Tumor-associated macrophages （TAMs）， as the main immune cells in the human body， are key factors in maintaining the homeostasis of the tumor microenvironment. With high plasticity， they can polarize into the classically activated （M1） macrophages or alternatively activated （M2） macrophages under different conditions. M1 macrophages can inhibit tumor growth by phagocytosis， and M2 can inhibit the immune microenvironment to promote tumorigenesis and immune escape. Small molecules of traditional Chinese medicine have been widely studied in gastrointestinal tumors. These small molecules exert anti-tumor activity by enhancing TAM activity and promoting the polarization of macrophages. Targeted intervention in TAMs with these molecules has the potential to inhibit the development of gastrointestinal tumors. This article summarizes the research status and significance of small molecules of traditional Chinese medicine targeting TAMs against gastrointestinal tumors， aiming to provide reference for the future studies in this field.

AIM: To evaluate the efficacy of 0.01% hypochlorous acid as a conjunctival sac disinfectant before cataract phacoemulsification and its impact on the ocular surface.METHODS: Randomized controlled clinical trial. A total of 285 patients who were scheduled for cataract phacoemulsification surgery were randomly divided into the hypochlorous acid group and the povidone iodine group. Before and after disinfection, conjunctival sac swabs were taken, and bacterial culture and colony-forming units(CFUs)testing were performed using blood agar and chocolate agar media, respectively. All patients were evaluated for ocular symptom scores and pain severity scores 2 h, 1 d, and 1 wk after disinfection, and underwent corneal fluorescein staining, eye redness index, tear meniscus height, and noninvasive breakup time(NIBUT)examination. The incidence of endophthalmitis after surgery was recorded.RESULTS: Conjunctival sac disinfection with 0.01% hypochlorous acid significantly reduced the rate of positive bacterial cultures and colony-forming ability of the conjunctival sac, with statistically significant differences compared with the pre-disinfection period(both P<0.01), and the disinfecting ability of hypochlorous acid was comparable to that of povidone-iodine(χ2=0.811, P=0.368). The scores of ocular symptoms and pain severity in the hypochlorous acid group were significantly lower than those in the povidone-iodine group(both P<0.01). The corneal fluorescein staining and eye redness index in the hypochlorous acid group were significantly lower than those in the povidone-iodine group(all P<0.01). No endophthalmitis occurred in either group of patients. CONCLUSION: As a conjunctival sac disinfectant, 0.01% hypochlorous acid is safe and effective, with minimal discomfort and damage to the ocular surface in patients.

ObjectiveTo systematically sort out the knowledge framework and conceptual logic relationship of "disease-syndrome-treatment-prescription-medicine" in the existing literature on traditional Chinese medicine（TCM） treatment of diabetic peripheral neuropathy（DPN）， to construct of the knowledge map of TCM treatment of DPN， and to promote the explicitation of the implicit knowledge in the literature on the treatment of DPN with TCM. MethodTaking the literature of China National Knowledge Infrastructure about TCM treatment of DPN as the main data source， TCM-related concepts and entities were constructed by manual citation， and the corresponding relationships between the entities were established. Structured data were formed by processing with Python 3.7， and the knowledge graph was constructed based on Neo4j 3.5.34 graph database. ResultThe resulting knowledge graph with TCM diagnosis and treatment logic， defined 12 node labels such as prescriptions， Chinese medicines and syndrome types at the schema layer， as well as 4 types of relationships， such as inclusion， correspondence， selection and composition. It could support the query and discovery of nodes（syndrome elements， syndrome types and treatment methods）， as well as the relationship between each node. ConclusionBased on the literature data， this study constructed a knowledge map for TCM treatment of DPN， which brought together various methods of TCM treatment of DPN， including internal and external treatment. The whole chain knowledge structure of syndrome differentiation and classification for DPN treatment is formed from syndrome element analysis， syndrome type composition to treatment method selection， which can provide new ideas and methods for literature data to serve clinical and scientific research work， as well as reference for visualization of TCM literature knowledge， intellectualization of TCM knowledge services and the standardization of TCM diagnosis and treatment.

OBJECTIVE To prepare meloxicam solid dispersions tablets, and to investigate their dissolution in vitro. METHODS Crystal inhibition experiments were carried out to screen the carrier materials, and the solid dispersion was characterized by X-ray diffraction(XRD) amd differential scanning calorimeter(DCS). The improved bioavailability of solid dispersions was evaluated through in vivo pharmacokinetic studies. The optimum preparation process of meloxicam solid dispersion tablets was investigated, and the in vitro dissolution curve similarity factor f2 was used as the main evaluation index to screen and optimize the dosage of pH regulator, filler, disintegrator, lubricant, flow aid and the mixing time in the prescription. RESULTS The solid dispersion prepared with Kollidon@VA64 as carrier effectively maintained the supersaturated state of the drug in solution. The results of XRD and DSC showed that the crystal state of meloxicam in the solid dispersion was completely transformed into amorphous state. Compared with meloxicam, solid dispersions significantly increased the solubility, and its peak blood concentration(Cmax) and relative bioavailability were increased by 208.09% and 241.78%, respectively. The optimal formulation and process of meloxicam solid dispersion tablets prepared by direct powder pressing method were meloxicam solid dispersion 35.2%, lactose∶microcrystalline cellulose =1∶1.5, sodium citrate 9.8%, crosslinked povidone 8%, magnesium stearate 0.75%, silica 0.8%, and mixing time 5 min. The dissolution similarity factor f2 of the prepared meloxicam solid dispersion tablets and the original reference preparation in different pH medium was above 50. CONCLUSION Meloxicam solid dispersible tablets are prepared by hot melt extrusion and powder pressing method. The dissolution and bioavailability of meloxicam are improved, and the dissolution behavior of meloxicam is similar to that of the original reference preparation.

Objective:To investigate HER2 mRNA expression in breast cancer with HER2 immunohistochemistry (IHC) 0 and to analyze the feasibility of distinguishing between the tumor with HER2 μltra-low expression and the one without expression of HER2 (no staining by IHC) by HER2 mRNA level preliminarily.Methods:HER2 mRNA was analyzed by reverse transcription digital PCR in 41 cases of formalin-fixed paraffin-embedded surgical tissue samples of invasive breast cancer obtained between January 2020 and March 2023 at Peking Union Medical College Hospital. The cohort included 21 HER2 IHC 1+ and 20 IHC 0 (12 ultra-low and 8 non-expression of HER2). HER2 mRNA expression level was quantitatively evaluated by the FAM (HER2)/VIC (reference gene) ratio.Results:The expression of HER2 mRNA for the cases with 1+, ultra-low, and non-expression of HER2 by IHC was 0.30 to 1.78 (average 0.90, median 0.82), 0.55 to 1.51 (average 0.93, median 0.90) and 0.22 to 0.78 (average 0.41, median 0.36), respectively. For the mean and median HER2 mRNA levels, there was no significant difference between HER2 IHC 1+ and HER2 ultra-low expression diseases ( P=0.757). A remarkable difference in HER2 gene expression was found between the tumors with 1+ and non-expression of HER2 by IHC ( P=0.002). And, HER2 ultra-low cases contained statistically higher levels of HER2 mRNA compared with non-expression of HER2 subgroup by IHC ( P=0.001). Conclusions:Based on HER2 mRNA, HER2 non-expression and HER2 weak expression (including HER2 IHC 1+ and ultra-low) belong to two different types of the tumor and the disease with HER2 IHC 1+ and HER2 ultra-low expression may be the same. It is necessary to further test the performance of HER2 mRNA detection for stratifying the HER2 weak expression subgroup and to determine the threshold.

AIM:To establish a severe pneumonia mouse model induced by bacterial infection.METHODS:A total of 102 male SPF C57BL/6J mice were randomly divided into a control group and a model group.Klebsiella pneu-moniae was administered via tracheal instillation at a concentration of 5×109 CFU.Mice were euthanized on days 1,2,4,8,and 14 post-infection to assess general condition,body weight,mortality,white blood cell and neutrophil counts,in-flammatory markers,and pathological changes in lung,heart,liver,spleen,kidney,and intestinal tissues.RESULTS:Mice in the model group exhibited symptoms such as dyspnea and huddling from 6 hours to 4 days post-infection,which progressively worsened,accompanied by continuous weight loss(P<0.01).These symptoms gradually resolved between days 5 and 14.Arterial oxygen saturation in the model group dropped to 80.7%from days 1 to 8(P<0.01)but returned to normal from days 9 to 14.A total of 23 model mice died between days 1 and 9,with no deaths thereafter,resulting in a mortality rate of 31.9%(P<0.01).Pathological examination revealed inflammatory cell infiltration,congestion,and ede-ma in lung tissue from days 1 to 2,with continued inflammatory cell infiltration,alveolar structural disorganization from days 4 to 8,and alveolar rupture and fusion by day 14(P<0.05 or P<0.01).Additionally,model mice showed significant increases in neutrophil count,white blood cell count,protein content in bronchoalveolar lavage fluid,total cell count,neutrophil ratio,and levels of inflammatory factors tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β)and IL-6 in peripheral blood from days 1 to 8(P<0.05 or P<0.01).No significant pathological changes were observed in heart and liver tissues,while spleen,kidney,and intestinal tissues exhibited notable pathological changes:indistinct boundaries be-tween red and white pulp in the spleen,significant congestion and edema around renal glomeruli,renal tubules,and col-lecting ducts,and extensive inflammatory cell infiltration in the colonic mucosa.CONCLUSION:Tracheal instillation of 5×109 CFU Klebsiella pneumoniae induces severe pathological changes in the lungs of mice,offering a robust model for studying the pathogenesis and treatment of severe pneumonia.

Objective To explore the changes in macrophage infiltration behavior during the dynamic evolution of thrombi following the formation of acute carotid artery thrombosis occlusion(ACTO).Methods 15 healthy male New Zealand rabbits were selected to establish an ACTO model by causing injury to the rabbit carotid artery using surgical sutures treated with ferric chloride.All rabbits were randomly divided into 5 groups according to the end-point time using the random number table method,namely 24-hour group,1 week group,4week group,8 week group,and 12week group postoperatively,with 3 rabbits in each group.At 24 hours post-operation,the ACTO model was examined by DS A.At 24 hours,1 week,4 weeks,8 weeks,and 12 weeks post-operation,samples were taken from the thrombotic arterial segment of the 3 rabbits in each group and embedded in paraffin.The thrombus samples were stained with hematoxylin-eosin(HE)and Martius scarlet blue(MSB)to analyze changes in thrombus morphology and composition(including red blood cells,fibrin and collagen fibers).Orbit Imaging Analysis software was used for semi-quantitative analysis of the thrombus composition components.Using immunohistochemistry to detect the distribution of MO and M2 macrophages in thrombi,aimed to summarize the dynamic evolution of thrombus morphology,composition,and macrophage infiltration behavior at different stages following ACTO occurrence.Results The 24-hour DSA results indicated that all experimental rabbits successfully established the ACTO model.(1)HE staining showed a continuous increase in thrombus size from 24 hours to 1 week.By 4 weeks,signs of thrombus dissolution appeared,and at 8 weeks,neovascularization was observed within the thrombus.By 12 weeks,signs of fibrosis were evident in the thrombus.(2)MSB staining revealed that during the acute phase of thrombus formation(within 24 hours after surgery),red blood cells were the predominant component initially,but after this period,fibrin and collagen fibers became the main components.(3)The detection results of MO macrophages showed that 24 hours after surgery,MO macrophages in the thrombus were not evenly distributed throughout the thrombus,but mainly gathered at the thrombus edge;at 1 week after surgery,the positive area percentage of MO macrophage in the thrombus increased compared with 24 hours after surgery(thrombus edge:[41.7±27.0]％vs.[24.6±16.7]％,thrombus core:[35.7±19.6]％vs.[11.1±10.4]％,all P＜0.001),and evenly distributed within the thrombus;at 4 weeks after surgery,MO macrophages in the thrombus decreased compared with 1 week after surgery(thrombosis edge:[10.7±6.1]％vs.[41.7±27.0]％,thrombus core:[12.1±8.5]％vs.[35.7±19.6]％,all P＜0.001),the differences were statistically significant.At 4,8,and 12 weeks after surgery,MO macrophages within the thrombus did not change significantly with time(thrombus edge:[10.7±6.1]％,[8.0±7.7]％,and[8.9±5.3]％;thrombus core:[12.1±8.5]％,[9.5±4.2]％,and[15.7±11.0]％),and the differences were not statistically significant(all P＞0.05).In addition,at 12 weeks after surgery,MO macrophages at the thrombus edge was less than the thrombus core([8.9+5.3]％vs.[15.7±11.0]％,P＜0.01).The detection results of M2 macrophages showed that 24 hours after surgery,M2 macrophages in the thrombus were widely distributed throughout the thrombus;at 1 week after surgery,the positive area percentage of M2 macrophages in the thrombus increased compared with 24 hours after surgery(thrombus edge:[22.1±11.3]％vs.[11.4±8.7]％,P＜0.001;thrombus core:[24.5±9.8]％vs.[7.6±6.0]％,P＜0.001);at 4 weeks after surgery,M2 macrophage in the thrombus decreased compared with 1 week after surgery(thrombosis edge:[10.6±3.7]％vs.[22.1±11.3]％,P＜0.001;thrombus core:[9.2±4.3]％vs.[24.5±9.8]％,P＜0.001);at 8 weeks after surgery,M2 macrophages in the thrombus increased compared with 4 weeks after surgery([17.9±8.8]％vs.[9.2±4.3]％,P＜0.001),and the differences were statistically significant.However,M2 macrophages in the thrombus did not change significantly from 8 weeks to 12 weeks after surgery(thrombus edge:[9.4±6.3]％vs.[8.5±5.3]％,P＞0.05;thrombus core:[17.9±8.8]％vs.[14.4±10.0]％,P＞0.05).In addition,at 8 and 12 weeks after surgery,M2 macrophages in the thrombus core was greater than the thrombus edge(8 weeks after surgery:[17.9±8.8]％vs.[9.4±6.3]％,P＜0.001;12weeks after surgery:[14.4±10.0]％vs.[8.5±5.3]％,P＜0.001).Conclusions This study successfully established an ACTO animal model and demonstrated for the first time the dynamic evolution of macrophages within 12 weeks post-thrombus formation.Macrophages may played a significant role in both thrombus formation and fibrinolysis,as well as in the promotion of thrombus dissolution and the formation of new blood vessels within the thrombus which may potentially promote the spontaneous reperfusion of the occluded vessels.The results of this study need further verification.

Objective:To investigate the clinical characteristics and correlation of sleep disturbances(SD)with cognitive impairment-associated cerebral small vascular disease(CSVD-CI)in elderly patients.Methods:In this cross-sectional study, 261 elderly CSVD-CI patients admitted to the Department of Neurology, Second Hospital of Tianjin Medical University between December 2019 and December 2021 were continuously enrolled.The Pittsburgh Sleep Index Scale(PSQI)was used to evaluate the overall sleep quality.Those with a PSQI score ≥7 was assigned to the CSVD-CI with sleep disturbances(CSVD-CI-SD)group, while those with a PSQI score <7 was assigned to the CSVD-CI without SD(CSVD-CI-NSD)group.The Montreal Cognitive Assessment(MoCA)was used to evaluate the cognitive function of patients with CSVD-CI, and scores on the overall cognitive function and various cognitive domains were compared between the CSVD-CI-SD group and the CSVD-CI-NSD group.Results:There were no significant differences between the CSVD-CI-SD group and the CSVD-CI-NSD group in sex ratio, age, education level and comorbidities( P>0.05). Compared with the CSVD-CI-NSD group, patients in the CSVD-CI-SD group took longer to fall asleep, had worse sleep efficiency, a shorter sleep duration, more obvious SD at night, worse sleep quality, more use of sleeping drugs, and more obvious daytime dysfunction(all P<0.05). Compared with the CSVD-CI-NSD group, the total MoCA score, attention score and orientation score in the CSVD-CI-SD group were significantly decreased( P<0.01). Correlation analysis results showed that the total MoCA score and attention in the CSVD-CI-SD group were negatively correlated with SD at night( r=-0.198, r=-0.115, P<0.05 for both), and orientation was negatively correlated with sleep quality( r=-0.170, P<0.05). Conclusions:The prevalence of SD is high in CSVD-CI patients, with CSVD-CI-SD patients showing more obvious overall cognitive, attention and orientation impairment in MoCA.Additionally, the total MoCA score and attention are negatively correlated with nighttime SD, and orientation is negatively correlated with sleep quality in CSVD-CI-SD patients.

The spectrum of biopsy-confirmed kidney disease varies with regions and periods. We describe the distribution of pathological types and epidemiological characteristics of kidney diseases in Northwest China due to regional differences in geographical environment, social economy, and dietary habits. Methods: Kidney biopsy cases from 2005 to 2020 in Xijing Hospital were retrospectively analyzed. Pathological characteristics of patients in different periods were analyzed using the t test or chi-square test. Joinpoint regression was used to analyze trends in pathological types and disease spectrum. Results: A total of 10,528 eligible patients were included. Primary glomerular disease (PGD) accounted for the majority of the cases and exhibited an obvious downward trend, whereas secondary glomerular disease (SGD) showed an obvious upward trend. Among PGD, immunoglobulin A nephropathy (IgAN) remained the most common pathological type, and the detection rate of membranous nephropathy (MN) was significantly increased. Among SGD, Henoch-Schönlein purpura nephritis (HSPN) was the most common pathological type and may present a significant characteristic of Northwest China. Diabetic nephropathy (DN) exhibited the most obvious upward trend in the whole process, whereas the fastest growth since 2012 was in hypertensive nephropathy. Conclusion: The proportion of SGD increased whereas PGD declined. IgAN remained the most common PGD, and HSPN was the most common SGD. MN and DN showed the most obvious upward trend among PGD and SGD, respectively. Changes in the spectrum of kidney disease, especially the constituent ratio of SGD, pose a great challenge to public health.

Objective:To investigate the influencing factors of recurrence after radical resection of middle and low rectal cancer, and to establish a prediction model based on magnetic resonance imaging (MRI) measurement of perirectal fat content and investigate its application value.Methods:The retrospective cohort study was constructed. The clinicopathological data of 254 patients with middle and low rectal cancer who were admitted to Tianjin Union Medical Center from December 2016 to December 2021 were collected. There were 188 males and 66 females, aged (61±9)years. All patients underwent radical resection of rectal cancer and routine pelvic MRI examina-tion. Observation indicators: (1) follow-up and quantitative measurement of perirectal fat content; (2) factors influencing tumor recurrence after radical resection of middle and low rectal cancer; (3) construction and evaluation of the nomogram prediction model of tumor recurrence after radical resection of middle and low rectal cancer. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M(rang) and M( Q1, Q2). Count data were described as absolute numbers. Univariate and multivariate analyses were conducted using the COX regression model. The rms software package (4.1.3 version) was used to construct the nomogram and calibration curve. The survival software package (4.1.3 version) was used to calculate the C-index. The ggDCA software package (4.1.3 version) was used for decision curve analysis. Results:(1) Follow-up and quantitative measurement of perirectal fat content. All 254 patients were followed up for 41.0(range, 1.0?59.0)months after surgery. During the follow-up period, there were 81 patients undergoing tumor recurrence with the time to tumor recurrence as 15.0(range, 1.0?43.0)months, and there were 173 patients without tumor recurrence. The preoperative rectal mesangial fascia envelope volume, preoperative rectal mesangial fat area, preoperative rectal posterior mesangial thickness were 159.1(68.6,266.5)cm3, 17.0(5.1,34.4)cm2, 1.2(0.4,3.2)cm in the 81 patients with tumor recurrence, and 178.5(100.1,310.1)cm3, 19.8(5.3,40.2)cm2 and 1.6(0.3,3.7)cm in the 173 patients without tumor recurrence. (2) Factors influencing tumor recurrence after radical resection of middle and low rectal cancer. Results of multivariate analysis showed that poorly differentiated tumor, tumor pathological N staging as N1?N2 stage, rectal posterior mesangial thickness ≤1.43 cm, magnetic resonance extra mural vascular invasion, tumor invasion surrounding structures were independent risk factors of tumor recurrence after radical resection of middle and low rectal cancer ( hazard ratio=1.64, 2.20, 3.19, 1.69, 4.20, 95% confidence interval as 1.03?2.61, 1.29?3.74, 1.78?5.71, 1.02?2.81, 2.05?8.63, P<0.05). (3) Construction and evaluation of the nomogram prediction model of tumor recurrence after radical resection of middle and low rectal cancer. Based on the results of multivariate analysis, the tumor differentiation, tumor pathological N staging, rectal posterior mesangial thickness, magnetic resonance extra mural vascular invasion, tumor invasion surrounding structures were included to construct the nomogram predic-tion model of tumor recurrence after radical resection of middle and low rectal cancer. The total score of these index in the nomogram prediction model corresponded to the probability of post-operative tumor recurrence. The C-index of the nomogram was 0.80, indicating that the prediction model with good prediction accuracy. Results of calibration curve showed that the nomogram prediction model with good prediction ability. Results of decision curve showed that the prediction probability threshold range was wide when the nomogram prediction model had obvious net benefit rate, and the model had good clinical practicability. Conclusions:Poorly differentiated tumor, tumor pathological N staging as N1?N2 stage, rectal posterior mesangial thickness ≤1.43 cm, magnetic resonance extra mural vascular invasion, tumor invasion surrounding structures are independent risk factors of tumor recurrence after radical resection of middle and low rectal cancer. Nomogram prediction model based on MRI measurement of perirectal fat content can effectively predict the probability of postoperative tumor recurrence.