and sperm-associated antigen 6 (SPAG6), a marker of the spring layer, revealed disrupted expression of both proteins in the patients' spermatozoa. Altogether, these findings demonstrated that SPAG17 maintains the integrity of spermatozoal flagellar axoneme, expanding the phenotypic spectrum of SPAG17 mutations in humans.
Humans ; Male ; Infertility, Male/pathology* ; Sperm Tail/ultrastructure* ; Homozygote ; Microtubule-Associated Proteins/genetics* ; Axoneme/genetics* ; Spermatozoa/ultrastructure* ; Adult ; Mutation ; Sperm Motility/genetics* ; Pedigree ; Microtubules ; Microtubule Proteins/genetics*

Mycophenolic acid (MPA), the active moiety of both mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS), serves as a primary immunosuppressant for maintaining solid organ transplants. Therapeutic drug monitoring (TDM) enhances treatment outcomes through tailored approaches. This study aimed to develop an evidence-based guideline for MPA TDM, facilitating its rational application in clinical settings. The guideline plan was drawn from the Institute of Medicine and World Health Organization (WHO) guidelines. Using the Delphi method, clinical questions and outcome indicators were generated. Systematic reviews, Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence quality evaluations, expert opinions, and patient values guided evidence-based suggestions for the guideline. External reviews further refined the recommendations. The guideline for the TDM of MPA (IPGRP-2020CN099) consists of four sections and 16 recommendations encompassing target populations, monitoring strategies, dosage regimens, and influencing factors. High-risk populations, timing of TDM, area under the curve (AUC) versus trough concentration (C₀), target concentration ranges, monitoring frequency, and analytical methods are addressed. Formulation-specific recommendations, initial dosage regimens, populations with unique considerations, pharmacokinetic-informed dosing, body weight factors, pharmacogenetics, and drug‍-‍drug interactions are covered. The evidence-based guideline offers a comprehensive recommendation for solid organ transplant recipients undergoing MPA therapy, promoting standardization of MPA TDM, and enhancing treatment efficacy and safety.
Mycophenolic Acid/administration & dosage* ; Drug Monitoring/methods* ; Humans ; Organ Transplantation ; Immunosuppressive Agents/administration & dosage* ; Delphi Technique

Objective To analyze the incidence and mortality of malignant tumors among the middle-aged and elderly population in Chengguan district of Lanzhou from 2011 to 2021,and to discuss the related risk factors.Methods Using the research data of REACTION in Lanzhou,an epidemiological survey was conducted through cluster sampling in three communities in Chengguan district of Lanzhou since April 2011.The target population was middle-aged and elderly residents over 40 years old.Two follow-up surveys were carried out in 2014-2016 and 2021 successively,and 6543 people with complete follow-up data were finally included.The incidence and mortality rates of malignant tumors were calculated,as well as their age standardized rates with reference to the age composition of Segi's world standard population.Multivariate Cox regression analysis was used to screen the risk factors affecting the incidence and mortality of malignant tumors.Results After an average follow-up of 10.6 years,314 new cases of malignant tumors were found in middle-aged and elderly residents in Chengguan district of Lanzhou,with an incidence rate and age standardized incidence rate of 454.30/100 000 and 128.93/100 000,respectively.A total of 158 deaths were attributed to malignant tumors,with a mortality rate and age standardized rate of 228.41/100 000 and 607.9/100 000,respectively;The age standardized incidence rate and mortality rate of malignant tumors males were both higher than those females(P＜0.05).During the follow-up period,the age standardized incidence rate of malignant tumors in the general population showed an significant upward trend(P＜0.05),whereas the age standardized mortality rate gradually decreased after a brief increase(P＜0.05).Lung cancer,colorectal cancer,gastric cancer,and liver cancer were the main types of malignant tumors ranking in the top five in terms of incidence and mortality by gender.Multivariate Cox regression results indicate that male,age≥60 years old,college education level or above,smoking history,drinking history,having been hit by major stressful events,central obesity,hypertension,and coronary heart disease are risk factors for the onset or death of malignant tumors(HR＞1).Married,with family size≥4,frequent consumption of fresh fruit,frequent consumption of fresh vegetables,frequent consumption of grains and tubers are protective factors for the onset or death of malignant tumors(HR＜1).Conclusion The incidence of malignant tumors among middle-aged and elderly people in Chengguan district of Lanzhou from 2011 to 2021 showed an increasing trend,while the overall mortality was decreasing.Our study indicates early cancer screening in elderly populations,maintaining a healthy lifestyle and strengthening the management of chronic diseases are crucial for the prevention and treatment of malignant tumors.

BACKGROUND:Achilles tendon adhesion after Achilles tendon injury can lead to decreased biomechanical properties,weakened healing ability,and ultrastructural changes of Achilles tendon,which further affects patients'daily life and work ability.Therefore,how to effectively deal with and prevent Achilles tendon adhesion has become a hot and difficult problem in clinical treatment. OBJECTIVE:To analyze the effects of biological amniotic membranes on postoperative Achilles tendon adhesion,biomechanics,and ultrastructural changes in rats with Achilles tendon rupture. METHODS:Sixty 6-week-old SD rats were selected to establish bilateral Achilles tendon rupture models and divided into two groups(n=30 per group)by the random number table method.In the model group,the severed end of the tendon was sutured directly.In the amniotic membrane group,the biological amniotic membrane was wrapped around the broken anastomosis and fixed by a suture.The adhesion,biomechanics,morphology,and structure of the Achilles tendon and the expression of p38 and ERK1/2 protein were evaluated 1,2,and 4 weeks after surgery. RESULTS AND CONCLUSION:(1)1 week after operation,the Achilles tendon and peritendinous tissues of the two groups were mildly edema,and the adhesion of the Achilles tendon tissues in the model group was more obvious.2 weeks after the intervention,the Achilles tendon and peritendinous tissues of the model group still had edema,and the adhesion degree between the Achilles tendon and the surrounding tissues was heavier than that of the amniotic membrane group.4 weeks after operation,there was no edema around the Achilles tendon in both groups,and the healing was well.The adhesion degree of the Achilles tendon in the amniotic membrane group was less than that in the model group.The maximum tension of Achilles tendons in the amniotic membrane group was higher than that in the model group at 2 and 4 weeks after operation(P<0.001).(2)Hematoxylin-eosin staining and transmission electron microscopy revealed that 1 week after operation,the tendon structure of rats of the two groups was disordered and the collagen fibers were sparsely arranged,in which the model group demonstrated obvious inflammatory reaction and adhesion to the Achilles tendon.Two weeks after operation,the model group still demonstrated obvious inflammatory response,adhesion of Achilles tendon,and irregular ordering of collagen fibers.The amniotic membrane group exhibited an orderly arrangement of collagen fibers and expansion of the endoplasmic reticulum of fibroblasts.At 4 weeks after operation,the collagen fibers of the Achilles tendon in the model group were thickened and disordered,and the rough endoplasmic reticulum was less in the fibroblasts,while the collagen fibers in the amniotic membrane group were ordered and thin,and the fibroblasts contained a large number of rough endoplasmic reticulum.(3)Four weeks after operation,western blot assay exhibited that the expressions of p38 and ERK1/2 protein in the Achilles tendon tissue of rats in the amniotic membrane group were lower than those in the model group(P<0.05).(4)The results confirm that the biologic amniotic membrane can promote the healing and inhibit the adhesion of Achilles tendon after the operation of the ruptured Achilles tendon,which may be associated with the regulation of the MAPK/ERK signaling pathway.

Echinococcosis is a common zoonotic disease in livestock; the type with the highest incidence is cystic echinococcosis (CE). In clinical management, patients with CE of the liver in which the cyst wall is calcified have been found to have better prognoses than those without calcification. In this study, we collected calcified and uncalcified cyst wall tissue from patients with hepatic CE and observed significant changes in the expression of 2336 messenger ribonucleic acids (mRNAs), 178 long noncoding RNAs (lncRNAs), 210 microRNAs (miRNAs), and 33 circular RNAs (circRNAs) using high-throughput sequencing (HTS). Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of differentially expressed RNAs (DERNAs: DEmRNAs, DElncRNAs, DEmiRNAs, and DEcircRNAs) were performed to explore these RNAs’ potential biological functions and signaling pathways. Ultimately, the results of hematoxylin and eosin (H&E) and terminal deoxynucleotidyl transferase deoxyuridine triphosphate (dUTP) nick end labeling (TUNEL) staining confirmed the correlation between calcification and apoptosis of the cyst wall. In summary, this study was an initial exploration of the molecular-biological mechanism underlying spontaneous calcification of the hydatid cyst wall, and it provides a theoretical basis for exploring new targets for drug treatment in CE.

Objective To explore the perioperative safety of video-assisted thoracic surgery (VATS) in Day Care Unit and the risk factors for delayed discharge under centralized management model. Methods The patients with VATS managed by the Day Care Unit of the Drum Tower Hospital Affiliated to Nanjing University Medical School in 2021 were retrospectively collected. The patients’ postoperative data and risk factors for delayed discharge were analyzed. Results A total of 383 patients were enrolled, including 179 males and 204 females with an average age of 46.09±14.82 years. Eleven (2.87%) patients developed grade 3-4 postoperative complications during the hospitalization. Eighteen (4.70%) patients visited unscheduled outpatient clinic within 7 days, and 6 (1.57%) patients were re-hospitalized within 30 days after discharge. The remaining patients had no significant adverse events during the 30-day follow-up. The average length of hospital stay was 2.27±0.35 d. The length of hospital stay was over 48 h in 48 (12.53%) patients. The independent risk factor for delayed discharge was lobectomy or combined resection (OR=3.015, 95%CI 1.174-7.745, P=0.022). Conclusion VATS can be safely conducted under the centralized management in Day Care Unit. The risk factor for delayed discharge is the extent of surgical resection.