Objective To investigate the relationship between insomnia,gastrointestinal symptoms,and glycosylated hemoglobin(HbA1c)levels in individuals diagnosed with type 2 diabetes mellitus(T2DM),as well as the related influencing factors.Methods A total of 910 T2DM patients treated in our multicenter from January 2022 to December 2022 were enrolled in this study.General information(gender,age,smoking and drinking history,exercise,course of disease,treatment and complications),HbA1c,Athens Insomnia Scale(AIS)scores and Gastrointestinal Symptoms Rating Scale(GSRS)scores of patients were collected.The differences of sleep and gastrointestinal symptoms between groups were analyzed,and the correlation between the differences and HbA1c was analyzed.Furthermore,the risk factors for non-standard HbA1c were analyzed.Results The AIS score and GSRS score in the HbA1c control group were less than those in the non-standard group(P＜0.01).Insomnia was reported by 37.0％of T2DM patients,and the HbA1c level in the insomnia group was significantly higher than that in the non-insomnia group(10.00％±2.38％vs.8.26％±1.73％,P＜0.01).Gastrointestinal symptoms were present in 57.5％of T2DM patients,and the HbA1c levels in the group with gastrointestinal symptoms were significantly higher than those in the group without gastrointestinal symptoms(9.26％±2.23％vs.8.43％±1.98％,P＜0.01).Furthermore,26.3％of T2DM patients experienced both insomnia and gastrointestinal symptoms.Remarkably,the HbA1c levels in the group with both insomnia and gastrointestinal symptoms were significantly higher than those in the group without either condition(10.18％±2.44％vs.8.45％±1.86％,P＜0.01).Correlation analysis demonstrated a significant association between sleep quality,gastrointestinal function,and HbA1c levels(P＜0.01).The logistic regression analysis result revealed that age,GSRS score,AIS score,and the presence of insomnia combined with gastrointestinal symptoms were independent risk factors for predicting HbA1c≥6.5％(P＜0.01).Having both insomnia and gastrointestinal symptoms concurrently was the strongest risk factor for substandard HbA1c control,and the risk of blood sugar control may increase about 5 times when both appear together.Conclusion Insomnia and gastrointestinal symptoms are common comorbidities in T2DM patients,showing a cross-interfering relationship,and they appear together with poor blood sugar control,interact causally,and amplify each other.

Objective To minimize variations in treatment outcomes of L5/S1 percutaneous intervertebral radiofrequency thermocoagulation(PIRFT)arising from physician proficiency and achieve precise quantitative risk assessment of the puncture paths.Methods We used a self-developed deep neural network DWT-UNet for automatic segmentation of the magnetic resonance(MR)images of the L5/S1 segments into 7 key structures:L5,S1,Ilium,Disc,N5,Dura mater,and Skin,based on which a needle insertion path planning environment was modeled.Six hard constraints and 6 soft constraints were proposed based on clinical criteria for needle insertion,and the physician's experience was quantified into weights using the analytic hierarchy process and incorporated into the risk function for needle insertion paths to enhance individual case adaptability.By leveraging the proposed skin entry point sampling sub-algorithm and Kambin's triangle projection area sub-algorithm in conjunction with the analytic hierarchy process,and employing various technologies such as ray tracing,CPU multi-threading,and GPU parallel computing,a puncture path was calculated that not only met clinical hard constraints but also optimized the overall soft constraints.Results A surgical team conducted a subjective evaluation of the 21 needle puncture paths planned by the algorithm,and all the paths met the clinical requirements,with 95.24%of them rated excellent or good.Compared with the physician's planning results,the plans generated by the algorithm showed inferior DIlium,DS1,and Depth(P<0.05)but much better DDura,DL5,DN5,and AKambin(P<0.05).In the 21 cases,the planning time of the algorithm averaged 7.97±3.73 s,much shorter than that by the physicians(typically beyond 10 min).Conclusion The multi-constraint optimal puncture path planning algorithm offers an efficient automated solution for PIRFT of the L5/S1 segments with great potentials for clinical application.

Objective To minimize variations in treatment outcomes of L5/S1 percutaneous intervertebral radiofrequency thermocoagulation(PIRFT)arising from physician proficiency and achieve precise quantitative risk assessment of the puncture paths.Methods We used a self-developed deep neural network DWT-UNet for automatic segmentation of the magnetic resonance(MR)images of the L5/S1 segments into 7 key structures:L5,S1,Ilium,Disc,N5,Dura mater,and Skin,based on which a needle insertion path planning environment was modeled.Six hard constraints and 6 soft constraints were proposed based on clinical criteria for needle insertion,and the physician's experience was quantified into weights using the analytic hierarchy process and incorporated into the risk function for needle insertion paths to enhance individual case adaptability.By leveraging the proposed skin entry point sampling sub-algorithm and Kambin's triangle projection area sub-algorithm in conjunction with the analytic hierarchy process,and employing various technologies such as ray tracing,CPU multi-threading,and GPU parallel computing,a puncture path was calculated that not only met clinical hard constraints but also optimized the overall soft constraints.Results A surgical team conducted a subjective evaluation of the 21 needle puncture paths planned by the algorithm,and all the paths met the clinical requirements,with 95.24%of them rated excellent or good.Compared with the physician's planning results,the plans generated by the algorithm showed inferior DIlium,DS1,and Depth(P<0.05)but much better DDura,DL5,DN5,and AKambin(P<0.05).In the 21 cases,the planning time of the algorithm averaged 7.97±3.73 s,much shorter than that by the physicians(typically beyond 10 min).Conclusion The multi-constraint optimal puncture path planning algorithm offers an efficient automated solution for PIRFT of the L5/S1 segments with great potentials for clinical application.

Diabetes retinopathy （DR） is an important cause that threatens the visual health of adults. There are some treatment methods of western medicine with definite efficacy， such as anti-vascular endothelial growth factor and laser photocoagulation， but they have many adverse reactions such as intraocular infection and visual field damage. Traditional Chinese medicine （TCM） therapies are safe and effective， which can complement western medicine. Phosphatidylinositol3-kinase （PI3K）/protein kinase B （Akt） signaling pathway regulates a range of processes including glucose metabolism， cell proliferation， and cell transcription and apoptosis， which is closely related to the occurrence and development of DR. Numerous studies have shown that TCM monomers can participate in maintaining the integrity of blood-retinal barrier and inhibiting retinal neovascularization and neurodegeneration in many aspects such as inhibiting oxidative stress and alleviating inflammatory reaction by regulating the PI3K/Akt pathway， so as to delay the progress of DR. Therefore， this study reviewed PI3K/Akt pathway and its relationship with DR， as well as the TCM monomers in interfering with DR based on PI3K/Akt pathway to provide some ideas for the prevention and treatment of DR in integrated TCM and western medicine.

Objective To evaluate the regulatory effects of lycopene on the key signaling receptors in human cutaneous squamous cell carcinoma cell line COLO16.Methods Cultured COLO16 cells were divided into 6 groups to be treated with lycopene at different concentrations of 0,5,10,15,20,and 25 μmol/L,respectively,for 24 hours (control group and 5,10,15,20,25 μmol/L lycopene groups),followed by estimation of the cell viability by lactate dehydrogenase (LDH) assay.Lycopene at a safe concentration was selected based on the LDH assay,and used for the determination of expression of signaling receptors,and Western blot analysis was performed to measure the expression of key signaling receptor proteins,including epidermal growth factor receptor (EGFR),glucocorticoid receptor (GR),retinoic acid receptor-alpha (RAR-α),retinoid X receptor-alpha (RXR-α),androgen receptor (AR) and progesterone receptor (PR).Statistical analysis was carried out by one-way analysis of variance (ANOVA),Tukey multiple comparison teat and Brown-Forsythe test with the SPSS software.Results After 24-hour treatment with lycopene at different concentrations,there were significant differences in the rate of cell death among these groups (F =13.116,P ＜ 0.05),and the rate of cell death in the 25 μmol/L lycopene group significantly differed from that in the control group (P ＜ 0.05).Therefor,lycopene at concentrations of 5,10 and 20 μmol/L were selected to treat COLO16 and HaCaT cells as well as human epidermal keratinocyte (HEK) for 24 hours in the following experiment.The treatment with lycopene significantly decreased the phosphorylation level of EGFR (P ＜ 0.05),but significantly increased the expression of GR protein (P ＜ 0.05),and showed no significant effects on the protein expression of RAR-α,RXR-α,AR,and PR in COLO16 cells.After 24-hour treatment with lycopene at concentrations of 5,10 and 20 μmol/L,there were no significant changes in the phosphorylation level of EGFR protein or the expression of GR protein in HaCaT cells and HEK (all P ＞ 0.05) compared with those without lycopene treatment.Conclusion Lycopene can decrease the viability of COLO16 cells,inhibit the activation of EGFR protein,and up-regulate the expression of GR,and these effects may be specific for tumor cells.

Objective To observe the effects of seawater immersion at different temperatures on survival time and mortality and physiological state of non-anesthetized rats.Methods Totally 100 SD male rats(The abdominal cavity was implanted with a temperature sensor in advance)were randomly divided into five groups which were immersed in 20 ℃,17 ℃,15 ℃,13 ℃ and 10 ℃ seawater,respectively.Each group contains 20 rats.The changes of respiration,heart rate and muscle fibrillation within 2 hours were observed and the survival time and mortality of each group were counted in 24 hours.The decrease trend of intraperitoneal temperature in rats was analyzed retrospectively within 2 hours.Results Soaking for 10 minutes,the respiratory and heart rate of each group were significantly increased,but there was no significant difference among groups(P>0.05).The respiratory and heart rate decreased rapidly between 10 and 40 minutes,and the decline was slower relatively between 40 and 80 minutes.Soaking for 80 minutes,the respiration rate of rats among groups had significant difference(P<0.05).Immersing for 100 minutes,the heart rates of rats in each group were significantly different(P<0.05).Soaking for 20 minutes,the muscle fibrillation of 15 ℃,13 ℃ and 10 ℃ group reached the peak,and there were significant differences among groups(P<0.05),then disappeared.However the rats in 20 ℃ and 17 ℃ group reached the peak at 30 minutes,but there was no significant difference between two groups(P>0.05),hereafter the muscle fibrillation was maintained at a certain level.The mean survival time of 20 ℃ group,17 ℃ group,15 ℃ group,13 ℃ group and 10 ℃ group in 24 hours were(23.6±1.23)hours,(15.0±4.16)hours,(7.7±3.21)hours,(2.4±0.91)hours and (1.1±0.39)hours,respectively,and the survival curve of each group was statistically significant(P<0.05).The intraperitoneal temperature of rats showed a decline in the cliff,the lower the water temperature,the faster the descending.Soaking for 40 minutes,the difference of intraperitoneal temperature of each group was statistically significant(P<0.05).Conclusion The effects of seawater immersion at different temperatures on the physiological state and survival time and mortality of rats are significantly different.With the decrease of water temperature,the physiological state changes more obviously,the survival time is shorter and the mortality rate is higher.

Objective To evaluate the synergistic effect of everolimus on cisplatin-mediated cytotoxicity against human cutaneous squamous cell carcinoma COLO-16 cells.Methods Cultured COLO-16 cells were divided into several groups to be treated with everolimus at different concentrations of 50,100 and 200 nmol/L or 25 μmol/L cisplatin for 12 and 24 hours.Acridine orange (AO)-labeled autophagic vesicles combined with lysomal enzyme inhibitors (E64d and pepstatin) were used to detect the levels of autophagy and autophagic flow.Western blot analysis was performed to track the conversion of the autophagosome marker microtubule-associated protein 1 light chain-3 (LC3)-Ⅰ to LC3-Ⅱ,as well as to detect cleavage levels of Caspase 3 and poly-ADP-ribose polymerase (PARP).Lactate dehydrogenase (LDH) assay was conducted to detect cell death,and Annexin V-EGFP staining to evaluate cell apoptosis.Results The LC3-Ⅱ / LC3-Ⅰ ratios (LC3-Ⅰ conversion to LC3-Ⅱ) after 12-and 24-hour treatment did not differ among the 50-,100-and 200-nmol/L everolimus groups (12 hours:3.52 ± 0.21 vs.4.03 ± 0.39 vs.5.05 ± 0.22,P ＞ 0.05;24 hours:3.38 ± 0.26 vs.3.29 ± 0.06 vs.6.57 ± 0.16,P ＞ 0.05),but were significantly higher in the three everolimus groups than in the control group receiving no treatment (12 hours:2.07 ± 0.05,P ＜ 0.05;24 hours:2.61 ± 0.16,P ＜ 0.05).After 12-hour treatment,no significant differences were observed in the ratio of LC3-Ⅱ to β-actin between the 50-nmol/L everolimus + E64d + pepstatin group (1.26 ± 0.40),100-nmol/L everolimus ± E64d + pepstatin group (1.16 ± 0.34),200-nmol/L everolimus + E64d + pepstatin group (1.21 ± 0.39) and E64d + pepstatin group (1.19 ± 0.27,P ＞ 0.05).Moreover,there was no significant difference in the percentages of autophagic vesicle-positive cells between the 100-nmol/L everolimus + E64d + pepstatin group and E64d + pepstatin group (2.06％ ± 0.61％ vs.1.68％ ± 0.62％,P ＞ 0.05).After 24-hour treatment,the everolimus + cisplatin group showed significantly increased rate of cell death compared with the cisplatin alone group (42.58％ ± 0.93％ vs.18.20％ ± 1.46％).However,no significant differences were observed in the cleavage levels of Caspase 3 and PARP,the number of annexin V-labelled cells and ratio of LC3-Ⅱ to β-actin between the everolimus + cisplatin group and the cisplatin-alone group (P ＞ 0.05).Conclusion Everolimus has a synergistic effect on the cisplatin-mediated COLO-16 cell death,and this effect does not depend on cell apoptosis or autophagy.

Objective To investigate molecular mechanisms underlying the synergistic damage to the human squamous cell carcinoma cell line COLO-16 by everolimus and cisplatin.Methods In the signaling pathway experiment,COLO-16 cells were divided into 4 groups:control group receiving no treatment,50,100 and 200 nmol/L everolimus groups treated with 50,100 and 200 nmol/L everolimus respectively.In the combined experiment,COLO-16 cells were divided into another 4 groups:control group,50 nmol/L everolimus group,25 mol/L cisplatin group,and 50 nmol/L everolimus + 25 mol/L cisplatin group.Western blot analysis was performed to analyze changes in mammalian target of rapamycin (mTOR) pathway,Akt pathway,DNA damage-related pathway and Csk homologous kinase (Chk) pathway.Results After the treatment with everolimus at different concentrations of 50,100 and 200 nmol/L for 12 and 24 hours,the phosphorylation levels of mTOR at ser2448 and ser2481 as well as Rictor at thr1 135 in COLO-16 cells were all decreased compared with the control group.However,there were no significant changes in the phosphorylation levels of downstream signals ULK1 at ser757,p70 S6 at thr389 and PKCα at thr638/64.The treatment with everolimus did not change the total protein level and phosphorylation of Akt.After the treatment with cisplatin for 12 and 24 hours,the phosphorylation levels of Rictor at thr1135 and Chk1 at ser345 were significantly increased,but the treatment with everolimus alone showed no such effects.After the combined treatment with everolimus and cisplatin for 12 and 24 hours,the upregulation of Chk1 and Rictor phosphorylation were significantly inhibited compared with the cisplatin alone group.Conclusions mTOR signaling is sensitive to everolimus in COLO-16 cells,but its targeted pathway is not regulated simultaneously to develop a cascade reaction.Everolimus may increase the cisplatin-induced death of COLO-16 cells by inhibiting the activation of Chk 1,but can not aggravate DNA damage induced by cisplatin.

BACKGROUND:Chronic visceral pain is one of major complaints of irritable bowel syndrome which seriously affects patient’s quality of life. Recent researches have shown that moxibustion therapy has positive effects on aleviating chronic visceral pain in irritable bowel syndrome patients.
OBJECTIVE: To study the clinical utility of moxibustion in coping with chronic visceral pain of irritable bowel syndrome patients, and shed light on the theoretical basis of moxibustion analgesia, thereby to give insights into the further research and application on moxibustion.
METHODS: With the key words of “moxibustion, irritable bowel syndrome, visceral pain, abdominal pain” in Chinese and in English, respectively, a computer-based search was performed in CNKI, VIP, Wanfang and PubMed databases for articles published from January 1990 to October 2014. After the initial screening, the remained articles went through further selection and categorization.
RESULTS AND CONCLUSION:The result shows promising results of moxibustion on relieving chronic visceral pain for both two subtypes of irritable bowel syndrome patients, diarrhea type and constipation type. Moxibustion may exert an analgesic effect on chronic visceral pain in irritable bowel syndrome patients through regulation of visceral hypersensitivity, gastrointestinal motility disorders, brain-gut axis and neuroendocrine system disorders, immune dysfunction and low-grade inflammation in the gut, psychological abnormalities, and alteration of intestinal flora. However, to fuly understand the analgesia effect of moxibustion and elucidate its mechanism, more standardized randomized controled trials employing advanced scientific techniques and equipments wil stil be needed in the future.

OBJECTIVE: To evaluate the safety of the circular round window and discus anatomic landmarks of posterior wall of internal auditory canal by investigating the microscopic anatomy of internal auditory canal area of the retrosigmold approach, which can provide the anatomical basis for acoustic neutrinomas surgery. METHOD: Fifteen adult cadaver heads (30 sides) fixed with formalin were used in the study. The retrosigmold approach operations were imitated to dissect the blood vessels and nerves in internal auditory canal area by opening round bony window and removing posterior wall of internal auditory canal. RESULT: Fifteen specimens of 30 sides circular bone window were opened without injury with transverse sinus and sigmoid sinus. The vertical distance between the highest point of bone window margo superior and the lowest point of transverse sinus margo inferior was (4.02 ± 0.32) mm. The vertical distance from the most anterior point of bone window leading edge to the most posterior point of sigmoid sinus trailing edge was (6.31 ± 0.43) mm. The internal auditory canal tubercle located in the anterior superior position of internal auditory canal. The vertical distance from the highest point of internal auditory canal tubercle to the upper margin of internal auditory canal was (2.31 ± 0.32) mm. To expose the whole internal auditory canal, the length and width of the internal auditory canal posterior wall removal was (7.29 ± 0.32) mm, (4.12 ± 0.29) mm. Within this removal range, no case of cochlea, semicircular canal or venous was injured in 30 specimens. CONCLUSION The method of opening round window through retrosigmold approach is simple, practial and convenient. With little variation and easiness of location, the sinternal auditory canal tubercle can be used in the identification of the internal auditory canal. When exposing the whole internal auditory canal, the removal scope of the posterior wall should be paid more attention to, in order to avoid the damage of cochlea, semicircular canal and jugular bulb.
Adult ; Cranial Sinuses ; Ear Canal ; Ear, Inner ; Humans ; Round Window, Ear ; anatomy & histology ; Semicircular Canals ; anatomy & histology ; Temporal Bone