Breast cancer is one of the most common and fatal malignancies among women worldwide, and its treatment efficacy is often limited by drug resistance and the presence of undruggable targets. Traditional small-molecule drugs have difficulty effectively modulating certain critical targets such as transcription factors and non-coding RNAs, necessitating new therapeutic strategies. Proteolysis-targeting chimeras (PROTACs) function by recruiting pathogenic proteins to the cellular ubiquitin-proteasome system, thereby inducing their specific degradation. In contrast, ribonuclease-targeting chimeras (RIBOTACs) utilize small-molecule ligands but bind to RNA and direct endogenous RNases to selectively degrade pathogenic RNA molecules. By employing a "degradation rather than inhibition" mechanism, targeting chimera technology broadens the druggable landscape and offers a novel precision therapeutic strategy for breast cancer, particularly for refractory and drug-resistant cases. This approach not only overcomes the limitations of traditional drugs, such as the absence of suitable binding sites or poor selectivity, but also reduces required dosages and potential adverse effects. Recent studies have preliminarily demonstrated the therapeutic potential of PROTACs and RIBOTACs in breast cancer, encompassing target design, mechanistic investigation, and preclinical as well as early clinical applications. Research into these technologies reveals their ability to tackle previously undruggable targets, thereby providing theoretical support for the development of safer and more effective precision therapies for breast cancer. In the future, with advances in drug delivery systems and clinical trials, PROTACs and RIBOTACs are expected to be used synergistically with immunotherapy and chemotherapy, offering breast cancer patients more promising comprehensive treatment options and potentially driving oncology toward broader intervention of undruggable targets.
Humans ; Breast Neoplasms/drug therapy* ; Female ; Proteolysis ; Ribonucleases/metabolism* ; Molecular Targeted Therapy/methods* ; Antineoplastic Agents/therapeutic use*

Objective:To study the application effect of the Hazard Analysis and Critical Control Point(HACCP)system in risk assessment and dynamic management of operational safety of medical equipment in surgery rooms.Methods:Based on the HACCP principle,hazard analysis and risk assessment were conducted on the operational safety of equipment in surgery room,and the critical control points were determined,and measures of monitor and management were formulated to conduct whole-process dynamic management for equipment in surgery room.A total of 120 medical equipment in use in the surgery room of Shaanxi Provincial Cancer Hospital from January 2022 to January 2024 were selected.According to random number table method,they were divided into conventional management mode group(60 equipment that received conventional management mode)and dynamic management mode group(60 equipment that received the mode of risk assessment and dynamic management based on HACCP system for operational safety of medical equipment in surgery rooms)to receive different managements.The effect,operational quality,the score of management standardization,and management level for equipment in managing and controlling risk of safety of equipment were compared between two management modes.Results:The average pressure-related injury,electrical injury,extravasation of body fluid,and incidence of unqualified cleaning and disinfection of equipment in the dynamic management mode group were respectively(3.01±1.01)%,(2.65±0.78)%,(1.65±0.64)%and(1.15±0.16)%,all of which were lower than those in the conventional management mode group,and the differences were statistically significant(t=16.311,13.434,12.018,12.629,P<0.05).The average utilization rate,cost-benefit amplification and social benefit amplification of the equipment in the dynamic management mode group were respectively(95.36±2.87)%,(7.98±1.32)%and(10.68±2.36)%,all of which were higher than those in the conventional management mode group,and the average operating rate in the dynamic management mode group was(9.87±1.54)%,which was lower than that in the conventional management mode group,and the differences of the above indicators were significant(t=7.657,15.567,10.354,12.466,P<0.05).The scores of the standard degrees of use and operation,disinfection and sterilization,operation and maintenance,and repairing fault of equipment in the dynamic management mode group were higher than those in the conventional management mode group,and the differences of the above data between two groups were statistically significant(t=16.289,11.415,13.396,9.420,P<0.05),respectively.The rate of standard placement,the rate of reasonable recording and integrity rate of equipment in the dynamic management mode group were higher than those in the conventional management mode group,and the failure rate was lower than that of the conventional management mode group,and the differences of the above indicators between the two groups were statistically significant(x2=6.708,7.070,8.491,13.333,P<0.05).Conclusion:The risk assessment and dynamic management based on HACCP system for operational safety of medical equipment in surgery room can improve the management effect for equipment in surgery room,and reduce the operational risk of equipment,and realize the whole-process management and control for medical equipment in surgery room.

Objective:To study the application effect of the Hazard Analysis and Critical Control Point(HACCP)system in risk assessment and dynamic management of operational safety of medical equipment in surgery rooms.Methods:Based on the HACCP principle,hazard analysis and risk assessment were conducted on the operational safety of equipment in surgery room,and the critical control points were determined,and measures of monitor and management were formulated to conduct whole-process dynamic management for equipment in surgery room.A total of 120 medical equipment in use in the surgery room of Shaanxi Provincial Cancer Hospital from January 2022 to January 2024 were selected.According to random number table method,they were divided into conventional management mode group(60 equipment that received conventional management mode)and dynamic management mode group(60 equipment that received the mode of risk assessment and dynamic management based on HACCP system for operational safety of medical equipment in surgery rooms)to receive different managements.The effect,operational quality,the score of management standardization,and management level for equipment in managing and controlling risk of safety of equipment were compared between two management modes.Results:The average pressure-related injury,electrical injury,extravasation of body fluid,and incidence of unqualified cleaning and disinfection of equipment in the dynamic management mode group were respectively(3.01±1.01)%,(2.65±0.78)%,(1.65±0.64)%and(1.15±0.16)%,all of which were lower than those in the conventional management mode group,and the differences were statistically significant(t=16.311,13.434,12.018,12.629,P<0.05).The average utilization rate,cost-benefit amplification and social benefit amplification of the equipment in the dynamic management mode group were respectively(95.36±2.87)%,(7.98±1.32)%and(10.68±2.36)%,all of which were higher than those in the conventional management mode group,and the average operating rate in the dynamic management mode group was(9.87±1.54)%,which was lower than that in the conventional management mode group,and the differences of the above indicators were significant(t=7.657,15.567,10.354,12.466,P<0.05).The scores of the standard degrees of use and operation,disinfection and sterilization,operation and maintenance,and repairing fault of equipment in the dynamic management mode group were higher than those in the conventional management mode group,and the differences of the above data between two groups were statistically significant(t=16.289,11.415,13.396,9.420,P<0.05),respectively.The rate of standard placement,the rate of reasonable recording and integrity rate of equipment in the dynamic management mode group were higher than those in the conventional management mode group,and the failure rate was lower than that of the conventional management mode group,and the differences of the above indicators between the two groups were statistically significant(x2=6.708,7.070,8.491,13.333,P<0.05).Conclusion:The risk assessment and dynamic management based on HACCP system for operational safety of medical equipment in surgery room can improve the management effect for equipment in surgery room,and reduce the operational risk of equipment,and realize the whole-process management and control for medical equipment in surgery room.

Background and purpose:For patients with human epidermal growth factor receptor 2(HER2)-positive metastatic breast cancer,trastuzumab treatment can prolong the overall survival and significantly improve the prognosis of patients.However,the reference original research trastuzumab(Herceptin?)is more expensive.Biosimilars have comparable efficacy and safety profiles while increasing patient access to treatment.This clinical trial aimed to evaluate the efficacy,pharmacokinetics,safety and immunogenicity of the trastuzumab biosimilar AK-HER2 compared to trastuzumab(Herceptin?)in patients with HER2-positive metastatic breast cancer.Methods:This multi-center,randomised,double-blind phase Ⅲ clinical trial was conducted in 43 subcenters in China.This study complied with the research protocol,the ethical principles stated in the Declaration of Helsinki and the quality management standards for drug clinical trials.It was approved by the hospital's medical ethics committee.The clinical trial registration agency is the State Food and Drug Administration(clinical trial approval number:2015L04224;clinical trial registration number:CTR20170516).Written informed consent was obtained from subjects before enrollment.Enrolled patients were randomly assigned to the AK-HER2 group and the control group,respectively receiving AK-HER2 or trastuzumab(initial loading dose 8 mg/kg,maintenance dose 6 mg/kg,every 3 weeks as a treatment cycle,total treatment time is 16 cycles)in combination with docetaxel(75 mg/m2,treatment duration is at least 9 cycles).The primary endpoint of this clinical trial was the objective response rate(ORR9)between the AK-HER2 group and the control group in the 9th cycle.Secondary efficacy endpoints included ORR16,disease control rate(DCR),clinical benefit rate(CBR),progression-free survival(PFS)and 1-year survival rate.In this study,100 subjects(AK-HER2 group to control group=1:1)were randomly selected for blood sample collection after the 6th cycle of medication,The collection time points were 45 minutes after infusion(the end of administration),4,8,24,72,120,168,336,and 504 hours after the end of administration.After collection,blood samples were analyzed by PK parameter set(PKPS).Other evaluation parameters included safety and immunogenicity assessment.Results:A total of 550 patients with HER2-positive metastatic breast cancer were enrolled in this clinical trial between Sep.2017 and Mar.2021.In the AK-HER2 group(n=237),129 subjects in the experimental group achieved complete response(CR)or partial response(PR),and the ORR9 was 54.4%.There were 134 subjects in the control group(n=241)who achieved CR or PR,and the ORR9 was 55.6%.The ORR9 ratio between the AK-HER2 group and the control group was 97.9%[90%confidence interval(CI):85.4%-112.2%,P=0.784],which was not statistically significant.In all secondary efficacy endpoints,no statistically significant differences were observed between the two groups.We conducted a mean ratio analysis of pharmacokinetics(PK)parameters between the AK-HER2 group and the control group,and the results suggested that the pharmacokinetic characteristics of the two drugs are similar.The incidence of treatment emergent adverse event(TEAE)leading to drug reduction or suspension during trastuzumab treatment was 3.6%(10 cases)in the AK-HER2 group and 8.1%(22 cases)in the control group.There was statistically significant difference between the two groups(P=0.027).The incidence rate was significantly lower in the AK-HER2 group than in the control group,and there was no statistically significant difference among the other groups.The differences in the positive rates of anti-drug antibodies(ADA)and neutralizing antibodies(NAB)between groups were of no statistical significance(P=0.385 and P=0.752).Conclusion:In patients with HER2-positive metastatic breast cancer,AK-HER2 was comparable to the trastuzumab(Herceptin?)in terms of drug efficacy,pharmacokinetics,safety and immunogenicity.

Objective:To determine the correlation of tumor volume and weight with biochemical parameters in patients with parathyroid adenoma (PA) .Methods:A prospective electronic database collected clinical data on 208 patients with PA treated for the first time by surgery at department of general surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College.The relationship between biochemical parameters and tumor volume and weight was analyzed with Spearman’s correlation.Results:Tumor volume and weight were positively correlated with parathyroid hormone (PTH) ( r=0.33, P<0.001; r=0.39, P<0.001), calcium ( r=0.16, P=0.018; r=0.18, P=0.007) and alkaline phosphatase levels ( r=0.24, P<0.001; r=0.27, P<0.001), respectively. Clinical correlates affecting serum PTH were age, serum calcium and tumor weight ( F=30.325, P<0.001) . Conclusions:Tumor burden in patients with PA correlates with some laboratory biochemical parameters. Age and cystic lesions of the tumor may influence the actual serum PTH levels.

Objective:To discuss the effects of superelastic nickel-titanium archwires(SENT)and heat-activated nickel-titanium archwires(HANT)on the initial alignment efficiency of mandibular anterior teeth and pain levels of the patients with extraction orthodontic treatment and non-extraction orthodontic treatment by using low-friction self-ligating brackets,and to provide the basis for the selection of the most suitable archwire in orthodontic clinical practice.Methods:Eighty patients underwent fixed orthodontic treatment with self-ligating brackets were randomly assigned to SENT or HANT subgroups,and there were 40 patients in extraction orthodontic treatment group and 40 patients in non-extraction orthodontic treatment group.A single operator fully engaged a 0.014-inch straight archwire into the brackets.The patients,operators,and data measurers were all blinded;the initial clinical alignment efficiency of the archwires of the patients in various groups was observed,and the Little's index was calculated;the visual analog scale(VAS)scores and pain perception of the patients in various groups were recorded 4 h after initial bonding of the appliances and every day before breakfast during the first week of orthodontic treatment;multivariate regression analysis was performed for the initial Little's index,gender,and age,and the influence factors of pain in the patients was analyzed.Results:There were no significant differences in age,gender,and initial Little's index among the patients in extraction group and non-extraction group(P＞0.05).Compared with before treatment,the Little's indexes of the patients in both HANT and SENT subgroups in non-extraction orthedontic treatment group were decreased 4 weeks after treatment,but the difference between groups was not significant(P＞0.05).Compared with SENT subgroup in non-extraction orthodontic treatment group,the Little's index of the patients in HANT subgroup was decreased(P＜0.05).In extraction orthodontic treatment group,there were no significant differences in Little's indexes of the patients between the HANT and SENT subgroups before and after treatment(P＞0.05).The pain perception peaked on the first day after initial bonding and gradually decreased to baseline levels.The patients in SENT and HANT subgroups in both extraction and non-extraction orthodontic treatment groups showed the similar patterns of pain change.There were no significant differences in the average VAS scores and maximum pain intensity scores between the patients in SENT and HANT subgroups at different time points(P＞0.05).The type of archwire had no significant effect on the degree of pain,while time significantly affected the degree of pain.The multivariate regression analysis results showed a significant correlation between initial Little's index and maximum VAS scores of the patients in extraction orthodontic treatment group(b=0.359,P=0.033).Gender and age did not affect the degree of pain of the patients in either group.Conclusion:When applying low-friction self-ligating brackets for orthodontic treatment,the initial alignment efficiency with 0.014-inch HANT archwires is superior to 0.014-inch SENT archwires in non-extraction treatment group,while both archwires show the same efficiency in extraction patients.SENT and HANT archwires do not affect the initial degrees of pain of the orthodontic patients.

Objective:To investigate the risk of adverse event (AE) associated with inclisiran and to provide reference for the safe use in clinical practice.Methods:The AE reports in the US FDA Adverse Event Reporting System (FAERS) database from the 4th quarter of 2004 to the 2nd quarter of 2023 with inclisiran as the primary suspect drug were collected. AE was standardized and classified using the preferred terminology (PT) and the system organ class (SOC) of the Medical Dictionary for Regulatory Activities 26.0. AE risk signal mining was performed using the report odds ratio (ROR) method and the UK Medicines and Healthcare Products Regulatory Agency (MHRA) comprehensive standard method. PT that was considered as an AE risk signal in both methods were defined as AE risk signals [ROR method: ≥3 reports and the lower limit of the 95% confidence interval ( CI) of the ROR>1; MHRA comprehensive standard method: ≥3 reports、 PRR ≥2 and χ2≥4]. A descriptive statistical analysis was performed. Results:A total of 1 888 AE reports were collected with inclisiran as the primary suspect drug, involving 1 888 patients and 835 PTs. The AE was predominantly reported in the United States (88.7%, 1 675/1 888), and predominantly by the consumer (62.1%, 1 171/1 886); there were a total of 484 reports (25.6%) about serious AE. Excluding non-drug and indication-related PTs, 85 PTs (involving 15 SOCs) met the criteria in both the ROR method and the MHRA comprehensive standard method, and defined as AE risk signals. The top 5 PTs ranked by the number of reports were arthralgia (248 cases), injection site pain (237 cases), limb pain (170 cases), myalgia (158 cases), and diarrhea (132 cases); the top 5 PTs ranked by the signal intensity included bladder discomfort ( ROR=28.87, PRR=28.85), injection site discomfort ( ROR=24.48, PRR=24.40), sinus pain ( ROR=23.20, PRR=23.19), injection site vesicles ( ROR=17.63, PRR=17.61), and injection site rash ( ROR=12.51, PRR=12.45). Among the top 20 PTs ranked according to the number of reports and signal intensity respectively, 8 and 13 PTs were not documented in domestic and international specifications, of which myalgia and hypoacusis had more reports and stronger signal intensity. Conclusion:The main AE of inclisiran in the US FAERS database were injection site reactions, followed by musculoskeletal-related AEs (arthralgia, myalgia, and myospasm, etc.) and infection-related AEs (such as urinary tract infections and bronchitis), which require clinical attention.

Objective:To investigate the risk of adverse event (AE) associated with inclisiran and to provide reference for the safe use in clinical practice.Methods:The AE reports in the US FDA Adverse Event Reporting System (FAERS) database from the 4th quarter of 2004 to the 2nd quarter of 2023 with inclisiran as the primary suspect drug were collected. AE was standardized and classified using the preferred terminology (PT) and the system organ class (SOC) of the Medical Dictionary for Regulatory Activities 26.0. AE risk signal mining was performed using the report odds ratio (ROR) method and the UK Medicines and Healthcare Products Regulatory Agency (MHRA) comprehensive standard method. PT that was considered as an AE risk signal in both methods were defined as AE risk signals [ROR method: ≥3 reports and the lower limit of the 95% confidence interval ( CI) of the ROR>1; MHRA comprehensive standard method: ≥3 reports、 PRR ≥2 and χ2≥4]. A descriptive statistical analysis was performed. Results:A total of 1 888 AE reports were collected with inclisiran as the primary suspect drug, involving 1 888 patients and 835 PTs. The AE was predominantly reported in the United States (88.7%, 1 675/1 888), and predominantly by the consumer (62.1%, 1 171/1 886); there were a total of 484 reports (25.6%) about serious AE. Excluding non-drug and indication-related PTs, 85 PTs (involving 15 SOCs) met the criteria in both the ROR method and the MHRA comprehensive standard method, and defined as AE risk signals. The top 5 PTs ranked by the number of reports were arthralgia (248 cases), injection site pain (237 cases), limb pain (170 cases), myalgia (158 cases), and diarrhea (132 cases); the top 5 PTs ranked by the signal intensity included bladder discomfort ( ROR=28.87, PRR=28.85), injection site discomfort ( ROR=24.48, PRR=24.40), sinus pain ( ROR=23.20, PRR=23.19), injection site vesicles ( ROR=17.63, PRR=17.61), and injection site rash ( ROR=12.51, PRR=12.45). Among the top 20 PTs ranked according to the number of reports and signal intensity respectively, 8 and 13 PTs were not documented in domestic and international specifications, of which myalgia and hypoacusis had more reports and stronger signal intensity. Conclusion:The main AE of inclisiran in the US FAERS database were injection site reactions, followed by musculoskeletal-related AEs (arthralgia, myalgia, and myospasm, etc.) and infection-related AEs (such as urinary tract infections and bronchitis), which require clinical attention.

The first bite syndrome is a rare maxillofacial pain syndrome easily ignored by clinicians. The pain caused by it not only makes it difficult for patients to eat and delays surgical wound healing, but also rises fear and anxiety of patients while they eat, which would severely reduce their life quality. There are few case reports about the first bite syndrome in China, and clinicians know little about it. Therefore, the early diagnosis and treatment of such a disease are important. In this review, we thoroughly reviewed the etiology and classification, pathogenesis, clinical manifestation, and current treatments of the first bite syndrome, aiming at providing some suggestions for clinicians.

Humans ; COVID-19 ; Pandemics ; SARS-CoV-2 ; Anxiety ; Brain ; Depression