BACKGROUND: In the interim analysis of MONARCH plus, adding abemaciclib to endocrine therapy (ET) improved progression-free survival (PFS) and objective response rate (ORR) in predominantly Chinese postmenopausal women with HR+/HER2- advanced breast cancer (ABC). This study presents the final pre-planned PFS analysis. METHODS: In the phase III MONARCH plus study, postmenopausal women in China, India, Brazil, and South Africa with HR+/HER2- ABC without prior systemic therapy in an advanced setting (cohort A) or progression on prior ET (cohort B) were randomized (2:1) to abemaciclib (150 mg twice daily [BID]) or placebo plus: anastrozole (1.0 mg/day) or letrozole (2.5 mg/day) (cohort A) or fulvestrant (500 mg on days 1 and 15 of cycle 1 and then on day 1 of each subsequent cycle) (cohort B). The primary endpoint was PFS of cohort A. Secondary endpoints included cohort B PFS (key secondary endpoint), ORR, overall survival (OS), safety, and health-related quality of life (HRQoL). RESULTS: In cohort A (abemaciclib: n  = 207; placebo: n  = 99), abemaciclib plus a non-steroidal aromatase inhibitor improved median PFS vs . placebo (28.27 months vs . 14.73 months, hazard ratio [HR]: 0.476; 95% confidence interval [95% CI]: 0.348-0.649). In cohort B (abemaciclib: n  = 104; placebo: n  = 53), abemaciclib plus fulvestrant improved median PFS vs . placebo (11.41 months vs . 5.59 months, HR: 0.480; 95% CI: 0.322-0.715). Abemaciclib numerically improved ORR. Although immature, a trend toward OS benefit with abemaciclib was observed (cohort A: HR: 0.893, 95% CI: 0.553-1.443; cohort B: HR: 0.512, 95% CI: 0.281-0.931). The most frequent grade ≥3 adverse events in the abemaciclib arms were neutropenia, leukopenia, anemia (both cohorts), and lymphocytopenia (cohort B). Abemaciclib did not cause clinically meaningful changes in patient-reported global health, functioning, or most symptoms vs . placebo. CONCLUSIONS: Abemaciclib plus ET led to improvements in PFS and ORR, a manageable safety profile, and sustained HRQoL, providing clinical benefit without a high toxicity burden or reduced quality of life. TRIAL REGISTRATION ClinicalTrials.gov (NCT02763566).
Humans ; Female ; Fulvestrant/therapeutic use* ; Breast Neoplasms/metabolism* ; Aminopyridines/therapeutic use* ; Benzimidazoles/therapeutic use* ; Middle Aged ; Aromatase Inhibitors/therapeutic use* ; Aged ; Receptor, ErbB-2/metabolism* ; Adult ; Letrozole/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Anastrozole/therapeutic use*

This consensus will introduce the characteristics of fillers used in the surgical cavities of domestic nasal surgery patients based on relevant literature and expert opinions. It will also provide recommendations for the selection of cavity fillers for different nasal diseases, with chronic sinusitis as a representative example.
Humans ; Nasal Cavity/surgery* ; Nasal Surgical Procedures ; China ; Consensus ; Sinusitis/surgery* ; Dermal Fillers

"Solid-liquid excipients" co-production is one of the typical processing methods of excipients used from ancient times to the present day, and is widely applied in various processing schools and regional specialty varieties. This method significantly reduces the toxicity of traditional Chinese medicine(TCM), moderates medicinal properties, and enhances clinical efficacy. However, modern scientific research has given it limited attention, and many co-production methods of "solid-liquid excipients" have not been applied in production and practice. This paper reviewed the historical development of "solid-liquid excipients" co-production, outlined modern processing standards and methods in different processing schools, and further elaborated on the purposes and effects of this co-production method. This study is expected to provide references and evidence for further in-depth research, inheritance, innovation, and practical application.
Chemistry, Pharmaceutical/history* ; Drug Compounding/methods* ; Drugs, Chinese Herbal/chemistry* ; Excipients/chemistry* ; History, 20th Century ; History, 21st Century ; History, Ancient ; Medicine, Chinese Traditional/history*

Evidence shows that acupuncture-moxibustion could promote the healing of pressure injuries (PI), but its action mechanism is not fully understood. This review summarizes the basic research literature of acupuncture-moxibustion for PI and identifies that the mechanism of acupuncture-moxibustion for PI is related with regulation of related signaling pathway target proteins, improvement of inflammatory response, modulation of vascular microenvironment, attenuation of oxidative stress damage, and inhibition of cell apoptosis. The review also points out the current limitations and future research directions. It emphasizes the need for further exploration of the upstream regulatory mechanism, specific cellular molecules, and the interactions among these molecules. A multi-level, multi-target, and multi-dimensional approach is required to fully understand the mechanism underlying the promotion of PI healing by acupuncture-moxibustion.
Humans ; Moxibustion ; Pressure Ulcer ; Acupuncture Therapy ; Acupuncture ; Apoptosis

Background Public places are frequently polluted by cigarette smoking, and there is a lack of accurate, real-time, and intelligent monitoring technology to identify smoking behavior. It is necessary to develop a tool to identify cigarette smoking behavior in public places for more efficient control of cigarette smoking and better indoor air quality. Objective To construct a model for recognizing cigarette smoking behavior based on real-time indoor concentrations of PM_2.5 in public places. Methods Real-time indoor PM_2.5 concentrations were measured for at least 7 continuous days in 10 arbitrarily selected places (6 public service providers and and 4 office or other places) from Oct. to Nov. 2022 in Pudong New Area, Shanghai. Indoor nicotine concentrations were monitored with passive samplers simultaneously. Outdoor PM_2.5 concentration data were obtained from three municipal environmental monitoring stations which were nearest to each monitoring point during the same period. Mann-Whitney U test was used to compare indoor and outdoor means of PM_2.5 concentrations, and Spearman rank correlation was used to analyze indoor PM_2.5 and nicotine concentrations. An interactive plot and a random forest model was applied to examine the association between video observation validated indoor smoking behavior and real-time indoor PM_2.5 concentrations in an Internet cafe. Results The average indoor PM_2.5 concentration in the places providing public services [(97.5±149.3) µg·m⁻³] was significantly higher than that in office and other places [(19.8±12.2) µg·m⁻³] (P=0.011). The indoor/outdoor ratio (I/O ratio) of PM_2.5 concentration in the public service providers ranged from 1.1 to 19.0. Furthermore, the indoor PM_2.5 concentrations in the 10 public places were significantly correlated with the nicotine concentrations (r_s=0.969, P<0.001). Among them, the top 3 highly polluted places were Internet cafes, chess and card rooms, and KTV. The results of random forest modeling showed that, for synchronous real-time PM_2.5 concentration, the area under the curve (AUC) was 0.66, while for PM_2.5 concentration at a lag of 4 min after the incidence of smoking behavior, the AUC increased to 0.72. Conclusion The indoor PM_2.5 concentrations in public places are highly correlated with smoking behavior. Based on real-time indoor PM_2.5 monitoring, a preliminary recognition model for smoking behavior is constructed with acceptable accuracy, indicating its potential values applied in smoking control and management in public places.

Objective: To investigate the surgical indications and perioperative clinical outcomes of pelvic exenteration (PE) for locally advanced, recurrent pelvic malignancies and complex pelvic fistulas. Methods: This was a descriptive study.The indications for performing PE were: (1) locally advanced, recurrent pelvic malignancy or complex pelvic fistula diagnosed preoperatively by imaging and pathological examination of a biopsy; (2)preoperative agreement by a multi-disciplinary team that non-surgical and conventional surgical treatment had failed and PE was required; and (3) findings on intraoperative exploration confirming this conclusion.Contraindications to this surgical procedure comprised cardiac and respiratory dysfunction, poor nutritional status,and mental state too poor to tolerate the procedure.Clinical data of 141 patients who met the above criteria, had undergone PE in the Sixth Affiliated Hospital of Sun Yat-sen University from January 2018 to September 2022, had complete perioperative clinical data, and had given written informed consent to the procedure were collected,and the operation,relevant perioperative variables, postoperative pathological findings (curative resection), and early postoperative complications were analyzed. Results: Of the 141 included patients, 43 (30.5%) had primary malignancies, 61 (43.3%) recurrent malignancies, 28 (19.9%) complex fistulas after radical resection of malignancies,and nine (6.4%)complex fistulas caused by benign disease. There were 79 cases (56.0%) of gastrointestinal tumors, 30 cases (21.3%) of reproductive tumors, 16 cases (11.3%) of urinary tumors, and 7 cases (5.0%) of other tumors such mesenchymal tissue tumors. Among the 104 patients with primary and recurrent malignancies, 15 patients with severe complications of pelvic perineum of advanced tumors were planned to undergo palliative PE surgery for symptom relief after preoperative assessment of multidisciplinary team; the other 89 patients were evaluated for radical PE surgery. All surgeries were successfully completed. Total PE was performed on 73 patients (51.8%),anterior PE on 22 (15.6%),and posterior PE in 46 (32.6%). The median operative time was 576 (453,679) minutes, median intraoperative blood loss 500 (200, 1 200) ml, and median hospital stay 17 (13.0,30.5)days.There were no intraoperative deaths. Of the 89 patients evaluated for radical PE surgery, the radical R0 resection was achieved in 64 (71.9%) of them, R1 resection in 23 (25.8%), and R2 resection in two (2.2%). One or more postoperative complications occurred in 85 cases (60.3%), 32 (22.7%)of which were Clavien-Dindo grade III and above.One patient (0.7%)died during the perioperative period. Conclusion: PE is a valid option for treating locally advanced or recurrent pelvic malignancies and complex pelvic fistulas.
Humans ; Pelvic Exenteration/methods* ; Pelvic Neoplasms/surgery* ; Retrospective Studies ; Neoplasm Recurrence, Local/surgery* ; Postoperative Complications

OBJECTIVE: To investigate whether circular RNA circRSF1 regulates radiation-induced inflammatory phenotype of hepatic stellate cells (HSCs) by binding to HuR protein and repressing its function. METHODS: Human HSC cell line LX2 with HuR overexpression or knockdown was exposed to 8 Gy X-ray irradiation, and the changes in the expression of inflammatory factors (IL-1β, IL-6 and TNF-α) were detected by qRT-PCR. The expressions of IκBα and phosphorylation of NF-κB were detected with Western blotting. The binding of circRSF1 to HuR was verified by RNA pull-down assay and RNA-binding protein immunoprecipitation (RIP). The expressions of inflammatory factors, IκBα and the phosphorylation of NF-κB were detected after modifying the interaction between circRSF1 and HuR. RESULTS: Knockdown of HuR significantly up- regulated the expressions of IL-1β, IL-6 and TNF-α, decreased IκBα expression and promoted NF-κB phosphorylation in irradiated LX2 cells, whereas overexpression of HuR produced the opposite changes (P < 0.05). Overexpression or knockdown of circRSF1 did not significantly affect the expression of HuR. RNA pull-down and RIP experiments confirmed the binding between circRSF1 and HuR. Overexpression of circRSF1 significantly reduced the binding of HuR to IκBα and down-regulated the expression of IκBα (P < 0.05). Overexpression of circRSF1 combined with HuR overexpression partially reversed the up-regulation of the inflammatory factors, down-regulated IκBα expression and increased phosphorylation of NFκB in LX2 cells, while the opposite effects were observed in cells with knockdown of both circRSF1 and HuR (P < 0.05). CONCLUSION circRSF1 reduces IκBα expression by binding to HuR to promote the activation of NF-κB pathway, thereby enhancing radiation- induced inflammatory phenotype of HSCs.
Humans ; Hepatic Stellate Cells/radiation effects* ; Interleukin-6 ; NF-kappa B ; NF-KappaB Inhibitor alpha ; Phenotype ; RNA ; RNA, Circular/metabolism* ; Tumor Necrosis Factor-alpha ; ELAV-Like Protein 1/metabolism*

OBJECTIVE: A dynamic gel loaded with lyophilized platelet-rich plasma-chitosan/difunctionalized polyethylene glycol (LPRP-CP) was prepared to investigate its hemostatic antibacterial and promoting wound healing of scald wounds through in vitro and in vivo experiments. METHODS: In this study, normal gauze/blank tablet (Ctrl), LPRP-CP, Chitosan HUCHUANG Powder(Chito P)and ChitoGauze XP PRO group (Chito G group) were set. The hemostatic effect and promoting healing effect of the four groups of materials were evaluated by establishing rabbit ear artery hemorrhage model and superficial Ⅱ° scalded model of skin on the back. The hemostatic time and bleeding amount were calculated and the gross and histological results of scald healing were observed. The antibacterial effect of the four groups of materials was evaluated by antibacterial test in vitro. RESULTS: In the rabbit ear arterial hemorrhage model, the hemostasis of all materials was successful. The hemostatic time of Ctrl, Chito P, LPRP-CP and Chito G groups was 213.33±38.30, 118.33±24.01, 115.00±8.37 and 111.67±11.69 s, respectively. The blood loss was 1233.83±992.27, 346.67±176.00, 193.33±121.47 and 147.50±80.66 mg, respectively. Compared with Ctrl, the hemostasis time of LPRP-CP, Chito P and Chito G group was significantly shorter (P<0.001), and the amount of blood loss of LPRP-CP and Chito G group was decreased (P<0.05). Compared with LPRP-CP, there were no significant differences in hemostatic time and blood loss between Chito P and Chito G group (P>0.05). In the model of superficial Ⅱ° scalded on the back of rabbit, the wound healing rate of LPRP-CP was faster than that of the other three groups at the same time, and the healing effect was perfect. In the antibacterial test in vitro, only LPRP-CP had better anti-S. aureus effect, and all groups had no anti-E. coli effect. CONCLUSION LPRP-CP is an excellent hemostatic material for superficial wounds, and has certain antibacterial and wound healing effects, which has a wide academic value and research prospects.
Animals ; Anti-Bacterial Agents/pharmacology* ; Chitosan/pharmacology* ; Hemorrhage ; Hemostasis ; Hemostatics ; Humans ; Platelet-Rich Plasma ; Rabbits

We aimed to confirm the predictive ability of the presence of intraductal carcinoma of the prostate (IDC-P) for prognosis and the associations between IDC-P and clinicopathological parameters. Studies were identified in PubMed, Cochrane Library, EMBASE, Web of Science, and SCOPUS up to December 1, 2019. Hazard ratios (HRs) for survival data and odds ratios for clinicopathological data with 95% confidence intervals (CIs) were extracted. Heterogeneity was evaluated by the I

Purpose: Accumulating evidence has suggested that toll-like receptor 4 (TLR4) is critically involved in the pathogenesis of asthma. The aim of this study was to investigate the role of TLR4 in toluene diisocyanate (TDI)-induced allergic airway inflammation. Methods: TLR4−/− and wild-type (WT) C57BL/10J mice were sensitized and challenged with TDI to generate a TDI-induced asthma model. B-cell lymphoma 2 (Bcl-2) inhibitors, ABT-199 (4 mg/kg) and ABT-737 (4 mg/kg), were intranasally given to TDI-exposed TLR4−/− mice after each challenge. Results: TDI exposure led to increased airway hyperresponsiveness (AHR), granulocyte flux, bronchial epithelial shedding and extensive submucosal collagen deposition, which were unexpectedly aggravated by TLR4 deficiency. Following TDI challenge, TLR4−/− mice exhibited down-regulated interleukin-17A and increased colony-stimulating factor 3 in bronchoalveolar lavage fluid (BALF), while WT mice did not. In addition, TLR4 deficiency robustly suppressed the expression of NOD-like receptor family pyrin domain containing 3 and NLR family CARD domain containing 4, decreased caspase-1 activity in TDI-exposed mice, but had no effect on the level of high mobility group box 1 in BALF. Flow cytometry revealed that TDI hampered both neutrophil and eosinophil apoptosis, of which neutrophil apoptosis was further inhibited in TDI-exposed TLR4−/− mice, with marked up-regulation of Bcl-2. Moreover, inhibition of Bcl-2 with either ABT-199 or ABT-737 significantly alleviated neutrophil recruitment by promoting apoptosis. Conclusions These data indicated that TLR4 deficiency promoted neutrophil infiltration by impairing its apoptosis via up-regulation of Bcl-2, thereby resulting in deteriorated AHR and airway inflammation, which suggests that TLR4 could be a negative regulator of TDI-induced neutrophilic inflammation.