OBJECTIVE: To determine whether monotropein has an anticancer effect and explore its potential mechanisms against colorectal cancer (CRC) through network pharmacology and molecular docking combined with experimental verification. METHODS: Network pharmacology and molecular docking were used to predict potential targets of monotropein against CRC. Cell counting kit assay, plate monoclonal assay and microscopic observation were used to investigate the antiproliferative effects of monotropein on CRC cells HCT116, HT29 and LoVo. Flow cytometry and scratch assay were used to analyze apoptosis and cell cycle, as well as cell migration, respectively in HCT116, HT29, and LoVo cells. Western blotting was used to detect the expression of proteins related to apoptosis, cell cycle, and cell migration, and the expression of proteins key to the Akt pathway. RESULTS: The Gene Ontology and Reactome enrichment analyses indicated that the anticancer potential of monotropein against CRC might be involved in multiple cancer-related signaling pathways. Among these pathways, RAC-beta serine/threonine-protein kinase (Akt1, Akt2), cyclin-dependent kinase 6 (CDK6), matrix metalloproteinase-9 (MMP9), epidermal growth factor receptor (EGFR), cell division control protein 42 homolog (CDC42) were shown as the potential anticancer targets of monotropein against CRC. Molecular docking suggested that monotropein may interact with the 6 targets (Akt1, Akt2, CDK6, MMP9, EGFR, CDC42). Subsequently, cell activity of HCT116, HT29 and LoVo cell lines were significantly suppressed by monotropein (P<0.05). Furthermore, our research revealed that monotropein induced cell apoptosis by inhibiting Bcl-2 and increasing Bax, induced G₁-S cycle arrest in colorectal cancer by decreasing the expressions of CyclinD1, CDK4 and CDK6, inhibited cell migration by suppressing the expressions of CDC42 and MMP9 (P<0.05), and might play an anticancer role through Akt signaling pathway. CONCLUSION Monotropein exerts its antitumor effects primarily by arresting the cell cycle, causing cell apoptosis, and inhibiting cell migration. This indicates a high potential for developing novel medication for treating CRC.
Humans ; Proto-Oncogene Proteins c-akt/metabolism* ; Cell Proliferation ; Matrix Metalloproteinase 9 ; Molecular Docking Simulation ; Cell Cycle ; ErbB Receptors ; Apoptosis ; Colorectal Neoplasms/pathology* ; Cell Line, Tumor

Aim Based on the apoptotic pathway mediated by receptor interacting protein kinase(RIP)1-RIP3-mixed spectrum kinase domain like protein(MLKL), to explore the effects of naringenin on ovarian granulosa cell apoptosis in rats with polycystic ovary syndrome(PCOS). Methods SD rats were randomly assigned into normal control group, model group, naringenin group, RIP1 inhibitor(Nec-1)group, RIP1-RIP3-MLKL necrosis signal activator(Z-VAD-fmk)group, naringenin+Z-VAD-fmk group, 15 rats per group. ELISA method was performed to measure the levels of IL-1β and TNF-α in ovarian tissue. HE method was performed to observe the shape of the ovary. Granular cells were isolated from ovarian tissue, and flow cytometry was performed to measure apoptosis rate and necrosis rate. Immunohistochemistry was performed to measure the positive expression of p-RIP1 in ovarian tissue. Western blot was employed to detect the expression of RIP1-RIP3-MLKL pathway. Results RIP1 specific inhibitor Nec-1 and naringenin could block the phosphorylation and activation of RIP1, inhibit the RIP1-RIP3-MLKL signaling pathway, reduce the inflammation level in PCOS rats, and alleviate the necrosis and apoptosis of ovarian granulosa cells(P<0.05). Z-VAD-fmk could promote the activation of RIP1-RIP3-MLKL pathway, aggravate the apoptosis of ovarian granulosa cells, and partially weaken the anti-apoptosis effect of naringenin(P<0.05). Conclusions Naringenin may inhibit the apoptosis of ovarian granulosa cells in PCOS rats by blocking the activation of the necrotic apoptotic pathway mediated by RIP1-RIP3-MLKL.

Management and treatment of terminal metastatic castration-resistant prostate cancer (mCRPC) remains heavily debated. We sought to investigate the efficacy of programmed cell death 1 (PD-1) inhibitor plus anlotinib as a potential solution for terminal mCRPC and further evaluate the association of genomic characteristics with efficacy outcomes. We conducted a retrospective real-world study of 25 mCRPC patients who received PD-1 inhibitor plus anlotinib after the progression to standard treatments. The clinical information was extracted from the electronic medical records and 22 patients had targeted circulating tumor DNA (ctDNA) next-generation sequencing. Statistical analysis showed that 6 (24.0%) patients experienced prostate-specific antigen (PSA) response and 11 (44.0%) patients experienced PSA reduction. The relationship between ctDNA findings and outcomes was also analyzed. DNA-damage repair (DDR) pathways and homologous recombination repair (HRR) pathway defects indicated a comparatively longer PSA-progression-free survival (PSA-PFS; 2.5 months vs 1.2 months, P = 0.027; 3.3 months vs 1.2 months, P = 0.017; respectively). This study introduces the PD-1 inhibitor plus anlotinib as a late-line therapeutic strategy for terminal mCRPC. PD-1 inhibitor plus anlotinib may be a new treatment choice for terminal mCRPC patients with DDR or HRR pathway defects and requires further investigation.
Male ; Humans ; Prostate-Specific Antigen ; Treatment Outcome ; Prostatic Neoplasms, Castration-Resistant/drug therapy* ; Immune Checkpoint Inhibitors/therapeutic use* ; Retrospective Studies

OBJECTIVE: To investigate whether 3D-printed artificial vertebral body can reduce prosthesis subsidence rate for patients with cervical chordomas, through comparing the rates of prosthesis subsidence between 3D printing artificial vertebral body and titanium mesh for anterior spinal reconstruction after total spondylectomy. METHODS: This was a retrospective analysis of patients who underwent surgical treatment for cervical chordoma at our hospital from March 2005 to September 2019. There were nine patients in the group of 3D artificial vertebral body (3D group), and 15 patients in the group of titanium mesh cage (Mesh group). The patients' characteristics and treatment data were extracted from the medical records, including age, gender, CT hounsfield unit of cervical vertebra and surgical information, such as the surgical segments, time and blood loss of surgery, frequency and degree of prosthesis subsidence after surgery. Radiographic observations of prosthesis subsidence during the follow-up, including X-rays, CT, and magnetic resonance imaging were also collected. SPSS 22.0 was used to analysis the data. RESULTS: There was no significant difference between the two groups in gender, age, CT hounsfield unit, surgical segments, time of surgery, blood loss of posterior surgery and total blood loss. Blood loss of anterior surgery was 700 (300, 825) mL in 3D group and 1 500 (750, 2 800) mL in Mesh group (P < 0.05). The prosthesis subsidence during the follow-up, 3 months after surgery, there was significant difference between the two groups in mild prosthesis subsidence (P < 0.05). The vertebral height of the 3D group decreased less than 1 mm in eight cases (no prosthesis subsidence) and more than 1 mm in one case (mild prosthesis subsidence). The vertebral height of the Mesh group decreased less than 1 mm in five cases (no prosthesis subsidence), and more than 1 mm in eight cases (mild prosthesis subsidence). Two patients did not have X-rays in 3 months after surgery. There was a statistically significant difference between the two groups in the prosthesis subsidence rate at the end of 12 months (P < 0.01). The vertebral height of eight cases in the 3D group decreased less than 1 mm (no prosthesis subsidence) and one case more than 3 mm (severe prosthesis subsidence). Four of the 15 cases in the Mesh group decreased less than 1 mm (no prosthesis subsidence), two cases more than 1 mm (mild prosthesis subsidence), and nine cases more than 3 mm (severe prosthesis subsidence). There was a statistically significant difference between the two groups in the prosthesis subsidence rate at the end of 24 months (P < 0.01). The vertebral height of seven cases in the 3D group decreased less than 1 mm (no prosthesis subsidence), one case more than 3 mm (severe prosthesis subsidence), and one case died with tumor. One case in the Mesh group decreased less than 1 mm (no prosthesis subsidence), one case more than 1 mm (mild prosthesis subsidence), 11 case more than 3 mm (severe prosthesis subsidence), one case died with tumor and one lost the follow-up. Moreover, at the end of 12 months and 24 months, there was significant difference between the two groups in severe prosthesis subsidence rate (P < 0.01). CONCLUSION 3D-printed artificial vertebral body for anterior spinal reconstruction after total spondylectomy for patients with cervical chordoma can provide reliable spinal stability, and reduce the incidence of prosthesis subsidence after 2-year follow-up.
Humans ; Chordoma/surgery* ; Retrospective Studies ; Vertebral Body ; Titanium ; Cervical Vertebrae/surgery* ; Printing, Three-Dimensional ; Spinal Fusion/methods* ; Treatment Outcome

Driven by initiatives of constructing the Four New Disciplines (new engineering, new medical sciences, new agriculture and new liberal arts) for higher education, Biochemistry teaching with ideological and political concerns is critical to the education achievements. Over the past 6 years, FMMU has carried out trials and practices on TCA model in Biochemistry teaching which can serve as a shared formula. TCA is originally an abbreviation for “tricarboxylic acid” cycle, and herein it stands for thinking and teamwork (T), critique (C) and appreciation (A), which hopefully could provide students with moral norms for cognition, science and life. Accordingly, a strategy is proposed to help systematically implement this “TCA” model, which highlights the notion of “3-integration for teaching”, “3-thinking for learning” and 3-step for setting”. Such “TCA”-based ideological and political model is adaptable to various universities in designing advanced teaching activities. In the case of FMMU, we created a “TCA pigeon” ideological and political pattern, with “pigeon” signifying medicine, the Air Force and peace, showing the distinctive features of a military medical university. Meanwhile, we have designed three advanced teaching activities. Specifically, “the magic biochemical-circle”, a shared learning platform that develops thinking abilities with a focus on autonomous learning and personal demonstration; “inter-guidance by basic and clinical teachers”, a heuristic large class that elicits critical thinking on basis of feedback, discussion and iteration; a task-driven “virtual reality (VR) program” enables students to deal with complicated situation and to undertake troubleshooting. The above “TCA pigeon” pattern has shown a generally favorable result among students in developing their skills such as holistic thinking, deep learning, introspecting and self-improvement. Yet, a few problems still occurred in practice and remained to be resolved.

H 1-antihistamines are widely used in the treatment of various allergic diseases, but there are still many challenges in the safe and rational use of H 1-antihistamines in pediatrics, and there is a lack of guidance on the prescription review of H 1-antihistamines for children.In this paper, suggestions are put forward from the indications, dosage, route of administration, pathophysiological characteristics of children with individual difference and drug interactions, so as to provide reference for clinicians and pharmacists.

Objective:To study the actual effect of the use of personal protective equipment of the examined individuals, and provide reference and basis for the correct use of personal protective equipment and the radiological health administrative law enforcement.Methods:From February to June 2022, the imaging department of Qingdao Municipal Hospital selected 170 patients who underwent X-ray imaging examination (oral panoramic, dental radiography, DR photography, CT scanning), including 25 with oral panoramic and dental radiography, 60 with CT scanning and 60 with DR imaging. The thermoluminescent dosimeter was used to detect the ambient dose equivalent at the point of concern for 170 examined individuals who have used personal protective equipment to cover their sensitive parts, and to analyze the data detected at the same point as above when routinely using the same equipment.Results:There was a statistically significant difference in the dose equivalent at the same points inside and outside the lead neckband ( t=-2.23, P<0.05). There was no statistically significant difference in the dose equivalent at the same point inside and outside the lead collar during dental radiography ( P>0.05). During DR photography (chest PA, lateral and lumbar AP), the examined individuals were wearing lead aprons. Among them, there was a statistically significant difference in the dose equivalent at the same points inside and outside the lead aprons of children′s chest PA and adults′ chest PA ( U=10.00, 19.00, P<0.05). There was no statistically significant difference in the dose equivalent at the same points inside and outside the lead aprons of adult′s chest PA and lumbar AP ( P>0.05). When performing CT scan (chest or upper abdomen), there was a statistically significant difference in the dose equivalent at the same points of wrapped lead aprons( U=878.50, 11.00, P<0.05). Conclusions:The correct use of personal protective equipment is a complex technical problem. It is very important to fully and accurately understand the optimization principle of radiation protection and correctly use personal protective equipment for the examined individuals. The administrative punishment of radiation health on the use of personal protective equipment of the examined individuals should be cautious.

During the coronavirus disease (COVID-19) epidemic, there have been concerns about the impact of vaccines on people's fertility, including the fertility of those who are currently preparing for pregnancy and those who might become pregnant in future. However, there is still a lack of research on the effect of the COVID-19 vaccine on male fertility, and it is not surprising that couples and donors have concerns regarding vaccination. In this study, a retrospective cohort study was conducted to examine semen quality before and after receipt of the inactivated COVID-19 vaccine. There were no statistically significant changes in semen parameters (volume, sperm concentration, progressive motility, and total progressive motile count) after two doses of vaccine (all P > 0.05). In summary, our study updates the most recent studies on the effects of the COVID-19 vaccine on male fertility, and the information from this study could be used to guide fertility recommendations for assisted reproductive technology (ART) patients and donors.
COVID-19 ; COVID-19 Vaccines ; Female ; Humans ; Male ; Pregnancy ; Retrospective Studies ; Semen ; Semen Analysis ; Sperm Count ; Sperm Motility ; Spermatozoa ; Vaccination ; Vaccines, Inactivated

OBJECTIVE To prepare curcumin /berberine co -loaded self -microemulsion drug delivery system （CUR/BER- SMEDDS）and evaluate its physicochemical properties and in vitro anti-tumor effects . METHODS Using CUR and BER as model drug，based on the screening of the type of oil phase ，emulsifier，co emulsifier and their mass ratio ，the formulation of CUR/BER - SMEDDS were optimized by central composite design -response surface methodology ，taking particle size and drug loading as evaluation parameters ，with the mass percentage of oil phase and the mass ratio of emulsifier to co emulsifier as factors ，and verification test was conducted . CUR/BER-SMEDDS prepared by optimized formulation were evaluated in terms of physicochemical properties，in vitro dissolution and in vitro anti-tumor effects . RESULTS The optimized formulation of CUR/BER -SMEDDS included that the oil phase was medium chain triglyceride （30.97%），the emulsifier was polyoxyl 40 hydrogenated castor oil （46.77%），the co emulsifier was polyethylene glycol 400（22.26%），and the mass ratio of emulsifier to co emulsifier was 2.10∶1. The validation experiments showed that mean particle size of CUR/BER -SMEDDS was（58.90±5.41）nm，the average drug loading was（94.94±3.87）mg/g，and the relative deviations from the predicted values were －2.90% and －0.14%，respectively. The CUR/ BER-SMEDDS prepared by optimal formulation was light yellow ，clear and transparent liquid after emulsified with water ，and its particles were spherical . The results of dissolution test in vitro showed that after SMEDDS was made ，the cumulative dissolution of CUR in artificial intestinal fluid and artificial gastric fluid and that of BER in artificial intestinal fluid were significantly higher than those of its raw material . Results of in vitro anti-tumor experiment showed that IC 50 values of CUR/BER -SMEDDS for PC -3 cells and DU -145 cells were （17.38±2.84）and（20.89±1.26）μmol/L，which were all lower than those of CUR and EBR significantly （P＜0.05）.CONCLUSIONS The optimized prepar ation process of CUR/BER -SMEDDS is stable and feasible . The drug release of CUR/BER-SMEDDS is more complete than that of single drug，and has stronger anti -prostate cancer effect in vitro .

OBJECTIVE: To explore clinical effect of bridge-link combined fixation system(BCFS) in treating open middle and lower tibial fractures by external fixation. METHODS: From October 2016 to September 2017, 11 patients with open middle and lower tibial fractures were treated with BCFS by external fixation, including 7 males and 4 females aged from 23 to 65 years old with an average of 44.2 years old;the course of disease ranged from 7 to 10 days. All fractures were open, middle and lower tibiofibular fractures. According to AO classification, 5 patients were type A, 5 patients were type B, and 1 patient was type C. All fractures were classified as typeⅡaccording to Gustilo-Anderson classification. The time of fracture healing, postoperative complications were observed, Johner-Wruhs standard were used to evaluate clinical effect. RESULTS: All patients were followed up from 7 to 13 months with an average of 10.1 months. Fracture healing time ranged from 4 to 8 months with an average of 6.2 months. The removal time of BCFS ranged from 5 to 11 months with an average of 7.8 months. No screws loosening and BCFS breakage occurred after operation, while 1 patient occurred infection of proximal and distal tibia after operation which was healed by anti-inflammatory treatment and dressing change. According to Johner-Wruhs standard, 8 patients were excellent and 3 patients good at the latest follow-up. CONCLUSION BCFS could be used to treat open middle and lower tibial fractures by external fixation, which had features of small size, flexible use, solid and elastic fixation. It could not effectively reduce tissue injury and promote fracture healing, but also have advantages of less postoperative complications and better recovery of limb function.
Adult ; Aged ; Bone Plates ; External Fixators ; Female ; Fracture Fixation ; Fracture Fixation, Internal ; Fracture Healing ; Fractures, Open ; Humans ; Male ; Middle Aged ; Tibial Fractures/surgery* ; Treatment Outcome ; Young Adult