Objective:To evaluate the efficacy of dexzopiclone combined with repetitive transcranial magnetic stimulation (rTMS) for post-stroke sleep disorders (PSSD) and its effects on sleep electroencephalography and neuroelectrophysiological parameters.Methods:180 PSSD patients admitted to Yulin First Hospital (December 2019-December 2020) were randomized into medication group ( n=90, dexzopiclone) and rTMS group ( n=90, dexzopiclone+rTMS). Outcomes included clinical efficacy, sleep quality [Pittsburgh Sleep Quality Index (PSQI), Self-Rating Scale for Sleep (SRSS)], electroencephalogram parameters [sleep latency (SL), total sleep time (TST), sleep efficiency], neuroelectrophysiological indices [bilateral motor thresholds], biochemical markers [S100β protein, brain-derived neurotrophic factor (BDNF)], adverse reactions, and 1-year recurrence rate. Results:After treatment, the rTMS group had a significantly higher efficacy (92.22%, 83/90) compared to the medication group (81.11%, 73/90) ( χ2=4.81, P=0.028). Compared to post-treatment, PSQI decreased to [7.47 (6.63,8.69) points vs. 13.56 (3.15,19.51) points] in the rTMS group and [9.56 (8.59,11.11) points vs. 14.01 (2.58,20.55) points] in the medication group ( U=8.82, 8.38; both P<0.001). SRSS scores decreased to [(15.23±2.88) points vs. (28.81±4.99) points) ( t=32.74, P<0.001) and (19.54±3.59) points vs. (28.15±4.71) points) ( t=19.68, P<0.001)], respectively. Compared to before treatment, the rTMS group had lower scores than the medication group ( U=7.80, t=8.88; P<0.01). SL reduced to (27.65±5.12) min vs. (44.92±8.21) min ( t=24.58, P<0.001) in rTMS group and (38.78±6.34) min vs. (45.23±8.56) min ( t=8.24, P<0.001) in medication groups. TST increased to (348.50±56.27) min vs. (299.21±52.14) min ( t=8.63, P<0.001) and (311.42±55.39) min vs. (275.65±52.23) min ( t=6.31, P<0.001), sleep efficiency improved to (70.96±12.33%) vs. (57.43±10.98%) ( t=11.01, P<0.001) and (62.37±11.28%) vs. (56.78±10.72%) ( t=4.82, P<0.001), while the rTMS group showed greater improvement ( t=4.46, 4.88; P<0.001). Compared to before treatment, left motor thresholds decreased to (55.65±2.48)% vs. (64.37±3.12)% and (61.76±3.17)% vs. (65.12±3.45)% post-treatment ( t=29.54, 9.63; P<0.001), with significant intergroup differences ( t=14.40, P<0.001). Right motor thresholds decreased to (56.28±3.45)% vs. (67.42±3.61)% and (60.89±3.39)% vs. (66.62±3.54)% ( t=29.94, 15.69; P<0.001), with intergroup differences ( t=9.04, P<0.01). Compared to before treatment, serum S100β levels decreased in both group post-treatment (23.65±3.23) ng/L vs. (65.37±7.89) ng/L and (29.76±3.61) ng/L vs. (63.48±7.34) ng/L ( t=71.19, 58.43; P<0.001), with lower levels in the rTMS group ( t=11.97, P<0.001). Compared to before treatment, BDNF increased to (554.48±69.78) ng/L vs. (502.82±64.11) ng/L and (524.90±67.66) ng/L vs. (505.12±64.45) ng/L post-treatment ( t=7.32, 2.84; P=0.001, 0.030), with higher levels in the rTMS group ( t=2.89, P=0.004). Adverse reaction rates were 4.44% (4/90) and 3.33% (3/90), respectively ( χ2=0.15, P=0.700). Recurrence rates were 1.18% (1/85) in the rTMS group and 3.90% (3/77) in the medication group ( χ2=0.37, P=0.544). Conclusion:The combination of dexzopiclone and repetitive transcranial magnetic stimulation (rTMS) demonstrates significant advantages and efficacy in treating post-stroke sleep disorders (PSSD). This approach comprehensively improves patients' sleep quality, EEG parameters and neuroelectrophysiological indicators while enhancing the regulatory effects of brain-derived neurotrophic factor (BDNF). Additionally, the therapy exhibits a favorable safety profile and prognosis.

Objective:To evaluate the efficacy of dexzopiclone combined with repetitive transcranial magnetic stimulation (rTMS) for post-stroke sleep disorders (PSSD) and its effects on sleep electroencephalography and neuroelectrophysiological parameters.Methods:180 PSSD patients admitted to Yulin First Hospital (December 2019-December 2020) were randomized into medication group ( n=90, dexzopiclone) and rTMS group ( n=90, dexzopiclone+rTMS). Outcomes included clinical efficacy, sleep quality [Pittsburgh Sleep Quality Index (PSQI), Self-Rating Scale for Sleep (SRSS)], electroencephalogram parameters [sleep latency (SL), total sleep time (TST), sleep efficiency], neuroelectrophysiological indices [bilateral motor thresholds], biochemical markers [S100β protein, brain-derived neurotrophic factor (BDNF)], adverse reactions, and 1-year recurrence rate. Results:After treatment, the rTMS group had a significantly higher efficacy (92.22%, 83/90) compared to the medication group (81.11%, 73/90) ( χ2=4.81, P=0.028). Compared to post-treatment, PSQI decreased to [7.47 (6.63,8.69) points vs. 13.56 (3.15,19.51) points] in the rTMS group and [9.56 (8.59,11.11) points vs. 14.01 (2.58,20.55) points] in the medication group ( U=8.82, 8.38; both P<0.001). SRSS scores decreased to [(15.23±2.88) points vs. (28.81±4.99) points) ( t=32.74, P<0.001) and (19.54±3.59) points vs. (28.15±4.71) points) ( t=19.68, P<0.001)], respectively. Compared to before treatment, the rTMS group had lower scores than the medication group ( U=7.80, t=8.88; P<0.01). SL reduced to (27.65±5.12) min vs. (44.92±8.21) min ( t=24.58, P<0.001) in rTMS group and (38.78±6.34) min vs. (45.23±8.56) min ( t=8.24, P<0.001) in medication groups. TST increased to (348.50±56.27) min vs. (299.21±52.14) min ( t=8.63, P<0.001) and (311.42±55.39) min vs. (275.65±52.23) min ( t=6.31, P<0.001), sleep efficiency improved to (70.96±12.33%) vs. (57.43±10.98%) ( t=11.01, P<0.001) and (62.37±11.28%) vs. (56.78±10.72%) ( t=4.82, P<0.001), while the rTMS group showed greater improvement ( t=4.46, 4.88; P<0.001). Compared to before treatment, left motor thresholds decreased to (55.65±2.48)% vs. (64.37±3.12)% and (61.76±3.17)% vs. (65.12±3.45)% post-treatment ( t=29.54, 9.63; P<0.001), with significant intergroup differences ( t=14.40, P<0.001). Right motor thresholds decreased to (56.28±3.45)% vs. (67.42±3.61)% and (60.89±3.39)% vs. (66.62±3.54)% ( t=29.94, 15.69; P<0.001), with intergroup differences ( t=9.04, P<0.01). Compared to before treatment, serum S100β levels decreased in both group post-treatment (23.65±3.23) ng/L vs. (65.37±7.89) ng/L and (29.76±3.61) ng/L vs. (63.48±7.34) ng/L ( t=71.19, 58.43; P<0.001), with lower levels in the rTMS group ( t=11.97, P<0.001). Compared to before treatment, BDNF increased to (554.48±69.78) ng/L vs. (502.82±64.11) ng/L and (524.90±67.66) ng/L vs. (505.12±64.45) ng/L post-treatment ( t=7.32, 2.84; P=0.001, 0.030), with higher levels in the rTMS group ( t=2.89, P=0.004). Adverse reaction rates were 4.44% (4/90) and 3.33% (3/90), respectively ( χ2=0.15, P=0.700). Recurrence rates were 1.18% (1/85) in the rTMS group and 3.90% (3/77) in the medication group ( χ2=0.37, P=0.544). Conclusion:The combination of dexzopiclone and repetitive transcranial magnetic stimulation (rTMS) demonstrates significant advantages and efficacy in treating post-stroke sleep disorders (PSSD). This approach comprehensively improves patients' sleep quality, EEG parameters and neuroelectrophysiological indicators while enhancing the regulatory effects of brain-derived neurotrophic factor (BDNF). Additionally, the therapy exhibits a favorable safety profile and prognosis.

Temporomandibular joint (TMJ) diseases are common clinical conditions. The number of patients with TMJ diseases is large, and the etiology, epidemiology, disease spectrum, and treatment of the disease remain controversial and unknown. To understand and master the current situation of the occurrence, development and prevention of TMJ diseases, as well as to identify the patterns in etiology, incidence, drug sensitivity, and prognosis is crucial for alleviating patients′suffering.This will facilitate in-depth medical research, effective disease prevention measures, and the formulation of corresponding health policies. Cohort construction and research has an irreplaceable role in precise disease prevention and significant improvement in diagnosis and treatment levels. Large-scale cohort studies are needed to explore the relationship between potential risk factors and outcomes of TMJ diseases, and to observe disease prognoses through long-term follw-ups. The consensus aims to establish a standard conceptual frame work for a cohort study on patients with TMJ disease while providing ideas for cohort data standards to this condition. TMJ disease cohort data consists of both common data standards applicable to all specific disease cohorts as well as disease-specific data standards. Common data were available for each specific disease cohort. By integrating different cohort research resources, standard problems or study variables can be unified. Long-term follow-up can be performed using consistent definitions and criteria across different projects for better core data collection. It is hoped that this consensus will be facilitate the development cohort studies of TMJ diseases.

ObjectiveThis study aims to examine the effect of Rhei Radix et Rhizoma-Coptidis Rhizoma on reducing insulin resistance in db/db mice by regulating the adenylate activated protein kinase （AMPK）/UNC-51-like kinase 1 （ULK1）/key molecule of autophagy， benzyl chloride 1 （Beclin1） pathway and elucidate the underlying mechanism. MethodSixty 6-week-old male db/db mice were studied. They were randomly divided into the model group， metformin group （0.26 g·kg^-1）， and low-， middle-， and high-dose groups （2.25， 4.5， 9 g·kg^-1） of Rhei Radix et Rhizoma-Coptidis Rhizoma. A blank group of db/m mice of the same age was set， with 12 mice in each group. After eight weeks of continuous intragastric administration， the blank group and model group received distilled water intragastrically once a day. The survival status of the mice was observed， and fasting blood glucose （FBG） was measured using a Roche blood glucose device. Fasting serum insulin （FINS） was measured using an enzyme-linked immunosorbent assay， and the insulin resistance index （HOMA-IR） was calculated. Hematoxylin-eosin （HE） staining was performed to observe the pathological changes in the liver of the mice. The protein expression levels of AMPK， Beclin1， autophagy associated protein 5 （Atg5）， and p62 in liver tissue were determined by using Western blot. The protein expression levels of autophagy associated protein 1 light chain 3B （LC3B） and ULK1 in liver tissue were determined using immunofluorescence. Real-time fluorescence quantitative PCR （Real-time PCR） was used to measure mRNA expression levels of AMPK， Beclin1， Atg5， ULK1， and p62. ResultCompared with the blank group， the model group exhibited a significant increase in body mass （P<0.01）. Additionally， the levels of FBG， FINS， and HOMA-IR significantly changed （P<0.01）. The structure of liver cells was disordered. The protein expression levels of AMPK， Beclin1， and Atg5 in liver tissue were significantly decreased （P<0.01）， while the expression level of p62 protein was significantly increased （P<0.01）. The expression levels of mRNA and proteins were consistent. Compared with the model group， the body mass of the metformin group and high and medium-dose groups of Rhei Radix et Rhizoma-Coptidis Rhizoma was significantly decreased （P<0.05）. FBG， FINS， and HOMA-IR were significantly decreased （P<0.05，P<0.01）. After treatment， the liver structure damage in each group was alleviated to varying degrees. The protein expressions of AMPK， Beclin1， Atg5， LC3B， and ULK1 were increased （P<0.05，P<0.01）， while the protein expression of p62 was decreased （P<0.01）. The expression levels of mRNA and proteins were generally consistent. ConclusionThe combination of Rhei Radix et Rhizoma-Coptidis Rhizoma can effectively improve liver insulin resistance， regulate the AMPK autophagy signaling pathway， alleviate insulin resistance in db/db mice， and effectively prevent the occurrence and development of type 2 diabetes.

Objective:To observe the effects of Mongolian medicine warm acupuncture treatment on the behavior and NLRP3, ASC, Caspase-1, GSDMD, and inflammatory factors in hippocampus of the depression model rats; To explore the mechanism.Methods:Totally 40 male SD rats were divided into control group, model group, warm acupuncture group, and fluoxetine group using a random number table method, with 10 rats in each group. Except for the control group, chronic unpredictable stress models were established in all other groups. After 1 hour of daily stress stimulation, the warm acupuncture group received Mongolian medicine warm acupuncture intervention. The fluoxetine group was orally administered with 2.1 mg/kg fluoxetine hydrochloride, while the control group and model group were orally administered with equal volumes of distilled water once a day for 21 days. The body weight of rats was measured, and their behavior was evaluated by sugar water consumption test, open field test, and Morris water maze test. ELISA was used to measure the levels of IL-1 β, IL-18, IL-6, and TNF-α in the serum. Western blot and PCR were used to detect the protein and mRNA levels of NLRP3, ASC, Caspase-1, GSDMD, and IL-1 in the hippocampus.Results:Compared with the model group, the warm acupuncture group and fluoxetine group showed an increase in body weight ( P<0.05), sugar water consumption ( P<0.05), vertical movement frequency and horizontal crossing grid number ( P<0.05), shortened escape latency ( P<0.05), and increased crossing platform frequency ( P<0.05); the levels of serum IL-1β, IL-18, TNF-α, and IL-6 decreased ( P<0.05); the protein and mRNA expressions of NLRP3, Caspase-1, ASC, GSDMD, IL-1β in the hippocampus of rats decreased ( P<0.05). Conclusion:Mongolian medicine warm acupuncture can prevent depressive behaviors in rats by reducing NLRP3-mediated cell death and inflammation.

OBJECTIVE To investigate the effects and mechanism of Yiqi huoxue decoction （YQHX） on lumbar disc herniation in rats. METHODS Rats were randomly divided into sham operation group， model group， NF-κB inhibitor group （QNZ group， 1 mg/kg）， YQHX group （9.1 g/kg） and combination group （YQHX+QNZ group， the same dose as each single drug group）， with 10 rats in each group. Except for sham operation group， lumbar disc herniation model of rats was induced in other groups； administration groups were given QNZ intraperitoneally or/and YQHX intragastrically， once a day， for 8 consecutive weeks. The severity of intervertebral disc herniation was evaluated in each group； the pathological changes of intervertebral discs and the changes of autophagy of nucleus pulposus cells were all observed； the level of tumor necrosis factor-α （TNF-α） in serum， and the ratios of Bcl-2/adenovirus E1B interacting protein 3 （BNIP3） and Beclin-1 positive cells in intervertebral disctissues were detected； the phosphorylation of nuclear factor-κB （NF-κB） p65， the expressions of tumor necrosis factor receptor- associated factor-2 （TRAF-2）， TRAF-3， BNIP3 and LC3B protein， and mRNA expressions of NF-κB p65， LC3B， p62，BNIP3 and Beclin-1 were determined. RESULTS Compared with model group， Pfirrmann grading score decreased significantly，the pathological injury of intervertebral disc tissue was relieved in YQHX group； the number of autophagosomes in nucleus pulposus cells increased； serum level of TNF-α and mRNA expression of p62 in intervertebral disc tissue decreased significantly； the ratios of BNIP3 and Beclin-1 positive cells， the phosphorylation of NF-κB p65， the expressions of TRAF-2， TRAF-3， BNIP3 and LC3B protein as well as the mRNA expressions of NF- κB p65， LC3B， BNIP3 and Beclin-1 decreased significantly in intervertebral disc tissues （P＜0.05）. The changes of above indexes in YQHX group were reversed partly in YQHX+QNZ group. CONCLUSIONS YQHX promotes the elevation of autophagy level of intervertebral discs， slows down the inflammatory response and the progression of lumbar disc herniation by activating the NF-κB signaling pathway.

Objective:To investigate the relationship between the expressions of checkpoint with forkhead-associated and ring finger(CHFR)and metastasis-associated protein 1(MACC1)and the sensitivity of patients with rectal cancer for neoadjuvant concurrent chemoradiotherapy(nCRT).Methods:The medical documents of 166 patients with rectal cancer admitted to First Hospital of Qinhuangdao from March 2017 to February 2022 were collected.All patients only received nCRT before surgery,and the radiotherapy adopted three-dimensional conformal intensity modulated radiotherapy,and chemotherapy adopted Capeox scheme.All patients successfully completed total mesorectal excision after 4-6 weeks of nCRT treatment.Immunohistochemical SP staining method was used to detect the protein expressions of CHFR and MACC1 in rectal cancer and its adjacent tissues.According to the tumor regressive grading(TRG)standard of the Joint Committee on Cancer Staging in the United States,75 patients who were grade 0-2 as TRG after nCRT were included in the nCRT insensitive group,and 91 patients who were grade 3-4 as TRG were included in the nCRT sensitive group.The expression levels of CHFR and MACC1 proteins in cancer tissues before and after treatment between the two groups were compared.And then,the relationship between clinically pathological characteristics of patients and nCRT sensitivity was analyzed,and the influencing factors of nCRT sensitivity were analyzed.The receiver operating characteristic(ROC)curves of them were drawn,and area under curve(AUC)values were calculated,and the predictive values of CHFR and MACC1 for the sensitivity of patients with rectal cancer to nCRT were further analyzed.Results:The CHFR positive expression rate in rectal cancer tissue was significantly lower than that in adjacent tissues of rectal cancer,and the MACC1 positive expression rate in rectal cancer tissue was significantly higher than that in adjacent tissues of rectal cancer(x2=81.373,87.150,P＜0.05),respectively.After 166 patients completed the nCRT treatment,there were 6 cases of TRG grade 0,8 cases of TRG grade 1,61 cases of TRG grade 2,59 cases of TRG grade 3 and 32 cases of TRG grade 4.The sensitivity rate of nCRT was 54.82%(91/166).The CHFR positive expression rate in the nCRT sensitive group was significantly higher than that in the nCRT insensitive group,and the MACC1 positive expression rate in the nCRT sensitive group was significantly lower than that in the nCRT insensitive group(x2=4.613,37.509,P＜0.05).The proportions of T4 stage and N+stage in the nCRT sensitive group were higher than those in the nCRT insensitive group,and the differences were statistically significant(x2=54.432,28.912,P＜0.05),respectively.The expressions of CHFR and MACC1 were respectively independent risk factor affected the sensitivity of patients with rectal cancer to nCRT[OR=2.456(95% CI:1.294-4.563),OR=3.281(95% CI:1.472-6.479),P＜0.05].The sensitivity and specificity of the combined detection of CHFR and MACC1 were respectively 65.89% and 69.46% in predicting the nCRT sensitivity for rectal cancer.The predictive value of the combined detection was higher than that of single CHFR detection and single MACC1 detection(AUC values of them were respectively 0.713,0.564,0.589,P＜0.05),respectively.Conclusion:CHFR and MACC1 are related to the sensitivity of patients with rectal cancer to nCRT,which means patients with high expression of CHFR and low expression of MACC1 are more sensitive to nCRT.Therefore,both of them may be indicators that predict the sensitivity of patients with rectal cancer to nCRT.

Necroptosis is a regulated process of programmed cell death independent of aspartic acid-specific cysteine protease,which can induce inflammation.Studies have shown that necroptosis is closely related to the progression and prognosis of pancreatic disease and plays an important two-way regulatory role in its progression.Related necroptosis inhibitors and inducers are expected to be used in the treatment of pancreatic disease.We herein review the mechanism of necroptosis and its role in the progression of pancreatic disease to provide a new understanding of the pathogenesis and treatment of pancreatic diseases and offer a theoretical basis for the research and development of targeted drugs.

ObjectiveTo explore the mechanism of Dahuang Mudantang in alleviating the intestinal injury in the rat model of acute pancreatitis via the high-mobility group box 1 （HMGB1）/receptor for advanced glycation endproduct （RAGE）/nuclear factor-κB （NF-κB） signaling pathway. MethodOne hundred and twenty SPF-grade Wistar rats received retrograde injection of 5% sodium taurocholate into the biliopancreatic duct for the modeling of intestinal injury in acute pancreatitis. The rats were randomized into blank， model， low-， medium-， and high-dose （3.5， 7， 14 g·kg^-1， administrated by gavage） Dahuang Mudantang， and octreotide （1×10^-5 g·kg^-1， subcutaneous injection） groups （n=20）. The rats in blank and model groups received equal volume of distilled water by gavage. Drugs were administered 1 h before and every 12 h after modeling， and samples were collected 24 h after modeling. The general status of the rats was observed. The biochemical methods were employed to measure the levels of amylase （AMS） and C-reactive protein （CRP） in the serum. The enzyme-linked immunosorbent assay （ELISA） was employed to measure the levels of tumor necrosis factor （TNF）-α， interleukin （IL）-1β， and IL-6 in the colon tissue. The morphological changes of pancreatic and colon tissues were observed by hematoxylin-eosin （HE） staining. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot were employed to measure the expression levels of HMGB1， RAGE， inhibitor of NF-κB kinase （IKK）， and NF-κB suppressor protein α（IκBα）in the colon tissue. ResultThe rats in the model group showed poor general survival， writhing response， reduced frequency of defecation， and dry stool. The symptoms of rats in the model group were mitigated in each treatment group， and the high-dose Dahuang Mudantang showed the most significant effect. Compared with the normal group， the model group had elevated AMS and CRP levels （P<0.05）， which were lowered by Dahuang Mudantang （P<0.05）， especially that at the high dose （P<0.05）. Compared with the normal group， the modeling elevated that levels of TNF-α， IL-1β， and IL-6 （P<0.05）. Such elevations were lowered by Dahuang Mudantang （P<0.05）， and the high-dose group and the octreotide group showed better performance （P<0.05）. The modeling caused necrotic， congested， and destructed pancreatic and colonic tissues， which were ameliorated by the drugs， especially high-dose Dahuang Mudantang. Compared with the normal group， the modeling up-regulated the mRNA levels of HMGB1， RAGE， IKK， IκBα， and NF-κB （P<0.05）. Compared with the model group， Dahuang Mudantang and octreotide down-regulated the mRNA levels of HMGB1， RAGE， IKK， IκBα， and NF-κB （P<0.05）， and the high-dose Dahuang Mudantang demonstrated the best performance （P<0.05）. Western blot results showed a trend consistent with the results of Real-time PCR. ConclusionDahuang Mudantang can improved the general status， reduce inflammation， and alleviate histopathological changes in the pancreatic and colon tissues in the rat model of acute pancreatitis by inhibiting the HMGB1/RAGE/NF-κB signaling pathway.

Objective To investigate the biological role of LINC01614 in non-small cell lung cancer A549 cells and its drug resistance-related mechanism. Methods The CRISPR/Cas9 technology was used to construct the A549 cell model with knockdown of LINC01614. Transcriptome sequencing was performed on A549 cells knocked down with LINC01614. We validated the transcriptomic differential genes MCAM and ABCC3 at the gene level and MCAM at the protein level, detected the IC₅₀ changes of A549 cells after knockdown of LINC01614 under the effect of different concentrations of cisplatin, and detected the effect of knockdown of LINC01614 on the migration ability of A549 cells. Results Of the 2 713 DEGs after knockdown of LINC01614, a total of 1 626 genes were up-regulated and 1, 087 genes were down-regulated. GO analysis showed that DEGs were associated with intracellular signaling, cell adhesion, and so on. Meanwhile, the KEGG analysis showed that DEGs were associated with the Wnt signaling pathway, TGF-β signaling pathway, and Rap1 signaling pathway. Selection of drug resistance-associated gene ABCC3 from DEGs for validation with MCAM: qRT-PCR results showed that knockdown of LINC01614 significantly down-regulated the expression of MCAM (P<0.05) and upregulated the expression of ABCC3 on A549 cells (P<0.05). After knockdown of LINC01614, the protein expression of MCAM, was significantly decreased in A549 cells (P<0.05); the IC₅₀ of A549 cells to cisplatin was significantly increased (P<0.05); and the scratch healing rate of A549 cells was also significantly decreased (P<0.05). Conclusion LINC01614 may be associated with the proliferation, invasion, and apoptotic pathways of A549 cells. In addition, LINC01614 may exert its migration ability through MCAM and chemoresistance to cisplatin through ABCC3.