Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.

Objective: To analyze the incidence and the related risk factors of retropharyngeal lymph node metastasis in patients with hypopharyngeal squamous cell carcinoma, evaluate the accuracy of preoperative enhanced CT in judging retropharyngeal lymph node metastasis, and investigate the impact of retropharyngeal lymph node metastasis on the prognosis. Methods: Retrospective analyses were made on 398 patients with hypopharyngeal squamous cell carcinoma who underwent surgery as the primary therapy and accepted retropharyngeal lymph node exploration and clearance during surgery in Shandong Provincial ENT Hospital from January 2014 to December 2019. Multivariate logistic regression analysis was used to clarify the related risk factors of retropharyngeal lymph node metastasis. Multivariate Cox regression analysis was used to investigate the impact of retropharyngeal lymph node metastasis on prognosis. The retropharyngeal lymph nodes of 218 cases with available preoperative enhanced CT images were evaluated by two experienced radiologists and compared with postoperative pathological results. Results: Retropharyngeal lymph node metastasis were confirmed in 54 of 398 (13.6%) cases according to postoperative pathology. The sensitivity and specificity of preoperative enhanced CT in the diagnosis of retropharyngeal lymph node metastasis were 34.6% and 91.1%, respectively, and the overall accuracy was 84.4%. Multivariate logistic regression analysis showed that the site of the primary lesion and pathological N stage were independent risk factors for retropharyngeal lymph node metastasis in hypopharyngeal squamous cell carcinoma. Patients with primary lesion located in the posterior wall of hypopharynx (OR=4.83, 95% CI: 1.27-18.40), N2 stage (OR=6.30, 95% CI: 2.25-17.67), and N3 stage (OR=26.89, 95% CI: 5.76-125.58) were prone to retropharyngeal lymph node metastasis. The 5-year overall survival rate of the 398 patients was 50.4%, and the 5-year disease-free survival rate was 48.3%. Multivariate Cox regression analysis showed that T stage, N stage, retropharyngeal lymph node metastasis, and radiotherapy were independent influencing factors for overall survival (T stage: HR=1.28, 95% CI: 1.06-1.54; N stage: HR=1.26, 95% CI: 1.14-1.40; retropharyngeal lymph node metastasis: HR=2.13, 95% CI: 1.47-3.08; radiotherapy: HR=0.54, 95% CI: 0.38-0.76) and disease-free survival of patients with hypopharyngeal squamous cell carcinoma (T stage: HR=1.26, 95% CI: 1.06-1.51; N stage: HR=1.25, 95% CI: 1.13-1.37; retropharyngeal lymph node metastasis: HR=2.24, 95% CI: 1.56-3.21; radiotherapy: HR=0.55, 95% CI: 0.40-0.77). Conclusions: Metastasis of retropharyngeal lymph nodes in hypopharyngeal squamous cell carcinoma is not rare. Enhanced CT is of low accuracy and limited value in diagnosing retropharyngeal lymph node metastasis. Primary lesions located in the posterior wall of the hypopharyngx, N2 stage, and N3 stage are independent high-risk factors for retropharyngeal lymph node metastasis. The prognosis of hypopharyngeal cancer patients with retropharyngeal lymph node metastasis is worse, and active surgical exploration and clearance can effectively reduce the mortality caused by retropharyngeal lymph node metastasis.
Humans ; Squamous Cell Carcinoma of Head and Neck/pathology* ; Lymphatic Metastasis/pathology* ; Retrospective Studies ; Carcinoma, Squamous Cell/surgery* ; Lymph Nodes/pathology* ; Hypopharyngeal Neoplasms/surgery* ; Prognosis ; Head and Neck Neoplasms/pathology* ; Neoplasm Staging

Objective: To retrospectively analyse the efficacy of surgerical comprehensive treatment for hypopharyngeal cancer. Methods: Four hundred and fifty-six cases of hypopharyngeal squamous cell carcinoma treated from Jan 2014 to Dec 2019 were analyzed retrospectively, including 432 males and 24 females, aged 37-82 years old. There were 328 cases of pyriform sinus carcinoma, 88 cases of posterior pharyngeal wall carcinoma, and 40 cases of postcricoid carcinoma. According to American Joint Committe on Cancer(AJCC) 2018 criteria, 420 cases were of stage Ⅲ or Ⅳ; 325 cases were of T3 or T4 stage. Treatment methods included surgery alone in 84 cases, preoperative planned radiotherapy plus surgery in 49 cases, surgery plus adjuvant radiotherapy or concurrent chemoradiotherapy in 314 cases, and inductive chemotherapy plus surgery and adjuvant radiotherapy in 9 cases. The primary tumor resection methods included transoral laser surgery in 5 cases, partial laryngopharyngectomy in 74 cases, of them 48 cases (64.9%) presented with supracricoid hemilaryngopharyngectomy, total laryngectomy with patial pharyngectomy in 90 cases, total laryngopharyngectomy or with cervical esophagectomy in 226 cases, and total laryngopharyngectomy with total esophagectomy in 61 cases. Among 456 cases, 226 cases received reconstruction surgery with free jejunum transplantation, 61 cases with gastric pull-up, and 32 cases with pectoralis myocutaneous flaps. All patients underwent retropharyngeal lymph node dissection, and high-definition gastroscopy was performed during admission and follow-up. SPSS 24.0 software was used to analyze the data. Results: The 3-year and 5-year overall survival rates were respectively 59.8%, and 49.5%. The 3-year and 5-year disease specific survival rates were respectively 69.0% and 58.8%. Total metastasis rate of retropharyngeal lymph nodes was 12.7%. A total of 132 patients (28.9%) suffered from simultaneous and metachronous multiple primary carcinoma of the hypopharynx. Multivariate Logistic regression analysis showed that T3-4 disease, cervical lymph node metastasis, retropharyngeal lymph node metastasis and postoperative adjuvant radiotherapy were independent factors affecting the prognosis of patients (all P<0.05). As of April 30, 2022, a total of 221 patients died during follow-up, of 109 (49.3%) with distant metastases, which were the main cause of death. Conclusions: The efficacy of comprehensive treatment for hypopharyngeal cancer can be improved by accurate preoperative evaluation, improved surgical resection, active retropharyngeal lymph node dissection and full process intervention of the second primary cancer.
Male ; Female ; Humans ; Adult ; Middle Aged ; Aged ; Aged, 80 and over ; Hypopharyngeal Neoplasms/pathology* ; Carcinoma, Squamous Cell/pathology* ; Lymphatic Metastasis ; Retrospective Studies ; Neck Dissection/methods* ; Head and Neck Neoplasms/surgery*

Objective: To analyze the incidence and the related risk factors of retropharyngeal lymph node metastasis in patients with hypopharyngeal squamous cell carcinoma, evaluate the accuracy of preoperative enhanced CT in judging retropharyngeal lymph node metastasis, and investigate the impact of retropharyngeal lymph node metastasis on the prognosis. Methods: Retrospective analyses were made on 398 patients with hypopharyngeal squamous cell carcinoma who underwent surgery as the primary therapy and accepted retropharyngeal lymph node exploration and clearance during surgery in Shandong Provincial ENT Hospital from January 2014 to December 2019. Multivariate logistic regression analysis was used to clarify the related risk factors of retropharyngeal lymph node metastasis. Multivariate Cox regression analysis was used to investigate the impact of retropharyngeal lymph node metastasis on prognosis. The retropharyngeal lymph nodes of 218 cases with available preoperative enhanced CT images were evaluated by two experienced radiologists and compared with postoperative pathological results. Results: Retropharyngeal lymph node metastasis were confirmed in 54 of 398 (13.6%) cases according to postoperative pathology. The sensitivity and specificity of preoperative enhanced CT in the diagnosis of retropharyngeal lymph node metastasis were 34.6% and 91.1%, respectively, and the overall accuracy was 84.4%. Multivariate logistic regression analysis showed that the site of the primary lesion and pathological N stage were independent risk factors for retropharyngeal lymph node metastasis in hypopharyngeal squamous cell carcinoma. Patients with primary lesion located in the posterior wall of hypopharynx (OR=4.83, 95% CI: 1.27-18.40), N2 stage (OR=6.30, 95% CI: 2.25-17.67), and N3 stage (OR=26.89, 95% CI: 5.76-125.58) were prone to retropharyngeal lymph node metastasis. The 5-year overall survival rate of the 398 patients was 50.4%, and the 5-year disease-free survival rate was 48.3%. Multivariate Cox regression analysis showed that T stage, N stage, retropharyngeal lymph node metastasis, and radiotherapy were independent influencing factors for overall survival (T stage: HR=1.28, 95% CI: 1.06-1.54; N stage: HR=1.26, 95% CI: 1.14-1.40; retropharyngeal lymph node metastasis: HR=2.13, 95% CI: 1.47-3.08; radiotherapy: HR=0.54, 95% CI: 0.38-0.76) and disease-free survival of patients with hypopharyngeal squamous cell carcinoma (T stage: HR=1.26, 95% CI: 1.06-1.51; N stage: HR=1.25, 95% CI: 1.13-1.37; retropharyngeal lymph node metastasis: HR=2.24, 95% CI: 1.56-3.21; radiotherapy: HR=0.55, 95% CI: 0.40-0.77). Conclusions: Metastasis of retropharyngeal lymph nodes in hypopharyngeal squamous cell carcinoma is not rare. Enhanced CT is of low accuracy and limited value in diagnosing retropharyngeal lymph node metastasis. Primary lesions located in the posterior wall of the hypopharyngx, N2 stage, and N3 stage are independent high-risk factors for retropharyngeal lymph node metastasis. The prognosis of hypopharyngeal cancer patients with retropharyngeal lymph node metastasis is worse, and active surgical exploration and clearance can effectively reduce the mortality caused by retropharyngeal lymph node metastasis.
Humans ; Squamous Cell Carcinoma of Head and Neck/pathology* ; Lymphatic Metastasis/pathology* ; Retrospective Studies ; Carcinoma, Squamous Cell/surgery* ; Lymph Nodes/pathology* ; Hypopharyngeal Neoplasms/surgery* ; Prognosis ; Head and Neck Neoplasms/pathology* ; Neoplasm Staging

Objective: To investigate the relationship between the cervical lymph node density (LND) and the prognosis of hypopharyngeal carcinoma. Methods: The clinical and pathological data of 241 patients with hypopharyngeal carcinoma who underwent surgery in Shandong Provincial ENT Hospital from January 2014 to December 2017 were retrospectively analyzed, including 229 males and 12 females, aged 37-81 years. The LND was calculated, i.e. the ratio of the number of lymph nodes with metastasis to the total number of lymph nodes removed. The patients were divided into low LND group and high LND group based on the cutoff value of LND determined by receiver operating characteristic curve (ROC curve). The univariate and multivariate analyses of the disease-free survival (DFS) and the overall survival (OS) were performed in two groups. Results: With the cutoff value of 0.068, 165 patients were in the low LND group (<0.068) and 76 patients in the high LND group (≥0.068). T stage, N stage, maximum lymph node diameter, extracellular invasion of lymph node, and postpharyngeal lymph node metastasis were associated with LND (statistical values were -3.15, -6.82, 23.37, 20.44, and 30.18, respectively, all P values were<0.05). The univariate analysis showed that age, T stage, N stage, maximum diameter of cervical lymph nodes, extracapsular invasion, retropharyngeal lymph node metastasis and LND were the main factors affecting the patients' DFS (χ²=9.31, 7.30, 20.09, 15.30, 9.04, 19.44, 50.27, all P values<0.05) and OS (χ² were 5.02, 12.94, 18.28, 15.91, 7.95, 16.88, 49.45, all P values<0.05). Multivariate analysis showed that patients with age≤60 years old and LND≥0.068 had reduced DFS [HR values were 0.61 (95%CI 0.43-0.88) and 2.23 (95%CI 1.44-3.45), both P values<0.05]; patients with advanced T stage and LND≥0.068 had reduced OS [HR values were 1.73 (95%CI 1.02-2.93) and 2.39 (95%CI 1.51-3.80), both P values<0.05]. Conclusion: LND is a prognostic factor for patients with hypopharyngeal carcinoma after surgery, with worse prognosis in patients with LND≥0.068.
Carcinoma, Squamous Cell/pathology* ; Female ; Humans ; Hypopharyngeal Neoplasms/surgery* ; Lymph Nodes/pathology* ; Lymphatic Metastasis/pathology* ; Male ; Middle Aged ; Neoplasm Staging ; Prognosis ; Retrospective Studies

OBJECTIVE: Androgen deficiency is common in aging males and may have unfavourable health consequences. Large-scale studies suggested low testosterone level might increse mortality and morbidity in ageing males. However, young men with low testosterone level might be neglected. Recent studies reported young men with infertility may have reduced testosterone level. To investigate the incidence of androgen deficiency in males with infertility and possible factors affecting the low testosterone level. METHODS: Between January 2011 and December 2012, 407 men with infertility caused by varicocele (VC), obstructive azoospermia (OA) and nonobstructive azoospermia (NOA) in our center were included. The number of men in each group of OA, NOA and VC was 141, 97 and 169, respectively. All the eligible patients underwent a serum testosterone assessment by a single morning blood draw (between 8:00 to noon) to test for concentration of the total testosterone. All serum samples were determined by radioimmunoassay in our andrology laboratory. Androgen deficiency was defined as having a total testosterone level less than 300 ng/dL. RESULTS: The mean age was (30.4±5.8) years. The mean testosterone level was (4.18±1.64) ng/dL (range 0.30 to 11.32 ng/dL). The overall incidence of androgen deficiency was 26.5% (108/407). The incidences of androgen deficiency in NOA, OA and VC groups were 40.2% (39/97), 19.1% (27/141) and 24.9% (42/169), respectively, which were significantly higher in the NOA than in the VC and OA groups (P < 0.001). The incidences had no difference between the VC and OA groups (P=0.229). Univariate analysis revealed the cause of infertility, FSH and the mean testis volume as possible affecting factors for androgen deficiency. However, on multivariate analysis the only cause of infertility was an independent predictor. The incidence of androgen deficiency was the highest in the NOA group [OR 0.492 (95% confidence interval 0.288-0.840)]. CONCLUSION NOA and varicocele might be risk factors of androgen deficiency. Young men with NOA may have a higher possibility of low testosterone level. Testosterone level should be followed up after NOA and varicocele treatment. Androgen deficiency should be assessed in males with infertility in clinical practice.
Adult ; Androgens ; Azoospermia/etiology* ; Female ; Humans ; Male ; Testis ; Testosterone ; Varicocele/complications* ; Young Adult

In order to reveal the molecular mechanism of blue labeled genic male sterility (BM-type GMS) and utilize the heterosis of BM-type GMS, we used the anthers of white-seed plants WS (sterile) and light blue seed plants WF (normal fertility) as experimental materials to analyze the differences in gene expression between them by transcriptome technology. And we also verified the genes expressed in anthocyanin synthesis in this study. Compared with WF, a total of 2352 differentially expressed genes were detected in WS. According to GO functional annotation, these genes could be divided into 3 categories and 43 subgroups. They are mainly involved in biosynthesis, phenylpropane metabolism, L-phenylalanine catabolism, membrane components, plasma membrane, cytoplasm, ATP binding, protein serine/threonine kinase activity, etc. KEGG pathway analysis showed that there were 159 genes enriched in the phenylpropanoid biosynthesis pathway, followed by the phenylalanine pathway, including 136 differentially expressed genes. Other genes are also involved a variety of amino acid metabolism, purine metabolism, pyrimidine metabolism and sugar metabolism pathway. Related to anthocyanin metabolism, several structural genes of key enzymes were differentially expressed, and most of them were up-regulated in WF, while only Flavanone 3-hydroxylase (F3H) and colorless anthocyanin dioxygenase (ANS) were down-regulated. Quantitative real-time PCR showed that the expression of 10 genes related to anthocyanin metabolism had the same trend as that in transcriptome sequencing data. Sequence homology analysis showed that the two selected transcription factors (DN48762c2g1 and DN25944c0g1) are clustered into the same cluster as the transcription factors regulating anthocyanin biosynthesis in maize, rice and Arabidopsis thaliana, which might be candidate genes for the blue aleurone layer of light blue seed plants in wheat. And fluorescence quantitative analysis showed that the expression level of DN48762c2g1 and DN25944c0g1 in WF was significantly higher than that in WS. In conclusion, the genes related to the anthocyanin biosynthesis pathway are not only related to the blue grain trait, but also may be involved in the anther abortion of BM-type GMS.

Objective: To determine the association between pulse pressure and the risk of new-onset diabetes in hypertensive patients. Methods: In this prospective cohort study, hypertensive patients from the Kailuan Study, who were diagnosed in 2006-2007 check-up, were screened for enrollment. Participants who finished the biennial follow-up until December 31, 2017 were finally included in this analysis. The primary outcome was incident diabetes development. The pulse pressure variables were divided into quartiles (Q₁-Q₄), and the Kaplan-Meier curve was used to examine and estimate the cumulative incidence of new-onset diabetes among quartiles. Cox proportional hazards regression model was performed to explore the association between pulse pressure and the risk of new-onset diabetes in hypertensive patients. Results: During an average follow-up of 8.17 years, 6 617 new-onset diabetes were identified out of the 32 917 hypertensive patients with no history or evidence of diabetes in 2006-2007 check-up. Participants were classified into quartiles according to pulse pressure levels as follows: Q₁ group(<41 mmHg (1mmHg=0.133kPa))(n=7 995); Q₂ group(41-<51 mmHg) (n=8 196); Q₃ group (51-<61 mmHg) (n= 8 270); Q₄ group (≥61 mmHg) (n=8 456). The cumulative incidences of new-onset diabetes across the quartiles were 16.94%, 19.61%, 21.07%, and 22.33%, respectively, with the incidence density was 20.27, 23.20, 24.92, and 26.10 per 1 000 person-years, respectively. The cumulative incidence of new-onset diabetes increased in proportion with increasing pulse pressure levels (P<0.01 by the Log-rank test). After multivariate adjustment, compared with the first quartile, the hazard ratios for new-onset diabetes in the third and fourth quartiles were 1.13 (95%CI 1.04-1.22, P<0.01) and 1.14 (95%CI 1.05-1.24, P<0.01), respectively. The risk of new-onset diabetes increased 5%(HR=1.05, 95%CI 1.02-1.08, P<0.01) with the fractional pulse pressure increased per 1 SD (0.13). Findings from the three sensitivity analyses were consistent with the main results in this cohort. Conclusions: Pulse pressure at baseline is positively associated with the incidence of new-onset diabetes among hypertensive individuals, and pulse pressure is an independent risk factor for the development of diabetes in hypertensive patients.

To investigate the effect and mechanism of psoralen on calvarial osteoblasts injuries caused by tricalcium phosphate (TCP) wear particles in vitro. Primary osteoblasts were obtained from the calvaria of neonatal SD rat by the series of digestion and were identified with ALP staining. Calvarial osteoblasts were treated with TCP wear particles for 48 h to establish the in vitro model of osteoblasts injuries. The rat osteoblasts were randomly divided into control group, TCP wear particles (0.1 mg/ml) group, psoralen treated (at the concentrations of 10, 10, 10 mol/L) groups. WST assay and the flow cytometry were used to detect the cell viability of osteoblasts and apoptosis, respectively. Chemical colorimetry was performed to examine ALP activity of osteobalsts. When the osteoblasts were treated for 14 day, mineral nodules formation was observed with alizarin red S staining. Western blot was applied to examine protein expressions of glucose regulated protein78/94(GRP78/94), inositol dependent enzyme 1 alpha (IREα), spliced X-box binding protein 1 (XBP1s) and phosphorylated c-Jun N-terminal kinase (p-JNK) in calvarial osteoblasts. Compared with control group, the cell viability of osteoblasts, ALP activity and mineral nodules formation in TCP group were decreased significantly (P＜0.05), while the percentage of apoptosis and protein expressions of GRP78/94, IRE1α, XBP1 and p-JNK were obviously increased in calvarial osteoblasts (P＜0.05). Compared with TCP group, the injuries of calvarial osteoblasts and cell apoptosis in psoralen treated groups were obviously decreased (P＜0.05), and the expression levels of GRP78/94, IRE1α, XBP1 and p-JNK were down-regulated remarkably (P＜0.05). Psoralen prevents osteoblasts injuries caused by TCP wear particles through IRE1α-XBP1s-JNK signaling pathway activation.

OBJECTIVE: To explore the association between anemia and cardiovascular disease and all-cause mortality among diabetic patients, and whether the association is modified by the presence of chronic kidney disease (CKD). METHODS: Physical examination data of 8 563 patients with diabetes who met the inclusion and exclusion criteria between 2010 and 2011 were collected, based on the prospective cohort data of Kailuan study. The deadline of the follow-up was December 31, 2015, and the endpoints comprised all-cause mortality and cardiovascular disease. Survival analysis was performed by Kaplan-Meier method. Cox proportional hazards regression model was used to assess the association between anemia with or without CKD, and cardiovascular events and all-cause mortality after adjustment for confounding factors. RESULTS: The average age of the subjects was (57.3±10.3) years, of whom the patients with anemia accounted for 5.2%. The proportion of the patients with anemia combined with CKD was higher than that of the patients without anemia (27.2% vs. 20.8%, P=0.001). The median follow-up time was 4.9 years (interquartile range: 4.6-5.2 years). During the follow-up period, 559 patients died, and 434 patients had cardiovascular disease. Compared with the patients without anemia, the all-cause mortality rate of the patients with anemia was higher (3 220.3/100 000 person-years vs. 1 257.9/100 000 person-years, P<0.001). There was no statistically significant difference in the incidence of cardiovascular disease between the above two groups (999.8/100 000 person-years vs. 1 081.2/100 000 person-years, P>0.05). The mortality and incidence of cardiovascular disease among the patients with CKD were higher than those of the patients without CKD (2 558.3/100 000 person-years vs. 1 044.0/100 000 person-years, P<0.001; 1 605.9/100 000 person-years vs. 941.6/100 000 person-years, P<0.001). Results of Cox regression model showed that, after adjustment for confounding factors, the all-cause mortality risk increased by 95% in the diabetic patients with anemia (HR=1.95, 95% CI: 1.50-2.54). Anemia and CKD significantly increased the mortality risk among diabetic patients (HR=3.61, 95% CI: 2.48-5.26). The CKD patients without anemia had an increased risk of cardiovascular disease (HR=1.41, 95% CI: 1.13-1.74). CONCLUSION Anemia is associated with an increased mortality risk in Chinese diabetic patients. Patients with CKD have an increased risk of cardiovascular disease and mortality. The all-cause mortality risk increases significantly in anemia patients with the presence of CKD, which indicates that we should focus on the prevention and treatment of diabetic patients with anemia and CKD.
Anemia/epidemiology* ; Cardiovascular Diseases/epidemiology* ; Diabetes Mellitus, Type 2 ; Humans ; Proportional Hazards Models ; Prospective Studies ; Renal Insufficiency, Chronic/epidemiology* ; Risk Factors ; Survival Analysis