Potential mechanism of action of Jing Fang Bai Du San in the treatment of COVID-19 using docking and network pharmacology.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), severely infects people and has rapidly spread worldwide. JingFangBaiDu San (JFBDS) has been used to treat prevalent epidemic pathogens, common cold, headache, cough due to lung-cold, and other symptoms; however, its treatment for COVID-19 is unknown. Molecular docking and network pharmacology were applied to obtain ingredient-protein structures and the herb-ingredient-disease target network model, respectively, to explore the potential mechanism of JFBDS in COVID-19 treatment. Network pharmacology analysis showed that acacetin, wogonin, and isorhamnetin were the main active ingredients of JFBDS, and EGFR, PIK3CA, LCK, MAPK1, MAPK3, MAPK8, STAT3, TNF, IL2, and RELA were speculated to be crucial therapeutic targets. Moreover, the Toll-like receptors, HIF-1, PIK3K/AKT, MAPK, NF-κB and NOD-like receptor signaling pathways were important for JFBDS in COVID-19 treatment. Molecular docking analysis indicated that ingredients of JFBDS could bind to angiotensin converting enzyme II, spike protein, and chymotrypsin like protease (3CLpro), which inhibits virus entry and replication in host cells. This study provides a new perspective for understanding potential therapeutic effects and mechanisms of JFBDS in COVID-19 and may facilitate its clinical application.

Diagnosis of glossopharyngeal obstruction using nasopharyngeal tube versus CT scan in obstructive sleep apnea-hypopnea syndrome.

The polysomnography after nasopharyngeal tube insertion (NPT-PSG) was used to assess glossopharyngeal airway obstruction in patients with moderate-to-severe obstructive sleep apnea-hypopnea syndrome (OSAHS), and was compared with that obtained using spiral computed tomography (CT). A total of 125 patients diagnosed with moderate-to-severe OSAHS using PSG were subjected to PSG after NPT insertion, and spiral CT was used for continuous scan of the upper respiratory tract. The NPT-PSG and CT scan results were subjected to correlation analysis. In addition, the two sets of data were used separately to determine whether there was glossopharyngeal airway stenosis or obstruction, and the results were compared. Neither apnea hypopnea index (AHI) nor lowest oxygen saturation (LSaO2) obtained from the first PSG was significantly correlated with the cross-sectional area or the inner diameter of the glossopharyngeal airway. NPT-PSG AHI was significantly correlated with the cross-sectional area and anteroposterior diameter of the glossopharyngeal airway, with correlation coefficients of 0.264 and 0.185, and P values of 0.003 and 0.039, respectively. NPT-PSG AHI was not significantly correlated with the left-right diameter of the airway, and NPT-PSG LSaO2 was not significantly correlated with the cross-sectional area or the inner diameter of the glossopharyngeal airway. With NPT-PSG, 52 patients showed obvious glossopharyngeal airway stenosis while 73 patients did not, and with CT scan 41 patients showed obvious glossopharyngeal airway stenosis while 84 patients did not. The two methods reached the same diagnosis in 86 cases, with a consistency rate of 68.8 %. Spiral CT and NPT-PSG show certain degrees of consistency by assessing the presence of glossopharyngeal airway stenosis or obstruction, and there are also notable differences. Clinical assessment on glossopharyngeal airway obstruction should be based on a combination of multiple methods.

Lingua-epiglottis position predicts glossopharyngeal obstruction in patients with obstructive sleep apnea hypopnea syndrome.

The objective of the study was to investigate the relationship between lingua-epiglottis position and glossopharyngeal obstruction in patients with obstructive sleep apnea hypopnea syndrome (OSAHS). One hundred and four patients with OSAHS diagnosed by polysomnography (PSG) were enrolled. Lingua-epiglottis position was visualized using endoscopy and classified into three types. Spiral CT imaging of the upper respiratory tract was performed to measure the cross-sectional area and inner diameter of the glossopharyngeal airway. The PSG was repeated after nasopharyngeal tube insertion (NPT-PSG). The NPT-PSG results, CT-measured data and incidence of stenosis were compared among the different lingua-epiglottis position groups. Obstructive sleep apnea hypopnea syndrome patients with different lingua-epiglottis positions had similar demographics. As lingua-epiglottis position type varied from type I to type III, cross-sectional area and inner diameter of the glossopharyngeal area decreased, glossopharyngeal airway stenosis rate increased, and apnea hypopnea index measured by NPT-PSG increased. The lowest oxygen saturation decreased. Lingua-epiglottis position was significantly related to glossopharyngeal obstruction. Lingua-epiglottis position should be used in clinical practice for the preliminary assessment of glossopharyngeal obstruction.

[Practice of medical care and rescue Amne Machin extreme cross-country challenge].

OBJECTIVE: To share the practice of medical care and rescue in the 2017-2019 Amne Machin extreme cross-country challenge. METHODS: At the invitation of the Organizing Committee of Amne Machin extreme cross-country challenge of Maqin County of Qinghai Province. More than 150 medical personnel were sent to make the rescue plan and implement the medical security for three consecutive years. The support was divided into leading command group, expert consulting group, on-site medical support group, rear medical support group, and medical material support group. The on-site medical support group was equipped with the ambulance, corresponding emergency medical equipments and medicines to provide medical support at eight medical stations from the starting point to the endpoint and along the route between each station. RESULTS: There were no cardiac arrest and sudden death cases during the three competitions. A total of 56 patients (5 cases of combined injuries) were received, including 21 cases of mild altitude reaction, 8 cases of abrasions, 13 cases of muscle spasm and strain, 11 cases of hypoglycemia, and 3 cases of abdominal pain. All the injured were treated and observed in time. Each patient achieved a complete remission. CONCLUSIONS: To achieve the success of medical security of the highest average altitude cross-country race certified by International Trail Running Association (ITRA), we must formulate a scientific and perfect medical security work plan in the first place: pre competition physical examination, especially the application of sports cardiopulmonary function test, screen out athletes who may have medical accidents; during the competition, focus on monitoring and tracking the players who may have problems; each support point is closely connected with the support vehicle; do a good job of first aid training for all kinds of personnel, so that medical accidents can be found, aided, and transferred at the first time. The medical care and rescue of Amne Machin extreme cross-country challenge have played a good role in the security of the international plateau sports events, which provides a reference for the security of similar events.

N-terminal truncated carboxypeptidase E represses E-cadherin expression in lung cancer by stabilizing the Snail-HDAC complex.

The N-terminal truncated carboxypeptidase E (CPEΔN) protein, an alternative splicing product of the carboxypeptidase E gene, has recently been recognized as an independent predictor for the recurrence and metastasis of lung adenocarcinoma. In this study, we showed that CPEΔN may accelerate lung cancer invasion via an E-cadherin-dependent mechanism. In vitro experiments and in vivo bioluminescence imaging assay revealed CPEΔN promoted the mobility and invasion of human lung cancer cells by suppressing endogenous expression of E-cadherin, a critical regulator for epithelial tissue homeostasis. Further mechanistic analyses revealed that CPEΔN directly interacted with and stabilized the Snail/HDAC1/HDAC3 complex within the promoter region of the E-cadherin-encoding CDH1 gene. CPEΔN overexpression led to a reduction of histone H3K9 acetylation and an increase of H3K9 and H3K27 trimethylation in the CHD1 gene promoter and ultimately inhibited E-cadherin transcription. In addition, correlations among CPEΔN, E-cadherin expression and tumor progression in 195 cases of lung adenocarcinoma patients were analyzed. Higher nuclear expression of CPEΔN was detected in patients with advanced stage of lung adenocarcinoma. Nuclear expression of CPEΔN was negatively correlated with the cell membrane expression of E-cadherin. Collectively, our findings illustrated that CPEΔN was involved in the transcriptional regulation of the epithelial-mesenchymal transition-related gene CDH1 and provide novel insights into CPEΔN-associated lung cancer metastasis.

N-terminal truncated carboxypeptidase E expression is associated with poor prognosis of lung adenocarcinoma.

Lung cancer is a malignant tumor with high morbidity and mortality rates. To date, no suitable molecular diagnostic tool to predict disease recurrence and metastasis has been identified. The current study aimed to evaluate the potential of N-terminal truncated carboxypeptidase E (CPEΔN) to predict the recurrence and metastasis of lung adenocarcinoma. Western blotting revealed the co-expression of CPE and CPEΔN in the surgically collected pathological and pericarcinoma tissues tissues of 62.1% (59/95) lung adenocarcinoma patients. The full length CPE protein was predominantly expressed in pericarcinoma tissues and CPEΔN expression was identified in the pericarcinoma normal tissues of only 5.26% (5/95) patients. The 3-year postoperative recurrence and metastasis rates were significantly higher in patients with positive CPEΔN expression than in patients with negative CPEΔN expression (P=0.009). Furthermore, the overall survival rate of patients with predominant nuclear CPE expression was lower than that of patients with predominant cytoplasmic CPE expression (46.3 vs. 64.7%); however, no statistically significant difference was identified (P=0.125). Thus, the results of the current study indicated that CPEΔN may present a novel molecular biomarker for predicting recurrence and metastasis of lung adenocarcinoma, which may aid with stratifying patients by risk and thus, may facilitate individualized therapy.

The nasopharyngeal tube: a simple and effective tool to indicate the need for uvulopalatopharyngoplasty.

OBJECTIVES/HYPOTHESIS: To compare polysomnography (PSG) data after nasopharyngeal tube (NPT) insertion and uvulopalatopharyngoplasty (UPPP), and explore the possibility of predicting UPPP outcomes with NPT-PSG. STUDY DESIGN: Prospective nonrandomized study. METHODS: PSG was performed after NPT insertion in 73 inpatients with obstructive sleep apnea-hypopnea syndrome (OSAHS). All patients accepted UPPP surgery. PSG was repeated after 12 months of UPPP to assess curative effects. Data were then compared to correlate NPT-PSG with the efficacy of UPPP. RESULTS: NPT insertion decreased the overall apnea-hypopnea index (AHI) and increased the lowest oxygen saturation (LaSO2 ). NPT-PSG results correlated well with surgical outcomes 12 months post-UPPP. The correlation coefficient for AHI and LaSO2 were 0.571 (P < .001) and 0.268 (P = .033), respectively. Next, enrolled patients were divided into two groups based on NPT-PSG results: group A, AHI <15 times/hr, 50 cases; group B, AHI ≥15 times/hr, 23 cases. The UPPP surgery success rates of the two groups were 86.0% and 39.1%, respectively. CONCLUSIONS: NPT-PSG data are closely correlated with UPPP efficacy and may assist in the selection of appropriate OSAHS patients for UPPP. An AHI ≥15 times/hr after NPT insertion indicates glossopharyngeal obstruction and suggests the need for appropriate intervention. LEVEL OF EVIDENCE: 4.

Nasopharyngeal tube: a simple and effective tool to screen patients indicated for glossopharyngeal surgery.

STUDY OBJECTIVES: The aim of this prospective controlled study was to explore the diagnostic value of repeated polysomnography (PSG) post-nasopharyngeal tube insertion in the setting of glossopharyngeal obstruction in obstructive sleep apnea hypopnea syndrome (OSAHS). METHODS: Patients were eligible for this study if they were diagnosed as OSAHS by the first PSG and presented with moderate to severe OSAHS by repeated PSG scanning post-nasopharyngeal tube insertion (NPT-PSG). Fifty-nine patients were enrolled into this study and assigned to received either modified uvulopalatopharyngoplasty (H-UPPP; n = 25) or H-UPPP in combination with glossopharyngeal surgery (n = 34). RESULTS: General data and PSG data were collected prior to and following nasopharyngeal tube insertion and were found not to be significantly different. However, both the PSG and Epworth sleepiness scale (ESS) were significantly superior in the combination group compared to the UPPP alone group post-surgery. The success rates of surgery were 82.3% and 40.0%, respectively. CONCLUSION: Patients with moderate to severe OSAHS post-nasopharyngeal tube insertion generally have glossopharyngeal obstruction. Glossopharyngeal surgery can significantly improve surgical outcome in the setting of OSAHS.

Outcomes of upper airway reconstructive surgery for obstructive sleep apnea syndrome based on polysomnography after nasopharyngeal tube insertion.

BACKGROUND: The most common obstruction sites for obstructive sleep apnea hypopnea syndrome (OSAHS) are the oropharynx and the glossopharyx. The diagnosis of glossopharyngeal airway obstruction is difficult. The study aimed to assess the effect of upper airway reconstructive surgery for OSAHS based on polysomnography (PSG) after nasopharyngeal tube insertion (NPT-PSG), and to evaluate the clinical value of NPT-PSG in localizing the obstructive sites. METHODS: Seventy-nine OSAHS patients diagnosed with PSG were included in the study. PSG was repeated with a nasopharyngeal tube in place (NPT-PSG). RESULTS: of the two PSGs were compared. A NPT-PSG apnea hypopnea index (AHI) greater than 15 times per hour was used as a threshold for glossopharyngeal surgery. The cause of glossopharyngeal airway obstruction was taken into consideration in planning glossopharyngeal surgery. Assessment of efficacy was followed-up. RESULTS: After NPT-PSG, patients' AHI significantly decreased and lowest oxygen saturation (LaSO2) significantly increased. Of the 79 patients, 47 were treated with uvulopalatopharyngoplasty (UPPP) alone and 32 with UPPP + glossopharyngeal surgery. Thirty-two patients were considered cured, 33 markedly improved, and 14 failed. The overall surgery success rate was 82.3%. CONCLUSIONS: NPT-PSG can be used as a diagnosis tool for localizing airway obstruction in OSAHS patients. Surgical treatment based on NPT-PSG results in good treatment efficacy.

[Treatment and prevention of serious perioperative complications of obstructive sleep apnea hypopnea syndrome].

OBJECTIVE: To summarize experiences of serious perioperative complications management of obstructive sleep apnea hypopnea syndrome (OSAHS), and evaluate the effect of intervention in decreasing the incidence of serious complications. METHODS: Retrospective analysis of clinical data in Shenyang General Hospital of PLA and Liaoning Province Jinqiu Hospital of OSAHS surgery cases from January 1995 to December 2009 were included in this study, patients were divided into two groups according to with or without intervention. Experience and lessons were analyzed. RESULTS: Patients without and with intervention were 402 and 521 respectively, and uvulopalatopharyngoplasty (UPPP) cases in each group were 387 and 390. Five patients in the first group who accepted UPPP had breathing difficulty and were all successfully rescued, while no one in the second group had breathing difficulty. The difference was significant (P < 0.05). Sixteen patients in the first group had severe bleeding after UPPP, while only 5 patients had the severe bleeding in the second group. The difference was significant, too P < 0.05. No breathing difficulty cases in the second group, and serious bleeding cases in each group was 5 and in 1, there was no significant difference (P > 0.05). CONCLUSIONS: Breath difficulty and serious bleeding are serious perioperative complications of OSAHS surgery, and with systemic intervention the incidence of the complications can be decreased.

[Down-regulation of Twist1 increases the sensitivity of nasopharyngeal carcinoma cell lines HNE1 to taxol].

OBJECTIVE: To investigate whether down-regulation of Twist1 could change sensitivity of nasopharyngeal carcinoma cell line HNE1 to taxol. METHODS: HNE1 cells were transfected with the small interfering RNA (siRNA) expression vector pSuppressor-Retro-Si-Twist, containing the short hairpin RNA (shRNA) sequence targeting the Twist gene-coding region by Fugene 6. Positive clones were then selected in Neomycin (400 microg/ml) for 21 days. The low expressions of Twist1 were examined by real-time reverse-transcription polymerase chain reaction (RT-PCR) and Western blot. Drug sensitivity of si-Twist1 HNE1 to taxol was determined by Annexin V-fluorescein isothiocyanate( FITC)/propidium lodide (PI) double-labeled flow cytometry and detection of DNA ladder. The Effect of Twist1 inactivation on HNE1 cell proliferation was observed by MTT assay and flow cytometry. RESULTS: Annexin V- FITC-PI assay showed that apoptosis ratio was 40.2% in si-Twist HNE1 after treated with 10 ng/ml taxol, significantly higher than that in the control siRNA group 24.3%. The deference had statistic meaning. After the re-expression of HNE1, apoptosis ratio was 44.80% +/- 4.80% (x +/- s) in low Twist1 protein expression group and that was 27.00% +/- 2.91% in high expression group. The deference had statistic meaning (t = 4.374, P = 0.049). Real time PCR test revealed apoptosis protein bcl-2 expression in si-Twist HNE1 was 0.28 +/- 0.05, significantly lower than that in the control siRNA HNE1 (0.57 +/- 0.08, t = 6.710, P = 0.021), nevertheless, significant bax and bcl-XL changes were not observed (t = 2.000, P = 0.184 and t = 1.502, P = 0.272). MTT and FCM showed that down-regulation of Twist1 did not alter cell proliferation rate (P>0.05). CONCLUSIONS: Down-regulation of Twist1 could increase drug sensitivity of nasopharyngeal carcinoma cell line HNE1 to taxol by inducing apoptosis. These results suggested that Twist1 may be a promising treatment target for nasopharyngeal carcinoma therapy.

[Study of lingual arterial CT angiography and security of partial glossectomy in obstructive sleep apnea hypopnea syndrome].

OBJECTIVE: To explore the difference of lingual arterial CT angiography images(CTA) between obstructive sleep apnea hypopnea syndrome (OSAHS) patients and normal subjects, and to investigate the safety of partial glossectomy guided by lingual arteria CT angiography. METHODS: Seventy-four patients with OSAHS and 10 control adults were included in the study. The lingual upper airway and lingual arterial CT angiography were obtained. The area and the dimensions of lingual upper airway, and the length and thickness of lingua, length of lingual arteria, depth and bilateral lingual arteria spacing were studied. The CT measuring data of OSAHS patients and normal adults were compared. The multinomial logistic regression analysis was used to investigate the main factors which affects the lingual arterial measuring results. Guided by the lingual arterial CT angiography and measuring results, glossectomy was performed in 23 OSAHS patients with lingua hypertrophy. RESULTS: The area and dimensions of lingual airway of OSAHS patients were less than those of control adults, and the length and thickness of lingua of OSAHS were more than those of control adults (t test, P < 0.05 or P < 0.01). There were no difference in length of lingual arteria and bilateral lingual arteria spacing between OSAHS patients and control adults. The 3 measured points' depth (x(-) +/- s) of lingual arteria of OSAHS patients were (29.1 +/- 5.5) mm, (26.9 +/- 5.1) mm and (25.6 +/- 5.2) mm, respectively, and those of control adult were (23.0 +/- 3.8) mm, (22.6 +/- 2.7) mm and (21.5 +/- 2.6) mm, the depth of lingual arteria of OSAHS was more than that of control adults (t test, P < 0.05 or P < 0.01). The main factors affects lingual arterial depth were body mass index (BMI), lingual length and lingual thickness, unstandardized regression coefficient were 0.255, 0.11 and 0.03, respectively (analysis of variance, F = 6.216, P < 0.05). No damage of lingual arteria and nerve in 23 patients who had expanded glossectomy. CONCLUSIONS: The study showed statistical difference significance of lingual arterial CTA measurements between OSAHS patients and control adults. Guided with lingual arteria CTA data, the expanded glossectomy in OSAHS patients has proved good safety and high cure rate.

[Self-reported prevalence of allergic rhinitis in eleven cities in China].

OBJECTIVE: The aim of this study is to investigate the self-reported prevalence and other epidemiological characteristics of allergic rhinitis from 11 cities throughout the mainland of China. METHODS: Telephone interviews were conducted in the two main municipalities (Beijing, Shanghai) and eight capital cities (Changsha, Changchun, Hangzhou, Guangzhou, Nanjing, Shenyang, Wuhan, Urumqi and Xi'an) of main provinces throughout the mainland of China after sampling target phone numbers by the approach of random digital dialing (RDD) via computer. RESULTS: In total, the survey had sampled 684 blocks of telephone numbers in 11 cities, and dialed 119 319 telephone numbers. Of the 38 203 respondents, 4253 subjects reported allergic rhinitis, while the other 33 950 were screened negative in the telephone interviews. The self-reported prevalence of allergic rhinitis was lowest in Xi'an (8.0%), and highest in Urumqi (21.4%), with Nanjing having intermediate value (11.5%). The gender-adjusted prevalence ranged from 8.5% in Xi'an to 21.3% in Urumqi, while the age-adjusted prevalence of self-reported allergic rhinitis ranged from 8.7% in Beijing to 24.1% in Urumqi. CONCLUSIONS: The study demonstrates that the self-reported prevalence of allergic rhinitis in 11 cities throughout the mainland of China has wide variations, and the strategy of prevention for allergic rhinitis should be conducted according to the epidemic features of it.

[The effects of body posture on upper airway in OSAHS patients].

OBJECTIVE: To explore the effects of body posture on upper airway shapes in OSAHS patients. METHOD: Thirty-one male OSAHS patients were included in the study. The fibre endoscopic photos were taken on palate and lingua region upper airway at normal breath at supine with 30 degree neck flexion, supine and right lateral recumbent position, respectively. The cross section area and the dimensions of palate and lingua region upper airway were studied by running image tools software in computer. RESULT: In OSAHS patients, there were obviously difference in the area and arrowy dimension of palate airway among three posture, and so to in area, arrowy and coronary dimension of lingua airway. CONCLUSION: The study suggests that the body posture changes have obviously influence on upper airway, and the influence is the base of apnea increasing at special posture.

[Localization of upper airway stricture in patients with obstructive sleep apnea syndrome by CT scan].

OBJECTIVE: To evaluate the diagnostic significance of CT scan in the localization of the stricture in the upper airway in patients with obstructive sleep apnea syndrome (OSAS). METHODS: Fifty-four patients with OSAS were included in this study. CT scan evaluated the upper airway from the roof of nasopharynx to the glottis using a Phlips Tomoscan AV Expander E1 spiral scanner. The areas and the dimensions of palate, uvula, lingua and epiglottis region, as well as the thickness of retropharyngeal and lateral pharyngeal tissue was evaluated. The reference values had been set-up in 225 normal adult upper airways CT scan, some patients' results were compared with the CT scan results during apnea. RESULTS: There were no any upper airway stricture in 12 patients with OSAS, and there were one or more upper airway stricture sites in other 42 patients. Twenty-four patients had only one stricture site. Fourteen patients had 2 adjacent stricture sites. One patient had three stricture sites. Three patients had 4 upper airway strictures. There was a good concordance between the results of CT scans during awakening and sleeping in 14 patients. CONCLUSION: Most patients with OSAS had anatomic upper airway strictures, the CT scan can localize the stricture site very well.