At present, the incidence of overweight and obesity has reached epidemic levels worldwide, which call a challenge to the prevention and control of chronic metabolic diseases. Because obesity is a major risk factor for a range of metabolic diseases, including type 2 diabetes (T2DM), non-alcoholic fatty liver disease (NAFLD), cardiovascular and neurodegenerative diseases, sleep apnea, and some types of cancer. However, the drugs remain limited. Therefore, there is an urgent need to develop effective long-term treatments to address obesity-related complications. Fibroblast growth factor 1 (FGF1) is an important regulator of systemic energy homeostasis, glycolipid metabolism and insulin sensitivity. FGF1 is a non-glycosylated polypeptide consisting of 155 amino acids, consisting of 12 inverted parallel β chains with amino and carboxyl terminus, and N-terminus extending freely without the typical secretory signaling sequence, closely related to its own biological activity. Thus, FGF1 mutants or derivatives with different activities can be designed by substitution or splicing modification at theN-terminal. FGF1 plays an irreplaceable role in the development, deposition and function of fat. High-fat diet can regulate available FGF1 through two independent mechanisms of nutritional perception and mechanical perception, and influence the function of fat cells. FGF1 controls blood glucose through peripheral and central effects, enhances insulin sensitivity, improves insulin resistance, and plays a role in diabetic complications, which is expected to become a new target for the treatment of T2DM in the future. FGF1 may be involved in the regulation of NAFLD from mild steatosis to severe non-alcoholic steatohepatitis. FGF1 is closely related to the occurrence and development of a variety of cancers, improve the efficacy of anti-cancer drugs, and play a direct and indirect anti-cancer role. In addition, FGF1 plays an important role in the occurrence and development of the cardiovascular system and the improvement of cardiovascular diseases such as ischemia/reperfusion injury, myocardial infarction, pathological cardiac remodeling, cardiotoxicity. Therefore, FGF1 shows a number of therapeutic benefits in the treatment of obesity and obesity-related complications. But because FGF1 has strong mitotic activity and long-term use has been associated with an increased risk of tumorigenesis, its use in vivo has been limited and enthusiasm for developing it to treat obesity-related complications has been dampened. However, FGF1 was found to induce cell proliferation primarily through FGFR3 and FGFR4, but its metabolic activity was mainly mediated by FGFR1. That is, FGF1 activity that promotes mitosis and anti-obesity-related complications appears to be separable. Currently, many engineered FGF1 variants have been developed, such as FGF1^ΔHBS, MT-FGF1^ΔHBS, FGF1^∆NT, ∆nFGF1, FGF1^R50E. Although the effect of FGF1 or its analogues on obesity-related complications has been demonstrated in many rodent studies, there are no relevant clinical results. This may be due to the unknown safety and therapeutic efficacy of FGF1 in large animals and humans, as well as concerns about tumorigenesis that hinder its development into a lifelong therapeutic agent. This review summarizes recent advances in the development of FGF1-based biologic drugs for the treatment of obesity-related complications, highlights major challenges in clinical implementation, and discusses possible strategies to overcome these obstacles.

Objective To evaluate the efficacy and safety of Shenbao tablet in the treatment of kidney-yang deficiency syndrome.Methods Patients with kidney-yang deficiency syndrome,will were treated with Shenbao Tablets orally,3 tablets once,3 times a day,and the course of treatment was 56 days or 84 days,depending on the condition.By comparing the clinical efficacy,the changes of symptom scores and syndrome scores before and after treatment,and symptoms remission time,the effectiveness of Shenbao tablet in the treatment of kidney-yang deficiency syndrome was evaluated.The safety was evaluated by adverse reactions.Results There were 339 patients in the 56-day group and 345 patients in the 84-day group.After treatment,the clinical effective rates of the 56-day group and the 84-day group were 91.74％and 97.97％,respectively,and the difference was statistically significant(P＜0.05).In the 56-day group and the 84-day group,the excellent rate were 58.41％and 59.13％,clinical control rates were 18.58％and 27.54％,and the progress rates were 14.75％and 11.30％,respectively.After treatment,the symptom scores of kidney-yang deficiency syndrome were significantly reduced respectively within both groups(P＜0.05).In the 56-day group and the 84-day group,the nocturia scores of were 0.89±1.27 and 0.60±1.03,the soreness of waist scores were 1.31±1.19 and 0.72±1.00,the morning diarrhea scores were 0.28±0.74 and 0.19±0.61,the anaphrodisia scores were 0.65±1.13 and 0.53±0.98,the low spirits scores were 0.29±0.81 and 0.08±0.40,the cold limbs score were 1.09±1.20 and 0.55±0.93,the edema scores were 0.14±0.55 and 0.05±0.30,the bright pale complexion scores were 0.20±0.59 and 0.24±0.65,respectively.There were significant differences in the reduction of each symptom score between the two groups(P＜0.05);the 56-day group had a more significant decrease in the score of cold limbs than the 84-day group.The remaining symptom scores decreased more significantly in the 84-day group.After treatment,the syndrome scores of kidney-yang deficiency syndrome in the two groups were significantly lower than those before treatment(all P＜0.05);the change rates of score in the 56-day group and the 84-day group were(-72.33±24.57)％and(-78.77±19.53)％,respectively,and the difference was statistically significant(P＜0.05).The self-reported time to first symptom relief was(14.85±7.18)days in the 56-day group and(14.10±7.78)days in the 84-day group,with no significant difference(P＞0.05).The incidence of adverse reactions of Shenbao tablets was 5.37％,mainly reflected in hepatobiliary system diseases,gastrointestinal system diseases and various examination abnormalities.Conclusions After taking Shenbao tablets for 2 to 3 months,the clinical symptoms of kidney-yang deficiency were better improved,and the improvement was more significant after 3 months of treatment.The security of Shenbao Tablets was good.

Acute respiratory distress syndrome (ARDS) is severe respiratory failure in clinical practice, with a mortality rate as high as 40%. Injury of pulmonary endothelial cells and alveolar epithelial cells occurs during ARDS, and pulmonary endothelial injury results in endothelial barrier disruption, which usually occurs before epithelial injury. Especially, when harmful factors enter the blood, such as sepsis and hemorrhagic shock, the pulmonary endothelial cells are affected firstly. The injured endothelial cells may loss cell-to-cell connections and even die. After the endothelial barrier is disrupted, fluid and proteins cross the endothelial barrier, causing interstitial edema. The alveolar epithelium is more resistant to injury, and when the tight barrier of the epithelium is broken, fluids, proteins, neutrophils, and red blood cells in the interstitium enter the alveolar space. From this process, it is easy to find that the endothelium is the first barrier to prevent edema, therefore, the protection of endothelium is the key to the prevention and treatment of ARDS. In addition, the injured endothelial cells express selectin and cell adhesion molecules, promoting the recruitment of immune cells, which exacerbate the inflammatory response and pulmonary endothelial cell injury. Mesenchymal stem cells (MSCs) can be derived from umbilical cord, bone marrow, adipose and so on. Because of low immunogenicity, MSCs can be used for allogeneic transplantation and have great application potential in tissue repairing. Through paracrine effect, MSCs can promote cell survival and balance inflammatory response. MSCs infused intravenously can locate in lungs rapidly and interact with endothelial cells directly, thus MSCs have advantages in protecting pulmonary microvascular endothelial cells. Animal experiments and clinical trials have found that MSC transplantation can significantly improve the symptoms of ARDS and reduce inflammatory reactions and endothelial permeability. Mechanically, MSCs acts mainly through paracrine and immunomodulatory effects. Paracrine cytokines from MSCs can not only promote pulmonary endothelial proliferation, but also reduce inflammatory response and promote cell survival to maintain endothelial integrity. In addition to paracrine cytokines, extracellular vesicles of MSCs are rich in RNAs, proteins and bioactive substances, which can protect pulmonary endothelial cells by intercellular communication and substance transport. Furthermore, MSCs may protect pulmonary endothelial cells indirectly by regulating immune cells, such as reducing the formation of extracellular trapping network of neutrophils, regulating macrophage polarization and regulating Th17/Treg cell balance. Although the beneficial effects of MSCs are verified, much work still needs to be done. MSCs from different tissues have their own characteristics and the scope of application. Different lung diseases possess different endothelial injury mechanisms. Thus, determining the indications of MSCs derived from different tissues is the direction of pulmonary disease clinical trials. From the perspective of transplantation route, intravenous injection of MSCs may have better clinical application in pulmonary endothelial injury caused by endogenous harmful factors in blood. Previous reviews mostly focused on the protective effects of MSCs on alveolar epithelium. In this article, we focused on endothelial cells and reviewed the direct protective effects and mechanisms of MSCs on endothelium through paracrine cytokines and extracellular vesicles, and summarize the mechanisms by which MSCs may indirectly protect pulmonary endothelial cells by regulating immune cells.

OBJECTIVE: To evaluate the report quality of Chinese and English randomized controlled trials (RCTs) of acupuncture based on the CONSORT statement and STRICTA checklist. METHODS: The Chinese and English RCTs of acupuncture published from January 1, 2015 to December 31, 2019 were searched in 7 databases including PubMed. The report quality of the included RCTs was evaluated with the CONSORT 2010 statement and STRICTA checklist. RESULTS: A total of 506 Chinese RCTs and 76 English RCTs were included. According to the CONSORT statement, in Chinese RCTs, the items with report rate less than 50% accounted for 78.38% of all items, and the report rate of 25 items, such as background and reason, study design, outcome index, and sample size, was less than 10%. In English RCTs, the items with report rate less than 50% accounted for 35.14% of all items, and 5 items had a report rate of less than 10%. The difference of the report rate of 15 items, such as background, reason and study design, was more than 50% between Chinese and English RCTs. The report rate of all items of STRICTA checklist was relatively high in both Chinese and English RCTs. In Chinese RCTs, the items with report rate less than 50% accounted for 29.41% of all items, which included acupuncture rationale and depth of insertion. In English RCTs, only two items had a report rate less than 50%, which were acupuncture rationale, setting and context of treatment. The report rate of five items, including needle retention time, frequency and duration of treatment sessions, details of other interventions administered to the acupuncture group, setting and context of treatment, and precise description of the control or comparator in Chinese RCTs, were higher than in English RCTs. CONCLUSION The report quality of Chinese acupuncture RCT needs to be improved urgently, and corresponding measures should be taken to further standardize the writing and reporting of acupuncture clinical research.
Humans ; Acupuncture Therapy ; Checklist ; Randomized Controlled Trials as Topic/standards*

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.
Adult ; Humans ; Adolescent ; Imatinib Mesylate/adverse effects* ; Incidence ; Antineoplastic Agents/adverse effects* ; Retrospective Studies ; Pyrimidines/adverse effects* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Treatment Outcome ; Benzamides/adverse effects* ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Aminopyridines/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use*

Objective: To provide survival evidence of anthracycline-free neoadjuvant chemotherapy for patients with stages Ⅱ-Ⅲ human epidermal growth factor receptor-2 (HER-2) positive and hormone receptor (HR) negative breast cancer. Methods: The prospective cohort study was conducted at the Department of Medical Oncology of Cancer Hospital, Chinese Academy of Medical Sciences. Patients with HER-2 positive and HR negative breast cancer in stages Ⅱ-Ⅲ were enrolled to receive neoadjuvant therapy (NAT) of dose-dense paclitaxel (175 mg/m(2)) plus carboplatin (AUC=4.0) biweekly for 6 cycles in combination with trastuzumab (PCbH), and matched patients who received standard adjuvant therapy of physicians' choice were recruited for survival and safety comparison. Results: From July 2013 to November 2019, 166 patients were included (neoadjuvant 51, adjuvant 115). Compared with those who received adjuvant therapy, patients receiving NAT were younger (<35 years: 19.6% vs 5.2%, P=0.014), had larger tumors (T3: 62.7% vs 7.8%, P<0.001) and more advanced diseases (stage ⅡA: 2.0% vs 41.7%, P<0.001). Patients in the neoadjuvant group all received surgery, and 96 (83.5%) in the adjuvant group received anthracycline-and-taxane-containing regimens. A total of 98 patients (49 pairs) were matched, and the covariates between the two groups were acceptably balanced. Within a median follow-up of 46.5 (range, 14-87) months, the 4-year recurrence-free survival (RFS) rate among patients who received NAT was 73.3% (95% CI: 59.0%-87.6%), versus 80.6% (95% CI: 67.9%-93.3%) among those in the adjuvant group without statistical difference (P=0.418). A similar result was observed for the 4-year overall survival (OS) [neoadjuvant versus adjuvant: 91.5% (95% CI: 81.7%-100.0%) vs 97.8% (95% CI: 93.5%-100.0%), P=0.314]. Compared with standard adjuvant therapy, PCbH was related to less neutropenia and better cardiac safety. Conclusions: These results support the consideration of anthracycline-free neoadjuvant chemotherapy combined with anti-HER-2 therapy for patients with stages Ⅱ-Ⅲ HER-2-positive and HR-negative breast cancer. Optimized regimens with both efficacy and safety are needed and to be further investigated.
Female ; Humans ; Anthracyclines/therapeutic use* ; Antibiotics, Antineoplastic/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Carboplatin/therapeutic use* ; Chemotherapy, Adjuvant ; Hormones/therapeutic use* ; Neoadjuvant Therapy ; Paclitaxel/therapeutic use* ; Prospective Studies ; Receptor, ErbB-2/metabolism* ; Trastuzumab/therapeutic use* ; Triple Negative Breast Neoplasms/drug therapy*

Objective: To provide survival evidence of anthracycline-free neoadjuvant chemotherapy for patients with stages Ⅱ-Ⅲ human epidermal growth factor receptor-2 (HER-2) positive and hormone receptor (HR) negative breast cancer. Methods: The prospective cohort study was conducted at the Department of Medical Oncology of Cancer Hospital, Chinese Academy of Medical Sciences. Patients with HER-2 positive and HR negative breast cancer in stages Ⅱ-Ⅲ were enrolled to receive neoadjuvant therapy (NAT) of dose-dense paclitaxel (175 mg/m(2)) plus carboplatin (AUC=4.0) biweekly for 6 cycles in combination with trastuzumab (PCbH), and matched patients who received standard adjuvant therapy of physicians' choice were recruited for survival and safety comparison. Results: From July 2013 to November 2019, 166 patients were included (neoadjuvant 51, adjuvant 115). Compared with those who received adjuvant therapy, patients receiving NAT were younger (<35 years: 19.6% vs 5.2%, P=0.014), had larger tumors (T3: 62.7% vs 7.8%, P<0.001) and more advanced diseases (stage ⅡA: 2.0% vs 41.7%, P<0.001). Patients in the neoadjuvant group all received surgery, and 96 (83.5%) in the adjuvant group received anthracycline-and-taxane-containing regimens. A total of 98 patients (49 pairs) were matched, and the covariates between the two groups were acceptably balanced. Within a median follow-up of 46.5 (range, 14-87) months, the 4-year recurrence-free survival (RFS) rate among patients who received NAT was 73.3% (95% CI: 59.0%-87.6%), versus 80.6% (95% CI: 67.9%-93.3%) among those in the adjuvant group without statistical difference (P=0.418). A similar result was observed for the 4-year overall survival (OS) [neoadjuvant versus adjuvant: 91.5% (95% CI: 81.7%-100.0%) vs 97.8% (95% CI: 93.5%-100.0%), P=0.314]. Compared with standard adjuvant therapy, PCbH was related to less neutropenia and better cardiac safety. Conclusions: These results support the consideration of anthracycline-free neoadjuvant chemotherapy combined with anti-HER-2 therapy for patients with stages Ⅱ-Ⅲ HER-2-positive and HR-negative breast cancer. Optimized regimens with both efficacy and safety are needed and to be further investigated.
Female ; Humans ; Anthracyclines/therapeutic use* ; Antibiotics, Antineoplastic/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Carboplatin/therapeutic use* ; Chemotherapy, Adjuvant ; Hormones/therapeutic use* ; Neoadjuvant Therapy ; Paclitaxel/therapeutic use* ; Prospective Studies ; Receptor, ErbB-2/metabolism* ; Trastuzumab/therapeutic use* ; Triple Negative Breast Neoplasms/drug therapy*

The clinical evidences on acupuncture and moxibustion for the treatment of frozen shoulder were sorted and summarized systematically. The relevant articles of frozen shoulder treated with acupuncture and moxibustion were searched from PubMed, EMbase, Cochrane database of systematic review (CDSR), Cochrane database of controlled trials register (CENTRAL), China national knowledge infrastructure (CNKI), Wanfang, VIP, and Chinese biomedical literature databases (SinoMed), from database inception to May 31, 2021. Using AMSTAR-2, the methodological quality of the included systematic reviews was evaluated. With evidence map, the current status of clinical evidence was summarized on acupuncture and moxibustion in treatment of frozen shoulder. A total of 266 original studies and 6 systematic reviews were included finally. At present, many randomized controlled trials are designed with small sample size and the simple acupuncture and moxibustion therapy is dominant as the intervention, e.g. warm acupuncture, acupuncture with filiform needle, acupotomy and electroacupuncture. The outcomes considered in the current trials focus on clinical effective rate, the score of shoulder pain, the score of shoulder function and the score of quality of life. Most of the studies have shown that acupuncture and moxibustion is advantageous as an adjunctive therapy for frozen shoulder, but its clinical evidence is few in terms of the recurrence rate and safety. Moreover, it needs to improve the evidence quality of the relevant studies on acupuncture and moxibustion for frozen shoulder.
Acupuncture Therapy ; Bursitis/therapy* ; Electroacupuncture ; Humans ; Moxibustion ; Quality of Life

To explore the influencing factors of acupuncture curative effect in literature of experts' experience. The journal literature of experts' experience was retrieved from China National Knowledge Infrastructure (CNKI) and PubMed, starting from inception to September 4, 2020, and the influencing factors of acupuncture curative effect were extracted and analyzed. A total of 499 articles were included, involving 495 articles in Chinese and 4 articles in English. The influencing factors of acupuncture curative effect mainly include five aspects: diagnostic method, acupoint selection of acupuncture, acupuncture manipulation, regulating mind of acupuncture and acupuncture time, and provide reference for acupuncture protocol design in clinical trials.
Acupuncture ; Acupuncture Points ; Acupuncture Therapy/methods* ; PubMed ; Publications

Objective: To evaluate the efficacy and survival outcomes of dose-dense (biweekly) carboplatin plus paclitaxel (PC) as neoadjuvant chemotherapy (NAC) in triple-negative breast cancer (TNBC), and to explore an optimal neoadjuvant chemotherapy regimen for TNBC. Methods: Patients diagnosed as TNBC(cT1-4N0-3M0) in Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College Between January 2008 and September 2018 who received dose-dense PC and standard 3-weekly PC as NAC were 1∶1 matched using propensity score matching (PSM) to compare the efficacy, safety and survival outcomes. Results: One hundred of TNBC patients were enrolled (50 patients were divided in dose-dense group, 50 patients in standard group). The objective response rate (ORR) of dose-dense group and standard group were both 90.0% (45/50). The grade 3-4 neutropenia in dose-dense group was less than that of standard group (32.7% vs. 68.0%, P=0.001), while the rate of ALT/AST elevation in dose-dense group was higher than that of standard group (57.1% vs. 32.0%, P=0.012). The pathological complete response (pCR) rates were 34.0% (17/50) in dose-dense group and 38.0% (19/50) in standard group, without statistically significance (P=0.677). The median follow-up time was 55 months (3-150 months). The 5-year recurrence-free survival (RFS) in dose-dense group and standard group were 83.5% and 75.2%, respectively the 5-year overall survival (OS) in dose-dense and standard group were 87.9% and 84.5% the difference were not statistically significant (P=0.322 and 0.647, respectively). Patients with residual disease (tumor size≥1 cm or lymph node positive) had poor prognosis, the 5-year RFS and OS were 59.3% and 68.5%, respectively. Conclusions: Dose-dense PC has similar efficacy with standard 3-weekly PC and has a good safety profile. Since dose-dense regimen can shorten the duration of therapy, it can be an alternative in TNBC.
Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Carboplatin/therapeutic use* ; Humans ; Neoadjuvant Therapy/adverse effects* ; Paclitaxel/therapeutic use* ; Treatment Outcome ; Triple Negative Breast Neoplasms/pathology*