In recent years， the incidence of pulmonary nodules has kept rising. To give full play to the advantages of traditional Chinese medicine （TCM） in the treatment of pulmonary nodules and identify the breakthrough points of integrating TCM with Western medicine， the China Association of Chinese Medicine organized medical experts in TCM and western medicine to carry out in-depth discussion regarding this disease. The discussion encompassed the modern medical advances， TCM theories of etiology and pathogenesis， the role and advantages of TCM in the whole course management of pulmonary nodules， contents and methods of research on pulmonary nodules， and science popularization work， aiming to provide a reference for clinical practice and scientific research. After discussion， the experts concluded that the occurrence of pulmonary nodules was rooted in the deficiency of the lung and spleen and triggered by phlegm dampness， blood stasis， and Qi stagnation. TCM can treat pulmonary nodules by controlling and reducing nodules， improving physical constitution， ameliorating multi-system nodular diseases， reducing anxiety and avoiding excessive diagnosis and treatment， and serving as an alternative for patients who are unwilling or unfit for surgical treatment. At present， the optimal diagnosis and treatment strategy for pulmonary nodules has not been formed， which needs to be further studied from multiple perspectives such as clinical epidemiology， biology， and evidence-based medicine. The primary task of current research is to find out the advantages， effective prescriptions， and target populations and determine the effective outcomes of TCM in the treatment of pulmonary nodules. At the same time， basic research should be carried out to explore the etiology and biological behaviors of pulmonary nodules. The expert consensus on the diagnosis and treatment of pulmonary nodules with integrated TCM and Western medicine needs to be continuously revised to guide clinicians to conduct standardized， scientific， and accurate effective diagnosis and treatment.

Cancer seriously threatens human life and health, it is urgent for the development of rapid detection, precise localization and effective treatment of tumors. Chemical fluorescent probes that are sensitive to tumor-specific microenvironments have important significance in tumor theranostics and a variety of such probes have been developed. In this review, we classified chemical fluorescent probes that are sensitive to tumor microenvironments according to biological characteristics and microenvironmental changes while combining spectroscopy or response mechanisms, and systematically introduced the research progress of chemical fluorescent probes with sensitivity to hypoxia, low polarity, high viscosity, abnormal pH values and abundant reactive oxygen species in tumor microenvironments, in order to provide references for the development and applications of these probes.

Nowadays potential preclinical drugs for the treatment of nonalcoholic steatohepatitis (NASH) have failed to achieve expected therapeutic efficacy because the pathogenic mechanisms are underestimated. Inactive rhomboid protein 2 (IRHOM2), a promising target for treatment of inflammation-related diseases, contributes to deregulated hepatocyte metabolism-associated nonalcoholic steatohepatitis (NASH) progression. However, the molecular mechanism underlying Irhom2 regulation is still not completely understood. In this work, we identify the ubiquitin-specific protease 13 (USP13) as a critical and novel endogenous blocker of IRHOM2, and we also indicate that USP13 is an IRHOM2-interacting protein that catalyzes deubiquitination of Irhom2 in hepatocytes. Hepatocyte-specific loss of the Usp13 disrupts liver metabolic homeostasis, followed by glycometabolic disorder, lipid deposition, increased inflammation, and markedly promotes NASH development. Conversely, transgenic mice with Usp13 overexpression, lentivirus (LV)- or adeno-associated virus (AAV)-driven Usp13 gene therapeutics mitigates NASH in 3 models of rodent. Mechanistically, in response to metabolic stresses, USP13 directly interacts with IRHOM2 and removes its K63-linked ubiquitination induced by ubiquitin-conjugating enzyme E2N (UBC13), a ubiquitin E2 conjugating enzyme, and thus prevents its activation of downstream cascade pathway. USP13 is a potential treatment target for NASH therapy by targeting the Irhom2 signaling pathway.

Objective:To investigate the clinical characteristics of patients with malignant tumors and immune checkpoint inhibitors (ICI) related multisystem adverse events as well as therapeutic efficacy of ICI.Methods:The general data, immune-related adverse events (irAE) type, onset time, severity and ICI efficacy of patients with malignant tumors who developed irAE after receiving ICI in China-Japan Friendship Hospital between January 2019 and November 2021 were retrospectively analyzed. All patients were divided into multisystem irAE group and single system irAE group according to whether patients with more than 1 organ or system developed irAE for once. The occurrence of irAE was summarized, and the clinical characteristics of patients were compared. Progression-free survival analysis was not performed owing to the pause of immunotherapy caused by some irAE, so the efficacy of ICI was evaluated by using ICI treatment duration (TD).Results:A total of 47 patients with malignant tumors and irAE were included in this study, with 70 times of irAE in total. The median onset time was 90 d (35 d, 196 d). Among them, 12 patients (25.53%) developed multisystem irAE (32 times of irAE in total); the other 35 patients (74.47%) developed single system irAE (38 times of irAE in total). Cutaneous toxicity for 7 times, thyroid toxicity for 7 times and pulmonary toxicity for 5 times were the most frequent among multisystem irAE group; pulmonary toxicity for 13 times, thyroid toxicity for 12 times and cutaneous toxicity for 5 times were the most frequent among single system irAE group. There were no statistically significant differences in the proportion of patients stratified by age, gender, the combination of other treatments and different body mass between the two groups (all P > 0.05). The median follow-up time was 20 months (9-40 months). The median TD of ICI was 16.00 months (95% CI 3.62-31.22 months) in multisystem irAE group and 4.60 months (95% CI 4.12-11.30 months) in single system irAE group; TD in multisystem irAE group was longer than that in single system irAE group, and the difference was statistically significant ( HR = 0.413, 95% CI 0.202-0.844, P = 0.038). Conclusions:The efficacy of ICI in patients with malignant tumors and multisystem irAE is better than that in those with single system irAE. It suggests that the better efficacy of ICI may be associated with greater risk of irAE. There is no significant difference in the clinical features between multisystem irAE and single system irAE.

OBJECTIVE: To investigate the mechanism by which Chinese medicine Shengmai Yin (SMY) reverses epithelial-mesenchymal transition (EMT) through lipocalin-2 (LCN2) in nasopharyngeal carcinoma (NPC) cells CNE-2R. METHODS: Morphological changes in EMT in CNE-2R cells were observed under a microscope, and the expressions of EMT markers were detected using quantitative real-time PCR (RT-qPCR) and Western blot assays. Through the Gene Expression Omnibus dataset and text mining, LCN2 was found to be highly related to radiation resistance and EMT in NPC. The expressions of LCN2 and EMT markers following SMY treatment (50 and 100 µ g/mL) were detected by RT-qPCR and Western blot assays in vitro. Cell proliferation, migration, and invasion abilities were measured using colony formation, wound healing, and transwell invasion assays, respectively. The inhibitory effect of SMY in vivo was determined by observing a zebrafish xenograft model with a fluorescent label. RESULTS: The CNE-2R cells showed EMT transition and high expression of LCN2, and the use of SMY (5, 10 and 20 µ g/mL) reduced the expression of LCN2 and reversed the EMT in the CNE-2R cells. Compared to that of the CNE-2R group, the proliferation, migration, and invasion abilities of SMY high-concentration group were weakened (P<0.05). Moreover, SMY mediated tumor growth and metastasis in a dose-dependent manner in a zebrafish xenograft model, which was consistent with the in vitro results. CONCLUSIONS SMY can reverse the EMT process of CNE-2R cells, which may be related to its inhibition of LCN2 expression. Therefore, LCN2 may be a potential diagnostic marker and therapeutic target in patients with NPC.
Animals ; Humans ; Nasopharyngeal Carcinoma/genetics* ; Epithelial-Mesenchymal Transition ; Zebrafish ; Cell Proliferation ; Cell Line, Tumor ; Nasopharyngeal Neoplasms/radiotherapy* ; Cell Movement ; Gene Expression Regulation, Neoplastic

Objective: This study aimed to investigate the impact of molecular classification and PTEN, KRAS and PIK3CA gene mutation on the outcome of fertility-preserving treatment in the patients with endometrioid endometrial cancer (EEC) and endometrial atypical hyperplasia (EAH). Methods: This is a single-center retrospective study. A total of 135 patients with EEC and EAH receiving fertility-preserving treatment and molecular classification were reviewed. The distribution of the four types of molecular classification was described. The impact of non-specific molecular profile (NSMP), mismatch repair-deficiency (MMRd), and PTEN, KRAS and PIK3CA gene mutation on the outcome of fertility-preserving treatment was analyzed. Results: Of the patients analyzed, 86.7% (117/136) were classified as having NSMP; 14 (10.4%), MMRd; 1 (0.7%), POLEmut EAH; and 3 (2.2%), p53abn EEC. The patients having NSMP and MMRd achieved similar 16-, 32-, and 48-week complete response rates. The patients harboring tier I and tier II PTEN mutations (PTENmut-Clin) achieved lower cumulative 32-week CR rates than those with PTEN-others (without PTENmut-Clin) (22/47, 46.8% vs. 50/74, 67.6%; p=0.023; odds ratio=0.422; 95% confidence interval [CI]=0.199–0.896). Insulin-resistance (hazard ratio [HR]=0.435; 95% CI=0.269–0.702; p=0.001) and PTENmut-Clin (HR=0.535; 95% CI=0.324–0.885; p=0.015) were independent negative predictors for lower 32-week CR rates. Conclusion PTENmut-Clin is an independent risk factor for unfavorable fertility-preserving treatment outcomes in the patients with EEC and EAH. The patients with MMRd receiving fertility-preserving treatment achieved outcomes similar to those of the patients with NSMP. The molecular profiles might guide fertility-preserving treatment in the prognosis and clinical decisions.

China has a high incidence of esophageal cancer，more than 90% of which are esophageal squamous cell carcinoma （ESCC）. Abnormal proliferation，migration and new microvessels of intraepithelial neoplasia cells are the important pathogenic links in the transformation from esophageal intraepithelial neoplasia （EIN） to ESCC. Studies on the progression of esophageal precancerous lesions into esophageal cancer mostly focus on environment and genetic susceptibility，such as inflammatory factors，abnormal vascular endothelial growth factor （VEGF） signaling pathway transduction，p53 gene mutation，and DNA methylation. Some pharmacology studies have confirmed that traditional Chinese medicine （TCM） can inhibit inflammatory factors，regulate abnormal signaling pathways and improve the microenvironment. A large number of patients with esophageal cancer have been found to be in advanced stage，and the 5-year survival rate is low even after active treatment. The quality of life of patients in advanced stage is worrying due to esophageal obstruction and lung infection，and therefore， early prevention is important. Early intervention in patients with esophageal precancerous lesions is in line with clinical needs and embodies the TCM theory of “treating disease before its onset.” The mechanism of action and clinical efficacy of TCM has been gradually confirmed and promoted， with certain clinical significance. To explore simple，economical and effective TCM intervention measures conforms to the clinical diagnosis and treatment standards and the modernization of TCM.

OBJECTIVE: To explore the clinical effect of percutaneous endoscopic lumbar discectomy in the treatment of adjacent segment lumbar disc herniation after lumbar fusion. METHODS: From February 2010 to June 2018, 64 patients with adjacent segment lumbar disc herniation after lumbar fusion were retrospectively analyzed and divided into observation group and control group. In observation group, there were 23 males and 10 females performed with percutaneous endoscopic lumbar discectomy, including 27 cases of single segment fusion and 6 cases of double segment fusion, aged from 55 to 83 years old with an average of (65.7±7.4) years old. In control group, there were 22 males and 9 females performed with traditional open fusion revision, including 25 cases of single-segment fusion and 6 cases of double segment fusion, aged from 51 to 78 years old with an average of(64.8±7.8) years old. The operative time, intraoperative blood loss, fluoroscopy times, postoperative ambulation time and length of postoperative hospital stay were recorded. The clinical efficacy was evaluated by visual analogue scale(VAS) and Oswestry Disability Index(ODI). The complications between two groups were observed. RESULTS: All patients were followed up for at least 2 years. The observation group patients were followed up with an average of (2.4±0.5) years. The control group patients were followed up with an average of(2.6±0.7) years. Compared with control group, operation time, intraoperative blood loss, postoperative ambulation time and length of postoperative hospital stay of the observation group were significantly reduced (P<0.05), and the fluoroscopy times of observation group were significantly increased compared with control group(P<0.05). The VAS of low back and lower limb, and ODI at the latest follow-up between two groups were all significantly improved compared to those of pre-operation (P<0.05). The VAS of low back at each point and ODI at 1, 3 months after operation in observation group was significantly reduced compared with control group(P<0.05), however there was no significant difference in VAS for lower limb between two groups (P>0.05). The difference of complications between two groups was statistically significant (P<0.05). CONCLUSION Compared with traditional open fusion revision surgery, percutaneous endoscopic lumbar discectomy for the treatment of adjacent segment lumbar disc herniation after lumbar fusion has the advantages of reducing operation time and intra-operative blood loss, shortening ambulation time and the length of postoperative hospital stay, and promoting pain and functional improvement, and decrease incidence of complications. However, long-term clinical efficacy needs further study.
Aged ; Aged, 80 and over ; Blood Loss, Surgical ; Diskectomy ; Diskectomy, Percutaneous ; Endoscopy ; Female ; Humans ; Intervertebral Disc Degeneration/surgery* ; Intervertebral Disc Displacement/surgery* ; Lumbar Vertebrae/surgery* ; Male ; Middle Aged ; Retrospective Studies ; Treatment Outcome

To evaluate the clinical efficacy and safety of Hot AXIOS, a novel luminal metal stent with a cautery system guided by endoscopic ultrasound, for the treatment of infected pancreatic necrosis (IPN), 5 cases of IPN treated with endoscopic ultrasound-guided Hot AXIOS placement in Hangzhou First People's Hospital from December 2021 to January 2022 were retrospectively analyzed. The results showed that all 5 cases successfully completed the treatment, with 8-21 minutes of the operation time. The symptoms of abdominal pain and bloating on the first day after operation were significantly relieved, and the abdominal CT showed that the walled-off necrosis was significantly reduced. After 2-9 times of direct endoscopic necrosectomy, supplemented by antibiotics, patient's temperature and blood inflammatory indexes returned to normal, the cavity was reduced and necrosis was removed. The Hot AXIOS stent was indwelled for 12-40 days and then removed. After 25-113 days of the follow-up, all patients survived without recurrence. Preliminary results suggest that endoscopic ultrasound-guided Hot AXIOS placement is safe and effective for the treatment of IPN.

Objective:To analyze the effects of different blood pressure variables and their variabilities on diabetic nephropathy(DN)in patients with type 2 diabetes.Methods:This prospective cohort study included 3 050 type 2 diabetic patients without DN at baseline from Lee′s clinic in Taiwan, China. The metabolic parameters of patients were regularly checked, and urine albumin creatinine ratio(UACR)were evaluated annually. The average follow-up period was 7 years(3-10 years). The means and standard deviations(SD)of systolic blood pressure(SBP), diastolic blood pressure(DBP), pulse pressure(PP), and mean arterial pressure(MAP)were calculated. According to whether SBP-Mean was higher or lower than 130 mmHg(1 mmHg=0.133 kPa) and SBP-SD was higher or lower than 11.06 mmHg(average SBP-SD), these patients were divided into four groups: Q1(SBP-Mean<130 mmHg, SBP-SD<11.06 mmHg); Q2(SBP-Mean<130 mmHg, SBP-SD≥11.06 mmHg); Q3(SBP-Mean≥130 mmHg, SBP-SD<11.06 mmHg); Q4(SBP-Mean≥130 mmHg, SBP-SD≥11.06 mmHg). In the same way, according to whether PP-Mean was higher or lower than 80 mmHg(average PP-Mean)and PP-SD was higher or lower than 6.48 mmHg(average PP-SD), the patients were divided into Q1-Q4 groups.Results:After adjusting age, sex, and diabetes duration, Cox regression analysis showed that SBP-Mean, SBP-SD, PP-Mean, and PP-SD were the risk factors of DN. After the stratification according to SBP-Mean and SBP-SD, the patients in Q4 group( HR=1.976, P<0.001)had the highest risk while those in Q1 group displayed the lowest risk for DN. Additionally, the patients in Q3 group( HR=1.614, P<0.001)imposed a higher risk than that in Q2 group( HR=1.408, P<0.001). By stratificating the patients based on PP-Mean and PP-SD, the patients in Q4 group revealed the highest risk of DN( HR=1.370, P<0.001)while those in Q1 group had the lowest risk. In addition, the patients in Q3 group( HR=1.266, P<0.001)had a higher risk of DN compared with those in Q2 group( HR=1.212, P<0.001). Conclusion:SBP and PP variabilities are the predictors of DN in patients with type 2 diabetes.