Antibody-drug conjugates （ADCs） are a novel class of anti-tumor agents composed of a targeted monoclonal antibody， a cytotoxic drug， and a linker connecting the two. They combine the high specificity of antibodies with the potent cytotoxicity of chemotherapeutic agents. Triple-negative breast cancer （TNBC） is characterized by high aggressiveness， elevated risks of recurrence and metastasis， and poor prognosis， largely due to the lack of effective therapeutic targets. This review summarizes the research progress of ADCs in the treatment of TNBC. It has been found that ADCs targeting human epidermal growth factor receptor 2 （such as trastuzumab deruxtecan）， trophoblast cell surface antigen 2 （such as sacituzumab govitecan and datopotamab deruxtecan）， zinc transporter LIV-1 （such as ladiratuzumab vedotin）， HER-3 （such as patritumab deruxtecan）， epidermal growth factor receptor （such as AVID100）， and glycoprotein non-metastatic melanoma protein B （such as glembatumumab vedotin） have all demonstrated promising therapeutic effects against TNBC. Despite challenges including acquired resistance and treatment-related toxicities， ADCs are undoubtedly reshaping the therapeutic landscape for TNBC and are expected to occupy a more central position in TNBC treatment in the future.

ObjectiveTo evaluate the clinical efficacy of Fuzheng Huaji Formula （扶正化积方） for chronic hepatitis B to reduce the incidence of liver cirrhosis and hepatocellular carcinoma. MethodsA retrospective cohort study was conducted， collecting medical records of 118 patients with chronic hepatitis B and 234 patients with hepatitis B-related cirrhosis who visited the hospital between January 1， 2014， and December 31， 2018. The use of Fuzheng Huaji Formula was designated as the exposure factor. Patients receiving antiviral treatment for hepatitis B without concurrent Fuzheng Huaji Formula therapy were included in the western medicine group， while those receiving antiviral treatment combined with Fuzheng Huaji Formula for a cumulative treatment lasting longer than 3 months were included in the combined treatment group. The follow-up observation period was five years. Kaplan-Meier survival analysis was used to assess the cumulative incidence of cirrhosis in patients with chronic hepatitis B and the cumulative incidence of hepatocellular carcinoma in patients with hepatitis B-related cirrhosis. Univariate and multivariate Cox regression analyses were employed to examine the factors influencing the occurrence of cirrhosis and hepatocellular carcinoma. ResultsAmong patients with chronic hepatitis B， there were 55 cases in the combined treatment group and 63 cases in the western medicine group； among patients with hepatitis B-related cirrhosis， there were 110 cases in the combined treatment group and 124 cases in the western medicine group. Five-year follow-up outcomes for chronic hepatitis B patients showed that the cumulative incidence of cirrhosis was 5.45% （3/55） in the combined treatment group and 17.46% （11/63） in the western medicine group， with a statistically significant difference between groups （Z = 2.003， P = 0.045）. Five-year follow-up outcomes for hepatitis B-related cirrhosis patients showed that the cumulative incidence of hepatocellular carcinoma was 8.18% （9/110） in the combined treatment group and 22.58% （28/124） in the western medicine group， also showing a statistically significant difference （Z = 3.007， P = 0.003）. Univariate and multivariate Cox regression analyses indicated that treatment with Fuzheng Huaji Formula is an independent protective factor in preventing the progression of chronic hepatitis B to cirrhosis and the progression of hepatitis B-related cirrhosis to hepatocellular carcinoma （P＜0.05）. ConclusionCombining Fuzheng Huaji Formula with antiviral therapy for hepatitis B can effectively intervene in the disease progression of chronic hepatitis B， reducing the incidence of cirrhosis and hepatocellular carcinoma.

Primary liver cancer is one of the most common malignant tumors of the digestive system， and the “inflammation-to-cancer transformation” （ICT） of chronic hepatitis is the core pathological process of the progression of chronic hepatitis to liver cancer. Persistent and uncontrolled liver inflammation in patients with chronic hepatitis often leads to repeated liver tissue damage and repair， which gradually develops into liver fibrosis and cirrhosis， eventually leading to malignant transformation through the mechanisms such as gene mutation and microenvironment imbalance. ICT in chronic hepatitis is the key link between chronic hepatitis and liver cancer， and its dynamic evolution involves various pathogenic factors such as dampness， heat， deficiency， toxin， and stasis； among which damp-heat and vital energy deficiency are the initiating factors for ICT of chronic hepatitis， while intermingled stasis and toxin are the key pathological products that promote malignant transformation. Based on the concept of preventive treatment， traditional Chinese medicine can effectively delay and even block the ICT of chronic hepatitis by regulating inflammation， metabolism， and abnormal cell proliferation through multiple targets， which provides important strategies and research directions for the prevention and treatment of liver cancer.

Objective To establish a prediction model for the occurrence of non-occupational carbon monoxide poisoning events in Beijing, and to provide scientific basis and theoretical support for the prevention and warning of poisoning events. Methods Based on the monitoring data of non-occupational carbon monoxide poisoning events in Beijing from 2016 to 2024, the seasonal ARIMA model and seasonal index model were established to analyze the data and predict the occurrence of events. Results Between 2016 and 2024, a total of 436 cases of non-occupational carbon monoxide poisoning were reported in Beijing, showing a downward trend. The established SARIMA model and seasonal index model were SARIMA (1,0,0) (1,1,0) 12, Yt = (-0.0339t+5.8863) × St, and the average relative errors were 65.42% and 29.19%, respectively. In terms of months, the SARIMA model had better predictive performance during April and summer (June to August), while the seasonal index model was superior in other months. By combining the two models, the predicted number of events in 2025 was as follows: 3, 2, 2, 3, 1, 5, 2, 7, 1, 1, 1, and 2. Conclusion The seasonal index model has the best prediction effect on the non-occupational carbon monoxide poisoning events in Beijing throughout the year, and the number of summer events predicted by SARIMA model is closer to the actual values. The two models can be combined to predict the trend of non-occupational carbon monoxide poisoning, which provides a scientific basis for the prevention and control of carbon monoxide poisoning in the future.

OBJECTIVE: To analyze the short-term effectiveness and safety of personalized three-dimensional (3D) printed customized prostheses in severe Paprosky type Ⅲ acetabular bone defects. METHODS: A retrospective analysis was conducted on 8 patients with severe Paprosky type Ⅲ acetabular bone defects and met the selection criteria between January 2023 and June 2024. There were 3 males and 5 females, with an average age of 64.6 years ranged from 56 to 73 years. All primary replacement prostheses were non-cemented, including 1 ceramic-ceramic interface, 1 ceramic-polyethylene interface, and 6 metal-polyethylene interfaces. The time from the primary replacement to the revision was 4 days to 18 years. The reasons for revision were aseptic loosening in 5 cases, revision after exclusion in 2 cases, and repeated dislocation in 1 case. The preoperative Harris score was 39.5±3.7 and the visual analogue scale (VAS) score was 7.1±0.8. The operation time, intraoperative blood loss, hospital stay, and complications were recorded. The hip function was evaluated by Harris score, and the degree of pain was evaluated by VAS score. The acetabular cup abduction angle, anteversion angle, rotational center height, greater trochanter height, and femoral offset were measured on X-ray film. RESULTS: The operation time was 95-223 minutes, with an average of 151.13 minutes. The intraoperative blood loss was 600-3 500 mL, with an average of 1 250.00 mL. The hospital stay was 13-20 days, with an average of 16.88 days. All 8 patients were followed up 2-12 months, with an average of 6.4 months. One patient had poor wound healing after operation, which healed well after active symptomatic treatment. One patient had lower limb intermuscular vein thrombosis, but no thrombosis was found at last follow-up. No serious complications such as aseptic loosening, infection, dislocation, and periprosthetic fracture occurred during the follow-up. At last follow-up, the Harris score was 72.0±6.2 and the VAS score was 1.8±0.7, which were significantly different from those before operation ( t=-12.011, P<0.001; t=16.595, P<0.001). On the second day after operation, the acetabular cup abduction angle ranged from 40° to 49°, with an average of 44.18°, and the acetabular cup anteversion angle ranged from 19° to 26°, with an average of 21.36°, which were within the "Lewinneck safety zone". There was no significant difference in the rotational center height, greater trochanter height, and femoral offset between the healthy side and the affected side ( P>0.05). CONCLUSION The use of personalized 3D printed customized prostheses for the reconstruction of severe Paprosky type Ⅲ acetabular bone defects can alleviate pain and enhances hip joint function, and have good postoperative prosthesis position, without serious complications and have good safety.
Humans ; Printing, Three-Dimensional ; Male ; Female ; Middle Aged ; Acetabulum/surgery* ; Aged ; Retrospective Studies ; Hip Prosthesis ; Prosthesis Design ; Arthroplasty, Replacement, Hip/instrumentation* ; Reoperation ; Treatment Outcome

OBJECTIVE: To investigate the diagnostic efficacy of ^99mTc-MDP three-phase bone scintigraphy (TPBS) combined with C-reactive protein (CRP) for periprosthetic joint infection (PJI). METHODS: The clinical data of 198 patients who underwent revision surgery of artificial joint between January 2017 and January 2024 and received TPBS examination before surgery were retrospectively analyzed. There were 77 males and 121 females with an average age of 63.74 years ranging from 24 to 92 years. There were 90 cases of hip arthroplasty and 108 cases of knee arthroplasty. PJI was diagnosed according to the 2013 American Musculoskeletal Infection Society (MSIS) standard diagnostic criteria. The sensitivity, specificity, accuracy, negative predictive value (NPV), and positive predict value (PPV) were calculated. The receiver operating characteristic (ROC) curve was used to compare the diagnostic performance of the three methods, and the area under curve (AUC) was used to evaluate the diagnostic performance. RESULTS: According to the 2013 MSIS criteria, 116 cases were diagnosed as PJI, and the remaining 82 cases were aseptic loosening. The cases of PJI diagnosed by TPBS, CRP, and TPBS-CRP were 125, 109, and 137 respectively, and the cases of aseptic loosening were 73, 89, and 61 respectively. The sensitivity, accuracy, NPV, and PPV of TPBS-CRP combination in the diagnosis of PJI were higher than those of TPBS and CRP, but the specificity was lower than that of TPBS and CRP. ROC curve analysis further showed that the AUC value of TPBS-CRP combination was better than that of TPBS and CRP. The severity of bone defect and the duration of symptoms in patients with false positive TPBS diagnosis were worse than those in patients with true negative TPBS diagnosis (P<0.05), but there was no significant difference in the survival time of prosthesis between the two groups (P>0.05). Among the patients diagnosed with PJI by TPBS, CRP, and TPBS-CRP, 49, 35, and 54 patients had received antibiotic treatment 2 weeks before diagnosis, respectively. There was no significant difference in the diagnostic accuracy of TPBS and TPBS-CRP before diagnosis between patients treated with and without antibiotics and those not treated (P>0.05). The diagnostic accuracy of antibiotic therapy before CRP diagnosis was significantly lower than that of untreated patients (P<0.05). CONCLUSION TPBS and CRP have limited specificity in differentiating PJI from aseptic loosening. The TPBS-CRP combination diagnostic method can synergize the local bone metabolic characteristics and systemic inflammatory response to achieve higher diagnostic accuracy, but caution should be exercised in patients with severe bone defects and longer symptom duration.
Humans ; Prosthesis-Related Infections/blood* ; Middle Aged ; Male ; Female ; Aged ; C-Reactive Protein/metabolism* ; Retrospective Studies ; Adult ; Radionuclide Imaging/methods* ; Arthroplasty, Replacement, Knee/adverse effects* ; Aged, 80 and over ; Technetium Tc 99m Medronate ; Arthroplasty, Replacement, Hip/adverse effects* ; Sensitivity and Specificity ; Knee Prosthesis/adverse effects* ; ROC Curve ; Reoperation ; Radiopharmaceuticals ; Young Adult

OBJECTIVE To explore the molecular mechanism of Compound Dihuang Granule in treating Parkinson's disease(PD)with yin-deficiency and dynamic wind syndrome by regulating the changes of ubiquitin-proteasome system-related proteins.METHODS SPF male SD rats were randomly selected as normal control group and sham operation group,13 rats in each group.The remaining rats were treated with 6-hydroxydopamine lateral brain injection to damage the substantia nigra to establish PD yin-deficien-cy and dynamic wind syndrome rat model.The established rats were randomly divided into model group,madopar group(150 mg·kg-1),low,medium and high dose groups of Compound Dihuang Granule(1.75,3.5,7 g·kg-1),13 rats in each group.Each group was given drugs by intragastric gavage for 28 d.The general conditions and neurobehavioral manifestations of the rats were observed;the expression of ubiquitin(UB),ubiquitin activating enzyme(UBE1),ubiquitin conjugating enzyme(UBE2A)and ubiquitin carboxyl terminal hydrolase(UCH-L1)positive cells,protein and mRNA expression levels in the damaged lateral stria-tum of the brain of rats were detected by immunohistochemistry,Western blot and qPCR methods;changes of dopamine(DA)content in the damaged lateral striatum of the brain of rats were detected by ELISA.RESULTS There was no significant difference in general conditions between the normal control group and the sham operation group,and there was no significant difference in the number of ro-tations,suspension time and number of moving grids.Compared to the sham-op group,the model group rats showed poor spirit,irrita-bility,limb tremor,slow movement,dark yellow fur,less food intake,reduced body weight;the modeling increased number of rota-tions,decreased hanging time and number of moving grids(P<0.01),significantly decreased expression of UB,UBE1,UBE2A,and UCH-L1 positive cells,mRNA and protein expression levels in the damaged lateral striatum(P<0.01),and significantly decreased DA content(P<0.01).Compared with the model group,the general condition of the rats in the madopar group and Compound Di-huang Granule groups was improved,the number of rotations was reduced,the hanging time and number of moving grids were increased(P<0.05,P<0.01),the expression of UB,UBE1,UBE2A,and UCH-L1 positive cells,mRNA and protein expression levels were increased(P<0.05,P<0.01),and the DA content was increased(P<0.01);behavioral tests and the expression levels of various in-dicators were most significantly improved in the madopar group and the high-dose Compound Dihuang Granule group(P<0.05,P<0.01),and there was no statistical significance between the two groups.CONCLUSION Compound Dihuang Granule may play a role in treating PD yin-deficiency and dynamic wind syndrome by regulating the expression of ubiquitin-proteasome system-related proteins,reducing abnormal protein aggregation,and thus alleviating DA content deficiency,and the high-dose Compound Dihuang Granule has the best effect.

Objective:To analyze the temporal distribution characteristics of hand, foot and mouth disease (HFMD) in Beijing and provide reference evidence in HFMD prevention and control.Methods:The monthly incidence data of HFMD in Beijing from 2008 to 2023 were collected from Notifiable Disease Management Information System of the Chinese Information System of Disease Control and Prevention, and the epidemiological characteristics of HFMD were analyzed by the methods of time series seasonal decomposition graph, concentration degree, and circular distribution.The WPS office software 2019 was used to clean the data, Python software 3.12 was used to analyze and make statistical charts.Results:The monthly incidence fluctuation of HFMD in Beijing from 2008 to 2015 was higher than that from 2016 to 2022. From 2016 to 2022, the fluctuation range of monthly incidence showed a gradually decreasing trend.From 2008 to 2015, the concentration ( M) was 0.58, indicating a relatively strong seasonality; the mean angle ( α) calculated by the circular distribution method was 174.95°, and the mean angle standard deviation ( s) was 60.43°. The annual incidence peak occurred on June 27, and the incidence peak period was from April 27 to August 27. From 2016 to 2019 and 2023, the M was 0.57, indicating a relatively strong seasonality. The α was 228.05°, and s was 61.44°. The annual incidence peak occurred on August 20, and the incidence peak period was from June 18 to October 21. From 2020 to 2022, the M was 0.42, indicating a seasonality, the α was 238.27° and s was 76.35°. The annual incidence peak occurred on July 15, and the incidence peak period was from June 14 to November 14. The α of 2008-2015, 2016-2019 and 2023, and 2020-2022 were tested by the Watson-Williams method and the difference was statistically significant ( F=33 443.09, P<0.001). In 2023, the M was 0.77, indicating a strong seasonality. The incidence peak occurred on September 16, and the incidence peak period was from August 5 to October 28. Conclusions:The seasonality of HFMD in Beijing was obvious from 2008 to 2023, and the incidence peak day and peak period overall had rearward shifts. It is necessary to strengthen the comprehensive analysis of the distribution characteristics at different dimensions and the comprehensive prevention and control in key areas, places, and populations during the peak incidence period.

Objective To explore the clinical effect and safety of remimazolam combined with alfentanil in painless gastroenteroscopy in elderly patients.Methods 188 elderly patients who were scheduled to undergo painless gastroenteroscopy from October 2021 to February 2023 were selected and divided into group A,group B,group C,and group D by random number table method,with 47 cases in each group.The group A,group B and group C were used remimazolam 0.2,0.3 and 0.4 mg/kg,and alfentanil 3 μg/kg respectively,and the remimazolam 2.5 mg/time was added during the operation.The group D was used propofol 1.5 mg/kg and alfentanil 3 μg/kg,and a single dose of propofol 0.5 mg/kg was added during the operation.The hemodynamics at different time points[3 min before anesthesia administration(T0),immediately after endoscopy(T1),3 min after endoscopy(T2),at the end of examination(T3),at the time of awakening(T4)],anesthesia onset time,sedation success rate,gastrointestinal endoscopy time,awakening time,time to leave the observation room and intraoperative/postoperative complications were compared,and the test results of neurobehavioral cognitive state examination(NCSE)were compared at different times.Results The percutaneous arterial oxygen saturation(SpO2)at T1 and T2 time point were higher than group C and group D,and the differences were statistically significant(P<0.05).There was no statistically significant difference in the heart rate(HR)and mean arterial pressure(MAP)among group A,group B,group C and group D at each time point(P>0.05).There was no statistically significant difference in SpO2 between group A and group B at each time point(P>0.05).There was no statistically significant difference in the success rate of sedation,gastrointestinal endoscopy examination time and time of leaving the observation room among the four groups(P>0.05),but the onset time of anesthesia in group A was longer than that in group B,group C and group D,and the awakening time in group A and group B was shorter than that in group C and group D,and the differences were statistically significant(P<0.05).There was no statistically significant difference in awakening time between group A and group B(P>0.05).The incidence rate of bradycardia in group A and group B was lower than in group D,and the incidence rates of hypoxemia,respiratory depression,hypotension,and dizziness in group A were lower than those in group D,and the incidence rate of injection pain in group A,group B and group C was lower than that in group D,and the differences were statistically significant(P<0.05).After 10 minutes of complete wakefulness,there was no statistically significant difference in the passing rates of calculation ability and the memory tests between group A and group B(P>0.05),but the passing rates of calculation ability and memory test in group A were higher than those in group C and group D,and the differences were statistically significant(P<0.05).Conclusion During painless gastroenteroscopy in elderly patients,the sedative effect of using 0.3 mg/kg remimazolam combined with alfentanil is good,and it has stable hemodynamics,and the occurrence rate of complications such as bradycardia and espiratory depression is low,and the early postoperative cognitive function is recovered well.

BACKGROUND:Nowadays,there are increasing reports on the digitization and visualization system of acupuncture points for adults in traditional Chinese medicine,and the digitization and visualization system of acupuncture points for children in traditional Chinese medicine and the simulation system of acupuncture manipulation for Mongolian medicine training have been reported.However,there are no reports on relevant systems for children in Mongolian medicine. OBJECTIVE:To develop a simulation system of acupuncture points for children in Mongolian medicine,in the hope that it can be used for clinical teaching,manipulation practice and research on acupuncture safety. METHODS:Based on the tomographic anatomical dataset of preschool boys,a three-dimensional(3D)digital virtual anatomical model of children with multiple internal organs and tissues was constructed by using PhotoShop.2021 and Digihuman Reconstruction System software.The relevant annotation information database of 27 acupoints such as Dinghui acupoint of Mongolian medicine was compiled by the Unity database language.The Mongolian gold needle and silver needle were selected to record the acupuncture point teaching video on the 3D printed head and neck resin model of children.In Unity3D software,children's anatomical model,acupoint annotation information database and acupuncture operation video were integrated and coded,and a 3D digital children's Mongolian acupuncture acupoint visualization system integrating simulation acupuncture training,clinical teaching and acupuncture safety research was successfully created. RESULTS AND CONCLUSION:This study was based on real children's specimens.In order to reduce the error of two-dimensional segmentation,the manual layer-by-layer segmentation section image method was used to ensure the accuracy of the 3D model to the greatest extent.The Digihuman Reconstruction System was used to extract and save the individual segmentation data while maximizing the accuracy of the 3D model.PhotoShop.2021 software was used to complete the 3D reconstruction of the outer skin of the head and neck of children and the internal bony structure,cervical spinal cord,blood vessels and nerves,muscles and ligaments.After 3D reconstruction,the basic morphology of each independent structure and the integrity of the overall contour were verified in MeshLab software and the final fine adjustment and anatomical position confirmation were conducted using 3-matic research 13.0 software.The real anatomical morphology of the head and neck of preschool children was successfully simulated and restored.Unity3D software was used to integrate the 3D model of children,acupuncture operation video and acupoint annotation database,and the 3D digital Mongolian acupuncture acupoint visualization system for children was successfully constructed.Based on the real continuous fault ultra-thin dataset of preschool boys in China,China's first 3D digitization and visualization system of acupuncture points in the head and neck of children in Mongolian medicine was developed.Compared with the previous acupuncture soft works,this system is more suitable for the anatomical morphological development characteristics of Asian children,and has a high value of application in the fields of research on the safety of acupuncture in Mongolian medicine,clinical teaching and acupuncture simulation training.