To explore famous veteran traditional Chinese medicine( TCM) doctors' medication rules in treating spermatorrhea based on the medical cases about spermatorrhea collected from Hundred TCM Clinical Doctors of Hundred Years in China and Proven Cases and National Medical Master Test Case. Researchers extracted such data as medicinal and therapies from these cases according to the inclusion and exclusion criteria. Then,Excle 2010,SPSS Clementine 12. 0 and SPSS 22. 0 were adopted respectively for frequency analysis,association rules analysis,cluster analysis and factor analysis. Cluster analysis was carried out by Ochiai algorithm of binary variable data,one of the systematic clustering methods. And principal component analysis was used for factor analysis. Finally,27 medical cases and 41 prescriptions were included in total. The frequency analysis showed that the most common therapy was the astringent therapy( n = 28),which was followed by the tonifying method,tranquilizing method,heat-clearing method,damp-dispelling method and Qiregulating method. The top three kinds of high-frequency traditional Chinese medicines were Poria,Ostreae Concha and Dioscoreae Rhizoma. The association rules analysis found out 11 association rules of medicine pairs,23 association rules of medicine combinations of the three kinds of herbs and 6 association rules of medicine combinations of five kinds of herbs. Among them,the representatives were Rubi Fructus→Fossilia Ossis Mastodi,Rehmanniae Radix Praeparata + Corni Fructus→Dioscoreae Rhizoma,and Pinelliae Rhizoma→Citri Reticulatae Pericarpium,which showed the therapeutic characteristics of astringing,tonifying the kidney and replenishing essence,fortifying the spleen and dispelling dampness. Moreover,7 medicine groups with relevance were extracted from the tree map generated by cluster analysis,including " Phellodendri Chinensis Cortex and Anemarrhenae Rhizoma" and " Angelicae Sinensis Radix,Rehmanniae Radix,Bupleuri Radix and Glycyrrhizae Radix et Rhizoma",which demonstrated the effects of nourishing Yin and purging fire,tonifying and soothing the liver. Besides,totally 12 common factors were obtained according to factor analysis,including 14 drug combinations,like " Amomi Fructus,Anemarrhenae Rhizoma and Phellodendri Chinensis Cortex" and " Nelumbinis Stamen,Moutan Cortex,Poria and Scrophulariae Radix",which indicated the compatibility characteristics of tonifying the spleen and purging fire,dispelling dampness and clearing heat. In conclusion,data mining techniques( including frequency analysis,association rules analysis,cluster analysis and factor analysis) were used to comprehensively analyze the famous veteran TCM doctors' medication rules in treating spermatorrhea,which was helpful for guiding the clinical practice of treating spermatorrhea in TCM.
China ; Drug Combinations ; Drugs, Chinese Herbal ; Medicine, Chinese Traditional ; Physicians ; Veterans

Objective To explore the method and clinical value of sentinel lymph node biopsy for penile carcinoma guided by multispectral separate-merge guided surgery device (MGS).Methods The clinical data of 7 patients with sentinel lymph node biopsy of penile cancer guided by MGS from April 2017 to April 2018 were analyzed retrospectively at First Hospital of Shanxi Medical University.They were 62-78 years old,with an average age of 65 years.All of carcinoma was located in the glans or coronal sulcus,which diameter was 1.0-3.5 cm,with an average of 2.5 cm.Three cases of inguinal lymph nodes could be non-palpable and the others palpable.All patients were injected 0.25 ml (2.5 mg/ml) of indocyanine greensolution with 1 ml syringe at 12,4,6 and 9 points in the proximal normal skin of penile tumors.Immediately,the imaging probe was aligned with the injection point to observe the dynamic changes of fluorescence image on MGS display.Results There were 14 sides of groin in 7 patients,except for 1 side without images,other 13 sides developed well.The images displayed by MGS include visible image,fluorescent image and merged image,and the merged image was green pseudo color.According to the dynamic changes of the image,it could be divided into five parts:injection point,penile body,pubic symphysis,inguinal region and sentinel lymph node.In 13 well-developed sides,fluorescence gradually disappeared in other parts about 15 minutes after injection,and the location of sentinel lymph nodes was determined in vitro by gradually consolidating and fixing the fluorescence images in the inguinal region.The lymph node-like tissue with strong fluorescence intensity was observed immediately after the skin incision.There was a clear boundary between the lymph node-like tissue and the surrounding tissue.Along this boundary,lymph nodes were separated,ligated,excised.No lymph nodes were found on the undetected side.Postoperative pathology confirmed that lymph nodes were located by fluorescence imaging in vitro and traced by fluorescence imaging in vivo,the coincidence rate was 100％.There were residual fluorescent tissues on three sides and lymphatic vessels were removed.Conclusions MGS-assisted intraoperative fluorescence imaging could improve the doctor's visual depth so that physicians can real-time,dynamic,accurate in vitro location and in vivo tracking of sentinel lymph nodes of penile cancer.

PURPOSE: The measuring Epstein-Barr virus (EBV) DNA is an important predictor of nasopharyngeal carcinoma (NPC). This study evaluated the predictive value of pretreatment serum amyloid A (SAA) and C-reactive protein (CRP) comparing with EBV DNA in patients with NPC. MATERIALS AND METHODS: In an observational study of 419 non-metastatic NPC patients, we prospectively evaluated the prognostic effects of pretreatment SAA, CRP, and EBV DNA on survival. The primary end-point was progress-free survival (PFS). RESULTS: The median level of SAA and CRP was 4.28 mg/L and 1.88 mg/L, respectively. For the high-SAA group (> 4.28 mg/L) versus the low-SAA (≤ 4.28 mg/L) group and the high-CRP group (> 1.88 mg/L) versus the low-CRP (≤ 1.88 mg/L) group, the 5-year PFS was 64.5% versus 73.1% (p=0.013) and 65.2% versus 73.3% (p=0.064), respectively. EBV DNA detection showed a superior predictive result, the 5-year PFS in the EBV DNA ≥ 1,500 copies/mL group was obviously different than the EBV DNA < 1,500 copies/mL group (62.2% versus 77.8%, p < 0.001). Multifactorial Cox regression analysis confirmed that in the PFS, the independent prognostic factors were including EBV DNA (hazard ratio [HR], 1.788; p=0.009), tumour stage (HR, 1.903; p=0.021), and node stage (HR, 1.498; p=0.049), but the SAA and CRP were not included in the independent prognostic factors. CONCLUSION: The results of SAA and CRP had a certain relationship with the prognosis of NPC, and the prognosis of patients with high level of SAA and CRP were poor. However, the predictive ability of SAA and CRP was lower than that of EBV DNA.
C-Reactive Protein* ; DNA* ; Herpesvirus 4, Human* ; Humans ; Observational Study ; Prognosis ; Prospective Studies* ; Serum Amyloid A Protein* ; Survival Analysis

In this study a reduction-responsive nanoparticles (NPs) modified with hyaluronic acid (HA) was prepared for the co-delivery of doxorubicin (DOX) and siRNA and then evaluated as a lung cancer targeting delivery system in vitro. The amphiphilic polymer of poly-L-lysine-lipoic acid (PLA) based on poly-L-lysine (PLL) with lipoic acid (LA) was synthesized via amidation reaction and characterized by ¹H NMR. The DOX loaded PLA NPs were prepared via dialysis method, and siRNA was loaded via electrostatic attraction to prepare the co-delivery NPs system (PLA/DOX-siRNA-NPs). Then PLA/DOX-siRNA-NPs were coated with HA to obtain HA-PLA/DOX-siRNA-NPs. The tumor microenvironment-responsive properties under different pH or reduction condition of HA-PLA/DOX-siRNA-NPs were evaluated by investigating the particle size and zeta potential. Cellular uptake of HA-PLA/DOX-siRNA^FAM-NPs by A549 cells and endosomal escape of siRNA were studied using confocal laser scanning microscope (CLSM). ¹H NMR spectrum demonstrated that PLA was successfully synthesized with LA grafting rate of 25.1%. The encapsulation efficiency (EE) and drug loading (DL) of HA-PLA/DOX-NPs was (86.93±8.91)% and (4.17±0.68)%, respectively, and siRNA was loaded at an N/P of 6:1 in carrier. HA-PLA/DOX-siRNA-NPs exhibited a suitable size of (167.3±9.9) nm and negative charge of (-15.5±1.4) mV with the optimal ratio of PLA and HA of 1:3. Additionally, the zeta potential of HA-PLA/DOX-siRNA-NPs significantly increased with charge reversal from negative to positive after the treatment with HAase, and the particle size of HA-PLA/DOX-siRNA-NPs changed significantly under the condition of 10 mmol·L^-1 glutathione (GSH). The release profiles in vitro demonstrated that HA-PLA/DOX-NPs exhibited a maintained release behavior at pH 7.4 and the adding of GSH (10 mmol·L^-1) led to rapid release of DOX from NPs. In vitro cellular uptake and subcellular distribution study demonstrated that themodification of HA enhanced the affinity of NPs to A549 cells and targeting ability, and the cellular uptake of HA-PLA/DOX-siRNA^FAM-NPs significantly increased after the treatment with HAase. It was observed that HA-PLA/DOX-siRNA^FAM-NPs could escape from endo-lysosomes followed by sharp payloads release to their relative targets. All these results demonstrated that the co-loaded NPs have a high entrapment efficiency of DOX and siRNA. And they also exhibited an active tumor targeting efficiency and tumor microenvironment-responsive properties, which were beneficial to cellular uptake and intracellular release of DOX and siRNA. In conclusion, these reduction-responsive NPs modified with HA have great potential as co-delivery systems for antitumor agents and siRNA.

Along with the increase of clinical application, the safety of traditional Chinese medicine gained more and more attentions. In particular, the safety evaluation of Chinese medical injections has become a mandatory task should be completed by pharmaceutical companies under the supervision of China Food and Drug Administration(CFDA). Due to the weak foundation of previous studies, the safety issues of Chinese medical injections have not been fully understood, and lack of scientific and rational risk management programs. Clinical safety centralized monitoring(CSCM) is an important method for post-market safety evaluation of Chinese medicine. Due to the lack of appropriate norms and procedures, the quality of similar research is uneven, and the results vary. Combined with practical experience with experts' suggestions, we developed this expert consensus on the design and implementation of CSCM from three stages (design, implementation and report) with 20 technical points, which will provide technical support for future CSCM studies.

Objective To explore the ultrasound features and levels of cervical lymph node metastases in primary and recurrent/persistent papillary thyroid cancer (PTC).Methods We retrospectively analyzed the clinical data of 2181 patients who underwent cervical lymph nodes dissection for PTC from January 12015 to January 12016.Totally 418 PTC patients (with 622 lymph nodes) who met the inclusion criteria entered the final analysis.Patients who had not received any prior thyroid treatment (surgery with or without radioactive iodine) were categorized as the primary group (352 patients with 527 metastatic lymph nodes),and patients who had received prior treatment (thyroidectomy with or without radioactive iodine) for PTC were categorized as recurrent/persistent group (66 patients with 95 metastatic lymph nodes).Pathological results from lymph node dissections were used as the gold standards by means of level-to-level analysis.Results The mean of the minimum axis diameter of the lymph nodes in the primary group was (6.7±3.6)mm,and that of the recurrent/persistent group was (6.6±3.1)mm (U=0.180,P=0.857).The proportion of metastasis in the central area of primary group was 40.0%,which was significantly higher than that in the recurrent/persistent group (12.6%);the proportion of metastasis in the lateral area was 60.6% in the primary group,which was significantly lower than that in the recurrent/persistent group (87.4%)(χ=26.288,P<0.001).In lateral metastatic lymph nodes,Ⅲ level was the most common place in both groups.Level Ⅴ metastatic lymph was rare in both primary group and recurrent/persistent group.Calcifications (63.1% vs. 48.2%;χ=7.207,P=0.007) and peripheral vascularity (81.1% vs. 59.4%;χ= 16.147, P<0.001) were more common in the recurrent/persistent group.The round shape,absence of an echogenic hilum,hyperechogenicity,and cystic aspects were not significantly different between these two groups (all P>0.05).Conclusions Primary metastatic lymph nodes often occur in the central area of lymph nodes,while lateral metastatic lymph nodes are more common in recurrent/persistent PTC.For metastatic lymph nodes,calcifications and peripheral vascularity are more common in recurrent/persistent PTC.

Tongxie Yaofang (TXYF) is a famous formula that has been used for treating gastrointestinal diseases in traditional Chinese medicine(TCM). Saposhnikoviae Radix is considered as a meridian guiding drug in TXYF and could enhance the effectiveness of prescription. However, the scientific evidence for this effect is still not clear. To reveal the interactions of Saposhnikoviae Radix with other herbs, we conducted this study on the pharmacokinetic profile and tissue distribution of active ingredients of TXYF in rats. The concentrations of four components in blood and tissues were determined by UPLC-MS/MS after oral administration with TXYF. The detection was carried out by electrospray ionization mass spectrometry in the multiple reaction monitoring (MRM) mode. The positive and negative ion switching technique was performed in the same analysis. The results revealed that Saposhnikoviae Radix could enhance Cmax, AUC0-t, and AUC0-∞ of paeoniflorin and hesperidin, and increase the distribution of atractylenolide-I, paeoniflorin and hesperidin in liver, spleen, brain and small intestine. Saposhnikoviae Radix increased the ratio of brain to blood concentrations of atractylenolide-I, paeoniflorin and hesperidin. Meanwhile, it reduced the ratio of lung to blood concentrations of atractylenolide-I and paeoniflorin. Saposhnikoviae Radix, and may enhance the effectiveness of prescriptions by promoting distribution of other herbs in brain.

OBJECTIVETo explore the relationship between blood pressure variability (BPV) and combined cardiovascular events in 5-10 years in patients with hypertension.

METHODSA total of 367 hypertensive patients treated in our hospital from January, 2000 to January, 2005 were analyzed, and their BPV was assessed in comparison with 145 normotensive individuals. The hypertensive patients were classified into high BPV group and low BPV group, and the general clinical data and biochemical profiles were compared. The relationship between BPV and combined cardiovascular events of the patients within 5-10 years were explored.

RESULTSCompared with the normotensive individuals, the hypertensive patients showed significantly increased standard deviation and coefficient of variation of 24-h systolic blood pressure (SBP), 24-h diastolic blood pressrue (DBP), daytime SBP, daytime DBP, night-time SBP and night-time DBP (P<0.01). The percentages of drinking, smoking, diabetes and coronary heart disease were significantly higher in patients with high BPV than those with lower BPV (P<0.01 or 0.05); uric acid, homocysteine, urinary protein/creatinine ratio and urinary microalbumin increased more significantly in patients with high BPV (P<0.01 or 0.05). In addition, the combined cardiovascular events in 5-10 years were significantly higher in the patients with higher BPV than those with lower BPV (P<0.01 or 0.05). Logistic multivariate logistic regression analysis showed that alcohol, diabetes, coronary heart disease, uric acid and homocysteine were independent risk factors for cardiovascular events in hypertensive patients (P<0.01 or 0.05).

CONCLUSIONIn hypertensive patients, BPV is closely correlated with the long-term combined cardiovascular events, and a high BPV is associated with a greater likeliness of combined cardiovascular events.

Objective:To analyze losses and gains (L&G) of basic medical institutions induced by the Essen-tial Medicines Policy.Methods: Choosing some poverty-stricken county in western China as sample area to conduct field research,using 2009 as baseline year,to calculate L&G and L&G ratio of basic medical institutions caused by adjustments of drug policy,medical services prices, and government subsidies from 2009—2015. Results: Medical facilities have gained after the implementation of the Essential Medicines Policy as a whole. Gains were on an upward trend from 2009—2015,and L&G ratio increased from -2.15% in 2009 to 47.70% in 2015. For medical facilities at different levels, their gains attributed to different causes. Gains for medical facilities at village and town levels mainly attributed to government subsidies;gains for medical facilities at county level mainly attributed to adjustment of medical services prices. Conclusions:Implementation of the Essential Medicines Policy has helped adjust composi-tion of losses and gains of medical facilities. Moving forward,functions and development of medical facilities should be strengthened with a focus on adjusting medical services prices for medical facilities at town level.

BACKGROUND: The stress distribution is different between implants and natural teeth, and the biomechanical characters of implant-natural tooth supported fixed partial dentures need to be explored.OBJECTIVE: To analyze the distributions of stress and strain on the implant interface and natural tooth ligaments by loading a vertical force to a single implant crown, natural tooth crown and a implant-natural tooth supported fixed partial denture.METHODS: Two male healthy Beagle dogs were selected, and their right mandibular first molars were exacted under general anesthesia. Three months later, a 3.3 mm×10 mm RN ITI implant was implanted into the defect region of each dog. The dogs were killed under anesthesia after another 3 months to remove the mandible. One dog was restored by a single implant and natural tooth crown, and the other was restored by the implant-natural tooth supported fixed partial dentures. The specimens were fixed to the load device after embedded with self caring acrylic resin, and the strain gauges were pasted to the cortical bone around the implant and natural tooth neck. The vertical force was loaded to the implant, natural tooth and fixed denture with 40, 60, 80,120, and 160 N.RESULTS AND CONCLUSION: When the force was loaded to the implant of combined denture, the implant stress of combined denture was less than that of the single implant repair, and partial force was loaded on natural teeth; when the force was loaded to the natural tooth of combined denture, the stress to the natural tooth of combined denture was less than that of the single natural tooth repair. When the force was loaded to the natural tooth of combined denture, the stress was assumed by the whole prostheses. However, the stress was almost assumed by the implant when the force was loaded to the implant of combined denture. That is to say, it is feasible to use the implant-natural tooth supported fixed partial dentures.