Based on the modern understanding that lipid metabolism disorders mediate tumor microenvironmental imbalance in esophageal carcinoma， this paper proposes that failure of spleen and kidney warming and internal accumulation of phlegm-toxin constitute the core pathogenesis of esophageal carcinoma. Deficiency of spleen and kidney yang qi serves as the root cause， while impaired transformation and transportation of lipids and the accumulation of phlegm-toxin represent the superficial manifestations. Phlegm originates from the transformation of lipids， while toxin arises from and attaches to phlegm. Their interaction forms a sticky and persistent pathological state that runs throughout the entire disease process. The evolution of pathogenesis follows a dynamic and progressive pattern. In the early stage， failure of spleen and kidney warming and dysfunction of lipid metabolism mediate abnormalities in a lipid-enriched microenvironment； in the middle stage， lipid turbidity condenses into phlegm， and phlegm-toxin stasis promotes the formation of an inflammatory and hypercoagulable microenvironment； in the late stage， dysfunction of the sanjiao （三焦） warming function and impaired qi transformation lead to an imbalance in the hypoxic and metabolically dysfunctional microenvironment. Accordingly， a staged therapeutic approach is proposed， including warming the kidney and strengthening the spleen， transforming phlegm and resolving toxin， and warming and unblocking the sanjiao. By regulating lipid metabolism to restore tumor microenvironmental homeostasis， this approach provides a new theore-tical perspective and practical strategy for the intervention of esophageal cancer progression through traditional Chinese medicine.

Based on the modern understanding that lipid metabolism disorders mediate tumor microenvironmental imbalance in esophageal carcinoma， this paper proposes that failure of spleen and kidney warming and internal accumulation of phlegm-toxin constitute the core pathogenesis of esophageal carcinoma. Deficiency of spleen and kidney yang qi serves as the root cause， while impaired transformation and transportation of lipids and the accumulation of phlegm-toxin represent the superficial manifestations. Phlegm originates from the transformation of lipids， while toxin arises from and attaches to phlegm. Their interaction forms a sticky and persistent pathological state that runs throughout the entire disease process. The evolution of pathogenesis follows a dynamic and progressive pattern. In the early stage， failure of spleen and kidney warming and dysfunction of lipid metabolism mediate abnormalities in a lipid-enriched microenvironment； in the middle stage， lipid turbidity condenses into phlegm， and phlegm-toxin stasis promotes the formation of an inflammatory and hypercoagulable microenvironment； in the late stage， dysfunction of the sanjiao （三焦） warming function and impaired qi transformation lead to an imbalance in the hypoxic and metabolically dysfunctional microenvironment. Accordingly， a staged therapeutic approach is proposed， including warming the kidney and strengthening the spleen， transforming phlegm and resolving toxin， and warming and unblocking the sanjiao. By regulating lipid metabolism to restore tumor microenvironmental homeostasis， this approach provides a new theore-tical perspective and practical strategy for the intervention of esophageal cancer progression through traditional Chinese medicine.

Objective To investigate the value of monocyte to lymphocyte ratio(MLR)and neutrophil percentage to albumin ratio(NPAR)in predicting diabetic macular edema(DME).Methods One hundred and one diabetic retinopathy patients admitted to the Third Affiliated Hospital of Xinxiang Medical University from January 2018 to February 2023 were selected as the research subjects,and they were divided into DME group(n=56)and non-DME group(n=45)based on fun-dus examination results.The general data such as gender,age,course of diabetes and laboratory indicators were collected by consulting medical records.Fasting elbow venous blood was collected early in the morning of the next day after the diagnosis of DME in both groups,the monocytes(MONO)count,lymphocyte(LYM)count,white blood cell(WBC)count,percentage of neutrophils(NEUT),plasma albumin(ALB),glycosylated haemoglobin(HbA1c)were measured by full automatic blood routine analyzer,and MLR,NPAR were calculated.General information and laboratory indexes of patients in the two groups were compared,and risk factors for DME were analyzed by multivariate logistic regression,and receiver operator characteristic(ROC)curve was applied to evaluate the predictive value of MLR and NPAR for DME.Results The course of diabetes,MONO count,NEUT,MLR,NPAR,WBC count,and HbA1c level of patients between the DME group were significantly higher than those in the non-DME group(P＜0.05);there was no statistically significant difference in gender,age,LYM count,and ALB level of patients between the two groups(P＞0.05).Multivariate logistic regression analysis showed that increased levels of WBC,MLR,and NPAR were independent risk factors for the occurrence of DME(P＜0.05).The ROC curve showed that the best cut-off value of MLR was 0.192,and the area under the curve(AUC)for the prediction of DME was 0.729(95％confidence interval:0.631-0.826),with a sensitivity of 58.9％and a specificity of 82.2％;while the best cut-off value of NPAR was 1.404,and the AUC for predicting DME occurrence was 0.884(95％confidence interval:0.820-0.949),with a sensitivity of 75.0％and a specificity of 91.1％;the AUC of MLR and NPAP for predicting the occurrence of DME was 0.906(95％confidence interval:0.851-0.906),with a sensitivity of 69.6％and a specificity of 93.3％.With MLR＞0.192 as positive and NPAR＞1.404 as positive,the parallel test of MLR and NPAR predicted the occurrence of DME with a sensitivity of 87.5％,a specificity of 71.1％,and an accuracy of 80.2％;while the tandem test of MLR and NPAR predicted the occurrence of DME with a sensitivity of 46.4％,a specificity of 97.8％,and an accuracy of 69.3％.Conclusion Increased levels of MLR and NPAR are independent risk factors for the occurrence of DME and have certain predictive value for DME.The predictive value of combined MLR and NPAR test for DME is higher than that of separate test,and parallel experiment is more helpful for the early prediction of DME.

Objective To compare the clinical efficacy of 25G+and 27G+pars plana vitrectomy(PPV)in the treat-ment of idiopathic epiretinal membrane(iERM).Methods A total of 50 iERM patients(50 eyes)who were admitted to the Third Affiliated Hospital of Xinxiang Medical University from December 2019 to August 2022 were selected as the research subjects.These patients were divided into the control group and observation group based on different surgical methods,with 25 patients(25 eyes)in each group.Patients in the control group received 25G+PPV treatment,while patients in the observation group received 27G+PPV treatment.The surgical duration and postoperative 1-day incision subconjunctival hemorrhage and e-dema of patients in two groups were compared;central macular thickness(CMT)was measured by optical coherence tomo-graphy before surgery,1 day,1 week,1 month,and 3 months postoperatively in the two groups.Visual acuity of patients in both groups was assessed according to the early treatment diabetic retinopathy study(ETDRS)visual acuity chart.Intraocular pressure was measured by using a non-contact Callon tonometer.Complications,such as intraoperative macular injury,retinal hole,postoperative choroidal detachment,retinal hemorrhage,retinal detachment,and intraocular infection,were observed in both groups.Results The surgical duration of patients in the observation group was significantly shorter than that in the control group(t=2.314,P＜0.05).The extent of subconjunctival hemorrhage and edema of patients in the observation group was significantly smaller than that in the control group(t=13.706,P＜0.01).The ETDRS visual acuity of patients at 1 day,1 week,1 month,and 3 months after surgery in both groups was significantly higher than that before surgery(P＜0.05).There was no signifi-cant difference in ETDRS visual acuity of patients between the two groups at 1 day,1 week,1 month,and 3 months postoperatively(P＞0.05).At 1 day after surgery,the intraocular pressure of patients in the observation group was significantly higher than that in the control group(P＜0.05).At 1 week,1 month,and 3 months after surgery,there was no significant difference in intraocular pressure of patients between the two groups(P＞0.05).Two patients in the control group experienced transient ocular hypotension 1 day after surgery,while no such complication was observed in the observation group.Patients in both groups presented with varying degrees of retinal nerve epithelial layer traction,retinal edema,thickening,and vascular distortion before surgery.At 1 day after surgery,epiretinal membrane traction was relieved in both groups,and there was a significant improvement in the anatomical structure of the macular area compared to preoperative conditions.At 1 day,1 week,1 month,and 3 months after surgery,the CMT of patients in both groups was reduced compared to preoperative values(P＜0.05);there was no significant difference in CMT of patients between the two groups at 1 day,1 week,1 month,and 3 months after surgery(P＞0.05).In the control group,18 eyes(72.0％)were sutured at the scleral puncture sites due to leakage,while no suturing was performed in the observation group.Patients in both groups completed the surgery successfully,without any intraoperative complications such as macular injury or retinal hole.During the 3-month follow-up,no postoperative complications such as choroidal detachment,retinal hemorrhage,retinal detachment,or intraocular infection were observed in both groups.Conclusion Both 27G+PPV and 25G+PPV have good clinical effects and high surgical safety in the treatment of iERM.Compared with 25G+PPV,27G+PPV can shorten the surgical duration,better maintain postoperative intraocular pressure stability,and reduce the range of subconjunctival bleeding and edema.

The sternum is the pivotal component of the thoracic cavity. It is connected with the clavicle and ribs on the upper part and both sides respectively, and plays an important role in protecting the stability of the chest wall. Sternal resection usually results in a large segmental chest wall defect that causes the chest wall to float and requires sternal reconstruction. This paper reports a 62 years male patient with thymic squamous cell carcinoma with sternal metastasis, who underwent thymotomy, sternal tumor resection and autologous lilum graft combined with sternal reconstruction by titanium plate after relevant examination was completed and surgical contraindications were eliminated. The patient was followed up for 6 months, the respiratory and motor functions were normal and the thoracic appearance was good.

Objective To investigate the effect of Piezo1 activated by mechanical stress on knee osteoarthritis synovial fibrosis via the extracellular signal-regulated kinase(ERK)1/2 signaling pathway.Methods Twenty-five Sprague Dawley rats were divided into blank,exercise,exercise+GsMTx4,exercise+PD98059,and exercise+GsMTx4+PD98059 groups(n=5 per group).After modeling,serum and synovial tissue were extracted and collagen deposition was evaluated by Sirius red and Masson staining.Expression levels of Piezo1,ERK1/2,phospho(p)-ERK1/2,α-smooth muscle actin(SMA),transforming growth factor(TGF)-β,Collagen Ⅰ,and tissue inhibitor of metalloproteinase(TIMP)-1 were detected by Western blot and reverse transcription-quantitative polymerase chain reaction(RT-qPCR),and the interleukin(IL)-1β,IL-6,and tumor necrosis factor(TNF)-α contents were detected by enzyme-linked immunosorbent assay.For cell experiments,synovial cells were divided into blank,pull,pull+GsMTx4,pull+PD98059,and pull+GsMTx4+PD98059 groups and the above indices were detected in the model cells by Western blot,RT-qPCR,and other techniques.Results Mechanical stress increased collagen deposition in synovial tissues in the rats,and increased the protein and mRNA expression levels of the pathway-related and fibrosis-specific indicators Piezo1,p-ERK/ERK,α-SMA,TGF-β,Collagen I,and TIMP-1(P＜0.05).Piezo1 expression was significantly down-regulated by both inhibitors(P＜0.05),but the ERK inhibitor(PD98059)had no significant effect on Piezo1 gene expression.Levels of serum inflammatory factors were significantly higher in the exercise group compared with the blank group(P＜0.05),and levels were significantly reduced by the inhibitors(P＜0.05).The in vitro experiments showed the same trends as the animal experiments.Conclusions The Piezo1 ion channel can sense mechanical stress and activate the ERK 1/2 pathway to mediate knee synovial fibrosis.

Objective To investigate the expression and significance of Src homology 2 domain-containing protein tyrosine phosphatase 2(SHP2)and phosphorylated SHP2(P-SHP2)in oxygen-induced retinopathy(OIR).Methods Twenty clean-grade C57BL/6J(B6)7-day-old neonatal mice were randomly divided into normal control group and OIR group,with 10 mice in each group.The mice in the normal control group and the nursing mother mice were fed together in a normal oxygen and room temperature environment.Mice in the OIR group were placed in an oxygen chamber with a temperature of 22-25 ℃,humidity of(60±10)％and oxygen volume fraction stable at(75±5)％for five days together with the nursing mother mice,and then transferred to a normal oxygen environment.At 12,14,17 days of age,three mice were selected from the normal con-trol group and the OIR group,respectively;and the expressions of SHP2 and P-SHP2 proteins in the retinal tissues of mice in the two groups were detected by Western blot.Two 17-day-old mice were randomly selected from the normal control group and the OIR group,respectively;and the retinal histopathology of mice was observed by hematoxylin-eosin staining.Results In the normal control group,the cell structure in all layers of the retinal tissue of 17-day-old mice was orderly,the inner limiting mem-brane and endothelial nucleus were intact,and the shape was normal.In the OIR group,the intercellular structure in all layers of the retinal tissue of 17-day-old mice was disordered,and the vascular endothelial nucleus was seen to break through the reti-nal inner limiting membrane.There was no statistically significant difference in the relative expression of SHP2 protein in the retinal tissues of mice at different ages in the normal control group(F=2.052,P＞0.05).The relative expression level of P-SHP2 protein in the retinal tissues of mice at 14,17 days of age in the normal control group was significantly lower than that at 12 days of age(P＜0.05),and the relative expression level of P-SHP2 protein in the retinal tissues of mice at 17 days of age was significantly lower than that at 14 days of age(P＜0.05).The relative expression level of SHP2 protein in the retinal tissues of mice at 14 days of age in the OIR group was significantly higher than that at 12,17 days of age(P＜0.05).There was no statistically significant difference in the relative expression level of SHP2 protein in the retinal tissues between 17-day-old mice and 12-day-old mice in the OIR group(P＞0.05).The relative expression level of P-SHP2 protein in the retinal tissues of mice at 14 days of age in the OIR group was significantly higher than that at 12,17 days of age(P＜0.05).There was no statistically significant difference in the relative expression level of P-SHP2 protein in the retinal tissues between 17-day-old mice and 12-day-old mice in the OIR group(P＞0.05).The relative expression level of SHP2 protein in the retinal tissues of mice at 12,17 days of age in the OIR group was significantly lower than that in the normal control group(P＜0.05).There was no statistically significant difference in the relative expression level of SHP2 protein in the retinal tissues of mice at 14 days of age between the two groups(P＞0.05).The relative expression level of P-SHP2 protein in the retinal tissues of 12-day-old mice in the OIR group was significantly lower than that in the normal control group(P＜0.05),while the relative expression level of P-SHP2 protein in the retinal tissues of 17-day-old mice was significantly higher than that in the normal control group(P＜0.05).There was no statistically significant difference in the relative expression level of P-SHP2 protein in the retinal tissues of mice between the two groups at 14 days of age(P＞0.05).Conclusion SHP2 and P-SHP2 are expressed with tem-poral fluctuations in OIR.Hypoxia may promote conformational changes of SHP2 in OIR mice,and play an active role in phos-phorylation;and participate in and promote the occurrence and development of OIR.

SIRT6 belongs to the conserved NAD⁺-dependent deacetylase superfamily and mediates multiple biological and pathological processes. Targeting SIRT6 by allosteric modulators represents a novel direction for therapeutics, which can overcome the selectivity problem caused by the structural similarity of orthosteric sites among deacetylases. Here, developing a reversed allosteric strategy AlloReverse, we identified a cryptic allosteric site, Pocket Z, which was only induced by the bi-directional allosteric signal triggered upon orthosteric binding of NAD⁺. Based on Pocket Z, we discovered an SIRT6 allosteric inhibitor named JYQ-42. JYQ-42 selectively targets SIRT6 among other histone deacetylases and effectively inhibits SIRT6 deacetylation, with an IC₅₀ of 2.33 μmol/L. JYQ-42 significantly suppresses SIRT6-mediated cancer cell migration and pro-inflammatory cytokine production. JYQ-42, to our knowledge, is the most potent and selective allosteric SIRT6 inhibitor. This study provides a novel strategy for allosteric drug design and will help in the challenging development of therapeutic agents that can selectively bind SIRT6.

Irritable bowel syndrome( IBS)is a commonly seen chronic functional bowel disease,the prevalence showed a rising trend in recent year in China. At present,the etiology and pathogenesis of IBS have not yet been fully elucidated,and may be related to intestinal gas. Intestinal gas is usually composed of 59% N2 ,21% H2 ,9% CO2 ,7%methane(CH4 )and 4% O2 ,in which H2 and CH4 are produced only by intestinal bacteria metabolism. IBS patients usually manifested as having abdominal distension and symptoms of flatulence,suggesting the occurrence of accumulation of intestinal gas. In recent years,the relationship between symptoms of IBS and intestinal gas has attracted much attention. This article reviewed the progress in study on symptoms of IBS and intestinal gas.

Objective To explore the change in anatomical volume during intensity?modulated radiotherapy (IMRT) for different stages of nasopharyngeal carcinoma (NPC) and its influence on dose distribution, and to assess the necessity to modify the IMRT plan. Methods Twenty?four patients with newly diagnosed NPC who received IMRT and chemotherapy were enrolled in the study, and were divided into early?intermediate group ( 12 cases ) and locally advanced group ( 12 cases ) according to the 2008 staging system for NPC. Each patient had a repeated CT scan at week 5 of radiotherapy, and target volume and organs at risk ( OAR) were contoured. The dose distribution of the original plan shown on CT was calculated. Changes in target volume, OAR anatomical volume, and dose distribution were analyzed, and paired t?test and Spearman correlation analysis were performed. Results In the early?intermediate group, gross target volume of neck positive lymph nodes (GTVnd) was reduced during radiotherapy (P=0. 059), and gross target volume of nasopharynx ( GTVnx ) , high?risk clinical target volume ( CTV1 ) , and parotid volume were reduced significantly during radiotherapy ( P= 0. 001, 0. 012, 0. 002, and 0. 000, respectively) . In locally advanced group, GTVnx , GTVnd , CTV1 , and parotid volume were significantly reduced during IMRT (P=0. 000, 0. 000, 0. 003, 0. 003, and 0. 000, respectively). Compared with the values before radiotherapy, the parotid dose increased significantly in the two groups during IMRT ( P=0. 044, 0. 026, 0. 033, and 0. 026, respectively;P=0. 024, 0. 016, 0. 030, and 0. 015, respectively) , and the increase in GTVnd dose was observed in the locally advanced group ( P= 0. 029 and 0. 049 ) . Conclusions It is recommended to perform another CT scan for patients with locally advanced NPC at week 5 of radiotherapy and formulate a new IMRT plan to maintain target volume dose and guarantee a safe parotid dose.