ObjectiveZheng’s San Qi San (ZSQS) power, a classic traditional Chinese medicine (TCM) formula, is used for treating soft tissue injuries involving muscles, tendons, and ligaments. However, its underlying therapeutic mechanisms remain unclear. This study aimed to screen and identify pharmaceutically active ingredients and their candidate biomolecule targets, and further elucidate the molecular mechanism of ZSQS in the treatment of skeletal muscle injury. MethodsNetwork pharmacology was employed to construct “ZSQS-component-target”, “protein-protein interaction (PPI)” and “active ingredient-core protein-pathway” networks to predict the key active ingredients and potential core targets of ZSQS for skeletal muscle injury. The predicted results were then validated via microarray data from the GEO database. Molecular docking was then performed to assess the binding ability between the screened active ingredients of ZSQS and the candidate core targets. Moreover, liquid chromatography-mass spectrometry (LC-MS) was used for qualitative and quantitative analysis to verify the active components of the drug and ZSQS serum. Finally, an animal model of eccentric exercise-induced skeletal muscle injury and a myotube cell model of oxidative stress-induced injury were established to validate the effects of ZSQS and its interventional effects on the biological functions of critical targets, thereby demonstrating the potential therapeutic mechanism of ZSQS. ResultsAmong the 111 active components identified in ZSQS and their corresponding 204 targets related to the skeletal muscle injury repair process, 14 core targets (including AKT1) and 4 core active components (quercetin, luteolin, kaempferol, and β‑sitosterol) were screened out, while the corresponding metabolites of quercetin, luteolin and kaempferol were detected in the ZSQS serum. Among these targets, 5 candidate genes (IL-6, CASP3, HIF1A, STAT3, and JUN) overlapped with the differential expression screening results with GEO data, and IL-6 was confirmed to be enriched in the PI3K/AKT pathway. Combined with the prediction results of the AKT expression levels, these findings suggest that the phosphorylation level of AKT1 plays a core role in the therapeutic mechanism of ZSQS. Molecular docking analysis further revealed that the PH domain of AKT1 had high binding energy with all 4 core active components, as verified by LC-MS. Finally, animal model studies have shown the promoting effect of ZSQS administration on skeletal muscle injury repair and its possible antioxidant damage mechanism. Cell model studies further demonstrated that ZSQS-containing serum, core active ingredient combination therapy, and quercetin monomer could increase the phosphorylation level of AKT, promote the nuclear translocation of Nrf2, upregulate the expression of downstream antioxidant enzymes (SOD, GPx, and GR), and inhibit the expression of inflammatory factors (IL-6 and TNF-α), thereby alleviating oxidative stress and the inflammatory response. ConclusionZSQS alleviates skeletal muscle injury mainly by activating the AKT/Nrf2 signaling pathway, enhancing cellular antioxidant and anti-inflammatory capabilities. The results of this study provide a scientific basis for the clinical application and modernized development of ZSQS.

ObjectiveTo analyze the effects of the progestin-primed ovarian stimulation （PPOS） protocol on embryo euploidy rate and clinical pregnancy outcomes in infertile patients. MethodsWomen who underwent Preimplantation genetic testing for aneuploidy （PGT-A） cycles were selected as study participants （a total of 656 cycles and 3 081 blastocysts）. Participants were divided into two age groups （≤35 years and >35 years） and further stratified by ovarian stimulation protocol： the Progestin-Primed Ovarian Stimulation （PPOS） group （n=48 and 60， respectively）， the Luteal Phase Long Protocol （LP） group （n=160 and 57， respectively）， and the Gonadotropin-Releasing Hormone Antagonist Protocol （AP） group （n=220 and 111， respectively）. Baseline characteristics， ovarian stimulation outcomes， and embryo development parameters were compared among the three protocols within each age group. Additionally， clinical pregnancy outcomes of the first frozen embryo transfer （FET） cycle were compared. The primary outcome measure was the embryo euploidy rate. Results① In the ≤35 years age group， baseline follicle-stimulating hormone （bFSH） levels were significantly higher in the PPOS group compared to the LP and AP groups， and the bFSH/bLH ratio was significantly higher in the PPOS group than in the AP group （P < 0.05）. In the >35 years age group， bFSH levels in both the PPOS and AP groups were significantly higher than in the LP group （P < 0.05）.② In the ≤35 years group， there were no significant differences in the rates of metaphase II （MII） oocytes， 2-pronuclei （2 PN） zygotes， cleavage， 2 PN cleavage， blastocyst formation， high-quality embryos， or embryo euploidy between the PPOS group and either the LP or AP groups. However， the PPOS group showed significantly lower values for the following parameters compared to the other two groups： total oocytes retrieved， number of MII oocytes， number of 2 PN zygotes， number of cleaved embryos， number of 2 PN cleaved embryos， number of blastocysts formed， number of high-quality embryos， number of high-grade blastocysts， number of transferable embryos， number of cryopreserved embryos， number of biopsied blastocysts， number of euploid embryos， and the rate of obtaining at least one euploid embryo. In the >35 years group， no significant differences were observed among the PPOS， LP， and AP groups in the rates of MII oocytes， 2 PN cleavage， blastocyst formation， or in the number of euploid embryos， euploidy rate， and the rate of obtaining at least one euploid embryo. However， the PPOS group had significantly lower numbers of total oocytes retrieved， MII oocytes， 2 PN zygotes， cleaved embryos， 2 PN cleaved embryos， blastocysts formed， transferable embryos， and cryopreserved embryos compared to the LP group （P<0.05）. The high-quality embryo rate was significantly lower in the PPOS group than in the AP group （P<0.05）. The numbers of high-quality embryos， high-grade blastocysts， and biopsied blastocysts were significantly lower in the PPOS group than in both the LP and AP groups （P<0.05）. Notably， the 2 PN fertilization rate was significantly higher in the PPOS group than in the AP group， and the cleavage rate was significantly higher in the PPOS group than in both the LP and AP groups （P<0.05）.③ No significant differences were found among the three groups in the biochemical pregnancy rate， clinical pregnancy rate， live birth rate， early miscarriage rate， and late miscarriage rate following the first FET cycle. ConclusionCompared to the other two protocols， the PPOS protocol does not significantly affect embryo euploidy or clinical pregnancy rates. However， in freeze-all cycles with PGT-A， the PPOS protocol does not reduce the rate of chromosomally normal embryos but may decrease the total number of available embryos. It may not be the optimal choice for younger women， but it can be considered as a viable option for women of advanced maternal age.

Purpose: The genomic characteristics of uterine sarcomas have not been fully elucidated. This study aimed to explore the genomic landscape of the uterine sarcomas (USs). Materials and Methods: Comprehensive genomic analysis through RNA-sequencing was conducted. Gene fusion, differentially expressed genes (DEGs), signaling pathway enrichment, immune cell infiltration, and prognosis were analyzed. A deep learning model was constructed to predict the survival of US patients. Results: A total of 71 US samples were examined, including 47 endometrial stromal sarcomas (ESS), 18 uterine leiomyosarcomas (uLMS), three adenosarcomas, two carcinosarcomas, and one uterine tumor resembling an ovarian sex-cord tumor. ESS (including high-grade ESS [HGESS] and low-grade ESS [LGESS]) and uLMS showed distinct gene fusion signatures; a novel gene fusion site, MRPS18A–PDC-AS1 could be a potential diagnostic marker for the pathology differential diagnosis of uLMS and ESS; 797 and 477 uterine sarcoma DEGs (uDEGs) were identified in the ESS vs. uLMS and HGESS vs. LGESS groups, respectively. The uDEGs were enriched in multiple pathways. Fifteen genes including LAMB4 were confirmed with prognostic value in USs; immune infiltration analysis revealed the prognositic value of myeloid dendritic cells, plasmacytoid dendritic cells, natural killer cells, macrophage M1, monocytes and hematopoietic stem cells in USs; the deep learning model named Max-Mean Non-Local multi-instance learning (MMN-MIL) showed satisfactory performance in predicting the survival of US patients, with the area under the receiver operating curve curve reached 0.909 and accuracy achieved 0.804. Conclusion USs harbored distinct gene fusion characteristics and gene expression features between HGESS, LGESS, and uLMS. The MMN-MIL model could effectively predict the survival of US patients.

AIM:To compare the effects and effi-cacy of methoxyamine and norepinephrine on sub-lingual microcirculation in patients with high-alti-tude septic shock.METHODS:A total of forty-six patients with septic shock from the Xining area of Qinghai Province were randomized into two groups:the M-hydroxylamine group(Group M,n=22)and the norepinephrine group(Group N,n=24).Baseline data as well as the incidence of acute kid-ney injury(AKI),distal limb necrosis/ischemia,and 28-day survival rates were documented.Sublingual microcirculation parameters were monitored and recorded at four time points:before treatment(T0),24 hours post-treatment(T1),48 hours post-treatment(T2),and 72 hours post-treatment(T3)using side-flow dark-field(SDF)imaging.The pa-rameters included total vascular density(TVD),per-fused vascular density(PVD),perfused vessel ratio(PPV),microvascular flow index(MFI),and hetero-geneity index(HI).Additionally,changes in heart rate(HR),mean arterial pressure(MAP),blood urea nitrogen(BUN),serum creatinine(Cr),and lac-tate(Lac)levels were also recorded.RESULTS:There were no significant differences between the two groups in terms of baseline data,incidence of AKI,distal limb necrosis/ischemia,and 28-day sur-vival rate.Additionally,there were no significant differences in HR,MAP,and Lac indices between the two groups at any time point.However,within-group comparisons showed that HR,MAP,and Lac indices improved over the course of treatment,with statistically significant differences.The BUN level at the T3 time point was significantly lower in the mehydroxyamine group compared to the nor-epinephrine group(P<0.05).Similarly,Cr levels were significantly lower at both T2 and T3 time points(P<0.05).There were no significant differenc-es in sublingual microcirculation indices between the two groups at any time point.However,TVD,PVD,PPV,MIF,and HI in both groups improved over the course of treatment,with statistically sig-nificant differences.CONCLUSION:Both methoxy-amine and norepinephrine can enhance both the macrocirculation and sublingual microcirculation in patients with septic shock at high altitudes.Addi-tionally,methoxyamine leads to a faster recovery of creatinine levels within 72 hours.

BACKGROUND:The cryopreservation technology enables tissues/cells to be stored for a long time in a low-temperature environment while maintaining the integrity of their activity and function,which is of great significance for the construction of cell therapy,tissue engineering and biological sample banks.Cryoprotective agents often contain dimethyl sulfoxide and serum.To avoid the toxic side effects of dimethyl sulfoxide,the complexity of serum components and immune responses,although some finished cryoprotective agents have been marketed,they are faced with many difficulties such as high cost and limited application.Therefore,there is an urgent need to develop a cryoprotective agent with clear components and the ability to solve the above problems.OBJECTIVE:To evaluate the effects of a novel cryoprotectant on cryopreservation efficiency of different tissue and cell sources.METHODS:By applying the novel cryoprotectant as an experimental group with the commercially available and widely used cryoprotectant(control group)to umbilical cord Wharton's jelly tissue,umbilical cord mesenchymal stem cells,umbilical cord blood/peripheral blood mononuclear cells,NK and CIK cells,comparative analyses were conducted in terms of cell morphology,number,viability,surface markers,differentiation potential,and cell-killing toxicity assay before cryopreservation and after resuscitation thawing.We confirmed the cryopreservation effect of the new cryoprotectant and its potential application value.RESULTS AND CONCLUSION:(1)The novel cryoprotectant facilitated the normal growth of cryopreserved Wharton's jelly tissue upon recovery,exhibiting mesenchymal stem cell morphology.No significant differences were observed between the experimental and control groups in terms of cell recovery rate,surface markers,and differentiation potential.(2)There was no significant difference in the number and viability of cells between the experimental group and the control group after cryopreservation of cord blood/peripheral blood mononuclear cells,and the cryo-resuscitated cell numbers and viability of derived NK cells/CIK cells did not show significant difference between the experimental and control groups.(3)For NK cells derived and differentiated from cord blood/peripheral blood mononuclear cells,there was no significant difference in the proportion of CD56+CD16+cell subpopulations between the experimental group and the control group.For CIK cells derived and differentiated from cord blood/peripheral blood mononuclear cells,there was no significant difference in the proportions of CD3+CD8+and CD3+CD56+cell subpopulations between the experimental group and the control group.(4)In terms of cytotoxicity testing,when the effective-target ratio of immune cells and melanoma cell line Mel624 was 20:1,whether it was NK cells/CIK cells derived from cord blood or peripheral blood mononuclear cells,there was no significant difference in the tumoricidal activity of cells between the experimental group and the control group.These findings suggest that the novel cryoprotectant can replace existing commercially available and widely used cryoprotectants,and is applicable to Wharton's jelly tissue,umbilical cord mesenchymal stem cells,umbilical cord blood/peripheral blood mononuclear cells,as well as NK and CIK cells,providing a solid technical foundation for the scaling,standardization,and commercialization of universal cryoprotectants.

OBJECTIVE To systematically evaluate the risk factors for spontaneous bacterial peritonitis(SBP)in the cirrhosis patients with ascites so as to provide bases for reducing the incidence of SBP.METHODS The literatures regarding to cirrhosis ascites complicated with SBP were retrieved from the databases such as PubMed,Embase,Cochrane Library,CBM,CNKI,Wanfang and VIP.The time frame of retrieval was limited from the establish-ment of the databases to Jan.10,2024.The quality of the literatures was evaluated by Newcastle-Ottawa Scale(NOS).The data were analyzed by using STATA 16.0.RESULTS A total of 43 pieces of literatures were included in the study,involving 9877 research subjects,3384 of whom were complicated with SBP.The result of meta a-nalysis showed that the risk factors(P＜0.05)for SBP in the cirrhosis patients with ascites included the general factor(history of SBP),the disease factors(gastrointestinal hemorrhage,diarrhea,diabetes mellitus),drug fac-tors(use of proton pump inhibitors),physiological indexes[low blood sodium,low serum albumin,high serum bilirubin,rise of C-reactive protein(CRP)],liver function scoring indexes[Child-turcotte-pugh(CTP)grade C,model of end-stage liver disease(MELD)],and ascites indexes[low ascites albumin,rise of ascites white blood cells and rise of tumor necrosis factor-α(TNF-α)].CONCLUSIONS SBP is one of the most severe complications in the cirrhosis patients with ascites.Multiple risk factors may have remarkable influence on the occurrence and de-velopment of SBP.It is necessary to take targeted interventions to the controllable risk factors during the clinical practice so as to effectively reduce the risk of SBP in the cirrhosis patients with ascites.

OBJECTIVE To analyze the diagnosis of latent tuberculosis infection(LTBI)in hospitalized patients of a tertiary general hospital and investigate the current status of related comorbidities.METHODS The clinical data were collected from the 14 448 hospitalized patients who received tuberculin skin test(TST)or interferon-gamma release assay(IGRA)in China-Japan Friendship Hospital from Jan.1,2022 to Dec.31,2023,and the results were assessed.RESULTS The detection rate of LTBI was 23.62％(3413/14448)among the hospitalized patients who received the tests,and the rate of definite diagnosis was only 4.22％(144/3413).88.40％(3017/3413)of the hospitalized patients with LTBI had at least one type of comorbidity,and the top 5 comorbidities were in turn as follows:high blood pressure,hyperlipidemia,diabetes mellitus,malignant tumors and rheumatic immune disea-ses;the number of comorbidities was increased with the age(x2=291.199,P＜0.001).The rheumatic immune disease(73/144,50.69％)was the most common type of comorbidity among the hospitalized patients with definite diagnosis of LTBI,and less than half of the patients(66/144,45.83％)were treated in rheumatology and immu-nology department.CONCLUSION The two-way screening of LTBI and comorbidities is the core premise for the standardized management of LTBI.

Aim To investigate the protective effects of Tilianin on lipopolysaccharide(LPS)-induced septice-mia-induced myocardial injury in rats and to explore the related mechanisms.Methods Animals were ran-domly grouped and a rat septicemia-induced myocardial injury model was constructed.Echocardiography was used to assess the cardiac function of rats,left ventricu-lar internal diameter at end-diastole(LVIDd)and left ventricular internal diameter at end-systole(LVIDs)were measured,and left ventricular ejection fraction(LVEF)and left ventricular fractional shortening(LVFS)were calculated;the kits were used to detect the serum activity of the relevant cardiac enzymes and the level of inflammatory factors;HE staining was used to observe the morphological changes of myocardium;immunofluorescence staining of cardiac tissues was used to detect the nuclear translocation of NF-κB p65;Western blot was used to detect the expression of TLR4,MyD88,p-NF-κB p65,and NLRP3 proteins in cardiac tissues.Results Compared with the model group,each administration group differently upregulated LVEF,LVFS,and LVIDs,and improved the coordina-tion of LV wall fluctuations in the model group of rats;cardiac enzymes LDH and CK-MB levels increased,and levels of inflammatory factors TNF-α,IL-6,and IL-1 β were reduced,exerting cardioprotective effects;HE staining showed that myocardial tissue cell gap was re-duced,myocardial fiber breakage was reduced,cardio-myocyte arrangement tended to be normal,and inflam-matory cell infiltration was reduced;NF-κB p65 entry into the nucleus was reduced,and phosphorylated NF-κB p65(p-NF-κB p65)expression was reduced;and Western blot results showed that the expression of TLR4,MyD88,and NLRP3 proteins was reduced.Conclusions Tilianin pretreatment reduces serum my-ocardial enzymes and inflammatory factors and im-proves myocardial injury in rats with septicemia-in-duced myocardial injury,which may be related to the Tilianin anti-TLR4/NF-κB/NLRP3 inflammatory signa-ling pathway.

BACKGROUND:Cervical spondylosis is a chronic degenerative disease that has become one of the most common and frequent diseases threatening human health.At present,the initial diagnosis of the cervical spine and its surrounding structures mainly relies on the interpretation of medical images by radiologists,which not only requires a high level of technical requirements for operators,but also has the disadvantages of strong subjectivity,high labor intensity,and low efficiency.With the rapid development of artificial intelligence technology,its powerful data processing and image recognition capabilities have shown broad application prospects in the medical field.Deep learning has also made certain progress in the research of spinal diseases.OBJECTIVE:To summarize the current status and research progress in the application of artificial intelligence technology in cervical spine imaging images in recent years,evaluating the performance of artificial intelligence models as well as future trends and challenges to be overcome.METHODS:The first author searched the relevant articles in WanFang,CNKI,and PubMed in June 2024.The Chinese search terms were"artificial intelligence,deep learning,cervical spine."English serach terms were"artificial intelligence,Al,cervical vertebrae,cervical."Finally,101 articles were included and analyzed.RESULTS AND CONCLUSION:(1)Artificial intelligence technology can realize automatic segmentation of cervical vertebrae and measurement of curvature change by segmentation,classification,landmarks recognition of medical image parts,detect cervical vertebral fracture,nerve root,and spinal cord type cervical spondylosis,identify cervical spine ossification of posterior longitudinal ligament,and predict post-surgery related risk factors and cervical vertebra maturation classification.(2)Although artificial intelligence technology has shown great potential in the field of cervical spine research,it is still in the early stages of exploration and rapid development,with unlimited room for development and innovation.

Objective To analyze the risk factors for increased drainage volume after open transforaminal lumbar interbody fusion(TLIF),and to establish a predictive model and then validate it.Methods The clinical data of 680 patients who underwent open TLIF at the General Hospital of Northern Theater Command from January 2016 to December 2019 were collected and the patients were randomly divided into the training group(n=476)and the validation group(n=204).Taking the predictive factors screened out by LASSO regression analysis as independent variables,a multivariate Logistic regression predictive model was constructed.The model was internally validated through the receiver operating characteristic(ROC)curve,Hosmer-Lemeshow goodness-of-fit test,and calibration curve,and its clinical utility was assessed via decision curve analysis(DCA).Results LASSO regression analysis screened out four predictive variables:age,number of surgical segments,operative duration,and intraoperative blood loss.The multivariate Logistic regression predictive model demonstrated that age≥60 years,number of surgical segments≥4,operative duration≥2 hours,and intraoperative blood loss≥200 mL were independent influencing factors for the increased postoperative drainage volume in patients undergoing TLIF(P<0.05).ROC curve analysis revealed an area under the curve(AUC)of 0.816(95%CI:0.798 to 0.867)in the training group and 0.783(95%CI:0.685 to 0.823)in the validation group,indicating that the predictive model had good discriminatory ability.Additionally,the Hosmer-Lemeshow goodness-of-fit test and calibration curve indicated that the predictive model had a good degree of fit,and the predicted probability was basically consistent with the actual probability,demonstrating a good calibration.The DCA results confirmed that this predictive model could be applied in clinical practice.Conclusion The risk factors for increased drainage volume after open TLIF include age,number of surgical segments,operative duration,and intraoperative blood loss.The predictive model established based on these factors demonstrates good performance,and it can be applied in clinical guidance for the selection of drainage tube removal time after TLIF.