Pyroptosis: the dawn of a new era in endometrial cancer treatment.

Endometrial cancer (EC) is a malignancy of the inner epithelial lining of the uterus. While early-stage EC is often curable through surgery, the management of advanced, recurrent and metastatic EC poses significant challenges and is associated with a poor prognosis. Pyroptosis, an emerging form of programmed cell death, is characterized by the cleavage of gasdermin proteins, inducing the formation of extensive gasdermin pores in the cell membrane and the leakage of interleukin-1ß (IL-1ß) and interleukin-18 (IL-18), consequently causing cell swelling, lysis and death. It has been found to be implicated in the occurrence and progression of almost all tumors. Recent studies have demonstrated that regulating tumor cells pyroptosis can exploit synergies function with traditional tumor treatments. This paper provides an overview of the research progress made in molecular mechanisms of pyroptosis. It then discusses the role of pyroptosis and its components in initiation and progression of endometrial cancer, emphasizing recent insights into the underlying mechanisms and highlighting unresolved questions. Furthermore, it explores the potential value of pyroptosis in the treatment of endometrial cancer, considering its current application in tumor radiotherapy, chemotherapy, targeted therapy and immunotherapy.

Carbon Nitride-Based siRNA Vectors with Self-Produced O2 Effects for Targeting Combination Therapy of Liver Fibrosis via HIF-1α-Mediated TGF-ß1/Smad Pathway.

Hypoxia is an important feature, which can upregulate the hypoxia-inducible factor-1α (HIF-1α) expression and promote the activation of hepatic stellate cells (HSCs), leading to liver fibrosis. Currently, effective treatment for liver fibrosis is extremely lacking. Herein, a safe and effective method is established to downregulate the expression of HIF-1α in HSCs via targeted delivery of VA-PEG-modified CNs-based nanosheets-encapsulated (VA-PEG-CN@GQDs) HIF-1α small interfering RNA (HIF-1α-siRNA). Due to the presence of lipase in the liver, the reversible release of siRNA can be promoted to complete the transfection process. Simultaneously, VA-PEG-CN@GQD nanosheets enable trigger the water splitting process to produce O2 under near-infrared (NIR) irradiation, thereby improving the hypoxic environment of the liver fibrosis site and maximizing the downregulation of HIF-1α expression to improve the therapeutic effect, as demonstrated in liver fibrosis mice. Such combination therapy can inhibit the activation of HSCs via HIF-1α-mediated TGF-ß1/Smad pathway, achieving outstanding therapeutic effects in liver fibrosis mice. In conclusion, this study proposes a novel strategy for the treatment of liver fibrosis by regulating the hypoxic environment and the expression of HIF-1α at lesion site.

Estimated prevalence and sociodemographic correlates of mental disorders in medical students of Hebei Province, China: A cross-sectional study.

BACKGROUND: In China, the identification rate and treatment rate of mental disorders are low, and there are few surveys on the prevalence of mental disorders among college students using diagnostic tools such as Mini-International Neuropsychiatric Interview (MINI), so the prevalence and treatment of mental disorders among college students are unclear. AIM: To estimate prevalence of mental disorders among medical students in Hebei Province, and provide guidance for improving their mental health. METHODS: This was a cross-sectional study based on an Internet-based survey. Three levels of medical students in Hebei Province were randomly selected (by cluster sampling) for screening. Using the information network assessment system, the subjects scanned the 2D code with their mobile phones, clicked to sign the informed consent, and answered a scale. A self-designed general status questionnaire was used to collect information about age, gender, ethnicity, grade, and origin of students. The MINI 5.0. was used to investigate mental disorders. Data analysis was performed with SPSS software. Statistically significant findings were determined using a two-tailed P value of 0.05. RESULTS: A total of 7117 subjects completed the survey between October 11 and November 7, 2021. The estimated prevalence of any mental disorders within 12 mo was 7.4%. Mood disorders were the most common category (4.3%), followed by anxiety disorders (3.9%); 15.0% had been to psychological counseling, while only 5.7% had been to a psychiatric consultation, and only 10% had received drug therapy in the past 12 mo. CONCLUSION: Although the estimated prevalence of mental disorders in medical students is lower than in the general population, the rate of adequate treatment is low. We determined that improving the mental health of medical students is an urgent matter.

Clinical observation of acupoint application of Chinese herbal medicine in preventing postoperative nausea and vomiting after orthopaedic surgery under general anesthesia / 中国骨伤

OBJECTIVE@#To explore clinical effect of acupoint application of Chinese herbal medicine in preventing postoperative nausea and vomiting after orthopaedic surgery under general anesthesia.@*METHODS@#From January 2018 to December 2019, 168 patients who met inclusion criteria and were underwent selective spine surgery, were double-blind divided into two groups according to central random system, 84 patients in each group. In control group, there were 39 males and 45 females aged from 30 to 65 years old with an average of (53.83±9.17) years old, 37 patients were classified to typeⅠand 47 patients were typeⅡ according to American Society of Anesthesiologists (ASA) grading. In experiment group, there were 39 males and 45 females aged from 30 to 65 years old with an average of (54.08±9.00) years old; 32 patients were classified to typeⅠand 52 patients were typeⅡ according to ASA grading. Both of two groups were obtained acupoint application before anesthesia induction, and acupoint application were put on @*RESULTS@#There were no statistical differences in incidence of nausea vomiting, VAS of narusea degree at 24 h after operation (@*CONCLUSION@#The curative effect of acupoint application of traditional Chinese medicine on the prevention and treatment of postoperative nausea and vomiting is not obvious.

Analyzing the effects of public interventions on reducing public gatherings in China during the COVID-19 epidemic via mobile terminals positioning data.

At the beginning of 2020, the novel coronavirus disease (COVID-19) became an outbreak in China. On January 23, China raised its national public health response to the highest level. As part of the emergency response, a series of public social distancing interventions were implemented to reduce the transmission rate of COVID-19. In this article, we explored the feasibility of using mobile terminal positioning data to study the impact of some nonpharmaceutical public health interventions implemented by China. First, this article introduced a hybrid method for measuring the number of people in public places based on anonymized mobile terminal positioning data. Additionally, the difference-in-difference (DID) model was used to estimate the effect of the interventions on reducing public gatherings in different provinces and during different stages. The data-driven experimental results showed that the interventions that China implemented reduced the number of people in public places by approximately 60% between January 24 and February 28. Among the 31 provinces in the Chinese mainland, some provinces, such as Tianjin and Chongqing, were more affected by the interventions, while other provinces, such as Gansu, were less affected. In terms of the stages, the phase with the greatest intervention effect was from February 3 to 14, during which the number of daily confirmed cases in China showed a turning point. In conclusion, the interventions significantly reduced public gatherings, and the effects of interventions varied with provinces and time.

Clinical observation of ultrasound guided popliteal sciatic nerve combined saphenous nerve block for hallux valgus patients with metatarsophalangeal joint dislocation / 中国骨伤

<p><b>OBJECTIVE</b>To explore clinical effects of ultrasound guided popliteal sciatic nerve combined saphenous nerve block in patients with anterior foot orthopedics.</p><p><b>METHODS</b>From January 2017 to October 2017, 60 hallux valgus patients with metatarsophalangeal joint dislocation were randomly divided into experimental and control group according to random number table. Thirty patients in experimental group were treated by ultrasound guided popliteal sciatic nerve combined saphenous nerve block, including 13 males and 17 females, aged 31 to 76 years old with an average of (59.23±10.07) years old;and body mass index ranged from 21 to 30 kg/m² with an average of (24.57±1.85) kg/m²; 12 cases were grade I and 18 cases were grade II according to ASA grading. Thirty patients in control group were treated by spinal anesthesia, including 12 males and 18 females, aged from 20 to 74 years old with an average of (54.20±15.87) years old; and body mass index ranged from 20 to 29 kg/m² with an average of (24.43 ± 3.15) kg/m²; 11 cases were grade I and 19 cases were grade II according to ASA grading. Block time of anesthesia, onset time of sensory nerve block, onset time of motor nerve block, invalid time of motor nerve block, invalid time of sensory nerve block were compared between two groups. Hemodynamic changes before anesthesia(T₀), 15 min after block(T₁), 30 min after block(T₂), at the beginning of the operation(T₃), 30 min after the beginning(T₄) of surgery and at the end of operation(T₅), adverse reactions and subjective satisfactory between two groups were also recorded.</p><p><b>RESULTS</b>Both of the anesthetic protocol could achieved satisfied clinical effects. In experimental group, block time of patients, onset time of sensory block, invalid time of motor nerve block and invalid time of sensory nerve block were longer than those in control group, and there were significant differences between two groups(<0.001). There was no significant difference between two groups in onset time of motor nerve block(> 0.05). There were no significant differences of systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR) in experimental group at different time points(> 0.05). There were significant differences of SBP, DBP in control group at different time points (<0.05). There was no significant difference of HR in control group at different time points(> 0.05).</p><p><b>CONCLUSIONS</b>Ultrasound guided popliteal sciatic nerve combined saphenous nerve block could meet demand of hallux valgus patients with metatarsophalangeal joint dislocation. Compared with lumbar anesthesia, it could maintain hemodynamic stability, prolong effective analgesia time after operation, and improve patients' overall comfort and safety for free activity above the knee joint.</p>

Efficient induction of antimicrobial activity with vancomycin nanoparticle-loaded poly(trimethylene carbonate) localized drug delivery system.

Surgery and the local placement of an antibiotic are the predominant therapies to treat chronic osteomyelitis. Vancomycin-loaded N-trimethyl chitosan nanoparticles (VCM/TMC NPs) as a potential drug delivery system have high intracellular penetration and effective intracellular antibacterial activity. This study investigated the effects of a biocompatible material, poly(trimethylene carbonate) (PTMC), to increase the sustained effectiveness of an intracellular antibiotic and its potential application in antibiotic delivery. VCM/TMC NP-PTMC was characterized using scanning electron microscopy and Fourier transform infrared spectroscopy to determine the morphology, stability and chemical interaction of the drug with the polymer. Further, the biodegradation, antibacterial activity, protein adsorption, cell proliferation and drug release characteristics were evaluated. In addition, a Staphylococcus aureus-induced osteomyelitis rabbit model was used to investigate the antibiotic activity and bone repair capability of VCM/TMC NP-PTMC. The results showed that the composite beads of VCM/TMC NPs followed a sustained and slow release pattern and had excellent antibacterial activity and a higher protein adsorption and cell proliferation rate than the VCM-PTMC in vitro. Furthermore, VCM/TMC NP-PTMC inhibits bacteria and promotes bone repair in vivo. Thus, VCM/TMC NP-PTMC might be beneficial in periodontal management to reduce the bacterial load at the infection site and promote bone repair.

Clinical analysis of patients with Laryngopharyngeal reflux disease / 中国耳鼻咽喉头颈外科

OBJECTIVE To study the changes of symptoms and signs of laryngopharyngeal reflux diseases(LPRD) after treatment with esomeprazole.METHODS The suspected LPRD patients were treated with esomeprazole for 8 weeks.Reflux finding score(RFS) and reflux symptoms index(RSI) score were evaluated before and after treatment.RESULTS In RSI,84％ of the patients had the symptom of hoarseness or a problem with voice,87％ had clearing of throat,71％had excess throat mucus,58％ had difficulty swallowing food,52％ had coughing after eat or after lying down,68％ had breathing difficulties or chocking episodes,79％ had troublesome or annoying cough,92％ had lump in your throat or sensation of something sticking in throat,and 32％ had heartburn,chest pain,indigestion or stomach acid coming up.In the RFS,45％ of the patients had pseudosulcus,57％ had ventricular obliteration,94％ had erythema/hyperemia,85％ had vocal cord edema,82％ had diffuse laryngeal edema,83％ had posterior commissure hypertrophy,10％ had granuloma/granulation,and 58％ had thick endolaryngeal mucus.The RSI and RFS score had statistical difference before and after treatment(P＜0.001).CONCLUSION The main symptoms of LPRD were lump in throat or sensation of something sticking in throat,clearing of throat and hoarseness or a problem with voice.The main signs of LPRD were erythema/hyperemia,vocal cord edema and posterior commissure hypertrophy.The PPI has marked improved in symptoms and signs of LPRD.

Characteristics of the Cochlear Symptoms and Functions in Meniere's Disease / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Meniere's disease is a unique, progressive disease of the inner ear. The complex manifestation presents diagnostic challenges. The cochlear symptoms often present before vertigo and tend to be ignored. This study aimed to analyze the characteristics of cochlear symptoms and functions associated with Meniere's disease to investigate the regularity of the development of this disorder.</p><p><b>METHODS</b>One-hundred fifteen patients who were diagnosed with definite unilateral Meniere's disease at the Hearing and Vestibular Clinic of the Department of Otorhinolaryngology of Beijing Tongren Hospital from August 2013 to November 2015 were recruited in this retrospective study. Initial symptoms, duration from initial symptoms to the diagnosis, hearing thresholds, audiogram patterns, and caloric test results were collected and analyzed for each patient. Data were analyzed using SPSS 13.0 statistical software by Spearman's correlation, Kruskal-Wallis H test, Chi-square test, and Fisher's exact test.</p><p><b>RESULTS</b>The average hearing threshold of these patients was 45.24 ± 18.40 dB HL. A majority of the patients (55.65%) were in Stage 3. The initial presentation of the disorder in 58 cases (50.43%) comprised only cochlear symptoms without vertigo. A weak, positive correlation was found between the degree of hearing loss and duration of the disease from initial symptoms to the diagnosis (rs = 0.288, P = 0.002). Upward-sloping, inverted "V," downward-sloping, and flat pattern were the main audiometric patterns observed with a distinctive distribution between stages (P < 0.001). Based on the configurations of audiograms, the audiometric patterns had a weak correlation to the duration (rs = 0.269, P = 0.004), and there was a tendency of duration to rising from upward-sloping, inverted "V", downward-sloping to flat pattern. (H = 10.024, P = 0.018). Frequencies of tinnitus in 56 patients (64.4%) were at the lowest points of the audiograms, i.e., the frequencies of the poorest hearing threshold. The patients at an advanced stage (Stage 3 [56] and Stage 4 [73]) exhibited a significantly higher abnormality of canal paresis than those at the earlier stages (Stage 1 [23] and Stage 2 [42]) (χ2 = 5.973, P = 0.015).</p><p><b>CONCLUSIONS</b>Patients with definite Meniere's disease always have a moderate to severe sensorineural hearing loss before diagnosis. Cochlear symptoms are the most common initial presentation. With the progression of the duration, the hearing impairment becomes more severe and the distribution of the audiometric pattern is distinctive between stages.</p>

Application of cognitive theory of emotion in the study of tinnitus / 临床耳鼻咽喉头颈外科杂志

Tinnitus is a common clinical disorder, which may generate trom a lot of causes, including otological disease and other systemic diseases associated with tinnitus or some factors such as insomnia and emotional cognition. Some studies have found that mood is associated with the occurrence and development of tinnitus and that psychological factors play a role in the occurrence and development of tinnitus in the tinnitus patients with mood disorders. At the same time, the psychological distress and emotional problems caused by tinnitus have drawn more and more attention of clinicians. Based on this, the cognitive theory of emotion can be helpful for evaluating tinnitus, and patients with severe tinnitus can be relieved by biofeedback information in tinnitus management. This article will analyze literature in these disciplines.

Dendrimeric bowties featuring hemispheric-selective decoration of ligands for microRNA-based therapy.

Dendrimers feature a defined number of terminal groups that may bind RNA or be functionalized with bioactive molecules. These competing uses of terminal groups may create an impasse if the requisite density of ligands depletes the number of terminal groups for binding sufficient RNA, or vice versa. A novel dendrimeric platform is needed that maintains high ligand density while retaining sufficient microRNA-binding terminal groups. Here we present a dendrimeric "bowtie" consisting of one-half devoted to microRNA binding and the other half to ligand presentation. We demonstrate its suitability as a transfection agent by delivering miR-126 to human vascular endothial cells (HUVECs) via polyarginine- and RGD-modified bowties and evaluating the downstream effects on proliferation and tube formation. Our findings indicate that the bowtie elicits desired responses and may possess superior delivery properties compared to nondecorated dendrimeric materials. The bowtie system thereby provides a new design model for developing dendrimeric delivery vehicles for RNAi therapeutics.

Clinical observation of pentazocine for postoperative intravenous analgesia in patients with lumbar herniation / 中国骨伤

<p><b>OBJECTIVE</b>To observe the effects and side effects of Pentazocine for postoperative intravenous analgesia in patients with lumbar herniation, and to investigate the difference of Pentazocine with different doses.</p><p><b>METHODS</b>From January 2009 to December 2009, sixty patients undergone laminectomy and pedicle internal fixation, who using equal analgesic dosage of Pentazocine and Sulfentanil, were retrospectively analysed. The patients including 34 males and 26 females, aged 40 to 65 (average 59), weighted 60 to 80 kg (average 71 kg), ASA I-II, were divided into Sufentanil group and Pentazocine group I and Pentazocine group II, with 20 cases each. The regimens of the three groups included: Sufentanil of 2 g/kg; Pentazocine group I of 3 mg/kg; Pentazocine group II of 5 mg/kg. All were diluted with saline into 100 ml and were continuously infused at the rate of 2 ml/h. Visual analogue scale (VAS), Ramsay sedation scale and side effects were recorded at 4, 8, 12, 24, 36, and 48 h postoperatively.</p><p><b>RESULTS</b>The three groups had no significant difference in analgesic effects, VAS of all groups were below 3. The sedation scale of Pentazocine group II at 4, 8, 12 h was higher than that at 4 h, significantly different than the other two groups. The incidence of nausea, vomiting and pruritus in Sufentanil group were higher than that in the other two groups. The incidence of respiratory depression in Sufentanil group and Pentazocine group II were higher than that in Pentazocine group II. The incidence of dizziness in Pentazocine group II were higher than that in the other two groups.</p><p><b>CONCLUSION</b>Pentazocine can produce reliable postoperative analgesia for patients with lumbar herniation, as same as the effect of sulfentanil in equal dose. And Pentazocine has fewer adverse effects compared with sufentanil. 3 mg/kg of Pentazocine is an optimal dose for postoperative intravenous patient-control analgesia.</p>

Association of p53 codon 72 polymorphism with liver metastases of colorectal cancers positive for p53 overexpression / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

<p><b>OBJECTIVE</b>To evaluate the association between p53 codon 72 polymorphism (R72P) and the risk of colorectal liver metastases.</p><p><b>METHODS</b>The p53 R72P genotype was identified by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method in 78 consecutive colorectal cancer patients with liver metastases and 214 age- and sex-matched cases with nonmetastatic colorectal cancer.</p><p><b>RESULTS</b>The R allele of the p53 R72P polymorphism was more frequently found in metastatic cases than in nonmetastatic cases (P=0.075). Carriers of the 72R allele had a 2.25-fold (95% CI (confidence interval)=1.05 to approximately 4.83) increased risk of liver metastases. On the stratification analysis, 72R-carrying genotype conferred a 3.46-fold (95% CI=1.02 to approximately 11.72) and a 1.05-fold (95% CI=0.36 to approximately 3.08) increased risk of liver metastases for p53 overexpression-positive and negative colorectal cancers, respectively.</p><p><b>CONCLUSION</b>These results demonstrate for the first time that the 72R allele of the p53 polymorphism has an increased risk for liver metastases in colorectal cancers positive for p53 overexpression.</p>

Progress in the design of selective ATP-competitive kinase inhibitors / 药学学报

Kinases play crucial roles in the life of cell. Their functional abnormity usually leads to many human major diseases including tumors. The prospecting of ATP-competitive small-molecule kinase inhibitors targeting kinases of therapeutic interest has become the focus of researches. Due to the high conservation of the catalytic domain of kinases, the selectivity of kinase inhibitors is poor in general. However, along with the development of structural biology and computer-aided drug design, great progress in the research of selective, ATP-competitive kinase inhibitors has been achieved in recent years. In this account, the review has been made on the development of the design of selective kinase inhibitors.

Total hepatic ischemia-reperfusion-induced lung injury in rats and protective effects of melatonin / 北京大学学报(医学版)

Objective:To explore total hepatic ischemia-reperfusion(I/R)-induced lung injury in rats,its related mechanism and the protective effects of melatonin on lungs.Methods: This study was divided into 2 parts.In the first part,72 healthy male SD rats weighing 250-300 g were randomly divided into 2 groups: I/R group(ischemia-reperfusion,n=36) and sham-operation group(n=36).Total hepatic I/R was produced by occlusion of hepatic helium for 30 minutes,and the occlusion was then released for reperfusion.The animals were killed at 5 minutes prior to ischemia and 0 h,0.5 h,1 h,3 h and 6 h after reperfusion in sham-operation group and I/R group(n=6 at each time point),and the lung tissue was taken.Through comparisons of these two groups,we observed the dynamic changes of lung tissue after total hepatic I/R.In the second part,12 healthy male SD rats weighing 250-300 g were randomly divided into 2 groups: melatonin group(n=6) and vehicle group(n=6).Melatonin(0.5%,10 mg/kg)or vehicle of the same volume was injected via femoral vein 15 min before ischemia and 10 min before reperfusion,the animals were killed at 1 h after reperfusion,and the lung tissue was taken.Through comparisons of these two groups,we observed the effects of melatonin.Results:(1)Total hepatic I/R led to severe histological injury in lungs.Compared with those in sham-operation group,the MDA content and apoptotic index were increased,the SOD activity was decreased,the p-ERK/ERK ratio and PCNA-positive index were decreased respectively 0 h and 0.5 h after reperfusion,and then were increased gra-dually.Histological examination revealed that the alveolar architecture was destroyed with interstitial thickening and neutrophil infiltration in I/R group.Correlate analysis revealed that p-ERK/ERK ratio showed a positive correlation with PCNA-positive index(r=0.56,P