BACKGROUND:Chondrocyte apoptosis is an important factor in the development of osteoarthritis,and Complanatoside A has a flavonoid effect,which can inhibit apoptosis of various cells,but its effect on chondrocyte apoptosis and the mechanism of action are not clear. OBJECTIVE:To investigate the intrinsic association and mechanism of Complanatoside A in chondrocyte apoptosis based on the Wnt/β-catenin signaling pathway. METHODS:(1)The cartilage tissues of the femur and tibia transected during knee arthroplasty were collected,and chondrocytes were isolated,cultured in vitro,and identified.(2)Cell counting kit-8 was used to detect the optimal intervention concentration of Complanatoside A in the concentration range of 0-160 μmol/L.(3)Chondrocytes were divided into blank group,sodium nitroprusside(1.5 mmol/L)-induced group,and sodium nitroprusside(1.5 mmol/L)+Complanatoside A(5 μmol/L)group.The viability and apoptosis rate of the cells in each group were detected by cell counting kit-8 and flow cytometry.The expression of type Ⅱ collagen and SOX9 was detected by immunofluorescence staining.The expression of apoptosis-related proteins and Wnt/β-catenin pathway proteins was detected by western blot assay. RESULTS AND CONCLUSION:The cells extracted in vitro were cultured and stained,and were clearly identified as chondrocytes.Complanatoside A had no obvious cytotoxicity to chondrocytes in the concentration range of 0-80 μmol/L,and significantly improved the chondrocyte viability in the concentration range of 2.5-10 μmol/L,especially when the concentration was 5 μmol/L.The apoptotic rate of chondrocytes was higher in the sodium nitroprusside-induced group than the blank control group,while the apoptotic rate was lower in the sodium nitroprusside+Complanatoside A group than the sodium nitroprusside-induced group.The fluorescence intensity of type Ⅱ collagen and SOX9 in chondrocytes was weaker in the sodium nitroprusside-induced group than the blank control group,while the fluorescence intensity of type Ⅱ collagen and SOX9 in the sodium nitroprusside+Complanatoside A group was higher than that of the sodium nitroprusside-induced group.In the sodium nitroprusside-induced group,the protein expression of Bax,Caspase-3,matrix metalloproteinase 13,Wnt3a,Wnt5a and β-catenin was higher than that of the blank control group,while the protein expression of Bcl-2 was lower than that of the blank control group.In the sodium nitroprusside+Complanatoside A group,except for the protein expression of Bcl-2 which was higher than that of the sodium nitroprusside-induced group,the expression of the other aforementioned proteins was lower than that of the sodium nitroprusside-induced group.To conclude,Complanatoside A has a certain inhibitory effect on chondrocyte apoptosis,which could regulate apoptosis-related proteins and promote the expression of chondrocyte regulatory factors,and presumably might play a role through inhibiting the Wnt/β-catenin signaling pathway.

ObjectiveTo construct a comprehensive evaluation indicator system for clinical practice guidelines of traditional Chinese medicine （TCM） that is scientific， systematic， and reflects the characteristics of TCM. MethodsA systematic search was conducted in Chinese and English databases， including CNKI， Wanfang， VIP， SinoMed， PubMed， Embase， and Cochrane Library， to include literature on domestic and international guideline evaluation tools and TCM-related research. Document analysis and CiteSpace were utilized for keyword co-occurrence and clustering analysis. ResultsA total of 65 relevant studies were included， from which seven core thematic domains were identified. Based on the research objectives， a two-step construction strategy was adopted： first， an external evaluation framework was established by referencing international tools to cover methodological rigor and procedural standardization； second， an internal evaluation framework was developed to reflect the distinctive features of TCM clinical practice， including syndrome differentiation and efficacy feedback. Through expert consensus， the indicator system was refined， resulting in a dual-layered structure comprising 8 primary indicators， 22 secondary indicators， and 62 evaluation criteria. ConclusionThe comprehensive evaluation system for TCM clinical practice guidelines， based on bibliometric analysis and core element extraction， integrates both theoretical integrity and practical applicability. This study provides a preliminary research foundation for further optimization， validation， and development of a refined comprehensive evaluation system.

The paper introduces Professor LIU Xing's clinical experience and characteristics of integrative acupuncture and medication in treatment of primary trigeminal neuralgia (PTN). It is believed that the essential pathogenesis of PTN is pathogenic wind, and qi and blood obstruction results from invasion of pathogenic wind. Hence, dispelling wind is the key principle of treatment. Palpation is done at first in the neck, face and buccal mucosal region to detect the masses in treatment. Acupotomy is operated at the masses distributed at Shangguan (GB3), Xiaguan (ST7) and the white line of buccal mucosa, so as to release masses. Additionally, five-wind points (Fengfu [GV16], bilateral Fengchi [GB20], Yifeng [TE17], Bingfeng [SI12] and Fengmen [BL12]), three-nape points (bilateral Naokong [GB19], Tianzhu [BL10] and Jianjing [GB21]) and three-governor-vessel points (Baihui [GV20], Zhiyang [GV9] and Yintang [GV24⁺]) are selected to dispel wind and stop pain. Besides, herbal decoction (wu feng tang) and blood-letting at ear apex are administered in combination. The integration of acupuncture and medication obtains a holistic effect on PTN by dispelling wind pathogen, and promoting qi and blood circulation.
Humans ; Trigeminal Neuralgia/drug therapy* ; Acupuncture Therapy ; Acupuncture Points ; Female ; Male ; Middle Aged ; Drugs, Chinese Herbal/administration & dosage* ; Combined Modality Therapy ; Adult ; Aged

Metastatic dissemination is the major cause of death from breast-cancer (BC). Fusobacterium nucleatum (F.n) is widely enriched in BC and has recently been identified as one of the high-risk factors for promoting BC metastasis. Here, with an experimental model, we demonstrated that intratumoral F.n induced BC aggressiveness by transcriptionally activating Epithelial-mesenchymal transition-associated genes. Therefore, the F.n may be a potential target to prevent metastasis. Given the fact that cancer-associated fibroblasts (CAFs) are abundant in BC and located near blood vessels, we report an optogenetic system that drives CAF to in situ produce human antibacterial peptide LL37, with the characteristics of biosafety and freely intercellular trafficking, for depleting intratumoral F.n, leading to a 72.1% reduction in lung metastatic nodules number without affecting the balance of the systemic flora. Notably, mild photothermal treatment was found that could normalize CAF, contributing to synergistically inhibiting BC metastasis. In addition, the system can also simultaneously encode a gene of TNF-related apoptosis-inducing ligand to suppress the primary tumor. Together, our study highlights the potential of local elimination of tumor pathogenic bacteria to prevent BC metastasis.

Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder worldwide, causing dementia and affecting millions of individuals. One prominent characteristic in the brains of AD patients is glucose hypometabolism. In the context of galactose metabolism, intracellular glucose levels are heightened. Galactose mutarotase (GALM) plays a crucial role in maintaining normal galactose metabolism by catalyzing the conversion of β-D-galactose into α-D-galactose (α-D-G). The latter is then converted into glucose-6-phosphate, improving glucose metabolism levels. However, the involvement of GALM in AD progression is still unclear. In the present study, we found that the expression of GALM was significantly increased in AD patients and model mice. Genetic knockdown of GALM using adeno-associated virus did not change the expression of amyloid precursor protein (APP) and APP-cleaving enzymes including a disintegrin and metalloprotease 10 (ADAM10), β-site APP-cleaving enzyme 1 (BACE1), and presenilin-1 (PS1). Interestingly, genetic overexpression of GALM reduced APP and Aβ deposition by increasing the maturation of ADAM10, although it did not alter the expression of BACE1 and PS1. Further electrophysiological and behavioral experiments showed that GALM overexpression significantly ameliorated the deficits in hippocampal CA1 long-term potentiation (LTP) and spatial learning and memory in AD model mice. Importantly, direct α-D-G (20 mg/kg, i.p.) also inhibited Aβ deposition by increasing the maturation of ADAM10, thereby improving hippocampal CA1 LTP and spatial learning and memory in AD model mice. Taken together, our results indicate that GALM shifts APP processing towards α-cleavage, preventing Aβ generation by increasing the level of mature ADAM10. These findings indicate that GALM may be a potential therapeutic target for AD, and α-D-G has the potential to be used as a dietary supplement for the prevention and treatment of AD.
Animals ; ADAM10 Protein/metabolism* ; Alzheimer Disease/pathology* ; Amyloid Precursor Protein Secretases/metabolism* ; Disease Models, Animal ; Humans ; Mice ; Amyloid beta-Peptides/metabolism* ; Male ; Mice, Transgenic ; Membrane Proteins/metabolism* ; Cognitive Dysfunction/pathology* ; Mice, Inbred C57BL ; Amyloid beta-Protein Precursor/metabolism* ; Female ; Hippocampus/metabolism* ; Long-Term Potentiation/physiology*

Objective:To investigate the related risk factors of surgical appendectomy after endoscopic retrograde appendicitis therapy (ERAT) in children.Methods:From September 2019 to November 2023 at the Children's Hospital Affiliated to Shandong University,the data from all related children with appendectomy after ERAT were analyzed. The general situation and main clinical manifestations of the children were collected. According to the effect of ERAT,the patients were divided into transfer to surgical group and appendicitis recurrence group by the reasons and time of transfer to surgical treatment. The indexes such as ERAT and reoperation process and pathological types of appendix after operation were collected,and the clinical experience was summarized.Results:Among the 242 children who underwent ERAT,32 cases underwent appendectomy again,including 19 males and 13 females,with an average age of（9.16±2.77）years,and the reoperation rate was 13.2%. The clinical manifestation was abdominal pain (32 cases,100.0%),mainly right lower abdominal pain (28 cases,87.5%),and the main duration was less than 3 months (30 cases,93.8%). Abdominal ultrasound or CT before ERAT mainly indicated appendicitis (11 cases,34.4%) and appendicitis complicated with appendiceal calculus (11 cases,34.4%). There were 9 children in transferred to surgical group,of which 5 cases were transferred to surgery because of ERAT intubation failure,and 4 cases were transferred to surgery because of appendix perforation or abscess. Postoperative pathology showed acute suppurative appendicitis in 5 cases and acute gangrenous appendicitis in 4 cases. There were 23 children in appendicitis recurrence group,whose abdominal pain was relieved after ERAT,but their symptoms were repeated after discharge. After clinical evaluation,they were diagnosed as recurrent appendicitis and underwent surgical appendectomy. Most of them were reoperated within 6 months after ERAT (21 cases,91.3%).Postoperative pathology was mainly chronic appendicitis (10 cases,43.5%).Conclusion:Acute suppurative appendicitis and acute gangrenous appendicitis are prone to catheterization or endoscopic failure during ERAT,and there is a high risk of surgical transfer. ERAT may relieve the symptoms of chronic appendicitis in children. If the symptoms are repeated,surgery is still needed to remove the appendix.

Objective To investigate the effect of very-long-chain saturated fatty acids on Tau protein phosphorylation and membrane fluidity in human neuroblastoma SH-SY5Y cells,and to explore its role in the pathogenesis of Alzheimer's disease(AD).Methods Human neuroblastoma SH-SY5Y cells in logarithmic growth phase were randomly divided into control group,C22∶0 group,and C24:0 group.Cells in the control group were routinely cultured,while cells in the C22:0 and C24:0 groups were treated with culture medium containing 10 μmol·L-1very-long-chain saturated fatty acids C22:0 and C24:0,respectively.After 24 hours of incubation,cells were collected.The expression levels of total Tau protein,phosphorylated Tau protein at serine 396 site(p-Tau-ser396),glycogen synthase kinase 3β(GSK-3β),and phosphorylated GSK-3 β protein at serine 9 site(p-GSK-3β-Ser9)in cells of each group were detected by using Western blot.The malondialdehyde(MDA)level in cells of each group was determined by using the thiobarbituric acid method.The fluorescence recovery rate and diffusion coefficient of cell membranes were measured by using fluorescence recovery after photobleaching technique,and the fluidity of cell membranes was evaluated.Results The total Tau protein level in SH-SY5Y cells showed no statistically significant difference among the three groups(F=1.807,P＞0.05).However,there was a statistically significant difference in the level of p-Tau-ser396 in SH-SY5Y cells among the three groups(F=18.397,P＜0.05).Specifically,the level of p-Tau-ser396 in SH-SY5Y cells in the C22:0 and C24:0 groups was significantly higher than that in the control group(P＜0.05),and the level of p-Tau-ser396 in SH-SY5Y cells in the C24:0 group was significantly higher than that in the C22:0 group(P＜0.05).There was no statistically significant difference in the GSK-3 β protein level in SH-SY5Y cells among the three groups(F=0.351,P＞0.05).However,there was a statistically significant difference in the level of p-GSK-3β-Ser9 in SH-SY5Y cells among the three groups(F=13.330,P＜0.05).Specifically,the level of p-GSK-3β-ser9 in SH-SY5Y cells in the C22:0 and C24:0 groups was significantly lower than that in the control group(P＜0.05),and there was no statistically significant difference in the level of p-GSK-3β-ser9 in SH-SY5Y cells between the C22:0 group and C24:0 group(P＞0.05).The MDA level in SH-SY5Y cells in the C24:0 group was significantly higher than that in the control group and C22:0 group(P＜0.05);there was no statistically significant difference in the MDA level in SH-SY5Y cells between the control group and C22:0 group(P＞0.05).The fluorescence recovery rate and diffusion coefficient of SH-SY5Y cells in the C22:0 and C24:0 groups showed a decreasing trend compared to the control group,but there was no statistically significant difference in the fluorescence recovery rate and diffusion coefficient of SH-SY5Y cells among the three groups(F=3.891,3.649,P＞0.05).Conclusion Very-long-chain saturated fatty acids C22:0 and C24:0 can promote hyperphosphorylation of Tau protein,induce cellular oxidative damage,and tend to reduce the fluidity cell membranes.Very-long-chain saturated fatty acids may be one of the factors that cause the onset of AD.

Objective To systematically evaluate the psychological feelings and real experience of ICU nurses'moral dilemma,and the aim is to provide references for the formulation of targeted psychological intervention programs.Methods Pubmed,CINAHL,Embase,Web of Science,Cochrane Library,PsycNET,CNKI,Wanfang database,VIP database,and China Biomedical Literature Database were searched by computer to retrieve qualitative studies on psychological perceptions and real experiences of moral dilemmas of ICU nurses,and the search time was from the establishment of databases to March 2023.The quality of literature was evaluated using the 2016 version of the Australian JBI Centre for Evidence-Based Health Care Quality Evaluation Criteria for qualitative studies,and the results were integrated and analyzed by the Meta integration method.Results A total of 10 pieces of literature were included,including 3 phenomenological studies and 7 descriptive studies.The results of 27 studies were summarized into 8 new categories,and 3 integrated results were obtained:①The internal and external causes of moral dilemmas,including conflicting concepts of life and death,differences of the idea of the superior death,conflict of clinical decision-making,and insufficient organizational support;②The progressive effects of moral dilemmas,including aggravating negative emotional burden and breeding professional identity bias;③ Coping strategies for moral dilemmas,including active self-debugging and seeking support from colleagues.Conclusion It is urgent to popularize the scientific concept of life and death of patients and families,deepen the concept of superior death of ICU nurses,and alleviate the conflict of nursing and patient decision-making.It is important to pay attention to the negative emotional state of ICU nurses,improve their professional identity,improve the self-adjustment ways of ICU nurses,and to provide multi-organization support for ICU nurses.

Objective:To explore the clinical effects of parallel combined flow-through perforator flaps in the treatment of circular hot crush injuries in limbs with blood supply disorder.Methods:The study was a retrospective observational study. From April 2016 to December 2022, 4 cases with circular hot crush injuries in limbs with blood supply disorder were admitted to the Department of Burns and Plastic Surgery of the 988 th Hospital of Joint Logistics Support Force of PLA, including 3 males and 1 female, aged from 24 to 48 years. Among them, 2 cases were injured in the calf and 2 cases were injured in the forearm. After emergency debridement, the area of skin and soft tissue defects was from 20 cm×20 cm to 44 cm×20 cm. The patients had defects in tibialis anterior and posterior tibial arteries with a length of 13 to 18 cm, and in ulnar and radial arteries with a length of 9 to 12 cm. Flaps were designed and cut, including a flow-through anterolateral thigh perforator flap with area of 20 cm×9 cm to 24 cm×21 cm carrying the descending branch of the lateral circumflex femoral artery and the accompanying veins of 8 to 18 cm in length; and a flow-through posterior tibial artery perforator flap with area of 21 cm×13 cm and 20 cm×14 cm carrying the posterior tibial artery, the accompanying veins with a length of 14 and 17 cm respectively, and the great saphenous vein with a length of 22 and 21 cm. The circular hot crush injury wounds in the calf with blood supply disorder were repaired by a parallel combination of flow-through posterior tibial artery perforator flap and flow-through anterolateral thigh perforator flap, and the circular hot crush injury wounds in the forearm with blood supply disorder were repaired by a parallel combination of bilateral flow-through anterolateral thigh perforator flap, and the injured main vessels were reconstructed. The donor site wounds of flap were closed directly or treated with split-thickness skin grafts from abdomen. After surgery, the blood supply and survival of the flap and distal affected limb, the healing of wounds in the donor and recipient sites, the survival of the skin graft in the flap donor site were observed. During follow-up, the condition of flaps, the appearance, blood supply, and function of affected limbs were observed. At the last follow-up, the foot and ankle functions were evaluated according to the scoring standards of American Orthopedic Foot and Ankle Association, and the wrist and hand function was evaluated according to the trial standard of replantation of amputated upper limb function assessment of the Hand Surgery of Chinese Medical Association. Results:The flaps and distal affected limbs of 4 patients had good blood circulation and successfully survived after surgery. The wounds of 3 cases successfully healed, while one patient with circular hot crush injury in the forearm experienced exudation in the recipient site in the later stage, and the wound healed after re-expansion and suturing. The donor site wounds healed smoothly, and the skin grafts successfully survived. During follow-up of 12 to 24 months after surgery, the flaps were slightly swollen, the limbs had good appearance, normal blood circulation, and fine functional recovery. At the last follow-up, the foot and ankle function of 2 patients with circular hot crush injuries in the calf was evaluated as good in 1 case and commonly in 1 case; the wrist and hand function of 2 patients with circular hot crush injuries in the forearm was evaluated as excellent in 1 case and good in 1 case.Conclusions:The parallel combined flow-through perforator flap can reconstruct the damaged main blood vessels and repair the wound at the same time. It can not only effectively save the limb, but also restore part of the function of the affected limb. It is one of the effective methods to treat the circular hot crush injuries in limbs with blood supply disorder.

Objective To observe the effects of different surgical approaches on the complications and tumor markers of patients undergoing radical resection of esophageal cancer.Method A prospective study was conducted on 100 patients with esophageal cancer who underwent radical surgery in our hospital from October 2019 to October 2022.They were randomly divided into an observation group and a control group using a random number table method,with 50 patients in each group,he right thoracic approach was used in the observation group and the left thoracic approach was used in the control group.Perioperative indexes,inflammatory factors[Substance P(SP),hypersensitive C-reactive protein(hs-CRP),interleukin6(IL-6)],tumor markers[cytokeratin 19 fragment antigen(CYFRA21-1),squamous cell carcinoma antigen(SCC-Ag)and carbohydrate antigen 199(CA199)]and lung function of the two groups were compared before and after surgery Indicators[vital capacity(VC),forced vital capacity(FVC),and forced expiratory volume in the first second(FEV1)]and complication rate.Result The operating time,blood loss,indwelling time,hospitalization time,and number of lymph node dissection in the observation group were(247.65±27.33)minutes,(211.82±25.49)ml,(6.97±2.12)days,(16.11±3.81)days,and(19.67±5.21),respectively,which were higher than those in the control group[(217.63±23.69)minutes,(175.67±22.13)ml,(5.43±1.80)days,(12.68±3.24)days,(15.45±4.12)](P＜0.05).On average,there was a significant increase in SP,hs CRP,and IL-6 levels in both groups 3 days after surgery(P＜0.05).The levels of SP,hs CRP,and IL-6 in the observation group were(273.96±35.45)ng/L,(11.35±2.12)mg/L,and(8.19±1.67)p.g/ml,respectively,which were lower than the control group[(298.33±38.42)ng/L,(14.29±2.68)mg/L,(10.35±1.82)pg/ml](P＜0.05);One month after surgery,there was a significant decrease in CYFRA21-1,SCC-Ag,and CA199 in both groups(P＜0.05),and in the observation group,the data of CYFRA21-1,SCC-Ag,and CA199 were(2.59±0.37)μg/L,(45.62±6.18)pg/L and(59.37±6.12)U/ml,respectively,which were lower than those in the control group[(3.12±0.43)μg/L,(60.27±7.35)pig/L,(63.28±6.49)U/ml](P＜0.05);One month after surgery,there was a significant decrease in VC,FVC,and FEV1 in both groups(P＜0.05).However,the VC,FVC,and FEV1 in the observation group were(67.21±8.69)％,(70.33±9.41)％,and(72.88±10.12)％,respectively,which were higher than those in the control group[(54.35±8.27)％,(61.65±8.79)％,(65.37±9.24)％](P＜0.05).There was no significant difference in the incidence of complications between the two groups(P＞0.05).Conclusion Both approaches can effectively treat esophageal cancer.Among them,the right chest approach can significantly improve the effect of lymph node dissection,inhibit inflammatory reactions,reduce tumor marker levels,and have less impact on lung function,without significantly increasing the risk of complications.However,the surgical time,bleeding volume,and postoperative recovery time are relatively long.Therefore,a suitable approach should be selected in clinical practice based on the patient's actual situation.