BACKGROUND: Lung cancer is currently the most prevalent malignancy and the leading cause of cancer deaths worldwide. Although the early stage non-small cell lung cancer (NSCLC) presents a relatively good prognosis, a considerable number of lung cancer cases are still detected and diagnosed at locally advanced or late stages. Surgical treatment combined with perioperative multimodality treatment is the mainstay of treatment for locally advanced NSCLC and has been shown to improve patient survival. Following the standard methods of neoadjuvant therapy, perioperative management, postoperative adjuvant therapy, and other therapeutic strategies are important for improving patients' prognosis and quality of life. However, controversies remain over the perioperative management of NSCLC and presently consensus and standardized guidelines are lacking for addressing critical clinical issues in multimodality treatment. METHODS: The working group consisted of 125 multidisciplinary experts from thoracic surgery, medical oncology, radiotherapy, epidemiology, and psychology. This guideline was developed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. The clinical questions were collected and selected based on preliminary open-ended questionnaires and subsequent discussions during the Guideline Working Group meetings. PubMed, Web of Science, Cochrane Library, Scopus, and China National Knowledge Infrastructure (CNKI) were searched for available evidence. The GRADE system was used to evaluate the quality of evidence and grade the strengths of recommendations. Finally, the recommendations were developed through a structured consensus-building process. RESULTS: The Guideline Development Group initially collected a total of 62 important clinical questions. After a series of consensus-building conferences, 24 clinical questions were identified and corresponding recommendations were ultimately developed, focusing on neoadjuvant therapy, perioperative management, adjuvant therapy, postoperative psychological rehabilitation, prognosis assement, and follow-up protocols for NSCLC. CONCLUSIONS This guideline puts forward reasonable recommendations focusing on neoadjuvant therapy, perioperative management, adjuvant therapy, postoperative psychological rehabilitation, prognosis assessment, and follow-up protocol of NSCLC. It standardizes perioperative multimodality treatment and provides guidance for clinical practice among thoracic surgeons, medical oncologists, and radiotherapists, aiming to reduce postoperative recurrence, improve patient survival, accelerate recovery, and minimize postoperative complications such as atelectasis.
Humans ; Carcinoma, Non-Small-Cell Lung/therapy* ; Lung Neoplasms/therapy* ; Combined Modality Therapy ; Perioperative Care

Drug administration via hollow microneedles (HMN) have the advantages of painlessness, avoidance of first-pass effect, capability of sustained infusion, and no need for professional personnel operation. In addition, HMN can also be applied in the fields of body fluid extraction and biosensors, showing broad application prospects. However, traditional manufacturing technologies cannot meet the demand for low-cost mass production of HMN, limiting its widespread application. This paper reviews the main manufacturing technologies used for HMN in recent years, which include photolithography and etching, laser etching, sputtering and electroplating, micro-molding, three-dimensional (3D) printing and drawing lithography. It further analyzes the characteristics and limitations of existing manufacturing technologies and points out that the combination of various manufacturing technologies can improve production efficiency to a certain extent. In addition, this paper looks forward to the future trends of HMN manufacturing technology and proposes possible directions for its development. In conclusion, it is expected that this review can provide new ideas and references for follow-up research.
Printing, Three-Dimensional ; Needles ; Humans ; Drug Delivery Systems/methods* ; Equipment Design ; Microinjections/methods*

The study aims to observe the effects and explore the mechanisms of Buyang Huanwu Decoction and Astragali Radix-Angelicae Sinensis Radix combination in the treatment of the inflammatory response of mice with atherosclerosis(AS) via the Toll-like receptor 4(TLR4)/myeloid differentiation primary response protein 88(MyD88)/nuclear factor-κB(NF-κB) signaling pathway. Male ApoE~(-/-) mice were randomly assigned into a model group, a Buyang Huanwu Decoction group, an Astragali Radix-Angelicae Sinensis Radix combination group, and an atorvastatin group, and male C57BL/6J mice of the same weeks old were used as the control group. Other groups except the control group were given high-fat diets for 12 weeks to establish the AS model, and drugs were administrated by gavage. Aortic intimal hyperplasia thickness, blood lipid level, plasma inflammatory cytokine levels, M1/M2 macrophage markers, and expression levels of proteins in TLR4/MyD88/NF-κB pathway in the vessel wall were measured to evaluate the effects of drugs on AS lesions and inflammatory responses. The results showed that the AS model was successfully established with the ApoE~(-/-) mice fed with high-fat diets. Compared with the control group, the model group showed elevated plasma total cholesterol(TC), triglyceride(TG), and low-density lipoprotein cholesterol(LDL-c) levels(P<0.05), thickened intima(P<0.01), and increased plasma tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6) levels(P<0.01). Moreover, the model group showed increased expression of vascular cell adhesion molecule-1(VCAM-1) and inducible nitric oxide synthase(iNOS)(P<0.01), inhibited expression of endothelial nitric oxide synthase(eNOS) and cluster of differentiation 206(CD206)(P<0.01), and up-regulated mRNA and protein levels of TLR4, MyD88, NF-κB inhibitor alpha(IκBα), and NF-κB in the vessel wall(P<0.05). Compared with the model group, Buyang Huanwu Decoction and Astragali Radix-Angelicae Sinensis Radix combination lowered the plasma TC and LDL-c levels(P<0.01), alleviated the intimal hyperplasia(P<0.01), and reduced the plasma TNF-α and IL-6 levels(P<0.05). Moreover, the two interventions promoted the expression of eNOS and CD206(P<0.05), inhibited the expression of VCAM-1 and iNOS(P<0.01), and down-regulated the mRNA and protein levels of TLR4, MyD88, IκBα, and NF-κB(P<0.05) in the vessel wall. This study indicated that Buyang Huanwu Decoction and Astragali Radix-Angelicae Sinensis Radix combination could delay the progression of AS, inhibit the polarization of vascular wall macrophages toward M1 type, and attenuate vascular inflammatory response by inhibiting the activation of TLR4/MyD88/NF-κB signaling pathway in the vascular wall. Astragali Radix and Angelicae Sinensis Radix were the main pharmacological substances in Buyang Huanwu Decoction for alleviating the AS vascular inflammatory response.
Mice ; Male ; Animals ; NF-kappa B/metabolism* ; Toll-Like Receptor 4/metabolism* ; NF-KappaB Inhibitor alpha/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Interleukin-6/metabolism* ; Myeloid Differentiation Factor 88/metabolism* ; Vascular Cell Adhesion Molecule-1/metabolism* ; Cholesterol, LDL ; Hyperplasia ; Mice, Inbred C57BL ; Atherosclerosis/genetics* ; Apolipoproteins E/therapeutic use* ; RNA, Messenger

The present study aimed to investigate the effect of Xianglian Pills(XLP) on lipid metabolism in obese mice and explore the underlying mechanism based on network pharmacology and intestinal flora. Firstly, network pharmacology was used to predict the possible effect of XLP on obesity. Secondly, an obese mouse model induced by a high-fat diet was established to observe changes in mouse body weight, adiposity index, liver and adipose tissue pathology. Lipid profiles, liver and kidney function markers, insulin content, and the expression of recombinant uncoupling protein 1(UCP-1) and PR structural domain protein 16(PRDM16) were measured. The 16S rRNA gene sequencing technology was used to analyze the changes in the intestinal flora. Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis showed that XLP mainly played a role in improving obesity by regulating lipolysis, type 2 diabetes mellitus, and insulin resistance. The results of animal experiments showed that XLP significantly reduced body weight, adiposity, blood lipid levels, and serum insulin levels in obese mice, while enhancing the expression of UCP-1 and PRDM16 in adipose tissue without causing damage to the liver or kidneys. The 16S rRNA gene sequencing results showed that XLP decreased the Firmicutes/Bacteroidetes(F/B) ratio at the phylum level, increased the relative abundance of Akkermansia and Bacteroides at the family and genus levels, and reduced the abundance of Allobaculum. Therefore, XLP can effectively improve lipid metabolism disorders in high-fat diet-induced obese mice, and the mechanism is related to the improvement of brown adipose function, the browning of white fat, the accelerated lipid metabolism, and the improvement of intestinal flora. However, its effect on promoting the conversion of white adipose to brown adipose still needs to be further studied.
Mice ; Animals ; Mice, Obese ; Diet, High-Fat/adverse effects* ; Gastrointestinal Microbiome ; Network Pharmacology ; RNA, Ribosomal, 16S ; Diabetes Mellitus, Type 2/complications* ; Obesity/genetics* ; Body Weight ; Lipids ; Insulin ; Transcription Factors ; Dyslipidemias/genetics* ; Mice, Inbred C57BL ; Drugs, Chinese Herbal

Child ; Dysbiosis ; Gastrointestinal Microbiome ; Humans ; Immune System Diseases ; Nephrosis, Lipoid ; Nephrotic Syndrome

Child ; Consensus ; Drugs, Chinese Herbal ; Humans ; Medicine, Chinese Traditional ; Respiratory System

Objective:To study the effect of Suanzaoren Tang on energy metabolism of liver mitochondria in aged rats with chronic rapid eye movement （REM） sleep deprivation. Method:Fifty male Wistar rats were randomly divided into the control group， model group， estazolam group （0.18 mg·kg^-1·d^-1）， and low- （6.48 g·kg^-1·d^-1） and high-dose （12.96 g·kg^-1·d^-1） Suanzaoren Tang groups. Rats in all groups except for the control group received subcutaneous injection of D-galactose and then were deprived of sleep using the multiple platform method after the last administration. Following successful modeling， the rats in each group were treated with intragastric administration of the corresponding drugs for seven consecutive days. The morphology of liver mitochondria was observed under the transmission electron microscope. The content of adenosine triphosphate （ATP） in rat liver was detected by colorimetry， and the activities of ubiquinone oxidoreductase （complex Ⅰ）， succinate-ubiquinone oxidoreductase （complex Ⅱ）， ubiquinol-cytochrome c oxidoreductase （complex Ⅲ）， and cytochrome c oxidase （complex Ⅳ） in mitochondrial respiratory chain of rat liver were measured by colorimetry. The protein expression levels of citrate synthase （CS）， isocitrate dehydrogenase （IDH）， and ATP synthase， H⁺ transporting， mitochondrial F0 complex， subunit b， isoform 1 （ATP5F1） in rat liver were assayed by Western blot. Result:The mitochondrial damage in rat liver of the model group was more serious than that in the control group， manifested as mitochondrial swelling and deformation as well as cristae rupture and reduction. The comparison with the model group revealed that both the positive control and Suanzaoren Tang at the high dose obviously alleviated the mitochondrial swelling and deformation and reduced cristae rupture， with better improvements observed in the high-dose Suanzaoren Tang group. Compared with the control group， the content of ATP， the activities of mitochondrial respiratory chain complexes Ⅰ， Ⅱ， Ⅲ， and Ⅳ， and the protein expression levels of IDH， CS， and ATP5F1 in rat liver of the model group were all significantly decreased （P<0.01）. Compared with the model group， the content of ATP， the activities of mitochondrial respiratory chain complexes Ⅰ， Ⅱ， Ⅲ， and Ⅳ， and the protein expression levels of IDH， CS， and ATP5F1 in rat liver of the high-dose Suanzaoren Tang group were all significantly increased （P<0.05，P<0.01）. In the positive control group， the content of ATP， the activities of mitochondrial respiratory chain complexes I and Ⅲ， and the protein expression levels of CS and ATP5F1 in rat liver were significantly increased （P<0.05， P<0.01）. The activities of mitochondrial respiratory chain complexes Ⅰ and Ⅲ and the ATP5F1 protein expression in the low-dose Suanzaoren Tang group were significantly elevated （P<0.05， P<0.01）. Conclusion:Suanzaoren Tang alleviates the abnormal liver energy metabolism induced by chronic REM sleep deprivation in the elderly rats， which may be related to its enhancement of mitochondrial electron transport chain enzyme activities and the up-regulation of protein expression levels of CS， IDH and ATP5F1.

According to the different organs involved in patients, the concept of localized Eosinophilic granulomatous polyvasculitis(EGPA) was first proposed by consensus in 2018, which provides a basis for the early diagnosis and treatment of EGPA. The prognosis of patients with EGPA is related to the initial treatment. The treatment of EGPA depends on the severity of the disease, the organs involved and whether the disease is active or not. The overall treatment plan is divided into two stages: induction remission and maintenance therapy. Induced remission therapy mainly includes hormones and/or immunosuppressive agents(e.g. cyclophosphamide). After remission, azathioprine or methotrexate is recommended for maintenance therapy. In 2015, the global consensus of EGPA diagnostic and therapeutic experts recommended that the duration of treatment should be at least 24 months after remission. In combination with the latest international progress, the first Expert Consensus on Diagnosis and Treatment of EGPA in China 2018 consensus introduced the application of Bio-Targeting drugs in EGPA.

OBJECTIVE: To analyze the clinical characteristics of adolescent inguinal hernia, and to explore the reasonable repair methods. METHODS: The clinical data of 170 cases of adolescent aged between 14 to 18 years old with inguinal hernia admitted from January 2010 to January 2019 in West China Hospital of Sichuan University were analyzed retrospectively. The operation mode, anesthesia method, operation time, medical expenses, recurrence and complications were studied. RESULTS: Among the 170 patients, 16 patients were treated with traditional suture repairing Bassini method, 11 patients were treated with mesh plug repair, 3 patients were treated with plain film Lichtenstein method, 3 patients were treated with TAPP, and preperitoneal space repair was applied in 137 cases. Three patients with TAPP were treated with general anesthesia, 5 patients underwent continuous epidural anesthesia, and 162 patients underwent local infiltration anesthesia. The average operation time was(28.5±11.6)minutes. The median postoperative hospital stay was 1 day, including 159 cases(93.5%)of day surgery. The total cost of medical treatment was(7254.8±236.5)yuan per unilateral inguinal hernia, and the bilateral inguinal hernia was(13261.9±543.8)yuan. The follow-up rate was95%, and the follow-up time was 5 to 113 months. There was no recurrence. One patient with bilateral cryptorchidism developed fertility disorder, and two patients developed chronic pain. No serious complication occurred in remaining patients. CONCLUSION: Adolescent inguinal hernia should be selected from the individualized treatment plan.

Chondral injuries are short of self-healing ability and need to surgical repair after articular cartilage injury. Conventional treatment includes debridement and drainage under arthroscope, micro-fracture, osteochondral autograft transplantation (OATS), mosaiplasty and osteochondral allografts (OCA), autologous chondrocyte implantation (ACI). Debridement and drainage could remove pain factor, and has advantages of simple operation, wide clinical application and early clinical effect. Micro-fracture and osteochondral autograft transplantation is suitable for small area of cartilage repair, while the further effect showed that fibrous cartilage permeated by drill could decrease postoperative clinical effect. Osteochondral autograft transplantation has better advantages for reconstruction complete of wear-bearing joint. Autologous chondrocyte implantation and allogeneic cartilage transplantation are suitable for large area of cartilage defect, postoperative survival of allogeneic cartilage transplantation is effected by local rejection reaction and decrease further clinical effect. Cartilage tissue engineering technology could improve repair quality of autologous chondrocyte implantation, and make repair tissue close to transparent cartilage, but has limit to combined subchondral bone plate, reactive bone edema, bone loss and bad axis of lower limb. New technology is applied to cartilage injury, and has advantages of less trauma, simple operation, rapid recover, good clinical effect and less cost;and could be main method for treat cartilage injury with surgical repair technology. How to improve repair quality with compression resistance and abrasive resistance are expected to be solved.
Cartilage, Articular ; injuries ; surgery ; Chondrocytes ; transplantation ; Humans ; Knee Injuries ; surgery ; Knee Joint ; surgery ; Transplantation, Autologous