Objective:To investigate the effect of PIK3CA mutations on the tumor immune microenvironment in Luminal breast cancer and evaluate the potential of Alpelisib-loaded pH-responsive polymer micelles in modulating the tumor immune microenvironment.Methods:PIK3CA mutations in breast cancer were analyzed using bioinformatics tools.A mouse xenograft model of Luminal breast cancer harboring a PIK3CA mutation was established,and alterations in the tumor immune microenvironment were examined using mass cytometry(CyTOF).During the period from August 2004 to December 2008 in Tianjin Medical University Cancer Hospital,tissue biopsies of 62 Luminal breast cancer patients in the BRCA cohort were collected Study the relationship between PIK3CA mutations and tumor immune microenvironment at the organizational level.Alpelisib-loaded polymer micelles(Alpelisib@MSPM)were synthesized,characterized,and evaluated for thera-peutic efficacy in Luminal breast cancer with PIK3CA mutations.Results:PIK3CA is one of the most frequently mutated genes in breast can-cer,with the highest prevalence in Luminal subtypes.CyTOF analysis demonstrated that PIK3CA mutations contribute to a tumor immun-osuppressive microenvironment in xenografts.Multiplex fluorescence immunohistochemistry revealed that PIK3CA-mutated tumors exhib-ited more infiltration of myeloid-derived suppressor cells(MDSCs)and less infiltration of CD8? T cells.The synthesized Alpelisib-loaded pH-re-sponsive polymer micelles had an average size of approximately 127 nm.Treatment with Alpelisib and Alpelisib@MSPM reduced tumor growth in mice with PIK3CA-mutated Luminal breast cancer.Notably,the proportion of MDSCs decreased,whereas CD8? T cell infiltration in-creased significantly,with the more pronounced effect observed in the Alpelisib@MSPM treatment group.Conclusions:PIK3CA mutations drive the formation of a tumor immunosuppressive microenvironment in Luminal breast cancer.Targeted Alpelisib delivery via pH-respons-ive polymer micelles significantly enhances therapeutic efficacy in PIK3CA-mutated breast cancer.

Objective To analyze the epidemiological characteristics of influenza-like illness outbreaks in Yunnan Province from 2017 to 2023,and to provide the evidence for the prevention and control of influenza in Yunnan Province.Methods The data of influenza-like illness outbreaks and outbreak specimens were collected in Yunnan Province from 2017 to 2023.Descriptive epidemiological methods were used to describe and analyze the epidemic time,population,region and pathogen distribution.Results A total of 340 influenza-like illness outbreaks were reported in Yunnan Province from 2017 to 2023,with 12586 reported cases and a cumulative incidence of 2.34%.The outbreaks were mainly concentrated in November to January and March of the following year,with a high incidence in winter and spring.Schools were the most important place of outbreak,with primary and secondary school students being the main affected group.The cumulative number of reported cases in Dali Prefecture,Dehong Prefecture,Yuxi City and Kunming City ranked among the top in the province,accounting for 79.71%of the total number of outbreaks in the province.The pathogen types alternated and were mainly prevalent in H1N1(119 cases),H3N2(81 cases),and Victoria(83 cases).Conclusion The outbreak of influenza-like illness in Yunnan Province shows the obvious seasonality,and primary and secondary schools are the main outbreak sites.The outbreak surveillance in schools should be strengthened continuously to control the occurrence and development of the epidemic.

Objective To explore the value of preoperative amide proton transfer(APT)imaging combined with diffusion kurtosis imaging(DKI)in predicting lymphovascular space invasion(LVSI)in cervical cancer.Methods Fifty-one patients with cervical cancer who underwent preoperative MRI examination and had complete postoperative pathology were retrospectively selected.Pelvic MRI scans were performed 1-2 weeks preoperatively,and the corresponding APT values,mean kurtosis(MK)and mean diffusivity(MD)values were obtained respectively,and the occurrence of LVSI was determined based on postoperative pathology results.The predictive effects of APT-and DKI-derived parameters alone or in combination on the LVSI status of cervical cancer were compared.Results Among 51 cases of cervical cancer,36 cases had pathologically confirmed LVSI and 15 cases did not had LVSI.The area under the curve(AUC)of the receiver operating characteristic(ROC)curve for the preoperative APT values,MK and MD values alone and in combination to predict the LVSI status of cervical cancer were 0.820,0.788,0.762,0.894,0.885,and 0.896,respectively.APT values combined with DKI-derived parameters predicted LVSI better than when they were used separately,in which APT values combined with MK and MD values predicted LVSI of cervical cancer with the largest AUC,sensitivity of 91.7％,specificity of 80.0％,and Youden's index of 0.717.Conclusion Preoperative APT imaging and DKI have important value in predicting LVSI of cervical cancer,and the combined application of the two can improve the prediction efficacy,which has certain clinical application value.

Lumbar manipulation plays an important role in the non-surgical treatment of lumbar degenerative diseases.Lumbar manipulation is a compound technique that contains many mechanical elements and motion characteristics at the moment of operation.Quantifying and objectifying parameters of the manipulation,summarizing technical characteristics of the operation,and discussing biomechanical mechanism of the manipulation in-depth,can contribute to teaching assessment and clinical diagnosis and treatment standards of the manipulation,making the manipulation safer and efficient,and further promoting inheritance and development of the traditional Chinese medicine manipulation.This article reviews and synthesizes domestic and foreign biomechanical research papers on lumbar manipulation for the treatment of lumbar degenerative diseases in recent years.The biomechanical effects on the lumbar spine and its accessory structures under manual transient loading,the measurement of technical parameters,and the characteristics of manual operation are summarized.

Objective The relationship between serum uric acid(UA)levels and gait kinematics characteristics in patients with cerebral small vessel disease(CSVD)was investigated.Methods Retrospective analysis was conducted on patients with CSVD from outparient clinics of the Neurology and Rehabilitation Department of Zhongshan Hospital affiliated with Guangzhou University of Chinese Medicine from January 2023 to December 2023.The general information of patients were collected and the gait of patients was analyzed using three-dimensional gait analysis.Patients were then divided into mild gait disorder group(0-1 points),moderate gait disorder group(2-3 points),and severe gait dysfunction group(4-5 points)based on gait results.The total burden of CSVD imaging and serum results such as UA were collected.The relationship between UA level and CSVD gait disorders was analyzed.Results This study recruited 105 CSVD patients.Patients were divided into different groups based on the severity of their gait disorder including 40 in the mild group,49 in the moderate group,and 16 in the severe group.The blood uric acid level in the moderate group(358.43±13.44)μmol/L was higher than that in the mild group(336.00±12.48)μmol/L,and the blood uric acid level in the severe group(289.94±11.88)μmol/L was lower than that in the mild and moderate groups(P<0.05).The MoCA score in the severe gait disorder group(21.38±0.13)was lower than that in the mild and moderate groups(28.05±0.09 vs.25.22±0.10)(P<0.05).The step width of the CSVD severe load group was(13.26±2.80)cm compared to the light and moderate load groups[(11.22±1.70)cm vs.(11.65±2.70)cm]increased(P<0.05),and the left swing phase in the severe group(35.90%)decreased compared to the mild and moderate groups(38.50%vs.37.20%)(P<0.05).Spearman correlation analysis showed a negative correlation between UA levels and CMB(r=-0.20,P=0.04).Hyperuricemia was negatively correlated with brain atrophy(r=-0.20,P=0.04).In patients with mild to moderate gait disorders,there was a positive correlation between hyperuricemia and the total burden of gait disorders(r=0.25,P=0.02),and hyperuricemia and right gait speed(r=-0.22,P=0.04),Right stride(r=-0.29,P<0.01),Left step speed(r=-0.32,P<0.01),Left step frequency(r=-0.29,P<0.01),The left stride was negatively correlated(r=-0.26,P=0.01).Conclusion In CSVD patients with mild to moderate gait disorders,the levels of uric acid and hyperuricemia are positively correlated with the total burden of gait disorders.The gait disorders are mainly characterized by reduced bilateral pace,bilateral stride,and left step frequency.

Background:The incidence of perianal fistulizing Crohn's disease is increasing and can seriously affect patients'quality of life.The efficacy of perianal surgery combined with biological agents for perianal fistulizing Crohn's disease remains to be clarified.Aims:To evaluate the clinical efficacy of perianal surgery combined with anti-tumor necrosis factor(TNF)-α agents in the treatment of perianal fistulizing Crohn's disease systematically.Methods:Cohort studies on perianal surgery combined with anti-TNF-α agents in the treatment of perianal fistulizing Crohn's disease were retrieved from PubMed,Web of Science,Embase,Cochrane Library,CNKI,Wanfang Data,and SinoMed.The retrieval time span was from the establishment of each database to October 30,2024.Literatures were enrolled according to the inclusion and exclusion criteria,and the data were extracted.Newcastle-Ottawa scale was used to evaluate the quality of literature.Meta-analysis was conducted by RevMan 5.4 software.Results:A total of 9 literatures involving 736 patients with perianal fistulizing Crohn's disease were enrolled.Meta-analysis showed that perianal surgery combined with anti-TNF-α agents shortened the healing time of anal fistula(WMD=-0.76,95%CI:-1.06--0.46;Z=4.91,P<0.000 01),decreased the recurrence rate of perianal fistula(OR=0.47,95%CI:0.26-0.84;Z=2.55,P=0.01),and reduced the perianal disease activity index(PDAI)score(WMD=-1.51,95%CI:-1.84--1.18;Z=8.91,P<0.000 01)when compared with perianal surgery alone.However,no significant differences in complete healing rate,partial healing rate,and reoperation rate were found between the two groups(all P>0.05).Conclusions:Perianal surgery combined with anti-TNF-α agents in the treatment of perianal fistulizing Crohn's disease demonstrates superior efficacy compared to perianal surgery alone in terms of shortening healing time,reducing recurrence rate and decreasing PDAI score.

[Objective]To analyze the effect of lever positioning manipulation(LPM)on the stress and strain of lumbar spine and intervertebral disc in different regions by using three-dimensional finite element technique,so as to reveal the biomechanical mechanism of manipulation.[Methods]A three-dimensional finite element model of the whole lumbar spine was constructed based on lumbar CT images,and the validity of the model was verified.The finite element model was used to analyze and compare the differences in the stress and strain of lumbar vertebrae and intervertebral discs by LPM at different manipulation points.[Results]The finite element model constructed indicates the point of manipulation is about 15 mm beside the L4 spinous process,the stress around the L4-5 intervertebral disc is large and the intermediate stress is small.The minimum strain point of the L4-5 intervertebral disc is about the lateral area of the intervertebral disc.The stress and strain of other intervertebral discs are similar to those of L4-5 intervertebral discs.The nucleus pulposus of L4-5 intervertebral disc move forward relatively to the lumbar spine;the stress under the lumbar pedicle is large,L4 has a certain degree of activity in the direction of extension,left bending and right rotation.Manipulation point is in the L4 spinous process,the stress around the L4-5 intervertebral disc is large and the intermediate stress is small.The minimum strain point of the L4-5 intervertebral disc is about the central area of the intervertebral disc.The stress and strain of other intervertebral discs are similar to those of L4-5 intervertebral discs.The nucleus pulposus of L4-5 intervertebral disc move forward relatively to the lumbar spine;the stress under the lumbar pedicle is large,and L4 has activity in the extension direction,and the activity in other directions is almost zero.[Conclusion]The LPM has the tendency to restore lumbar curvature and correct lumbar scoliosis and rotation.It can make the lumbar intervertebral disc move closer to the middle and make the nucleus pulposus move forward relatively to the posterior edge of the lumbar spine to reduce disc herniation and release compression.In the treatment of lumbar disc herniation,the manipulation points of the corresponding position can be selected according to the prominent position.

Objective The relationship between serum uric acid(UA)levels and gait kinematics characteristics in patients with cerebral small vessel disease(CSVD)was investigated.Methods Retrospective analysis was conducted on patients with CSVD from outparient clinics of the Neurology and Rehabilitation Department of Zhongshan Hospital affiliated with Guangzhou University of Chinese Medicine from January 2023 to December 2023.The general information of patients were collected and the gait of patients was analyzed using three-dimensional gait analysis.Patients were then divided into mild gait disorder group(0-1 points),moderate gait disorder group(2-3 points),and severe gait dysfunction group(4-5 points)based on gait results.The total burden of CSVD imaging and serum results such as UA were collected.The relationship between UA level and CSVD gait disorders was analyzed.Results This study recruited 105 CSVD patients.Patients were divided into different groups based on the severity of their gait disorder including 40 in the mild group,49 in the moderate group,and 16 in the severe group.The blood uric acid level in the moderate group(358.43±13.44)μmol/L was higher than that in the mild group(336.00±12.48)μmol/L,and the blood uric acid level in the severe group(289.94±11.88)μmol/L was lower than that in the mild and moderate groups(P<0.05).The MoCA score in the severe gait disorder group(21.38±0.13)was lower than that in the mild and moderate groups(28.05±0.09 vs.25.22±0.10)(P<0.05).The step width of the CSVD severe load group was(13.26±2.80)cm compared to the light and moderate load groups[(11.22±1.70)cm vs.(11.65±2.70)cm]increased(P<0.05),and the left swing phase in the severe group(35.90%)decreased compared to the mild and moderate groups(38.50%vs.37.20%)(P<0.05).Spearman correlation analysis showed a negative correlation between UA levels and CMB(r=-0.20,P=0.04).Hyperuricemia was negatively correlated with brain atrophy(r=-0.20,P=0.04).In patients with mild to moderate gait disorders,there was a positive correlation between hyperuricemia and the total burden of gait disorders(r=0.25,P=0.02),and hyperuricemia and right gait speed(r=-0.22,P=0.04),Right stride(r=-0.29,P<0.01),Left step speed(r=-0.32,P<0.01),Left step frequency(r=-0.29,P<0.01),The left stride was negatively correlated(r=-0.26,P=0.01).Conclusion In CSVD patients with mild to moderate gait disorders,the levels of uric acid and hyperuricemia are positively correlated with the total burden of gait disorders.The gait disorders are mainly characterized by reduced bilateral pace,bilateral stride,and left step frequency.

Objective To explore the value of preoperative amide proton transfer(APT)imaging combined with diffusion kurtosis imaging(DKI)in predicting lymphovascular space invasion(LVSI)in cervical cancer.Methods Fifty-one patients with cervical cancer who underwent preoperative MRI examination and had complete postoperative pathology were retrospectively selected.Pelvic MRI scans were performed 1-2 weeks preoperatively,and the corresponding APT values,mean kurtosis(MK)and mean diffusivity(MD)values were obtained respectively,and the occurrence of LVSI was determined based on postoperative pathology results.The predictive effects of APT-and DKI-derived parameters alone or in combination on the LVSI status of cervical cancer were compared.Results Among 51 cases of cervical cancer,36 cases had pathologically confirmed LVSI and 15 cases did not had LVSI.The area under the curve(AUC)of the receiver operating characteristic(ROC)curve for the preoperative APT values,MK and MD values alone and in combination to predict the LVSI status of cervical cancer were 0.820,0.788,0.762,0.894,0.885,and 0.896,respectively.APT values combined with DKI-derived parameters predicted LVSI better than when they were used separately,in which APT values combined with MK and MD values predicted LVSI of cervical cancer with the largest AUC,sensitivity of 91.7％,specificity of 80.0％,and Youden's index of 0.717.Conclusion Preoperative APT imaging and DKI have important value in predicting LVSI of cervical cancer,and the combined application of the two can improve the prediction efficacy,which has certain clinical application value.

[Objective]To analyze the effect of lever positioning manipulation(LPM)on the stress and strain of lumbar spine and intervertebral disc in different regions by using three-dimensional finite element technique,so as to reveal the biomechanical mechanism of manipulation.[Methods]A three-dimensional finite element model of the whole lumbar spine was constructed based on lumbar CT images,and the validity of the model was verified.The finite element model was used to analyze and compare the differences in the stress and strain of lumbar vertebrae and intervertebral discs by LPM at different manipulation points.[Results]The finite element model constructed indicates the point of manipulation is about 15 mm beside the L4 spinous process,the stress around the L4-5 intervertebral disc is large and the intermediate stress is small.The minimum strain point of the L4-5 intervertebral disc is about the lateral area of the intervertebral disc.The stress and strain of other intervertebral discs are similar to those of L4-5 intervertebral discs.The nucleus pulposus of L4-5 intervertebral disc move forward relatively to the lumbar spine;the stress under the lumbar pedicle is large,L4 has a certain degree of activity in the direction of extension,left bending and right rotation.Manipulation point is in the L4 spinous process,the stress around the L4-5 intervertebral disc is large and the intermediate stress is small.The minimum strain point of the L4-5 intervertebral disc is about the central area of the intervertebral disc.The stress and strain of other intervertebral discs are similar to those of L4-5 intervertebral discs.The nucleus pulposus of L4-5 intervertebral disc move forward relatively to the lumbar spine;the stress under the lumbar pedicle is large,and L4 has activity in the extension direction,and the activity in other directions is almost zero.[Conclusion]The LPM has the tendency to restore lumbar curvature and correct lumbar scoliosis and rotation.It can make the lumbar intervertebral disc move closer to the middle and make the nucleus pulposus move forward relatively to the posterior edge of the lumbar spine to reduce disc herniation and release compression.In the treatment of lumbar disc herniation,the manipulation points of the corresponding position can be selected according to the prominent position.