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 explore influence of external factors of wind, cold and dampness on clinical symptoms in knee osteoarthritis (KOA) patients with different constitutions of traditional Chinese medicine. METHODS: A cross-sectional stratified study was performed to select 108 patients with GradeⅡKOA in Kellgren & Lawrence (K-L) classification, including 22 males and 86 females, aged from 47 to 75 years old with an average of (60.7±6.0) years old;body mass index(BMI) ranged from 17.87 to 31.22 kg·m^-2 with an average of (23.80±2.86) kg·m^-2. According to Classification and Judgment of TCM Physique (ZYYXH/T157-2009), the types of TCM physique were determined and divided into 4 layers according to the deficiency and actual physique. Among them, there were 24 patients without biased physique, 12 males and 12 females, aged from 51 to 73 years old with an average of(62.8±6.0) years old, BMI ranged from 17.87 to 31.14 kg·m^-2 with an average of (24.32±3.25) kg·m-2;there were 46 patients with virtual bias constitution, including 7 males and 39 females, aged from 47 to 70 years old with an average of (60.0±5.8) years old, BMI ranged from 19.38 to 31.22 kg·m^-2 with an average of(23.42±2.97) kg·m^-2;There were 26 patients with solid bias constitution, including 2 males and 24 females, aged from 48 to 75 years old with an average of (60.4±5.8) years old, BMI ranged from 21.16 to 30.76 kg·m^-2 with an average of (24.15±2.33) kg·m^-2;there were 9 patients with special constitution, 1 male and 8 female, aged from 53 to 75 years old with an average of (59.8±7.5) years old, BMI ranged from 19.26 to 26.67 kg·m^-2 with an average of (23.79±2.49) kg·m^-2. Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) was used to evaluate severity of clinical symptoms. The wind-cold-dampness external factor score was calculated through the questionnaire of wind-cold-dampness syndrome scale to evaluate degree of influence of wind-cold-dampness external factor. Pearson correlation analysis and partial correlation analysis were used to calculate the correlation coefficient between severity of external factors affecting wind, cold and dampness and severity of clinical symptoms in patients with different TCM constitution stratification. RESULTS: There was no statistical significance between total score of wind-cold-dampness and WOMAC score in patients with no biased constitution and special condition. Total wind-cold-dampness score of patients with virtual biased constitution was positively correlated with WOMAC stiffness score (r=0.327, P=0.032), and total wind-cold-dampness score of patients with solid biased constitution was positively correlated with WOMAC pain score (r=0.561, P=0.005) and WOMAC overall score (r=0.446, P=0.033). After further adjusting for the interaction of external factors of wind-cold-dampness, there was no statistical significance between wind-cold-dampness scores and WOMAC scores in patients with solid biased constitution. The score of dampness and pathogenic factors was positively correlated with WOMAC stiffness score (r=0.414, P=0.007). CONCLUSION The external factors of wind-cold dampness have different effects on the clinical symptoms of KOA patients with different TCM constitutions. Compared with other constitutions, the rigid symptoms of patients with asthenic biased constitutions are more susceptible to dampness pathogenic factors.
Aged ; Female ; Humans ; Male ; Middle Aged ; Cross-Sectional Studies ; Medicine, Chinese Traditional ; Osteoarthritis, Knee ; Syndrome ; Wind ; Cold Temperature

Objective: To explore the effects of porcine acellular dermal matrix (ADM) combined with human epidermal stem cells (ESCs) on wound healing of full-thickness skin defect in nude mice. Methods: The morphology of porcine ADM was analyzed by photograph of digital camera, the cell residues in porcine ADM were observed by hematoxylin-eosin (HE) staining, the surface structure of porcine ADM was observed by scanning electron microscope, the secondary structure of porcine ADM was analyzed by infrared spectrometer, the porcine ADM particle size was analyzed by dynamic light scattering particle size analyzer, and the porcine ADM potential was analyzed by nano-particle size potentiometer. The morphology of porcine ADM was observed by inverted fluorescence microscope when it was placed in culture medium for 30 min, 1 d, and 5 d (n=2). The porcine ADM was divided into 5 min group, 10 min group, 20 min group, 30 min group, 60 min group, and 120 min group according to the random number table (the same grouping method below) in static state at normal temperature for the corresponding time to calculate the water absorption by weighing method (n=3). Swiss white mouse embryonic fibroblasts (Fbs) were divided into blank control group (culture medium only), and 50.0 g/L ADM extract group, 37.5 g/L ADM extract group, 25.0 g/L ADM extract group, 12.5 g/L ADM extract group, and 6.5 g/L ADM extract group which were added with the corresponding final concentrations of ADM extract respectively. At post culture hour (PCH) 24, 48, and 72, the cell survival rate was detected by cell counting kit 8 and the cytotoxicity was graded (n=5). The erythrocytes of a 6-week-old male Sprague-Dawley male rat were divided into normal saline group, ultra-pure water group, and 5 mg/mL ADM extract group, 10 mg/mL ADM extract group, and 15 mg/mL ADM extract group which were treated with the corresponding final concentrations of porcine ADM extract respectively. After reaction for 3 h, the absorbance value of hemoglobin was detected by microplate reader to represent the blood compatibility of porcine ADM (n=3). ESCs were isolated and cultured from the discarded prepuce of a 6-year-old healthy boy who was treated in the Department of Urology of the First Affiliated Hospital of Army Medical University (the Third Military Medical University) in July 2020, and then identified by flow cytometry. The porcine ADM particles of composite ESC (hereinafter referred to as ESC/ADM) were constructed by mixed culture. After 3 days of culture, the composite effect of ESC/ADM was observed by HE staining and laser scanning confocal microscope. Thirty-six 7-8-week-old male non-thymic nude mice were divided into phosphate buffer solution (PBS) alone group, ADM alone group, ESC alone group, and ESC/ADM group, with 9 mice in each group, and the wound model of full-thickness skin defect was established. Immediately after injury, the wounds were treated with the corresponding reagents at one time. On post injury day (PID) 1, 7, 11, and 15, the wound healing was observed and the wound healing rate was counted (n=3). On PID 7, the epithelialization of wounds was observed by HE staining and the length of un-epithelialized wound was measured (with this and the following sample numbers of 4). On PID 11, the dermal area and collagen deposition of wounds were observed by Masson staining and the dermal area of wound section was calculated, the number of cells expressing CD49f, a specific marker of ESC, was calculated with immunofluorescence staining, the mRNA expression of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in ESC after wound transplantation was detected by real-time fluorescence quantitative reverse transcription polymerase chain reaction. Data were statistically analyzed with independent sample t test, one-way analysis of variance, analysis of variance for repeated measurement, and least significant difference t test. Results: The porcine ADM was white particles and composed of reticular structure, with no cells inside, disordered structure, and rough surface. The absorption peak of porcine ADM appeared at the wave numbers of 1 659, 1 549, and 1 239 cm^-1, respectively. The main particle size distribution of porcine ADM in solution was 500 to 700 nm, with negative charge on the surface. The morphology of porcine ADM in static state at 30 min and on 1 and 5 d was relatively stable. The water absorption of porcine ADM remained relatively high level in static state from 30 min to 120 min. The cytotoxicity of mouse embryonic Fbs in 6.5 g/L ADM extract group, 12.5 g/L ADM extract group, and 25.0 g/L ADM extract group was grade 1 at PCH 24, and the cytotoxicity of the other groups was 0 grade at each time point. After reaction for 3 h, the absorbance value of hemoglobin of erythrocytes in ultra-pure water group was significantly higher than the values in normal saline group and 15 mg/mL ADM extract group (with t values of 8.14 and 7.96, respectively, P<0.01). After 3 days of culture, the cells of the fourth passage showed pebble-like morphology, with low expression of CD71 and high expression of CD49f, which were identified as ESCs. There was ESC attachment and growth on porcine ADM particles. On PID 1, the wound sizes of nude mice were almost the same in PBS alone group, ADM alone group, ESC alone group, and ESC/ADM group. On PID 7, 11, and 15, the wound contraction of nude mice in each group was observed, especially in ADM alone group, ESC alone group, and ESC/ADM group. On PID 7, the wound healing rates of nude mice in ESC alone group and ESC/ADM group were significantly higher than the rate in PBS alone group (with t values of 2.83 and 4.72 respectively, P<0.05 or P<0.01). On PID 11, the wound healing rate of nude mice in ESC/ADM group was significantly higher than that in PBS alone group (t=4.86, P<0.01). On PID 15, the wound healing rates of nude mice in ADM alone group, ESC alone group, and ESC/ADM group were significantly higher than the rate in PBS alone group (with t values of 2.71, 2.90, and 3.23 respectively, P<0.05). On PID 7, the length of un-epithelialized wound of nude mice in ADM alone group, ESC alone group, and ESC/ADM group was (816±85), (635±66), and (163±32) μm, respectively, which were significantly shorter than (1 199±43) μm in PBS alone group (with t values of 5.69, 10.19, and 27.54 respectively, P<0.01). On PID 11, the dermal areas of wound section of nude mice in ADM alone group, ESC alone group, and ESC/ADM group were significantly larger than the area in PBS alone group (with t values of 27.14, 5.29, and 15.90 respectively, P<0.01); the collagen production of nude mice in ADM alone group and ESC/ADM group was more obvious than that in PBS alone group, and the collagen production of nude mice in ESC alone group and PBS alone group was similar. On PID 11, in the wounds of nude mice in ESC alone group and ESC/ADM group, the cells with positive expression of CD49f were respectively 135±7 and 185±15, and the mRNA expressions of GAPDH were positive; while there were no expressions of CD49f nor mRNA of GAPDH in the wounds of nude mice in PBS alone group and ADM alone group. Conclusions: ESC/ADM particles can promote the wound healing of full-thickness skin defects in nude mice, which may be related to the improved survival rate of ESCs after transplantation and the promotion of dermal structure rearrangement and angiogenesis by ADM.
Acellular Dermis ; Animals ; Fibroblasts ; Humans ; Male ; Mice ; Mice, Nude ; Rats ; Rats, Sprague-Dawley ; Stem Cells ; Swine ; Wound Healing

Bruceae Fructus is a Chinese herbal medicine with the chemical constituents mainly including Brucea javanica oil, quassinoids, flavonoids, steroids, triterpenoids, and alkaloids. Modern research demonstrates that Bruceae Fructus has anti-tumor, anti-malaria, anti-inflammatory, and lipid-lowering activities. This paper introduces the resource distribution, chemical constituents, and pharmacological activities of Bruceae Fructus. Further, according to the concept of quality marker(Q-marker), this paper predicts the Q-markers of Bruceae Fructus from the specificity of chemical components, pharmaceutical activity, measurability of chemical constituents, compatibility, and clinical efficacy, aiming to provide a theoretical basis for establishing the quality standard of Bruceae Fructus.
Fruit ; Drugs, Chinese Herbal/pharmacology* ; Quassins ; Flavonoids ; Biomarkers

Objective: To systematically summarize and analyze the clinical research progress of therapeutic vaccines for cervical cancer or precancerous lesions. Methods: English databases (PubMed, Embase, Web of Science, Cochrane library, Proquest, and ClinicalTrails.gov) and Chinese databases (SinoMed, CNKI, WanFang, and VIP Database) were systematically searched to collect literature on therapeutic vaccines for cervical cancer or precancerous lesions from inception to February 18, 2021. After screening, we evaluated the risk of bias of included studies, and combed the basic information of the literature, research designs, information of vaccines, study patients, outcome indicators and so on, qualitatively summarized the clinical research progress. Results: A total of 71 studies were included in this systematic review, including 14 random controlled trials, 15 quasi-random controlled trials, 4 cohort studies, 1 case-control study, 34 case series studies and 3 case reports. The study patients included women aged 15~79 with cervical cancer or precancerous lesions in 18 countries from 1989 to 2021. On the one hand, there were 40 studies on therapeutic vaccines for cervical precancerous lesions (22 867 participants), involving 21 kinds of vaccines in 6 categories. Results showed 3 marketed vaccines (Cervarix, Gardasil, Gardasil 9) as adjuvant immunotherapies were significant effective in preventing the recurrence of precancerous lesions compared with the conization only. In addition, MVA E2 vaccine had been in phase Ⅲ clinical trials as a specific therapeutic vaccine, with relative literature showing it could eliminate most high-grade precancerous lesions. Therapeutic vaccines for precancerous lesions all showed good safety. On the other hand, there were 31 studies on therapeutic vaccines for cervical cancer (781 participants), involving 19 kinds of vaccines in 7categories, with none had been marketed. 25 studies were with no control group, showing the vaccines could effectively eliminate solid tumors, prevent recurrence, and prolong the median survival time. However, the vaccines effectiveness couldn't be statistically calculated due to the lack of a control group. As for the safety of therapeutic vaccines for cervical cancer, 9 studies showed that patients experienced serious adverse events after treatments, where 7 studies reported that serious adverse events occurred in patients couldn't be ruled out as the results of therapeutic vaccines. Conclusions: The literature review shows that the literature evidence for the therapeutic vaccines for cervical precancerous lesions is relatively mature compared with the therapeutic vaccines for cervical cancer. The four kinds of vaccines on the market are all therapeutic vaccines for precancerous lesions, but they are generally used as vaginal infection treatments or adjuvant immunotherapies for cervical precancerous lesions, not used for the specific treatments of cervical precancerous lesions. Other specific therapeutic vaccines are in the early stage of clinical trials, mainly phase Ⅰ/Ⅱ clinical trials with small sample size. The effectiveness and safety data are limited, and further research is still needed.
Cancer Vaccines/therapeutic use* ; Cervical Intraepithelial Neoplasia/prevention & control* ; Female ; Humans ; Papillomavirus Infections/prevention & control* ; Papillomavirus Vaccines/therapeutic use* ; Precancerous Conditions/therapy* ; Uterine Cervical Neoplasms/prevention & control*

BACKGROUND: Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly spread throughout the world. In this study, we aimed to identify the risk factors for severe COVID-19 to improve treatment guidelines. METHODS: A multicenter, cross-sectional study was conducted on 313 patients hospitalized with COVID-19. Patients were classified into two groups based on disease severity (nonsevere and severe) according to initial clinical presentation. Laboratory test results and epidemiological and clinical characteristics were analyzed using descriptive statistics. Univariate and multivariate logistic regression models were used to detect potential risk factors associated with severe COVID-19. RESULTS: A total of 289 patients (197 nonsevere and 92 severe cases) with a median age of 45.0 (33.0, 61.0) years were included in this study, and 53.3% (154/289) were male. Fever (192/286, 67.1%) and cough (170/289, 58.8%) were commonly observed, followed by sore throat (49/289, 17.0%). Multivariate logistic regression analysis suggested that patients who were aged ≥ 65 years (OR: 2.725, 95% confidence interval [CI]: 1.317-5.636; P = 0.007), were male (OR: 1.878, 95% CI: 1.002-3.520, P = 0.049), had comorbid diabetes (OR: 3.314, 95% CI: 1.126-9.758, P = 0.030), cough (OR: 3.427, 95% CI: 1.752-6.706, P < 0.001), and/or diarrhea (OR: 2.629, 95% CI: 1.109-6.231, P = 0.028) on admission had a higher risk of severe disease. Moreover, stratification analysis indicated that male patients with diabetes were more likely to have severe COVID-19 (71.4% vs. 28.6%, χ2 = 8.183, P = 0.004). CONCLUSIONS The clinical characteristics of those with severe and nonsevere COVID-19 were significantly different. The elderly, male patients with COVID-19, diabetes, and presenting with cough and/or diarrhea on admission may require close monitoring to prevent deterioration.
Adult ; COVID-19/pathology* ; China/epidemiology* ; Comorbidity ; Cough ; Cross-Sectional Studies ; Diarrhea ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Risk Factors

Cephalosporins are widely used in the treatment of infectious diseases. The structural differences in cephalosporin drugs mainly lie in the C-7 amino side chain and the C-3 substituent. In this study, twenty-five haloacylated cephalosporins of five series were designed by using a strategy of introducing simple substituents at the C-7 amino group in four cephalosporin parent nucleus with different C-3 substituents and efficiently synthesized under optimized conditions. Their activities against human pathogenic bacteria, Pichia pastoris, citrus canker and citrus pathogenic fungi were evaluated. The results showed that most of the molecules had activity against human pathogenic bacteria, of which seven compounds including TM1f had stronger or equivalent inhibitory activities against eight human pathogens than the marketed drugs cefalotin, cefoxitin sodium and ceftizoxime sodium. The inhibitory activity of TM1s against Alternaria alternate Al.6 was stronger than that of cephalosporins and comparable to that of the positive control prochloraz. TM1f and TM1s are worthy of further study.

Sudden sensorineural hearing loss (SSNHL) refers to the sudden and unexplained sensorineural hearing loss within 72 h and a decrease in hearing of ≥30 dB affecting at least 3 consecutive frequencies. It is one of the common emergencies in neurology and otolaryngology. Early etiological evaluation and systematic and targeted treatment are very important for delaying the progression of SSNHL and restoring hearing. Recent studies have shown that SSNHL overlaps with vascular risk factors of ischemic stroke, and may predict the risk of ischemic stroke. SSNHL may be one of the clinical manifestation and even the prodromal symptoms of ischemic stroke, especially the infarction of the blood supply area of the anterior inferior cerebellar artery or its branch internal auditory artery. Although these factors can not fully reveal the relationship between SSNHL and ischemic stroke, they are enough to warn clinicians that they should consider the possibility of ischemic stroke when receiving patients with SSNHL. Screening of vascular risk factors for patients with SSNHL as early as possible is helpful to avoid the risk of recurrence of ischemic stroke.

Altitude ; China/epidemiology* ; Community-Acquired Infections/epidemiology* ; Humans ; Pneumonia/etiology* ; Tibet

Objective:To explore the effect of modified Chaiqin Wendantang on blood glucose level and gastrointestinal dysfunction in patients with diabetic gastroparesis (DGP) of weak spleen and stomach. Method:A total of 138 patients with DGP of weak spleen and stomach in Hainan Provincial Fourth People's Hospital from February 2017 to March 2019 were enrolled, and divided into two groups according to the random number table methods. Both groups received the routine treatment. In addition to this, study group received Chaiqin Wendantang, while control group received domperidone tablets. Traditional Chinese medicine (TCM) syndrome scores, blood glucose, gastrointestinal function, hemorheology index, gastric emptying function and gastric electrical activity, Pittsburgh Sleep Quality Index (PSQI) scale and clinical efficacy were compared. Result:After treatment, TCM symptom scores and total scores decreased (P<0.05), levels of fasting blood glucose (FBG), 2 hours postprandial blood glucose (2 h PBG), and glycated hemoglobin (HbA1c) decreased (P<0.05), serum motilin (MOT) and gastrin (GAS) levels increased (P<0.05), cholecystokinin (CCK) levels decreased (P<0.05), gastric emptying time shortened, frequency, amplitude and rhythm increased (P<0.05), PSQI score decreased (P<0.05), and whole blood viscosity (WBV) and fibrinogen (FIB) levels decreased (P<0.05), all of those changes were more obvious in study group than control group (P<0.05). The total effective rate in study group was higher than that in control group (P<0.05). During the treatment period, there were no obvious adverse reactions in study group, while there were 2 cases of transient dizziness and headache in control group, which were relieved after several seconds. The recurrence rate in study group was lower than that in control group (P<0.05). Conclusion:Modified Chaiqin Wendantang can effectively ameliorate the symptoms of gastric retention, improve sleep quality, control blood glucose levels, and improve hemodynamics for DGP of weak spleen and stomach patients. Besides, it can improve the gastrointestinal function by reducing serum CCK levels, so as to stimulate the secretion of MOT and GAS, increase gastric motility, shorten gastric emptying time, and promote the recovery of gastric electrical activity. With a high safety and low recurrence rate, it has clinical application value.