AIM: To explore the application value of machine learning models in predicting the myopia control efficacy of orthokeratology(OK)in pediatric population, and analyze the key factors affecting axial length(AL)elongation.METHODS: This retrospective study included myopic subjects aged 8-17 y who were fitted with OK lenses and completed a 6 mo follow-up between January 1, 2021 and December 1, 2023. Baseline demographic and ocular biometric parameters were collected, including age, eye laterality, cycloplegic refraction, corneal curvature(K1 and K2)and AL. AL change(ΔAL)at 6 mo after lens wearing was defined as the primary outcome. Four machine learning models—decision tree, random forest, extreme gradient boosting(XGBoost), and neural network—were developed to predict treatment efficacy, and their predictive performance was compared. Multiple linear regression analysis was performed to identify relevant factors associated with ΔAL.RESULTS: A total of 102 myopic patients(159 eyes)aged 8-17 y were included in this study, including 57 bilateral eyes and 45 unilateral cases. Among them, 56 were boys(54.9%)and 46 were girls(45.1%). The mean age was 11.98±1.93 y. At baseline, the mean spherical error was -2.28±1.37 D, the mean cylindrical power was -0.65±0.36 D, and AL was 24.60±0.82 mm, the mean flat keratometry(K1)was 42.55±1.39 D, and the mean steep keratometry(K2)was 43.58±1.44 D.After 6 mo of lens wear, the AL increased to 24.68±0.59 mm, The mean spherical power was -2.45±1.46 D, the cylindrical power was -0.68±0.38 D, the K1 value was 42.52±1.33 D, and the K2 value was 43.61±1.51 D. The mean ΔAL was 0.08±0.17 mm.The performance comparison of four machine learning models in predicting the efficacy of OK on AL control showed that the decision tree model achieved the best predictive performance(MAE=0.11, MSE=0.02, R2=0.44). Feature importance analysis indicated that age, baseline AL and K1 were the top three predictors. Multiple linear regression showed that age was negatively associated with ΔAL(β=-0.03, P<0.001), while other variables were not significantly associated(all P>0.05).CONCLUSION: Machine learning models can effectively predict the efficacy of OK in controlling axial elongation in children. The decision tree model shows the best performance. Age is a key factor affecting the therapeutic effect of OK, while baseline AL and corneal curvature also contribute to prediction.This study provides new data support for individualized myopia prevention and control strategies in the pediatric population.

Stem cell treatment may enhance erectile dysfunction (ED) in individuals with cavernous nerve injury (CNI). Nevertheless, no investigations have directly ascertained the implications of varying amounts of human umbilical cord-derived mesenchymal stem cells (HUC-MSCs) on ED. We compare the efficacy of three various doses of HUC-MSCs as a therapeutic strategy for ED. Sprague-Dawley rats (total = 175) were randomly allocated into five groups. A total of 35 rats underwent sham surgery and 140 rats endured bilateral CNI and were treated with vehicles or doses of HUC-MSCs (1 × 10 6 cells, 5 × 10 6 cells, and 1 × 10 7 cells in 0.1 ml, respectively). Penile tissues were harvested for histological analysis on 1 day, 3 days, 7 days, 14 days, 28 days, 60 days, and 90 days postsurgery. It was found that varying dosages of HUC-MSCs enhanced the erectile function of rats with bilateral CNI and ED. Moreover, there was no significant disparity in the effectiveness of various dosages of HUC-MSCs. However, the expression of endothelial markers (rat endothelial cell antigen-1 [RECA-1] and endothelial nitric oxide synthase [eNOS]), smooth muscle markers (alpha smooth muscle actin [α-SMA] and desmin), and neural markers (neurofilament [RECA-1] and neurogenic nitric oxide synthase [nNOS]) increased significantly with prolonged treatment time. Masson's staining demonstrated an increased in the smooth muscle cell (SMC)/collagen ratio. Significant changes were detected in the microstructures of various types of cells. In vivo imaging system (IVIS) analysis showed that at the 1 st day, the HUC-MSCs implanted moved to the site of damage. Additionally, the oxidative stress levels were dramatically reduced in the penises of rats administered with HUC-MSCs.
Male ; Animals ; Erectile Dysfunction/metabolism* ; Rats, Sprague-Dawley ; Mesenchymal Stem Cell Transplantation/methods* ; Rats ; Penis/pathology* ; Humans ; Disease Models, Animal ; Umbilical Cord/cytology* ; Peripheral Nerve Injuries/complications* ; Mesenchymal Stem Cells ; Nitric Oxide Synthase Type III/metabolism* ; Actins/metabolism* ; Nitric Oxide Synthase Type I/metabolism*

Objective To identify and cluster non-O1/O139 Vibrio cholerae(NOVC)using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry(MALDI-TOF MS),and evaluate the feasibility of MALDI-TOF MS as a method for the identification and clustering of NOVC.Methods The NOVC was identified by the MALDI-TOF MS equipped with V5 database,V12 database,highly pathogenic bacteria database,and V5 database combined with self-built spectrum projection and analyzed by the principal com-ponent analysis(PCA)and main spectrum projection(MSP)clustering.Results The NOVC was incorrectly identified as Vibrio al-bensis by the MALDI-TOF MS equipped with V5 database or V12 database,while the MALDI-TOF MS equipped with highly pathogenic bacteria database or V5 database combined with self-built spectrum projection could correctly identify NOVC.The PCA clustering of MALDI-TOF MS could distinguish NOVC from other bacterial strains and refine the differentiation of NOVC species to show the dis-tance relationship between NOVC species.Some spectrum projections of NOVC were extremely similar to the reference strains used to establish the database,and MSP clustering could not distinguish the differences between NOVC species.Conclusion The identifica-tion ability of MALDI-TOF MS for NOVC is limited by its database.The MALDI-TOF MS equipped with highly pathogenic bacteria da-tabase or V5 database combined with the self-built spectrum projection can accurately identify NOVC.The PCA clustering of MALDI-TOF MS has certain reference significance for the intra-and inter-species identification and homology analysis of NOVC.

Objective To perform the identification at the subspecies-level of Mycobacterium abscessus(M.abscessus)and analyze its characteristics based on matrix-assisted laser desorption ionization time-of-flight mass spectrometry(MALDI-TOF MS).Methods Bi-otyper software was used to construct the predicted peak spectrum of M.abscessus subsp.abscessus and M.abscessus subsp.massiliense.The predicted peak spectrum was constructed with expected maximum peak value number of 70 and peak frequency of 100％in the ex-perimental group and control group,respectively.A blind test was performed on 31 strains of M.abscessus that were not used to con-struct predictive peak spectra to evaluate the identification efficiency of predictive peak spectra.FlexAnalysis software was used to sum-marize and analyze the list of mass spectral peak value of M.abscessus,and screen the specific peaks in mass spectra of different sub-species of M.abscessus.The principal component analysis(PCA)algorithm was used to perform the cluster analysis for the data from mass spectrometry of M.abscessus,and explore the feasibility of PCA clustering in distinguishing the subspecies of M.abscessus.Results In the experimental group,96.8％(30/31)of the strains were correctly identified,and one strain of M.abscessus subsp.massiliense with rough colony form was mistakenly identified as M.abscessus subsp.abscessus.In control group,77.4％(24/31)of the strains were correctly identified,but 7 strains of M.abscessus subsp.massiliense were incorrectly identified or unable to be identified.The identification efficiency in the experimental group was significantly better than that in the control group with statistical difference(X2=5.167,P=0.026).M.abscessus subsp.abscessus exhibited three specific peaks(m/z 4 001.67,4 386.81 and 4 963.17),and M.abscessus subsp.massiliense also exhibited three specific peaks(m/z 4 950.48,4 381.78 and 5 214.90).In the PCA 3D scatter plot,the data points of M.abscessus subsp.abscessus and M.abscessus subsp.massiliense were relatively dispersed without obvious clus-tering.The PC A dendrograph could be divided into six branches in which only four branches were composed of a single subspecies.The minimum level value of distance between M.abscessus subsp.abscessus and M.abscessus subsp.massiliense was about 0.1.Conclusion The predicted peak spectrum based on MALDI-TOF MS with the expected maximum peak number of 70 could accurately identify M.abscessus at the subspecies level.The specific peak of mass spectrometry method in this study should be feasible to distinguish the subspecies of M.abscessus subsp.abscessus and the subspecies of M.abscessus subsp.Massiliense,but PCA cluster analysis cannot be used as a means to distinguish M.abscessus subsp.abscessus from M.abscessus subsp.massiliense.

Objective To identify and cluster non-O1/O139 Vibrio cholerae(NOVC)using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry(MALDI-TOF MS),and evaluate the feasibility of MALDI-TOF MS as a method for the identification and clustering of NOVC.Methods The NOVC was identified by the MALDI-TOF MS equipped with V5 database,V12 database,highly pathogenic bacteria database,and V5 database combined with self-built spectrum projection and analyzed by the principal com-ponent analysis(PCA)and main spectrum projection(MSP)clustering.Results The NOVC was incorrectly identified as Vibrio al-bensis by the MALDI-TOF MS equipped with V5 database or V12 database,while the MALDI-TOF MS equipped with highly pathogenic bacteria database or V5 database combined with self-built spectrum projection could correctly identify NOVC.The PCA clustering of MALDI-TOF MS could distinguish NOVC from other bacterial strains and refine the differentiation of NOVC species to show the dis-tance relationship between NOVC species.Some spectrum projections of NOVC were extremely similar to the reference strains used to establish the database,and MSP clustering could not distinguish the differences between NOVC species.Conclusion The identifica-tion ability of MALDI-TOF MS for NOVC is limited by its database.The MALDI-TOF MS equipped with highly pathogenic bacteria da-tabase or V5 database combined with the self-built spectrum projection can accurately identify NOVC.The PCA clustering of MALDI-TOF MS has certain reference significance for the intra-and inter-species identification and homology analysis of NOVC.

Objective To perform the identification at the subspecies-level of Mycobacterium abscessus(M.abscessus)and analyze its characteristics based on matrix-assisted laser desorption ionization time-of-flight mass spectrometry(MALDI-TOF MS).Methods Bi-otyper software was used to construct the predicted peak spectrum of M.abscessus subsp.abscessus and M.abscessus subsp.massiliense.The predicted peak spectrum was constructed with expected maximum peak value number of 70 and peak frequency of 100％in the ex-perimental group and control group,respectively.A blind test was performed on 31 strains of M.abscessus that were not used to con-struct predictive peak spectra to evaluate the identification efficiency of predictive peak spectra.FlexAnalysis software was used to sum-marize and analyze the list of mass spectral peak value of M.abscessus,and screen the specific peaks in mass spectra of different sub-species of M.abscessus.The principal component analysis(PCA)algorithm was used to perform the cluster analysis for the data from mass spectrometry of M.abscessus,and explore the feasibility of PCA clustering in distinguishing the subspecies of M.abscessus.Results In the experimental group,96.8％(30/31)of the strains were correctly identified,and one strain of M.abscessus subsp.massiliense with rough colony form was mistakenly identified as M.abscessus subsp.abscessus.In control group,77.4％(24/31)of the strains were correctly identified,but 7 strains of M.abscessus subsp.massiliense were incorrectly identified or unable to be identified.The identification efficiency in the experimental group was significantly better than that in the control group with statistical difference(X2=5.167,P=0.026).M.abscessus subsp.abscessus exhibited three specific peaks(m/z 4 001.67,4 386.81 and 4 963.17),and M.abscessus subsp.massiliense also exhibited three specific peaks(m/z 4 950.48,4 381.78 and 5 214.90).In the PCA 3D scatter plot,the data points of M.abscessus subsp.abscessus and M.abscessus subsp.massiliense were relatively dispersed without obvious clus-tering.The PC A dendrograph could be divided into six branches in which only four branches were composed of a single subspecies.The minimum level value of distance between M.abscessus subsp.abscessus and M.abscessus subsp.massiliense was about 0.1.Conclusion The predicted peak spectrum based on MALDI-TOF MS with the expected maximum peak number of 70 could accurately identify M.abscessus at the subspecies level.The specific peak of mass spectrometry method in this study should be feasible to distinguish the subspecies of M.abscessus subsp.abscessus and the subspecies of M.abscessus subsp.Massiliense,but PCA cluster analysis cannot be used as a means to distinguish M.abscessus subsp.abscessus from M.abscessus subsp.massiliense.

This study aims to investigate the protective effect and potential mechanism of Jingfang Granules(JF) on the mouse model of chronic fatigue syndrome(CFS). Mice were randomized into normal, model, and low-, medium-, and high-dose(0.9, 1.8, and 3.6 g·kg~(-1)·d~(-1), respectively) JF groups according to the body weight. In addition to the normal group, other groups of mice received exhaustive swimming training and tail suspension training every day for the modeling of CFS. The mice in each administration group were administrated with JF at the corresponding dose by gavage, and those in the other groups were administrated with an equal amount of purified water. The exhaustive swimming and tail suspension tests were conducted in each group. The UV-glutamate dehydrogenase method was used to determine the serum level of urea nitrogen(UREA), and the lactate dehydrogenase(LDH) assay kit was used to determine the LDH level. Enzyme-linked immunosorbent assay was employed to measure the levels of interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α) in the serum, muscle tissue, and brain tissue of mice in each group. Western blot was employed to determine the expression levels of Toll-like receptor 4(TLR4), myeloid differentiation factor 88(MyD88), nuclear factor-kappa B(NF-κB) and their phosphorylated proteins in the muscle tissue of mice. The 16S rDNA sequencing and ultra-high performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS) were adopted to detect the changes of intestinal flora and intestinal metabolites in mice. Compared with the model group, JF significantly prolonged the swimming exhaustion time and shortened the tail suspension time of the model mice, lowered the levels of LDH and UREA in the serum as well as the levels of IL-6 and TNF-α in the serum, muscle tissue, and brain tissue of CFS mice. In addition, JF down-regulated the expression of TLR4, MyD88, and p-NF-κB/NF-κB in the muscle tissue of CFS mice compared with the model group. The results of 16S rDNA sequencing demonstrated that JF ameliorated the intestinal flora disorder of CFS mice. The results of UPLC-MS/MS revealed that JF significantly affected the histidine metabolism pathway in the intestinal tract of CFS mice. Spearman analysis displayed that histamine, a metabolite involved in histidine metabolism, was negatively correlated with the abundance of Clostridia＿UCG-014, Dubosiella, and RF39 and positively correlated with the abundance of Coriobacteriaceae＿UCG-002. The metabolite imidazole-4-acetaldehyde was negatively correlated with the abundance of Clostridia＿UCG-014, Dubosiella, and RF39 and positively correlated with the abundance of Coriobacteriaceae＿UCG-002. In conclusion, JF can increase the swimming exhaustion time, reduce the immobility time of tail suspension, lower serum LDH and UREA levels, and alleviate inflammation response. It may exert the therapeutic effect by improving intestinal flora homeostasis and inhibiting histidine metabolism by down-regulating the expression of proteins in the TLR4/MyD88/NF-κB signaling pathway, thereby relieving the symptoms of CFS in mice.
Animals ; Mice ; Gastrointestinal Microbiome/drug effects* ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Metabolomics ; Fatigue Syndrome, Chronic/genetics* ; NF-kappa B/genetics* ; Humans ; Interleukin-6/genetics* ; Myeloid Differentiation Factor 88/genetics* ; Toll-Like Receptor 4/genetics* ; Tumor Necrosis Factor-alpha/genetics* ; Disease Models, Animal

In recent years, the development of host-acting antibacterial compounds has gradually become a hotspot in the field of anti-infection. Through research on the interaction mechanism between hosts and pathogenic bacteria, it has been found that the immune system is one of the key targets of host-acting antibacterial compounds. There is a communication system called the quorum sensing system in microorganisms, which mainly adjusts the structure of multi-microbial community and coordinates the group behavior. When the quorum sensing molecules secreted by microorganisms reach a threshold concentration, the quorum sensing system is activated and the overall gene expression of the microorganism is changed. In addition to regulating the density of microorganisms, quorum sensing molecules can also act as a link between pathogenic microorganisms and hosts, entering the host immune system and playing a role in affecting the morphological structure of immune cells, secreting cytokines, and inducing apoptosis, leading to host immune injury and causing host immune dysfunction.The key mechanism of 3-oxo-C12-HSL and other acyl-homoserine lactone (AHL) molecules in the innate immune system has been extensively studied. The lipid solubility allows AHLs to pass through the plasma membrane of host immune cells easily and induce dissolution of lipid domains. Then, it acts through signaling pathways such as p38MAPK and JAK-STAT, further influencing the immune cell’s defense response to bacteria and potentially leading to cell apoptosis. Additionally, the human lactonase paraoxonase 2, which can degrade3-oxo-C12-HSL, has been found in macrophage. It acts as an immune regulator that promotes macrophage phagocytosis of pathogens and is hypothesized to have the ability to reduce bacterial resistance. The mechanism of quorum sensing molecules in the adaptive immune system is less studied, the current results suggest that 3-oxo-C12-HSL is closely related to the mitochondrial pathway in host immune cells. For example, 3-oxo-C12-HSL induces apoptosis of Jurkat cells by inhibiting the expression of three mitochondrial electron transport chain proteins; it can also trigger mitochondrial dysfunction and induce mast cell apoptosis through Ca²⁺ signaling.Among the quorum sensing molecules, the AHLs have the greatest impact on plant immune system. The different effects on plant resistance depends on the chain lengths of acyl groups in bacterial-produced AHLs. Short-chain AHLs (C4-HSL and C8-HSL) induce plant resistance to pathogenic bacteria mainly through the auxin pathway and jasmonic acid pathway. Long-chain AHL (3-oxo-C14-HSL) is commonly used in hosts against fungal pathogens by inducing stomata defense responses, and the reaction process is related to salicylic acid. Diffusible signal factor molecules also interfere with the stomatal immunity caused by pathogens. It may act through the formin nanoclustering-mediated actin assembly and MPK3 pathway to inhibit the innate immunity of Arabidopsis. In summary, AHLs induced different plant pathways and affects the plant-bacteria interactions to trigger plant immunity. As a quorum sensing molecule of fungi, farnesol has similar effects on host immunity as AHLs, such as stimulating cytokine secretion and activating an inflammatory response. It also plays a unique role on dendritic cell differentiation and maturation. In addition, studies have found that farnesol has a protective effect on autoimmune encephalomyelitis, which may be related to its effect on the composition of intestinal microorganisms of the host.Therefore, targeting the host immune system and quorum sensing molecules to develop antibacterial compounds can effectively inhibit the invasion of pathogens and subserve the host to resist the influence of pathogenic bacteria. This article will review the mechanism of host immune responses triggered by important quorum sensing molecules, aiming to explore the targets of host-acting antibacterial compounds and provide new directions for the prevention or treatment of causative infectious sources and the development of related drugs.

Objective To explore the efficacy and safety of recombinant human anti-severe acute respiratory syn-drome coronavirus 2(anti-SARS-CoV-2)monoclonal antibody injection(F61 injection)in the treatment of patients with coronavirus disease 2019(COVID-19)combined with renal damage.Methods Patients with COVID-19 and renal damage who visited the PLA General Hospital from January to February 2023 were selected.Subjects were randomly divided into two groups.Control group was treated with conventional anti-COVID-19 therapy,while trial group was treated with conventional anti-COVID-19 therapy combined with F61 injection.A 15-day follow-up was conducted after drug administration.Clinical symptoms,laboratory tests,electrocardiogram,and chest CT of pa-tients were performed to analyze the efficacy and safety of F61 injection.Results Twelve subjects(7 in trial group and 5 in control group)were included in study.Neither group had any clinical progression or death cases.The ave-rage time for negative conversion of nucleic acid of SARS-CoV-2 in control group and trial group were 3.2 days and 1.57 days(P=0.046),respectively.The scores of COVID-19 related target symptom in the trial group on the 3rd and 5th day after medication were both lower than those of the control group(both P＜0.05).According to the clinical staging and World Health Organization 10-point graded disease progression scale,both groups of subjects improved but didn't show statistical differences(P＞0.05).For safety,trial group didn't present any infusion-re-lated adverse event.Subjects in both groups demonstrated varying degrees of elevated blood glucose,elevated urine glucose,elevated urobilinogen,positive urine casts,and cardiac arrhythmia,but the differences were not statistica-lly significant(all P＞0.05).Conclusion F61 injection has initially demonstrated safety and clinical benefit in trea-ting patients with COVID-19 combined with renal damage.As the domestically produced drug,it has good clinical accessibility and may provide more options for clinical practice.

Objective To investigate the therapeutic effects of proximal femoral nail antirotation(PFNA)assisted by robot navigation and PFNA guided by C-arm X-ray machine for the treatment of intertrochanteric fracture of femur(IFOF).Methods The 100 patients with unilateral IFOF in our hospital were selected as the study subjects.They were divided into the control group(50 cases)and the robot-assisted group(50 cases)according to random number table method.The control group was treated with PFNA internal fixation under C-arm X-ray machine fluoroscopy,and the robot-assisted group was treated with PFNA internal fixation assisted by robot navigation.Surgical indicators,fracture reduction and fracture healing,stress response indexes,hip joint function,quality of life score and incidence of surgery related complications were compared between the two groups.Results The operation time,total fluoroscopy time,nail placement time and fracture healing time of the robot-assisted group were shorter than those of the control group(P＜0.05);and the intraoperative blood loss,guide needle adjustment frequency,and fluoroscopy frequency of the robot-assisted group were less than those of the control group(P＜0.05).The fracture reduction and fracture healing in the robot-assisted group were better than those in the control group(P＜0.05).Two days after operation,the levels of serum norepinephrine(NE),angiotensin Ⅱ(Ang Ⅱ)and superoxide dismutase(SOD)in the two groups were higher than those before operation(P＜0.05),and the levels of serum NE,Ang Ⅱ and SOD in the robot-assisted group were lower than those in the control group(P＜0.05).The Harris score and 36-item short-form(SF-36)score of patients 7 days and 3 months after surgery in the two groups were higher than those before surgery(P＜0.05),and the above scores 3 months after surgery were higher than those 7 days after surgery(P＜0.05).Harris score and SF-36 score 7 days and 3 months after operation in the robot-assisted group were higher than those in the control group(P＜0.05).The incidence of complications in the robot-assisted group was lower than that in the control group(P＜0.05).Conclusion Compared with the C-arm X-ray machine fluoroscopy,the treatment of IFOF with PFNA assisted by robot navigation can further shorten the operation time,reduce the surgical trauma and the incidence of complications,achieve better effect of fracture reduction and healing,reduce stress response of the body,and improve hip joint function and quality of life for patients.