Background: Nasopharyngeal carcinoma (NPC) is characterized by high programmed death-ligand 1 (PD-L1) expression and abundant infiltration of non-malignant lymphocytes, which renders patients potentially suitable candidates for immune checkpoint blockade therapies. Palate, lung, and nasal epithelium clone (PLUNC) inhibit the growth of NPC cells and enhance cellular apoptosis and differentiation. Currently, the relationship between PLUNC (as a tumor-suppressor) and PD-L1 in NPC is unclear. Methods: We collected clinical samples of NPC to verify the relationship between PLUNC and PD-L1. PLUNC plasmid was transfected into NPC cells, and the variation of PD-L1 was verified by western blot and immunofluorescence. In NPC cells, we verified the relationship of PD-L1, activating transcription factor 3 (ATF3), and β-catenin by western blot and immunofluorescence. Later, we further verified that PLUNC regulates PD-L1 through β-catenin. Finally, the effect of PLUNC on β-catenin was verified by co-immunoprecipitation (Co-IP). Results: We found that PLUNC expression was lower in NPC tissues than in paracancer tissues. PD-L1 expression was opposite to that of PLUNC. Western blot and immunofluorescence showed that β-catenin could upregulate ATF3 and PD-L1, while PLUNC could downregulate ATF3/PD-L1 by inhibiting the expression of β-catenin. PLUNC inhibits the entry of β-catenin into the nucleus. Co-IP experiments demonstrated that PLUNC inhibited the interaction of DEAD-box helicase 17 (DDX17) and β-catenin. Conclusions PLUNC downregulates the expression of PD-L1 by inhibiting the interaction of DDX17/β-catenin in NPC.

Background: Nasopharyngeal carcinoma (NPC) is characterized by high programmed death-ligand 1 (PD-L1) expression and abundant infiltration of non-malignant lymphocytes, which renders patients potentially suitable candidates for immune checkpoint blockade therapies. Palate, lung, and nasal epithelium clone (PLUNC) inhibit the growth of NPC cells and enhance cellular apoptosis and differentiation. Currently, the relationship between PLUNC (as a tumor-suppressor) and PD-L1 in NPC is unclear. Methods: We collected clinical samples of NPC to verify the relationship between PLUNC and PD-L1. PLUNC plasmid was transfected into NPC cells, and the variation of PD-L1 was verified by western blot and immunofluorescence. In NPC cells, we verified the relationship of PD-L1, activating transcription factor 3 (ATF3), and β-catenin by western blot and immunofluorescence. Later, we further verified that PLUNC regulates PD-L1 through β-catenin. Finally, the effect of PLUNC on β-catenin was verified by co-immunoprecipitation (Co-IP). Results: We found that PLUNC expression was lower in NPC tissues than in paracancer tissues. PD-L1 expression was opposite to that of PLUNC. Western blot and immunofluorescence showed that β-catenin could upregulate ATF3 and PD-L1, while PLUNC could downregulate ATF3/PD-L1 by inhibiting the expression of β-catenin. PLUNC inhibits the entry of β-catenin into the nucleus. Co-IP experiments demonstrated that PLUNC inhibited the interaction of DEAD-box helicase 17 (DDX17) and β-catenin. Conclusions PLUNC downregulates the expression of PD-L1 by inhibiting the interaction of DDX17/β-catenin in NPC.

Background: Nasopharyngeal carcinoma (NPC) is characterized by high programmed death-ligand 1 (PD-L1) expression and abundant infiltration of non-malignant lymphocytes, which renders patients potentially suitable candidates for immune checkpoint blockade therapies. Palate, lung, and nasal epithelium clone (PLUNC) inhibit the growth of NPC cells and enhance cellular apoptosis and differentiation. Currently, the relationship between PLUNC (as a tumor-suppressor) and PD-L1 in NPC is unclear. Methods: We collected clinical samples of NPC to verify the relationship between PLUNC and PD-L1. PLUNC plasmid was transfected into NPC cells, and the variation of PD-L1 was verified by western blot and immunofluorescence. In NPC cells, we verified the relationship of PD-L1, activating transcription factor 3 (ATF3), and β-catenin by western blot and immunofluorescence. Later, we further verified that PLUNC regulates PD-L1 through β-catenin. Finally, the effect of PLUNC on β-catenin was verified by co-immunoprecipitation (Co-IP). Results: We found that PLUNC expression was lower in NPC tissues than in paracancer tissues. PD-L1 expression was opposite to that of PLUNC. Western blot and immunofluorescence showed that β-catenin could upregulate ATF3 and PD-L1, while PLUNC could downregulate ATF3/PD-L1 by inhibiting the expression of β-catenin. PLUNC inhibits the entry of β-catenin into the nucleus. Co-IP experiments demonstrated that PLUNC inhibited the interaction of DEAD-box helicase 17 (DDX17) and β-catenin. Conclusions PLUNC downregulates the expression of PD-L1 by inhibiting the interaction of DDX17/β-catenin in NPC.

Objective:To evaluate the value of target blood pressure management based on cerebral oximetry index (COx) during cardiopulmonary bypass (CPB) in preventing postoperative delirium (POD) in patients with acute type A aortic dissection (ATAAD).Methods:One hundred and fifty-seven patients with ATAAD, aged 18-64 yr, regardless of gender, were divided into 2 groups by a random number table method: traditional experience group (group C, n=81) and COx management group (group M, n=76). The mean arterial pressure in group C was maintained in the traditional range of 60-80 mmHg during CPB. In group M, the mean arterial pressure range was obtained based on the COx and maintained within this range during CPB. The primary outcome assessed was the development of delirium within 7 days after surgery. Secondary outcomes included other postoperative complications, tracheal extubation time, and duration of cardiac intensive care unit stay. Results:Compared with group C, the incidence and severity scores of POD were significantly decreased, the duration of POD was shortened, the duration of POD was shortened, the extubation time and duration of cardiac intensive care unit stay were shortened, and the incidence of postoperative cerebral infarction and acute kidney injury was decreased in group M ( P<0.05). Conclusions:Target blood pressure management based on COx during CPB is helpful in reducing the occurrence of POD and improving the prognosis of patients undergoing surgery for ATAAD.

OBJECTIVE To prepare the Eriodictyol chewable tablet and to evaluate its quality. METHODS The chewable tablet was prepared by the wetting granulation method by using microcrystalline cellulose （MCC） and mannitol as fillers， polyvinylpyrrolidone （PVP） as adhesive， citric acid and sucralose as flavor correction agents， magnesium stearate as lubricant. The comprehensive evaluation was conducted on Eriodictyol chewable tablets with the dosage of each excipient as a factor using the appearance， taste， flavor and texture as indicators. The ratio of excipients was optimized by orthogonal test， and the quality of Eriodictyol chewable tablets prepared by optimized formulation was evaluated in terms of appearance， weight difference， hardness， fragility， eriodictyol content， dissolution and content uniformity. RESULTS The optimal formulation was as follows： 26.4% eriodictyol （50 mg each piece）， 45% mannitol， 25% MCC， 0.3% citric acid， 0.3% sucralose， 1% magnesium stearate， 2% PVP （preparing 5% solution using purified water）. The scores of 3 batches of Eriodictyol chewable tablets in the validation test were 8.76， 8.75 and 8.80 （RSD＝0.30%， n＝3）， respectively. The Eriodictyol chewable tablet had a complete appearance and a smooth surface； the average tablet weight was 192.57 mg， the average hardness was 57.36 N， the fragility was 0.09%， the average content of eriodictyol per tablet was 50.74 mg， the cumulative dissolution within 30 min was exceeding 80%， and the content uniformity was 5.51. CONCLUSIONS Eriodictyol chewable tablet prepared by optimal formulation conforms to the requirements of the 2020 edition of Chinese Pharmacopoeia.

OBJECTIVE To evaluate the rationality of epinephrine in the treatment of drug-induced anaphylactic shock， and to provide a reference for further standardizing the treatment measures of anaphylactic shock. METHODS According to the relevant data of the reports of severe adverse drug reaction （ADR） of drug-induced anaphylactic shock provided by Chongqing ADR Monitoring Center from 2015 to 2022， the selection of treatment drugs， and the application of epinephrine in anaphylactic shock were analyzed retrospectively； the clinical outcomes of anaphylactic shock with different epinephrine administration methods were investigated. RESULTS A total of 1 415 cases of severe ADR related to drug-induced anaphylactic shock were reported， with a male-to-female ratio of 1.04∶1； the drugs that caused allergic shock mainly included anti-infective drugs （47.92%）， TCM injections （9.12%）； the patients who suffered from drug-induced anaphylactic shock within 10 min after medication accounted for 43.96%； 97.24% of patients were cured or improved， and 2.76% of patients died or did not been improved. Among 1 415 patients， 63.39% of patients were treated with epinephrine， and the patients who preferred epinephrine treatment accounted for 53.14%； the intramuscular injection， subcutaneous injection， intravenous injection and intravenous drip accounted for 33.78%， 30.32%， 25.75% and 1.23%， respectively. The initial dose range of epinephrine was 0.01-10 mg， and the most frequent single dose was 1 mg （44.70%）. Excessive single doses of intramuscular injection， subcutaneous injection and intravenous injection accounted for 51.03% （148 cases）， 53.13% （136 cases） and 91.47% （193 cases） respectively， and the risk of overdose in intravenous injection was higher （P＜0.05）. The patients receiving initial treatment with epinephrine had a higher improvement rate/cure rate than those who did not use epinephrine （98.14% vs. 96.23%， P＝0.029）； the patients who preferred epinephrine had a higher improvement rate/cure rate than those who did not preferred epinephrine （98.14% vs. 95.17%， P＝0.031）； the improvement rate/cure rate of patients receiving intramuscular injection of epinephrine was higher than those without intramuscular injection （99.01% vs. 96.69%， P＝0.038）. CONCLUSIONS There are some unreasonable phenomena in the treatment of drug-induced anaphylactic shock， such as inappropriate selection of drugs， insufficient use of epinephrine， delay of administration， inappropriate route of administration and excessive single dose.

Objective:To explore the current status of surgery for portal hypertension to grasp current status and future development of surgery in China.Methods:This study is jointly sponsored by China Hepatobiliary & Pancreatic Specialist Alliance & Portal Hypertension Alliance in China (CHESS).Comprehensive surveying is conducted for basic domestic situations of surgery for portal hypertension, including case load, surgical approaches, management of postoperative complications, primary effects, existing confusion and obstacles, liver transplantation(LT), laparoscopic procedures and transjugular intrahepatic portosystemic shunt(TIPS), etc.Results:A total of 8 512 cases of portal hypertension surgery are performed at 378 hospitals nationwide in 2021.Splenectomy plus devascularization predominated(53.0%)and laparoscopy accounted for 76.1%.Primary goal is preventing rebleeding(67.0%) and 72.8% of hospitals used preventive anticoagulants after conventional surgery.And 80.7% of teams believe that the formation of postoperative portal vein thrombosis is a surgical dilemma and 65.3% of hospitals practiced both laparoscopy and TIPS.The major reasons for patients with portal hypertension not receiving LT are due to a lack of qualifications for LT(69.3%)and economic factors(69.0%).Conclusions:Surgery is an integral part of management of portal hypertension in China.However, it is imperative to further standardize the grasp of surgical indications, the handling of surgical operation and the management of postoperative complications.Moreover, prospective, multi-center randomized controlled clinical studies should be performed.

OBJECTIVES: This study aimed to conduct a meta-analysis of the efficacy of mandibular advance clear alig-ners with traditional functional appliances as the control group. METHODS: PubMed, Web of Science, Embase, Cochrane Library, China Biomedical Abstracts Database, China Knowledge Network Database, Wanfang Database, and Weipu Database were used in this study. The two groups of researchers screened the literature and extracted data based on the inclusion and exclusion criteria established by PICOS entries, and used the ROBINS-I scale for quality evaluation. Revman 5.4 and Stata 17.0 software were used for meta-analysis. RESULTS: Nine clinical controlled trials were included in this study with a total sample size of 283 cases. No significant difference was found in SNA, SNB, ANB, Go-Pog, U1-SN, Overjet, and other aspects between the invisible group and the traditional group in the treatment of skeletal class Ⅱ ma-locclusion patients; there was a 0.90° difference in mandibular plane angle between the two groups; the growth of the mandibular ramus (Co-Go) in the traditional group was 1.10 mm more than that in the invisible group; the lip inclination of the lower teeth in the invisible group was better controlled, 1.94° less than that in the control group. CONCLUSIONS The invisible group can better control the lip inclination of the mandibular anterior teeth when guiding the mandible. Furthermore, the mandibular plane angle (MP-SN) can remain unchanged, but the growth of the mandibular ramus is not as good as the traditional group, and auxiliary measures should be taken to improve it in clinical practice.
Humans ; Malocclusion, Angle Class II/therapy* ; Mandibular Advancement ; Orthodontics, Corrective ; Orthodontic Appliances, Functional ; Mandible ; Orthodontic Appliances, Removable ; Cephalometry

OBJECTIVE To evalu ate the effects of perimenopausal one-day outpatient multidisciplinary model on the cognition of women to menopause hormone therapy （MHT）. METHODS The perimenopausal one-day outpatient service opened by the Third Affiliated Hospital of Chongqing Medical University in 2017 was introduced ，which was participated by doctors ，pharmacists， nutritionists，music psychotherapists ，nurses and other multidisciplinary members to provide systematic ，all-round，humanistic and face-to-face group science popularization and education ，practical experience and Q&A for women in perimenopause or about to enter perimenopause （called“students”）. The students who participated in one-day outpatient service in 2020 were selected as the survey object ， and the questionnaire was CMEI2020KPYJ（ZAMM）00206] designed to analyze the understanding of perimenopausal syndrome，awareness rate of MHT ，willingness to use and concerns. RESULTS A total of 295 students completed the questionnaire. Compared with before participation ， after participated in one-day outpatient service ，the cognition level of the students were all improved significantly ，including perimenopausal age （96.61％ vs. 99.32％，P＝0.037），the importance of perimenopausal health care knowledge （91.19％ vs. 96.95％，P＜0.001），whether the perimenopausal syndrome needs treatment （88.47％ vs. 99.32％，P＜0.001），willingness to use MHT （70.59％ vs. 94.48％ ，P＜0.001），MHT treatment timing （60.50％ vs. 95.17％ ，P＜0.001），reducing the risk of cardiovascular disease （51.68％ vs. 96.55％ ，P＜0.001），delaying aging （69.75％ vs. 97.59％ ，P＜0.001），preventing osteoporosis（65.13％ vs. 97.59％），P＜0.001）；the medical staff were higher than the non-medical staff （P＜0.05）. Totally 90％ of the students said they had gained knowledge about the prevention and treatment of common diseases ，nutrition and guidance， psychological regulation guidance hormone therapy related knowledges and exercise methods ；the proportion of the students who were willing to use MHT for 1 to 5 years（31.09％ vs. 47.93％）increased significantly. The proportion of the students who concerned about the risk of thrombosis （60.24％ vs. 36.81％），weight gain （59.64％ vs. 14.84％）and life-long dependence （52.41％ vs. 18.13％）was significantly reduced ，but that of the students who concerned about cancer risk was not diminished. From 2017 to 2020，the utilization rate of MHT was increased from 2.22％ to 62.16％ in non-medical staff among the students. CONCLUSIONS The multidisciplinary model of perimenopausal one-day outpatient service can improve the awareness of MHT among perimenopausal women ，eliminate misunderstandings ，and increase the utilization rate of MHT.

OBJE CTIVE To investigate the clinical characteristics of a dverse drug reactions of asparaginase-associated pancreatitis（AAP），so as to provide reference for clinical safe medication. METHODS Analysis and identification were performed on a severe adverse reaction case of acute pancreatitis complicated with diabetic ketoacidosis and liver injury in a patient with acute lymphoblastic leukemia in our hospital after using pegaspargase. Retrieved from Wanfang database ，CNKI，PubMed and Embase database，case reports of AAP were collected and summarized in terms of patient demographics ，drug use ，incubation period and adverse reaction outcome. Combined with this case ，the disease characteristics and potential risk factors of AAP were analyzed and discussed. RESULTS After analysis and identification ，it was determined that AAP occurred in this patient. A total of 47 case reports were retrieved from the database ，and a total of 52 patients（including this patient ）were included in the analysis ，including 29 males and 23 females，mainly minors （65.4％）. L-asparaginase was the main asparaginase preparation that causes AAP （80.8％）. Gastrointestinal symptoms were the main prodromal symptoms （92.3％），which could be accompanied by other asparaginase related adverse reactions. AAP could occur after 1-33 times of administration ，and the median latency was 14 days after administration；compared with children ，median latency of AAP in adult patients was shortened significantly （11 d vs. 16 d，P＝ 0.049）；the median latency of AAP had longer tendency in patients treated with pegaspargase than that of L-asparaginase （17 d vs. 12.5 d，P＝0.490）. Of the cases included in the analysis ，8 patients died due to AAP ，1 of which was related to re-exposure to asparaginase preparations. CONCLUSIONS Acute pancreatitis is a serious and potentially fatal adverse drug reaction of ； asparaginase preparations. Clinical medical staff should pay attention to the characteristics of AAP ，consider the possibility ： of AAP when the patients have gastrointestinal symptoms and do a good job in patient education and pharmaceutical care to minimize the damage caused by AAP to patients.