Objective: To explore the application and efficacy of paclitaxel liposome in the treatment of advanced breast cancer among Chinese population in the real world. Methods: The clinical characteristics of patients with advanced breast cancer who received paclitaxel liposome as salvage treatment from January 1, 2016 to August 31, 2019 in 11 hospitals were collected and retrospectively analyzed. The primary outcome was progression free survival (PFS), and the secondary outcome included objective response rate (ORR) and safety. The survival curve was drawn by Kaplan-Meier analysis and the Cox regression model were used for the multivariate analysis. Results: Among 647 patients with advanced breast cancer who received paclitaxel liposome, the first-line treatment accounted for 43.3% (280/647), the second-line treatment accounted for 27.7% (179/647), and the third-line and above treatment accounted for 29.1% (188/647). The median dose of first-line and second-line treatment was 260 mg per cycle, and 240 mg in third line and above treatment. The median period of paclitaxel liposome alone and combined chemotherapy or targeted therapy is 4 cycles and 6 cycles, respectively. In the whole group, 167 patients (25.8%) were treated with paclitaxel liposome combined with capecitabine±trastuzumab (TX±H), 123 patients (19.0%) were treated with paclitaxel liposome alone (T), and 119 patients (18.4%) were treated with paclitaxel liposome combined with platinum ± trastuzumab (TP±H), 108 patients (16.7%) were treated with paclitaxel liposome combined with trastuzumab ± pertuzumab (TH±P). The median PFS of first-line and second-line patients (5.5 and 5.5 months, respectively) were longer than that of patients treated with third line and above (4.9 months, P<0.05); The ORR of the first line, second line, third line and above patients were 46.7%, 36.8% and 28.2%, respectively. Multivariate analysis showed that event-free survival (EFS) and the number of treatment lines were independent prognostic factors for PFS. The common adverse events were myelosuppression, gastrointestinal reactions, hand foot syndrome and abnormal liver function. Conclusion: Paclitaxel liposomes is widely used and has promising efficacy in multi-subtype advanced breast cancer.
Humans ; Female ; Breast Neoplasms/chemically induced* ; Paclitaxel/adverse effects* ; Liposomes/therapeutic use* ; Retrospective Studies ; Treatment Outcome ; Trastuzumab/therapeutic use* ; Capecitabine/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/adverse effects*

OBJECTIVE: To explore influence of external factors of wind, cold and dampness on clinical symptoms in knee osteoarthritis (KOA) patients with different constitutions of traditional Chinese medicine. METHODS: A cross-sectional stratified study was performed to select 108 patients with GradeⅡKOA in Kellgren & Lawrence (K-L) classification, including 22 males and 86 females, aged from 47 to 75 years old with an average of (60.7±6.0) years old;body mass index(BMI) ranged from 17.87 to 31.22 kg·m^-2 with an average of (23.80±2.86) kg·m^-2. According to Classification and Judgment of TCM Physique (ZYYXH/T157-2009), the types of TCM physique were determined and divided into 4 layers according to the deficiency and actual physique. Among them, there were 24 patients without biased physique, 12 males and 12 females, aged from 51 to 73 years old with an average of(62.8±6.0) years old, BMI ranged from 17.87 to 31.14 kg·m^-2 with an average of (24.32±3.25) kg·m-2;there were 46 patients with virtual bias constitution, including 7 males and 39 females, aged from 47 to 70 years old with an average of (60.0±5.8) years old, BMI ranged from 19.38 to 31.22 kg·m^-2 with an average of(23.42±2.97) kg·m^-2;There were 26 patients with solid bias constitution, including 2 males and 24 females, aged from 48 to 75 years old with an average of (60.4±5.8) years old, BMI ranged from 21.16 to 30.76 kg·m^-2 with an average of (24.15±2.33) kg·m^-2;there were 9 patients with special constitution, 1 male and 8 female, aged from 53 to 75 years old with an average of (59.8±7.5) years old, BMI ranged from 19.26 to 26.67 kg·m^-2 with an average of (23.79±2.49) kg·m^-2. Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) was used to evaluate severity of clinical symptoms. The wind-cold-dampness external factor score was calculated through the questionnaire of wind-cold-dampness syndrome scale to evaluate degree of influence of wind-cold-dampness external factor. Pearson correlation analysis and partial correlation analysis were used to calculate the correlation coefficient between severity of external factors affecting wind, cold and dampness and severity of clinical symptoms in patients with different TCM constitution stratification. RESULTS: There was no statistical significance between total score of wind-cold-dampness and WOMAC score in patients with no biased constitution and special condition. Total wind-cold-dampness score of patients with virtual biased constitution was positively correlated with WOMAC stiffness score (r=0.327, P=0.032), and total wind-cold-dampness score of patients with solid biased constitution was positively correlated with WOMAC pain score (r=0.561, P=0.005) and WOMAC overall score (r=0.446, P=0.033). After further adjusting for the interaction of external factors of wind-cold-dampness, there was no statistical significance between wind-cold-dampness scores and WOMAC scores in patients with solid biased constitution. The score of dampness and pathogenic factors was positively correlated with WOMAC stiffness score (r=0.414, P=0.007). CONCLUSION The external factors of wind-cold dampness have different effects on the clinical symptoms of KOA patients with different TCM constitutions. Compared with other constitutions, the rigid symptoms of patients with asthenic biased constitutions are more susceptible to dampness pathogenic factors.
Aged ; Female ; Humans ; Male ; Middle Aged ; Cross-Sectional Studies ; Medicine, Chinese Traditional ; Osteoarthritis, Knee ; Syndrome ; Wind ; Cold Temperature

Complicated chemical reactions occur in the decoction of traditional Chinese medicines(TCMs) which features complex components, influencing the safety, efficacy, and quality controllability of TCMs. Therefore, it is particularly important to clarify the chemical reaction mechanism of TCMs in the decoction. This study summarized eight typical chemical reactions in the decoction of TCMs, such as substitution reaction, redox reaction, isomerization/stereoselective reaction, complexation, and supramolecular reaction. With the "toxicity attenuation and efficiency enhancement" of aconitines and other examples, this study reviewed the reactions in decoction of TCMs, which was expected to clarify the variation mechanisms of key chemical components in this process and to help guide medicine preparation and safe and rational use of medicine in clinical settings. The current main research methods for chemical reaction mechanisms of decoction of TCMs were also summed up and compared. The novel real-time analysis device of decoction system for TCMs was found to be efficient and simple without the pre-treatment of samples. This device provides a promising solution, which has great potential in quantity evaluation and control of TCMs. Moreover, it is expected to become a foundational and exemplary research tool, which can advance the research in this field.
Medicine ; Medicine, Chinese Traditional ; Research Design

Quality is the guarantee for the clinical safety and effectiveness of Chinese medicine. Accurate quality evaluation is the key to the standardization and modernization of Chinese medicine. Efforts have been made in improving Chinese medicine quality and strengthening the quality and safety supervision in China, but rapid and accurate quality evaluation of complex Chinese medicine samples is still a challenge. On the basis of the development of ambient mass spectrometry and the application in quality evaluation of complex Chinese medicine systems in recent years, the authors developed the multi-scenario Chinese medicine quality evaluation strategies. A systematic methodology was proposed in specific areas such as real-time monitoring of the quality of complex Chinese medicine decoction system, rapid toxicity grading of compound Chinese patent medicine, and evaluation of bulk medicinals of Chinese patent medicine. Allowing multi-scenario analysis of Chinese medicine, it is expected to provide universal research ideas and technical methods for rapid and accurate quality evaluation of Chinese medicine and boost the high-quality development of Chinese medicine industry.
China ; Drugs, Chinese Herbal ; Mass Spectrometry ; Medicine, Chinese Traditional ; Nonprescription Drugs ; Reference Standards

OBJECTIVE: To propose the an optimal screw placement scheme to prevent femoral neck shortening, finite element analysis was used to evaluate the biomechanical outcome of different numbers formed by full threaded screws at different positions in the treatment of femoral neck fractures of Pauwels type Ⅱ. METHODS: Recruited for this study was a 55-year-old female volunteer with a weight of 70 kg and a height of 165 cm. CT scan data of her right femur was collected. The models of femoral of Pauwels typeⅡ and fully threaded screw(FTS) and partially threaded screw(PTS) were constructed in three-dimensional modeling software. All these screw placement schemes were divided into eight groups simulated the inverted triangular configuration:three PTSs, an anterosuperior FTS and two PTSs, a posterosuperior FTS and two PTSs, an inferior FTS and two PTSs, an anterosuperior PTS and two FTSs, a posterosuperior PTS and two FTSs, an inferior PTS and two FTSs and three FTSs. All fracture internal fixation models were processed in finite element analysis software. Parameters of postoperative femoral neck length, displacement distribution and peak displacement of screws and VonMises stress distribution and peak stress of screws, the proximal femur and fracture section were collected. RESULTS: The maximum VonMises stress of screws was 239.71, 213.44, 199.37, 230.82, 201.63, 215.72, 185.65 and 192.64 MPa, respectively, which was concentrated in the inferior screw near the fracture line. The maximum Von Mises stress of the proximal femur was 269.48, 241.62, 249.43, 269.69, 271.60, 346.64, 236.97 and 439.62 MPa, respectively, which was concentrated in the inferior medial area of subtrochanteric femur. The maximum Von Mises stress of fracture section was 149.12, 143.04, 140.47, 139.63, 139.81, 130.07, 117.77 and 57.89 MPa, respectively, which was concentrated around the partially threaded screw channel instead of the fully threaded screw channel. The maximum displacement of screws was 5.52, 5.43, 5.32, 5.17, 5.05, 5.13, 5.28 and 5.04 mm, respectively, which was along the axis of the femoral neck, and the displacement distribution was concentrated on the tip of the screw. The length of postoperative femoral neck length was 74.69, 74.72, 74.70, 74.70, 74.72, 74.70, 74.72 and 74.74 mm, respectively. CONCLUSION The placement of one anterosuperior partially threaded screw and two fully threaded screws with an inverted triangular distribution can not only meet the sliding compression effect to promote femoral neck healing and ensure the stability of the proximal femur, but also reduce the degree of postoperative femoral neck shortening and reduce the incidence of hip joint dysfunction. This study provides a new optimal screw placement solution for the treatment of femoral neck fractures.
Female ; Humans ; Middle Aged ; Bone Screws ; Femoral Neck Fractures/surgery* ; Femur Neck ; Finite Element Analysis ; Software ; Fracture Fixation, Internal

Objective: To evaluate the efficacy of in-situ full size split liver transplantation(fSLT) for adult recipients using the living donor liver transplantation(LDLT) technique and to compare the characteristics of the left hemiliver graft (LHG) and the right hemiliver graft(RHG)transplantation. Methods: Deceased donor and recipient data of 25 consecutive cases of fSLT at Department of Hepatopancreatobiliary Surgery, Ningbo Medical Center Lihuili Hospital from March to December 2021 was retrieved and the patients divided into two groups:LHG group and RHG group. Among the 13 donors,11 were male and 2 were female,aged (M(IQR))38(19) years(range: 25 to 56 years),with height of 168(5) cm(range:160 to 175 cm) and weight of 65(9) kg(range: 50 to 75 kg). The median age of the 25 recipients was 52(14) years(range:35 to 71 years),17 were male and 8 were female,15 had primary liver cancer and 10 had benign end-stage liver disease,model for end-stage liver disease score was 10(9) points(range:7 to 23 points). Of the 25 recipients,10 recipients had previously undergone hepatobiliary surgery. The follow-up period was to January 2022. Demographic,clinicopathological,surgical outcomes and postoperative complications were evaluated and compared between the two groups. Continuous quantitative data were compared using Mann-Whitney U test. Classification data were expressed as frequencies,and were compared between groups using χ² test or Fisher exact probability method. Results: Using LDLT technique,in-situ full-left/full-right liver splitting was performed and 13 viable pairs of hemiliver grafts were harvested with acquisition time of 230(53) minutes(range:125 to 352 minutes) and blood loss of 250(100) ml(range:150 to 1 000 ml). A total of 25 hemiliver grafts(13 LHG and 12 RHG) were allocated to patients listed for liver transplantation in our center by China Organ Transplant Response System. In the LHG group(13 cases),there were more females and more patients with benign end-stage liver disease than in the RHG group(12 cases)(P<0.05). The body weight and graft weight of recipients in the LHG group were lower than that in RHG group(both P<0.05). There were no significant differences in other baseline data between the two groups(all P>0.05). The graft to recipient weight ratio(GRWR) was 1.2(0.4)%(range:0.7% to 1.9%) for 25 recipients,1.1(0.5)%(range:0.7% to 1.6%)for the LHG group and 1.3(0.5)%(range:0.9% to 1.9%)for the RHG group. There was no significant difference between the two groups (P>0.05). Sharing patterns of hepatic vessels and the common bile duct are as follows:all the trunk of middle hepatic vein were allocated to the LHG group. The proportion of celiac trunk,main portal vein and common bile duct assigned to LHG and RHG was 10∶3 (P=0.009), 9∶4 (P>0.05) and 4∶9 (P=0.027),respectively. The vena cava of 12 donors in early stage retained in LHG and that of last one was shared between LHG and RHG (P<0.01). The median cold ischemia time of 25 hemiliver grafts was 240(90) minutes(range:138 to 420 minutes). For the total of 25 fSLT,the median anhepatic phase was 50(16) minutes(range:31 to 98 minutes) and the operation time was 474(138)minutes(range:294 to 680 minutes) with blood loss of 800(640) ml(range:200 to 5 000 ml). There were no significant differences in all of operation data between two groups. In the LHG group,3 patients with GRWR≤0.8% had postoperative small-for-size syndrome which improved after treatment. Postoperative Clavien-Dindo grade≥Ⅲ complications were observed in 6 cases(24.0%),4 cases(4/13) in the LHG group and 2 cases(2/12) in the RHG group,respectively. The difference was not statistically significant. Among them,5 cases improved after re-operation and intervention,1 case in LHG group died of secondary infection 2 weeks after operation,and the mortality was 4.0%. Analysis of serious postoperative complications and death has suggested that conventional caval interposition should not be used for LHG transplantation. Conclusion: Relying on accurate donor-recipient evaluation and the apply of LDLT technique,the morbidity and mortality of in-situ fSLT in adults is acceptable.
Adult ; Aged ; End Stage Liver Disease/surgery* ; Female ; Humans ; Liver/surgery* ; Liver Transplantation/methods* ; Living Donors ; Male ; Middle Aged ; Postoperative Complications ; Retrospective Studies ; Severity of Illness Index ; Treatment Outcome

Cervical cancer (CC) is recognized as the most common neoplasm in the female reproductive system worldwide. The lack of chemotherapeutic agents with outstanding effectiveness and safety severely compromises the anti-cipated prognosis of patients. Aloperine (ALO) is a natural quinolizidine alkaloid with marked anti-cancer effects on multiple malignancies as well as favorable activity in relieving inflammation, allergies and infection. However, its therapeutic efficacy and underlying mechanism in CC are still unclear. In the current study, MTT assay was employed to evaluate the viability of HeLa cells exposed to ALO to preliminarily estimate the effectiveness of ALO in CC. Then, the effects of ALO on the proliferation and apoptosis of HeLa cells were further investigated by plate colony formation and flow cytometry, respectively, while the migration and invasion of ALO-treated HeLa cells were evaluated using Transwell assay. Moreover, nude mice were subcutaneously inoculated with HeLa cells to demonstrate the anti-CC properties of ALO in vivo. The molecular mechanisms underlying these effects of ALO were evaluated by Western blot and immunohistochemical analysis. This study experimentally demonstrated that ALO inhibited the proliferation of HeLa cells via G2 phase cell cycle arrest. Simultaneously, ALO promoted an increase in the percentage of apoptotic HeLa cells by increasing the Bax/Bcl-2 ratio. Additionally, the migration and invasion of HeLa cells were attenuated by ALO treatment, which was considered to result from inhibition of epithelial-to-mesenchymal transition. For molecular mechanisms, the expression and activation of the IL-6-JAK1-STAT3 feedback loop were markedly suppressed by ALO treatment. This study indicated that ALO markedly suppresses the proliferation, migration and invasion and enhances the apoptosis of HeLa cells. In addition, these prominent anti-CC properties of ALO are associated with repression of the IL-6-JAK1-STAT3 feedback loop.
Animals ; Apoptosis ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Feedback ; Female ; HeLa Cells ; Humans ; Interleukin-6/genetics* ; Janus Kinase 1 ; Mice ; Mice, Nude ; Quinolizidines ; STAT3 Transcription Factor/genetics* ; Signal Transduction ; Uterine Cervical Neoplasms/drug therapy*

The growth years of traditional Chinese medicinal materials are closely related to their quality, which directly affects the efficacy and safety of clinical medication. Therefore, it is particularly important to establish an identification method for the growth years of traditional Chinese medicinal materials. In this review, the identification methods for the growth years of traditional Chinese medicinal materials were summarized systematically, and were divided into four types according to the identification principles and methods: traditional identification, molecular identification, physical/chemical identification, and integrated identification. Relying on rich experience, objective molecular markers, various physical/chemical methods and integrated identification techniques(including infrared spectroscopy, nuclear magnetic resonance spectroscopy, high performance liquid chromatography, gas chromatography, mass spectrometry, bionic identification technology and their tandem technologies, etc.), the differences of characters or chemical fingerprints were compared in depth. The growth years of traditional Chinese medicinal materials were quickly identified or predicted by the appearance and characters, the whole fingerprint information or the content of specific chemical markers, and their content ratios. Through the case analysis of mature varieties, we intend to promote the establishment of a perfect technology system for the identification of the growth years of traditional Chinese medicinal materials, and to provide a reference for other perennial herbal materials, finally resulting in the accurate and precise quality control of traditional Chinese medicinal materials.
China ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal ; Gas Chromatography-Mass Spectrometry ; Humans ; Medicine, Chinese Traditional

Parathyroid hormone is one kind of osteoanabolic agents widely used in clinic for osteoporosis. However, parathyroid hormone needs to be further optimized in the treatment of osteoporosis due to its two way regulatory effect of bone formation with low-dose intermittent treatmentand bone resorption with high-dosecontinuous treatment. Hence, based on the molecular mechanism of parathyroid hormone regulating bone metabolism, we conclude that parathyroid hormone regulates bone metabolism mainly through the following signaling pathways: (1) Gs/cAMP/PKA signaling pathway, whichis the main mechanism of parathyroid hormone regulating bone metabolism to lead to bone formation or bone resorption. (2) G
Bone Resorption ; Humans ; Osteogenesis ; Osteoporosis ; Parathyroid Hormone ; Signal Transduction

Shugoshin-1 (SGOLl) is one of the human homologues of yeast Shugoshin that locates in the centromeric region. It prevents premature division of the eentromerie cohesin complex and maintaining chromosome stability. Very recently, the role of SGOLl in tumors has emerged, but its role in lung cancer is unclear. In this study, we identify that SGOLl was upregulated in lung cancer samples from the TCGA database (n=529, P< 0.00001), which was correlated to the overall survival time of lung cancer patients (P = 0.0049). Detected by qRT-PCR and Western blotting, we demonstrate that SGOLl was consistently upregulated in lung cancer cell lines than normal epithelial cell line. Regulatory effects of SGOLl on cell viability, clonality, migration and invasion of lung cancer cells A549 and NCI-H2405 were examined by Cell Counting Kit-8 (CCK8), Colony formation, Scratch and Transwell assays, respectively. Compared with the control group, knockdown of SGOLl significantly inhibited proliferation, migration and invasion in A549 and NCI-H2405 cells (P<0. 05). A positive correlation was identified between expression levels of pyruvate kinase muscle isoenzyme 2 (PKM2) and SGOLl in the TCGA data-base (r=0. 38, P = 0). Western blotting results showed that knockdown of SGOLl in A549 and NCI-H2405 cells down-regulated PKM2 as well. In addition, co-interventions of SGOLl and PKM2 were performed in A549 and NCI-H2405 cells to clarify the interaction mechanism between them. The results showed that overexpression of PKM2 in lung cancer cells could partially reverse the regulatory effects of SGOLl knockdown on proliferation, migration and invasion (P<0. 05). Therefore, our study showed that SGOLl promoted the proliferation, migration and invasion of lung cancer cells by regulating PKM2. This study provided a theoretical basis for the mechanism of SGOLl in lung cancer.