1.Expert consensus on cryoablation therapy of oral mucosal melanoma
Guoxin REN ; Moyi SUN ; Zhangui TANG ; Longjiang LI ; Jian MENG ; Zhijun SUN ; Shaoyan LIU ; Yue HE ; Wei SHANG ; Gang LI ; Jie ZHNAG ; Heming WU ; Yi LI ; Shaohui HUANG ; Shizhou ZHANG ; Zhongcheng GONG ; Jun WANG ; Anxun WANG ; Zhiyong LI ; Zhiquan HUNAG ; Tong SU ; Jichen LI ; Kai YANG ; Weizhong LI ; Weihong XIE ; Qing XI ; Ke ZHAO ; Yunze XUAN ; Li HUANG ; Chuanzheng SUN ; Bing HAN ; Yanping CHEN ; Wenge CHEN ; Yunteng WU ; Dongliang WEI ; Wei GUO
Journal of Practical Stomatology 2024;40(2):149-155
Cryoablation therapy with explicit anti-tumor mechanisms and histopathological manifestations has a long history.A large number of clinical practice has shown that cryoablation therapy is safe and effective,making it an ideal tumor treatment method in theory.Previously,its efficacy and clinical application were constrained by the limitations of refrigerants and refrigeration equipment.With the development of the new generation of cryoablation equipment represented by argon helium knives,significant progress has been made in refrigeration efficien-cy,ablation range,and precise temperature measurement,greatly promoting the progression of tumor cryoablation technology.This consensus systematically summarizes the mechanism of cryoablation technology,indications for oral mucosal melanoma(OMM)cryotherapy,clinical treatment process,adverse reactions and management,cryotherapy combination therapy,etc.,aiming to provide reference for carrying out the standardized cryoablation therapy of OMM.
2.Conical beam CT measurement of alveolar bone structure remodeling in patients with skeletal class Ⅲ malocclusion after orthodontic-orthognathic treatment
Qihang ZHAO ; Xin LU ; Lei TONG ; Yonghui SHANG ; Shuai LI ; Wen LIU ; Jianhua ZHOU ; Rongtao YUAN ; Qingyuan GUO
Chinese Journal of Tissue Engineering Research 2024;28(23):3729-3735
BACKGROUND:Most of the studies on combined orthodontic-orthognathic treatment of skeletal class Ⅲ malocclusions have focused on the improvement of the patient's lateral appearance and recovery in the later stages of the treatment,while there are fewer studies observing the microcosmic nature of the alveolar bone remodeling of the lower anterior teeth. OBJECTIVE:To evaluate the therapeutic effect of lower anterior tooth decompensation and alveolar bone remodeling in patients with skeletal class Ⅲ malocclusion before and after orthodontic-orthognathic treatment based on oral X-ray lateral films and oral cone-beam CT. METHODS:From January 2015 to May 2023,15 patients with skeletal class Ⅲ malocclusion who underwent orthodontic-orthognathic surgery at Qingdao Hospital of Rehabilitation University were enrolled.All patients underwent lateral cephalography and cone beam computed tomography before and after treatment.Cephalometric measurement items related to the angle and line distance,lip/lingual bone cracking length(d-La/d-Li)and bone cracking/bone fenestration of the lower anterior teeth before and after treatment were measured. RESULTS AND CONCLUSION:Lateral X-ray films showed that the amount of alveolar bone remodeling after decompensation of the lower anterior teeth showed significant changes compared to before treatment.The root of the tooth moved significantly towards the center of the alveolar bone,and the specific data was closer to normal data,but there were still some differences compared with normal individuals.Based on the cone-beam CT measurement,the bone cracking/bone fenestration length and width of the alveolar bone were improved in almost all the teeth after orthodontic-orthognathic combined treatment,alveolar bone remodeling in some teeth even reached the level of healthy individuals.Before treatment,most patients often experienced bone fenestration/cracking on the lip/lingual side of the lower incisor due to compensatory tooth growth.However,during the preoperative orthodontic stage,decompensation triggered alveolar bone remodeling and significant changes in tooth angle.Preoperative orthodontic treatment caused the upper anterior teeth to retract and the lower anterior teeth to tilt and control the root,but the amount of decompensation before surgery was often insufficient.In the orthognathic surgery stage,the jaw was removed through the positioning guide plate,the maxilla moved forward,and the mandible retreated.During the postoperative orthodontic process,the effect of fine adjustment was better.Although there is a certain degree of recurrence trend in the position of teeth and jawbones,the postoperative orthodontic treatment is closer to the normal value.
3.Expert consensus on surgical treatment of oropharyngeal cancer
China Anti-Cancer Association Head and Neck Oncology Committee ; China Anti-Cancer Association Holistic Integrative Oral Cancer on Preventing and Screen-ing Committee ; Min RUAN ; Nannan HAN ; Changming AN ; Chao CHEN ; Chuanjun CHEN ; Minjun DONG ; Wei HAN ; Jinsong HOU ; Jun HOU ; Zhiquan HUANG ; Chao LI ; Siyi LI ; Bing LIU ; Fayu LIU ; Xiaozhi LV ; Zheng-Hua LV ; Guoxin REN ; Xiaofeng SHAN ; Zhengjun SHANG ; Shuyang SUN ; Tong JI ; Chuanzheng SUN ; Guowen SUN ; Hao TIAN ; Yuanyin WANG ; Yueping WANG ; Shuxin WEN ; Wei WU ; Jinhai YE ; Di YU ; Chunye ZHANG ; Kai ZHANG ; Ming ZHANG ; Sheng ZHANG ; Jiawei ZHENG ; Xuan ZHOU ; Yu ZHOU ; Guopei ZHU ; Ling ZHU ; Susheng MIAO ; Yue HE ; Jugao FANG ; Chenping ZHANG ; Zhiyuan ZHANG
Journal of Prevention and Treatment for Stomatological Diseases 2024;32(11):821-833
With the increasing proportion of human papilloma virus(HPV)infection in the pathogenic factors of oro-pharyngeal cancer,a series of changes have occurred in the surgical treatment.While the treatment mode has been im-proved,there are still many problems,including the inconsistency between diagnosis and treatment modes,the lack of popularization of reconstruction technology,the imperfect post-treatment rehabilitation system,and the lack of effective preventive measures.Especially in terms of treatment mode for early oropharyngeal cancer,there is no unified conclu-sion whether it is surgery alone or radiotherapy alone,and whether robotic minimally invasive surgery has better func-tional protection than radiotherapy.For advanced oropharyngeal cancer,there is greater controversy over the treatment mode.It is still unclear whether to adopt a non-surgical treatment mode of synchronous chemoradiotherapy or induction chemotherapy combined with synchronous chemoradiotherapy,or a treatment mode of surgery combined with postopera-tive chemoradiotherapy.In order to standardize the surgical treatment of oropharyngeal cancer in China and clarify the indications for surgical treatment of oropharyngeal cancer,this expert consensus,based on the characteristics and treat-ment status of oropharyngeal cancer in China and combined with the international latest theories and practices,forms consensus opinions in multiple aspects of preoperative evaluation,surgical indication determination,primary tumor re-section,neck lymph node dissection,postoperative defect repair,postoperative complication management prognosis and follow-up of oropharyngeal cancer patients.The key points include:① Before the treatment of oropharyngeal cancer,the expression of P16 protein should be detected to clarify HPV status;② Perform enhanced magnetic resonance imaging of the maxillofacial region before surgery to evaluate the invasion of oropharyngeal cancer and guide precise surgical resec-tion of oropharyngeal cancer.Evaluating mouth opening and airway status is crucial for surgical approach decisions and postoperative risk prediction;③ For oropharyngeal cancer patients who have to undergo major surgery and cannot eat for one to two months,it is recommended to undergo percutaneous endoscopic gastrostomy before surgery to effectively improve their nutritional intake during treatment;④ Early-stage oropharyngeal cancer patients may opt for either sur-gery alone or radiation therapy alone.For intermediate and advanced stages,HPV-related oropharyngeal cancer general-ly prioritizes radiation therapy,with concurrent chemotherapy considered based on tumor staging.Surgical treatment is recommended as the first choice for HPV unrelated oropharyngeal squamous cell carcinoma(including primary and re-current)and recurrent HPV related oropharyngeal squamous cell carcinoma after radiotherapy and chemotherapy;⑤ For primary exogenous T1-2 oropharyngeal cancer,direct surgery through the oral approach or da Vinci robotic sur-gery is preferred.For T3-4 patients with advanced oropharyngeal cancer,it is recommended to use temporary mandibu-lectomy approach and lateral pharyngotomy approach for surgery as appropriate;⑥ For cT1-2N0 oropharyngeal cancer patients with tumor invasion depth>3 mm and cT3-4N0 HPV unrelated oropharyngeal cancer patients,selective neck dissection of levels ⅠB to Ⅳ is recommended.For cN+HPV unrelated oropharyngeal cancer patients,therapeutic neck dissection in regions Ⅰ-Ⅴ is advised;⑦ If PET-CT scan at 12 or more weeks after completion of radiation shows intense FDG uptake in any node,or imaging suggests continuous enlargement of lymph nodes,the patient should undergo neck dissection;⑧ For patients with suspected extracapsular invasion preoperatively,lymph node dissection should include removal of surrounding muscle and adipose connective tissue;⑨ The reconstruction of oropharyngeal cancer defects should follow the principle of reconstruction steps,with priority given to adjacent flaps,followed by distal pedicled flaps,and finally free flaps.The anterolateral thigh flap with abundant tissue can be used as the preferred flap for large-scale postoperative defects.
4.Endoscopic Submucosal Dissection versus Surgical Treatment for Early Esophagogastric Junction Adenocarcinoma:Propensity Score Matching Analysis
Xue-Tong ZHANG ; Ying-Ling LIU ; Chao XU ; Si-Qing SHANG ; Kai-Guang ZHANG
Modern Interventional Diagnosis and Treatment in Gastroenterology 2024;29(4):422-428
Objective To compare the clinical efficacy and prognosis of endoscopic submucosal dissection(ESD)and surgical methods in the treatment of early esophagogastric junction adenocarcinoma(AEG),and to analyze factors influencing prognosis.Methods Hospitalized patients with early AEG who underwent ESD or surgical treatment at Anhui Provincial Hospital from January 2010 to December 2022 were collected.Among them,186 patients underwent ESD and 364 patients underwent surgical treatment.Propensity score matching was used with a ratio of 1∶1,with 164 patients in each group.Clinical outcomes,survival outcomes,and postoperative complications were compared before and after matching.Factors influencing mortality and recurrence in EGJ patients were analyzed.Results 1.Before and after matching,the ESD group had lower surgical time,hospital stay,hospital costs,intraoperative bleeding volume,and adverse events compared to the surgical group(P<0.001).2.The matched ESD group had 1-,3-,and 5-year overall survival rates of 99.5%,94.5%,and 90.2%,respectively,while the surgical group had rates of 100%,99.4%,and 97.5%for the same periods.The 1-,3-,and 5-year recurrence-free survival rates in the matched ESD group were 99.5%,96.3%,and 93.4%,respectively,compared to 100%,98.6%,and 92.5%in the surgical group.Kaplan-Meier survival analysis before and after matching showed no significant difference in overall survival and recurrence-free survival between the two groups(P>0.05).3.Age,poor differentiation,and vascular invasion were independent risk factors for OS;age and tumor size were independent risk factors for RFS.Conclusion Patients with early AEG undergoing ESD or surgical treatment have consistent clinical outcomes.ESD can be considered an effective and safe treatment for early AEG.
5.Application of absorbable anchor combined with Kirschner wire in reconstruction of extension function of old mallet finger.
Dongdong CHENG ; Zhengbing ZHOU ; Zixuan LIN ; Hui LIU ; Fan YANG ; Jin WANG ; Shang GUO
Chinese Journal of Reparative and Reconstructive Surgery 2023;37(4):443-446
OBJECTIVE:
To investigate the feasibility and effectiveness of absorbable anchor combined with Kirschner wire fixation in the reconstruction of extension function of old mallet finger.
METHODS:
Between January 2020 and January 2022, 23 cases of old mallet fingers were treated. There were 17 males and 6 females with an average age of 42 years (range, 18-70 years). The cause of injury included sports impact injury in 12 cases, sprain in 9 cases, and previous cut injury in 2 cases. The affected finger included index finger in 4 cases, middle finger in 5 cases, ring finger in 9 cases, and little finger in 5 cases. There were 18 patients of tendinous mallet fingers (Doyle type Ⅰ), 5 patients were only small bone fragments avulsion (Wehbe type ⅠA). The time from injury to operation was 45-120 days, with an average of 67 days. The patients were treated with Kirschner wire to fix the distal interphalangeal joint in a mild back extension position after joint release. The insertion of extensor tendon was reconstructed and fixed with absorbable anchors. After 6 weeks, the Kirschner wire was removed, and the patients started joint flexion and extension training.
RESULTS:
The postoperative follow-up ranged from 4 to 24 months (mean, 9 months). The wounds healed by first intention without complications such as skin necrosis, wound infection, and nail deformity. The distal interphalangeal joint was not stiff, the joint space was good, and there was no complication such as pain and osteoarthritis. At last follow-up, according to Crawford function evaluation standard, 12 cases were excellent, 9 cases were good, 2 cases were fair, and the good and excellent rate was 91.3%.
CONCLUSION
Absorbable anchor combined with Kirschner wire fixation can be used to reconstruct the extension function of old mallet finger, which has the advantages of simple operation and less complications.
Male
;
Female
;
Humans
;
Adult
;
Bone Wires
;
Fracture Fixation, Internal
;
Finger Injuries/surgery*
;
Fractures, Bone/surgery*
;
Tendon Injuries/surgery*
;
Fingers
;
Treatment Outcome
;
Finger Joint/surgery*
6.Pure single-port lumpectomy non-lipolysis breast-conserving surgery in the treatment of early-stage breast cancer
Qianhe ZHOU ; Yuefeng SHANG ; Tong LIU ; Bo LEI ; Runze SHI ; Jianyu LIU ; Zhigao LI
Chinese Journal of Endocrine Surgery 2023;17(2):143-149
Objective:To summarize the clinical data and experience of pure single-port lumpectomy non-lipolysis breast-conserving surgery (PSLN-BCS) in patients with early-stage breast cancer.Methods:A retrospective analysis was conducted on 400 patients who underwent breast-conserving surgery for early-stage breast cancer in the Second Department of Breast Surgery at Harbin Medical University Cancer Hospital from Jan. 2022 to Jan. 2023. Patients were divided into two groups: PSLN-BCS group ( n=200) and conventional breast-conserving surgery (C-BCS) group ( n=200). The surgical time, intraoperative blood loss, postoperative drainage within three days, and short-term (3 months to 6 months after surgery) complications, including the incidence of residual fluid after drain removal and incision infection were observed. Long-term (6 months after surgery) complications, including the incidence of skin and pectoralis major muscle adhesions in the surgical area and cosmetic results after breast-conserving surgery, were also evaluated. Statistical analysis was performed using R language, and quantitative data were expressed as mean ± standard deviation ( ± s) and analyzed using t-test, while count data were analyzed using χ2 test. A p-value less than 0.05 was considered statistically significant. Results:PSLN-BCS had a longer average surgical time than C-BCS (198.341min vs 62.961min, P<0.001, 95% CI:132.028 vs 138.732). PSLN-BCS had less intraoperative bleeding (18.824 ml vs 22.627 ml, P=0.003, 95% CI: -6.294 vs -1.311) and lower postoperative drainage volume (346.157 ml vs 406.191 ml, P<0.001, 95% CI: -70.571-a-49.496). There were no significant differences in short-term postoperative complications such as subcutaneous fluid accumulation ( χ2=2.33, P=0.127) or incisional infection ( χ2=0.14, P=0.708) between the two groups. The incidence of skin and muscle adhesions in the surgical area was lower in patients who underwent PSLN-BCS at 6 months postoperatively ( χ2=11.58, P<0.001). Patients who received PSLN-BCS achieved better cosmetic outcomes, with a statistically significant difference ( χ2=273.00, P<0.001) compared to those who received C-BCS. Conclusion:Pure single-port lumpectomy non-lipolysis breast-conserving surgery is a safe and effective treatment option for early-stage breast cancer and can be considered as a surgical option for patients with cosmetic requirements.
7.Preliminary study on the mechanism underlying the ecological isolation of Oncomelania hupensis populations in Changde City
Shen CHEN ; Lei DUAN ; Shengming LI ; Jie ZHOU ; Yingcai ZHOU ; Yuanzhi YANG ; Mengli LIU ; Yanren WANG ; Shang XIA ; Jing XU ; Shan LÜ
Chinese Journal of Schistosomiasis Control 2023;35(2):147-154
Objective To investigate ecological isolation between Oncomelania hupensis snail populations in hilly regions and marshland and lake regions in Yuanjiang valley, Changde City, Hunan Province, and to unravel its underlying mechanisms. Methods Taoyuan County, Shimen County, Linli County and Lixian County in Changde City were selected as snail sampling sites in hilly regions, and Lixian County, Jinshi City, West Lake Administration District, Hanshou County and Dingcheng District were selected as snail sampling sites in marshland and lake areas. Cytochrome C oxidase 1 (cox 1) gene was amplified in snail samples and sequenced. The genetic sequences of O. hupensis snails were aligned using the software MEGA 11, and the haplotypes of O. hupensis snails were determined using the software DNASP 5.10.01. The phylogenetic tree was generated using Bayesian inference with the software MrBayes 3.2, and analysis of molecular variance (AMOVA) was performed to analyze the source of genetic divergence and estimate the genetic divergence index (FST) among snail populations with the software Arlequin 3.5.2.2. The genetic barrier among 11 O. hupensis snail populations was estimated using the Monmonier algorithm of adegenet toolkit in R package. The settings with “land in winter and water in summer” in the Yuanjian River section were divided into two categories according to the upstream and downstream, and the areas with “land in winter and water in summer” in the upstream and downstream were transformed into raster data, and then loaded into the software Fragstats 4 for analysis of landscape indicators. The trends in changes of digital elevation were extracted from the Yuanjiang River section based on the digital elevation model, and made three-dimensional visualization using the R package. Results The mitochondrial cox 1 gene were amplified in 165 O. hupensis snais from 11 sampling sites and sequenced, and a total of 152 valid gene sequences were obtained, with 46 haplotypes or 9 populations determined. No haplotype was shared in snails between Taoyuan County and Dingcheng District and Hanshou County along the downstream of the Yuanjiang River. The total area of settings with “land in winter and water in summer” was 617.66 hm2 in the upsteram of the Yuanjiang River, which consisted of 473 patches, with each patch measuring 1.31 hm2, the largest area index of 0.735 2, the landscape division index of 0.999 9, and the landscape shape index of 45.293 7. The total area of settings with “land in winter and water in summer” was 9 956.92 hm2 in the downstream of the Yuanjiang River, which consisted of 771 patches, with each patch measuring 12.91 hm2, the largest area index of 97.839 9, the landscape division index of 0.042 7, and the landscape shape index of 7.249 6. The area of settings with “land in winter and water in summer” was much larger in the downstream than that in the upstream of the Yuanjiang River, and the stronger landscape connectivity and non-remarkable alteration of riverbed elevation provided suitable habitats for snail breeding. Conclusion The hydrological and environmental characteristics of the upstream of the Yuanjiang River restrain the breeding and spread of O. hupensis, resulting in ecological isolation between Oncomelania hupensis in Taoyuan County and those in the downstream of Yuanjiang River.
8.Neuroglobin Facilitates Neuronal Oxygenation through Tropic Migration under Hypoxia or Anemia in Rat: How Does the Brain Breathe?
Chun-Yang LI ; Hai-Feng JIANG ; Li LI ; Xiao-Jing LAI ; Qian-Rong LIU ; Shang-Bin YU ; Cheng-La YI ; Xiao-Qian CHEN
Neuroscience Bulletin 2023;39(10):1481-1496
The discovery of neuroglobin (Ngb), a brain- or neuron-specific member of the hemoglobin family, has revolutionized our understanding of brain oxygen metabolism. Currently, how Ngb plays such a role remains far from clear. Here, we report a novel mechanism by which Ngb might facilitate neuronal oxygenation upon hypoxia or anemia. We found that Ngb was present in, co-localized to, and co-migrated with mitochondria in the cell body and neurites of neurons. Hypoxia induced a sudden and prominent migration of Ngb towards the cytoplasmic membrane (CM) or cell surface in living neurons, and this was accompanied by the mitochondria. In vivo, hypotonic and anemic hypoxia induced a reversible Ngb migration toward the CM in cerebral cortical neurons in rat brains but did not alter the expression level of Ngb or its cytoplasm/mitochondria ratio. Knock-down of Ngb by RNA interference significantly diminished respiratory succinate dehydrogenase (SDH) and ATPase activity in neuronal N2a cells. Over-expression of Ngb enhanced SDH activity in N2a cells upon hypoxia. Mutation of Ngb at its oxygen-binding site (His64) significantly increased SDH activity and reduced ATPase activity in N2a cells. Taken together, Ngb was physically and functionally linked to mitochondria. In response to an insufficient oxygen supply, Ngb migrated towards the source of oxygen to facilitate neuronal oxygenation. This novel mechanism of neuronal respiration provides new insights into the understanding and treatment of neurological diseases such as stroke and Alzheimer's disease and diseases that cause hypoxia in the brain such as anemia.
Rats
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Animals
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Neuroglobin/metabolism*
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Globins/metabolism*
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Nerve Tissue Proteins/metabolism*
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Neurons/metabolism*
;
Hypoxia/metabolism*
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Brain/metabolism*
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Oxygen
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Anemia/metabolism*
;
Adenosine Triphosphatases/metabolism*
9.Treatment Outcomes in COVID-19 Patients with Brucellosis: Case Series in Heilongjiang and Systematic Review of Literature.
Man Li YANG ; Jing Ya WANG ; Xing Yu ZONG ; Li GUAN ; Hui Zhen LI ; Yi Bai XIONG ; Yu Qin LIU ; Ting LI ; Xin Yu JI ; Xi Yu SHANG ; Hui Fang ZHANG ; Yang GUO ; Zhao Yuan GONG ; Lei ZHANG ; Lin TONG ; Ren Bo CHEN ; Yi Pin FAN ; Jin QIN ; Fang WANG ; Gang LIN ; Nan Nan SHI ; Yan Ping WANG ; Yan MA
Biomedical and Environmental Sciences 2023;36(10):930-939
OBJECTIVE:
Clinical characteristics and outcome in COVID-19 with brucellosis patients has not been well demonstrated, we tried to analyze clinical outcome in local and literature COVID-19 cases with brucellosis before and after recovery.
METHODS:
We retrospectively collected hospitalization data of comorbid patients and prospectively followed up after discharge in Heilongjiang Infectious Disease Hospital from January 15, 2020 to April 29, 2022. Demographics, epidemiological, clinical symptoms, radiological and laboratory data, treatment medicines and outcomes, and follow up were analyzed, and findings of a systematic review were demonstrated.
RESULTS:
A total of four COVID-19 with brucellosis patients were included. One patient had active brucellosis before covid and 3 patients had nonactive brucellosis before brucellosis. The median age was 54.5 years, and all were males (100.0%). Two cases (50.0%) were moderate, and one was mild and asymptomatic, respectively. Three cases (75.0%) had at least one comorbidity (brucellosis excluded). All 4 patients were found in COVID-19 nucleic acid screening. Case C and D had only headache and fever on admission, respectively. Four cases were treated with Traditional Chinese medicine, western medicines for three cases, no adverse reaction occurred during hospitalization. All patients were cured and discharged. Moreover, one case (25.0%) had still active brucellosis without re-positive COVID-19, and other three cases (75.0%) have no symptoms of discomfort except one case fell fatigue and anxious during the follow-up period after recovery. Conducting the literature review, two similar cases have been reported in two case reports, and were both recovered, whereas, no data of follow up after recovery.
CONCLUSION
These cases indicate that COVID-19 patients with brucellosis had favorable outcome before and after recovery. More clinical studies should be conducted to confirm our findings.
Female
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Humans
;
Male
;
Middle Aged
;
Brucellosis
;
COVID-19
;
Retrospective Studies
;
SARS-CoV-2
;
Treatment Outcome
;
Case Reports as Topic
10.Inhibitory effect and molecular mechanism of sinomenine on human hepatocellular carcinoma HepG2 and SK-HEP-1 cells.
Ying-Ying TIAN ; Bei-Bei MA ; Xin-Yue ZHAO ; Chuang LIU ; Yi-Lin LI ; Shang-Yue YU ; Shi-Qiu TIAN ; Hai-Luan PEI ; Ying-Nan LYU ; Ze-Ping ZUO ; Zhi-Bin WANG
China Journal of Chinese Materia Medica 2023;48(17):4702-4710
This study aimed to investigate the effect and molecular mechanism of sinomenine on proliferation, apoptosis, metastasis, and combination with inhibitors in human hepatocellular carcinoma HepG2 cells and SK-HEP-1 cells. The effect of sinomenine on the growth ability of HepG2 and SK-HEP-1 cells were investigated by CCK-8 assay, colony formation assay, and BeyoClick~(TM) EdU-488 staining. The effect of sinomenine on DNA damage was detected by immunofluorescence assay, and the effect of sinomenine on apoptosis of human hepatocellular carcinoma cells was clarified by Hoechst 33258 staining and CellEvent~(TM) Cystein-3/7Green ReadyProbes~(TM) reagent assay. Cell invasion assay and 3D tumor cell spheroid invasion assay were performed to investigate the effect of sinomenine on the invasion ability of human hepatocellular carcinoma cells in vitro. The effect of sinomenine on the regulation of protein expression related to the protein kinase B(Akt)/mammalian target of rapamycin(mTOR)/signal transducer and activator of transcription 3(STAT3) signaling pathway in HepG2 and SK-HEP-1 cells was examined by Western blot. Molecular docking was used to evaluate the strength of affinity of sinomenine to the target cysteinyl aspartate specific proteinase-3(caspase-3) and STAT3, and combined with CCK-8 assay to detect the changes in cell viability after combination with STAT3 inhibitor JSI-124 in combination with CCK-8 assay. The results showed that sinomenine could significantly reduce the cell viability of human hepatocellular carcinoma cells in a concentration-and time-dependent manner, significantly inhibit the clonogenic ability of human hepatocellular carcinoma cells, and weaken the invasive ability of human hepatocellular carcinoma cells in vitro. In addition, sinomenine could up-regulate the cleaved level of poly ADP-ribose polymerase(PARP), a marker of apoptosis, and down-regulate the protein levels of p-Akt, p-mTOR, and p-STAT3 in human hepatocellular carcinoma cells. Molecular docking results showed that sinomenine had good affinity with the targets caspase-3 and STAT3, and the sensitivity of sinomenine to hepatocellular carcinoma cells was diminished after STAT3 was inhibited. Therefore, sinomenine can inhibit the proliferation and invasion of human hepatocellular carcinoma cells and induce apoptosis, and the mechanism may be attributed to the activation of caspase-3 signaling and inhibition of the Akt/mTOR/STAT3 pathway. This study can provide a new reference for the in-depth research and clinical application of sinomenine and is of great significance to further promote the scientific development and utilization of sinomenine.
Humans
;
Carcinoma, Hepatocellular/genetics*
;
Proto-Oncogene Proteins c-akt/metabolism*
;
Caspase 3/metabolism*
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Liver Neoplasms/genetics*
;
Molecular Docking Simulation
;
Sincalide/pharmacology*
;
Cell Line, Tumor
;
Cell Proliferation
;
Hep G2 Cells
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TOR Serine-Threonine Kinases/metabolism*
;
Apoptosis


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