It is believed that the occurrence and development of squamous cell carcinoma （SCC） is closely associated with inflammatory responses. The theory of fire and heat， advocated by LIU Wansu， provides significant clinical guidance for understanding the pathogenesis and treatment of SCC. Based on this theory， the pathological mechanisms and clinical characteristics of SCC at different stages were analyzed. In the precancerous and early stages， the primary pathogenesis is qi stagnation leading to internal generation of constrained heat； in post-surgery， the condition shifts to qi deficiency with latent yin fire； during the treatment phase， the pathogenesis involves accumulation of pathogenic factors， excess toxins， and severe heat toxicity； in the late stage， the main pathology is yin deficiency with toxic heat， and phlegm-stasis obstruction of the internal organs. Corresponding stage-based treatment strategies are proposed. In the early stage， regulating qi movement to dissipate constrained heat； for post-surgery， tonifying qi and raising yang to dispel latent fire； during treatment stage， clearing heat and detoxifying to eliminate cancerous toxins； and in the late stage， nourishing yin and unblocking the bowels to clear deficiency heat.

Lung cancer （LC） is a significant global public health issue， with both its incidence and mortality rates ranking among the highest worldwide. The age-standardized incidence and mortality rates are increasing annually， posing a serious threat to the life and health of LC patients. Radical surgical resection is the primary treatment for malignant lung tumors. However， postoperative multidimensional functional impairments， including respiratory， mucosal， and psychological functions， are common. These impairments not only reduce patients' quality of life and affect their treatment tolerance and duration， but also negatively correlate with prognosis， facilitating disease recurrence and metastasis. At present， postoperative functional dysfunction after LC surgery remains a key clinical challenge that urgently needs to be addressed. There is a lack of standardized and regulated postoperative rehabilitation treatment management and traditional Chinese medicine （TCM） differentiation and treatment strategies for LC. Focusing on the core underlying pathogenesis of "Qi sinking" after LC surgery， and guided by the classical TCM theory of "lungs governing Qi"， this study， based on the core concept of the "five perspectives on treatment" theory， innovatively proposes the respiratory dysfunction as the core pathogenesis of "Qi sinking in the chest" during the rapid rehabilitation phase， mucosal dysfunction as the core pathogenesis of "Yin deficiency and Qi sinking" during the postoperative adjuvant treatment phase， and the psychological dysfunction as the core pathogenesis of "Qi sinking with emotional constraint" during the consolidation phase. Accordingly， stage-specific dynamic functional protection strategies are constructed. In the rapid rehabilitation phase， the strategy emphasizes tonifying Qi and uplifting sinking Qi， with differentiation and treatment based on the principle of ''descending before ascending''. In the adjuvant treatment phase， the approach focuses on nourishing Yin and uplifting Qi， with prescription combinations that integrate unblocking and tonification. In the consolidation phase， the strategy aims to resolve constraint and uplift Qi， with clinical treatment emphasizing a combination of dynamic and static methods. At each stage of functional rehabilitation， clinical differentiation and treatment should support healthy Qi and eliminate pathogenic factors simultaneously. This study is the first to propose the concept of postoperative functional protection in TCM， offering a new approach for TCM differentiation and treatment in the full-cycle， stage-based， and dynamic protection of postoperative function in LC patients. It is expected to contribute to the construction and development of an integrated TCM-Western medicine comprehensive program for cancer prevention and treatment in China.

Tumor treatment-related adverse reactions are a major focus of clinical concern， among which recurrent aphthous oral ulcers （RAU） associated with targeted therapy for lung cancer （LC） are among the most painful and distressing for patients. Currently， modern medical interventions show limited efficacy， and there is an urgent need for more effective treatment strategies. This study differentiates RAU associated with targeted therapy for LC from chemotherapy-related and ordinary oral ulcers， elucidates the pathophysiological basis of such ulcers， and traces the theoretical origin of "Yin deficiency and Qi collapse". Based on the new system of "five perspectives on diagnosis and treatment" for tumor prevention and treatment， with a focus on the core and symptom perspectives and rooted in the traditional concept of "lung dominating Qi"， we innovatively propose the concept of "medicine-induced ulcer" and are the first to introduce the theory of "Yin deficiency and Qi collapse" into the syndrome differentiation and treatment of RAU associated with targeted therapy for LC （i.e.， medicine-induced ulcer）. We propose that "Yin deficiency and Qi collapse" is the core pathogenesis of medicine-induced ulcers， in which the collapse of formless Qi is the key to their onset， while the deficiency and stasis of tangible Yin and blood constitute the root of recurrence. A hierarchical strategy for syndrome differentiation and treatment is established： first treating the collapse of formless Qi， then replenishing tangible deficiencies， and concurrently preventing recurrence. We emphasize that treatment should address both root and manifestation， with appropriate prioritization. In the acute phase， while relieving symptoms and promoting ulcer healing by nourishing Qi， uplifting collapse， and generating body fluids， attention should also be paid to nourishing spleen Yin， facilitating the circulation of nutritive Qi， and alleviating stasis to target the root pathogenesis and reduce recurrence. A verified case is presented to support this approach. This study enriches the theoretical framework and clinical methods of traditional Chinese medicine （TCM） in the treatment of RAU associated with targeted therapy for LC， promotes symptom management of treatment-related adverse reactions through integrated TCM and Western medicine， and provides theoretical support for the construction and development of a comprehensive differentiation and treatment system for lung cancer prevention， treatment， and rehabilitation.

"Stagnation" is an important pathological state in the development and progression of malignant tumors. However， its intrinsic connection with different stages of tumor evolution has not been clearly elucidated in previous studies. Drawing on clinical practice， this paper proposes the theory of stagnant toxin， emphasizing stage-specific pathogenesis and differentiated treatment strategies for tumors based on the varying manifestations of stagnation at each phase. The theory interprets the pathogenesis of stagnant toxin across the stages of tumor development through the five elements "wood， fire， earth， metal， and water" corresponding respectively to wood stagnation in the precancerous stage， metal stagnation in the postoperative phase， fire stagnation during adjuvant therapy， earth stagnation in the progressive stage， and water stagnation in the advanced stage. Each type of stagnation reflects a distinct pathogenic mechanism， such as wood stagnation giving rise to disease， metal stagnation inducing residual symptoms， fire stagnation resulting in ulceration， earth stagnation spreading toxin transmission， and water stagnation leading to critical deterioration. Accordingly， the treatment principles include guiding wood stagnation with counterflow， dispersing metal stagnation to harmonize symptoms， venting fire stagnation to regress ulcers， depleting earth stagnation to block progression， and controlling water stagnation to preserve vitality. This theoretical framework offers a traditional Chinese medicine perspective for understanding and treating malignant tumors based on the concept of stagnant toxin.

Objective:To investigate the clinical and radiologic characteristics of children with congenital pseudarthrosis of the tibia (CPT) in a single center.Methods:This is a retrospective case series study. According to inclusion and exclusion criteria, clinical data of 497 children(507 limbs) with CPT who were treated at Department of Orthopedics, the Children′s Hospital Affiliated to Xiangya School of Medicine, Central South University from January 2011 to December 2020 were collected. Baseline data included gender, age at initial visit, age at onset of symptoms, accompanying symptoms, domicile, whether first treated at our hospital, and treatment-related information such as surgical or conservative treatment, surgical complications, etc., were extracted and analyzed using the health information system. Imaging data of the children, including Crawford classification, bilateral leg lengths, presence of fibular pseudarthrosis, and location of pseudarthrosis along the tibia segment, were analyzed using the Picture Archiving and Communication System. Data were compared using independent sample t test or χ2 tests. Results:Among 497 children with CPT, there were 305 males (61.4%) and 192 females (38.6%). The age at initial visit was (3.6±3.2) years (range: 0.1 to 16.2 years). Neurofibromatosis type 1 (NF1) symptoms were positive in 340 children (68.4%), and negative in 157 children (31.6%). Among NF1-positive children, those with symptoms onset before 1 year of age were significantly more than NF1-negative children (74.1%(252/340) vs. 66.2%(104/157); χ2=9.24, P=0.001), and the proportion of fractures (92.9%,316/340) was significantly higher than that in the NF1-negative group (84.7%,133/157) ( χ2=8.33, P=0.004). According to imaging data, Crawford type Ⅳ was the most common type, with 321 limbs (63.3%), followed by type Ⅱ in 100 limbs (19.7%), type Ⅲ in 54 limbs (10.7%) and type Ⅰ in 32 limbs (6.3%). Pseudarthrosis occurred in the proximal third of the tibia in 14 limbs (2.8%), in the middle third in 185 limbs (36.5%), and in the distal third in 308 limbs (60.8%). Seventy-four children (14.9 %) had associated fibular pseudarthrosis. The lateral proximal tibial angle was 86.91°±5.21°(range: 72.17° to 102.08°), and the lateral distal tibial angle was 87.27°±10.73°(range: 51.07° to 128.17°). A total of 421 children (84.7%) underwent surgical treatment with (3.1±2.4) surgeries performed per child (range:0 to 12 surgeries); 76 children (15.3%) received conservative treatment. Postoperative complications mainly included ankle valgus (77 cases), leg length discrepancy (71 cases),refracture (48 cases), osteomyelitis (11 cases), and hardware failure (10 cases). NF1-positive children underwent more surgeries than NF1-negative children ((5.1±2.2)times vs.(2.1±1.8)times; t=14.93, P<0.01). Conclusions:Crawford type Ⅳ is the most common type of CPT in children in this study. CPT predominantly occurs in the middle or distal third of the tibia. The majority of children with CPT experienced symptoms and were seen at outpatient clinics before the age of 3 years. The main surgical complications currently associated with CPT treatment are ankle valgus and leg length discrepancy. Compared with CPT without NF1, children with NF1-positive CPT tend to have earlier symptom onset and may require more frequent treatments.

Objective:To investigate the clinical and radiologic characteristics of children with congenital pseudarthrosis of the tibia (CPT) in a single center.Methods:This is a retrospective case series study. According to inclusion and exclusion criteria, clinical data of 497 children(507 limbs) with CPT who were treated at Department of Orthopedics, the Children′s Hospital Affiliated to Xiangya School of Medicine, Central South University from January 2011 to December 2020 were collected. Baseline data included gender, age at initial visit, age at onset of symptoms, accompanying symptoms, domicile, whether first treated at our hospital, and treatment-related information such as surgical or conservative treatment, surgical complications, etc., were extracted and analyzed using the health information system. Imaging data of the children, including Crawford classification, bilateral leg lengths, presence of fibular pseudarthrosis, and location of pseudarthrosis along the tibia segment, were analyzed using the Picture Archiving and Communication System. Data were compared using independent sample t test or χ2 tests. Results:Among 497 children with CPT, there were 305 males (61.4%) and 192 females (38.6%). The age at initial visit was (3.6±3.2) years (range: 0.1 to 16.2 years). Neurofibromatosis type 1 (NF1) symptoms were positive in 340 children (68.4%), and negative in 157 children (31.6%). Among NF1-positive children, those with symptoms onset before 1 year of age were significantly more than NF1-negative children (74.1%(252/340) vs. 66.2%(104/157); χ2=9.24, P=0.001), and the proportion of fractures (92.9%,316/340) was significantly higher than that in the NF1-negative group (84.7%,133/157) ( χ2=8.33, P=0.004). According to imaging data, Crawford type Ⅳ was the most common type, with 321 limbs (63.3%), followed by type Ⅱ in 100 limbs (19.7%), type Ⅲ in 54 limbs (10.7%) and type Ⅰ in 32 limbs (6.3%). Pseudarthrosis occurred in the proximal third of the tibia in 14 limbs (2.8%), in the middle third in 185 limbs (36.5%), and in the distal third in 308 limbs (60.8%). Seventy-four children (14.9 %) had associated fibular pseudarthrosis. The lateral proximal tibial angle was 86.91°±5.21°(range: 72.17° to 102.08°), and the lateral distal tibial angle was 87.27°±10.73°(range: 51.07° to 128.17°). A total of 421 children (84.7%) underwent surgical treatment with (3.1±2.4) surgeries performed per child (range:0 to 12 surgeries); 76 children (15.3%) received conservative treatment. Postoperative complications mainly included ankle valgus (77 cases), leg length discrepancy (71 cases),refracture (48 cases), osteomyelitis (11 cases), and hardware failure (10 cases). NF1-positive children underwent more surgeries than NF1-negative children ((5.1±2.2)times vs.(2.1±1.8)times; t=14.93, P<0.01). Conclusions:Crawford type Ⅳ is the most common type of CPT in children in this study. CPT predominantly occurs in the middle or distal third of the tibia. The majority of children with CPT experienced symptoms and were seen at outpatient clinics before the age of 3 years. The main surgical complications currently associated with CPT treatment are ankle valgus and leg length discrepancy. Compared with CPT without NF1, children with NF1-positive CPT tend to have earlier symptom onset and may require more frequent treatments.

More than 300 million people world-wide suffer from asthma,and the incidence is in-creasing year by year.As one of the most common chronic diseases,asthma is an immune-mediated inflammatory disease with complex triggering mechanisms and strong heterogeneity.With the in-depth study of physiological and pathological mech-anisms,therapeutic small molecule and hormone drugs have been introduced to control and treat most patients,but about 5％-10％of patients still suffer from various subtypes of difficult to control and treat asthma,that is,severe asthma.In the past decade,with the rapid development of bio-pharmaceutical research,protein and antibody have become the key drugs for the treatment of se-vere asthma with high efficacy,high specificity and high safety.However,biological drugs are usually administered by injection,they cannot be noninva-sive and directly delivered into the lung to quickly absorb and take effect.Therefore,there is an ur-gent need for the introduction of inhaled biologics with quick effectiveness,convenience,economy and safety in clinical.The review summarizes the existing small molecule,hormone and biological therapy drugs,and summarizes the development of inhalable biological agents of asthma,and ana-lyzes the future prospects of the inhalable biologi-cal drugs,which is designed to deepen the percep-tion of the direction of the inhalable biological drugs research,and update the information of the field,in order to provide reference for the develop-ment of more inhalable biologics.

More than 300 million people world-wide suffer from asthma,and the incidence is in-creasing year by year.As one of the most common chronic diseases,asthma is an immune-mediated inflammatory disease with complex triggering mechanisms and strong heterogeneity.With the in-depth study of physiological and pathological mech-anisms,therapeutic small molecule and hormone drugs have been introduced to control and treat most patients,but about 5％-10％of patients still suffer from various subtypes of difficult to control and treat asthma,that is,severe asthma.In the past decade,with the rapid development of bio-pharmaceutical research,protein and antibody have become the key drugs for the treatment of se-vere asthma with high efficacy,high specificity and high safety.However,biological drugs are usually administered by injection,they cannot be noninva-sive and directly delivered into the lung to quickly absorb and take effect.Therefore,there is an ur-gent need for the introduction of inhaled biologics with quick effectiveness,convenience,economy and safety in clinical.The review summarizes the existing small molecule,hormone and biological therapy drugs,and summarizes the development of inhalable biological agents of asthma,and ana-lyzes the future prospects of the inhalable biologi-cal drugs,which is designed to deepen the percep-tion of the direction of the inhalable biological drugs research,and update the information of the field,in order to provide reference for the develop-ment of more inhalable biologics.

Objective To explore the impact of high glucose(HG)intervention on immune escape of pancreatic cancer cells and its molecular mechanisms.Methods PANC-1 cells were treated with different concentrations of glucose(0,7.5,15,30 mmol/L)for 24 h to establish high glucose intervention PANC-1 cells.miR-429 mimics and its negative control(mimics NC)were transfected into PANC-1 cells,which were divided into control group,HG group,HG+mimics NC group,HG+mimics group,HG+mimics+oe-NC group,and HG+mimics+oe-ZEB1 group.Flow cytometry was utilized to measure the expression level of cell surface molecule PD-L1;qRT-PCR was used to detect the expression levels of miR-429 and ZEB1 mRNA in cells;Western blot was used to detect the ex-pression level of ZEB1 protein in cells.The above-mentioned PANC-1 cells from each group were co-cultured with CD8+T cells to establish a co-culture system,and CCK-8 was used to assess cell proliferation activity;apoptosis levels of cells were measured using flow cytometry;lactate dehydrogenase(LDH)release assay was used to detect the killing effect of CD8+T cells on PANC-1 cells;dual-luciferase reporter system was used to validate the target-regulatory relationship between mi R-429 and ZEB1.Results HG could promote the expression of cell surface mole-cules PD-L1 and ZEB1 in PANC-1 cells(P＜0.05),inhibit the expression of miR-429,and exhibit concentration dependence.Overexpression of miR-429 could significantly suppress the expression of cell surface molecule PD-L1 induced by HG in PANC-1 cells,while overexpression of ZEB1 could reverse the inhibitory effect of miR-429 over-expression on the expression of cell surface molecule PD-L1 induced by HG.After establishing a co-culture system with CD8+T cells,compared with the control group,the proliferation activity of PANC-1 cells in the HG group sig-nificantly increased,and the apoptosis rate and cytotoxicity significantly decreased(P＜0.05).Compared with the HG+mimics NC group,the proliferation activity of PANC-1 cells in the HG+mimics group significantly decreased,and the apoptosis level and cytotoxicity significantly increased(P＜0.05).Compared with the HG+mimics group,the proliferation activity of PANC-1 cells in the HG+mimics+oe-ZEB1 group significantly increased,and the apop-tosis rate and cytotoxicity significantly decreased(P＜0.05).Dual luciferase reporter gene assay confirmed that miR-429 negatively regulated ZEB1.Conclusion High glucose promotes immune escape of PANC-1 cells by down-regulating the expression level of miR-429,negatively regulating the expression of ZEB1 mRNA,and increasing the expression level of cell surface molecule PD-L1 in PANC-1 cells.

Objective:Study on the correlation between the active components of Salviea Miltiorrhizae Radix et Rhizoma screened by high-throughput sequencing and the regulation of lncRNA-mRNA in human lung adenocarcinoma A549 cells.Methods:A549 cells were cultured, and the IC 50 dose of cryptotanshinone and tanshinone ⅡA was confirmed according to the cell proliferation experiment. A549 cells were randomly divided into blank control group, cryptotanshinone group, and tanshinone IIA group using a random number table method. After 24 hours of intervention, the cell cycle was detected by flow cytometry. High-throughput sequencing technique was used to detect the expressions of lncRNA and mRNA in A549 cells in intervention group and non-intervention group. By analyzing the expression profiles of differential genes related to cryptotanshinone and tanshinone ⅡA, the obtained differential genes were analyzed by GO and KEGG. Results:The cell cycle results showed that the proportion of G0/G1 phase cells in cryptotanshinone and Tanshinone ⅡA was increased ( P<0.01), the proportion of S phase cells was decreased ( P<0.01), and the proportion of G2/M phase cells in cryptotanshinone was decreased ( P<0.01). The results of high-throughput screening showed that cryptotanshinone could up-regulate 4 698 lncRNA, down-regulate 1 557 lncRNA, up-regulate 4 810 mRNA and down-regulate 5 644 mRNA. Tanshinone ⅡA could up-regulate 1 348 lncRNA, down-regulate 1 299 lncRNA, up-regulate 4646 mRNA and down-regulate 4 741 mRNA. The function and pathway enrichment analysis of differential lncRNA and mRNA showed that the differentially expressed genes of cryptotanshinone and tanshinone ⅡA were mainly related to cell cycle, autophagy, AMPK signaling pathway, FoxO signaling pathway and EGFR signaling pathway. GAS5 may be one of the targets for the inhibitory effects of cryptotanshinone and tanshinone ⅡA. Conclusion:Cryptotanshinone and tanshinone ⅡA have certain inhibitory effects on A549 cells, and there are differentially expressed genes of lncRNA-mRNA, which are closely related to cell cycle and signal pathway.