Identification and preservation of arm lymphatics in axillary lymph node dissection to prevent arm lymphedema: a single center randomized controlled trial / 中华肿瘤杂志

Objective: To evaluate the feasibility of identification and preservation of arm lymphatics (DEPART) in axillary lymph node dissection (ALND) for breast cancer to prevent arm lymphedema. Methods: A randomized controlled study method was used. Two hundred and sixty-five patients who underwent breast cancer surgery at the Department of Thyroid and Breast Surgery, Zhongnan Hospital of Wuhan University from November 2017 to June 2018 were included, and the patients were randomly divided into ALND+ DEPART group (132 patients) and standard ALND group (133 patients) by random number table method. In the ALND+ DEPART group, indocyanine green and methylene blue were injected as tracers before surgery, and the arm sentinel nodes was visualized by staged tracing during intraoperative dissection of axillary lymph nodes. Partial frozen sections were made of arm lymph nodes >1 cm in length and hard and suspicious of metastasis, and arm lymph nodes and lymphatic vessels were selectively preserved. Patients in the standard ALND group underwent standard ALND. Objective and subjective indexes of arm lymphedema were evaluated by 5-point circumference measurement and Norman questionnaire. Results: Among 132 breast cancer patients in the ALND+ DEPART group, 121 (91.7%) completed DEPART. There were no statistically significant differences in age, body mass index, pathological type, dissection number of axillary lymph node, N stage, TNM stage, molecular typing, and regional radiotherapy between the ALND+ DEPART and standard ALND groups (P>0.05). At a median follow-up of 24 months, assessment by the 5-point circumference measurement showed that the incidence rates of lymphedema in the ALND+ DEPART and standard ALND groups were 5.0% (6/121) and 15.8% (21/133), respectively, with statistically significant differences (P=0.005). Assessment by the Norman questionnaire showed that the incidence rates of lymphedema in the ALND+ DEPART and standard ALND groups were 5.8% (7/121) and 21.8% (29/133), respectively, with a statistically significant difference (P<0.001). No local regional recurrence was observed in either group during the follow-up period. Conclusion: For breast cancer patients with positive axillary lymph nodes, the administration of DEPART during ALND can reduce or avoid the occurrence of arm lymphedema without compromising oncology safety.

Application value of intraoperative neuromonitoring plus "classification of EBSLN" to protect the external branch of the superior laryngeal nerve / 中华耳鼻咽喉头颈外科杂志

Objective: To investigate the application efficacy of the "classification of external branch of superior laryngeal nerve (EBSLN)" combined with intraoperative neuromonitoring (IONM) in the dissection of EBSLN for protecting the nerve from injuery, compared with ligation of branches of the superior thyroid vessels without attempts to visually identify the nerve. Methods: A prospective randomized controled study was performed in our center. Patients subjected to thyroidectomy from January 2017 to June 2019 were randomly divided into 2 groups, patients in experimental group underwent thyroidectomy and "classification of EBSLN" with IONM to dissect EBSLN, and patients in control group received synchronous surgery without attempts to visually identify the nerve. The anatomical subtypes of EBSLN in experimental group were recorded. The voice handicap index 10 (VHI-10) score was evaluated and the movement of bilateral vocal cords was examined by laryngoscope before surgery, 1 month, 3 months, and 6 months after surgery, respectively. SPSS 26.0 statistical software was used for statistical analysis. Results: Among the 1 377 EBSLN from 827 patients (317 males and 510 females, aged 24-58 years old), 691 EBSLNs in experimental group and 686 EBSLNs in control group. Totally 98.3% of EBSLNs in experimental group were identified by IONM including 16.4% (113/691) for type Ⅰ, 21.3% (147/691) for type Ⅱa, 31.4% (217/691) for type Ⅱb, 10.4% (72/691) for type Ⅲa, 3.9% (27/691) for type Ⅲb, 16.6% (115/691) for type Ⅲc. There was no statistical significance difference in baseline data between 2 groups (all P>0.05). All patients were followed up for more than 6 months. The postoperative nerve injury rate of experimental group was significantly lower than that of control group (1.2% vs. 7.5%, χ²=12.659, P<0.001), and the VHI-10 scores and laryngoscope results of experimental group were better than those of control group in three follow-up visits (P<0.001). With postoperative laryngoscope examination, 3 patients in the experimental group and 23 patients in the control group showed vocal cord relaxation, bilateral oblique asymmetry and other phenomena, which were considered as the results of permanent injury. Other patients with symptoms were relieved to varying degrees during the follow-up, and their symptoms were considered as the results of temporary injury. Conclusion: IONM combined with "classification of EBSLN" can reduce significantly the risk of EBSLN injury in thyroidectomy, which is better than direct ligation of branches without attempts to visually identify the nerve.

Parathyroid hormone assay with eluent of aspirated tissues in parathyroidectomy / 中华耳鼻咽喉头颈外科杂志

Objective: To explore the values of intraoperative fine-needle aspiration (IFNA) and parathyroid hormone (PTH) detection in the eluate of aspirated tissue during parathyroidectomy. Methods: Fifty-four patients with secondary hyperparathyroidism (SHPT) including 24 males and 30 females, aged 20-83 years, admitted to Zhongnan Hospital of Wuhan University from January 2019 to October 2019, were included. All patients received subtotal parathyroidectomy with autologous transplantation, during surgery, IFNA and PTH detection in the eluate of aspirated tissue were performed, and also routine postoperative pathological examination was performed. The results of PTH detection in the eluate of aspirated tissue and postoperative pathological examinations were compared and analyzed by SPSS and R software for evaluating of the sensitivity, specificity, positive predictive value, negative predictive value, misdiagnosis rate, missed diagnosis and accuracy. Results: Surgery was completed successfully in all patients. After surgery, the symptoms were improved in the patients except two who were asymptomatic. None had any serious postoperative complications such as hypocalcaemia or hoarseness. A total of 231 aspirated tissue samples were tested, of which 216 were identified as parathyroid and 15 non-parathyroid based on intraoperative PTH detection in tissue eluate; while 217 were confirmed as parathyroid tissues and 14 non-parathyroid tissues with postoperative pathological examinations. The specificity and sensitivity of intraoperative IFNA and PTH detection in tissue eluate for identifying parathyroid tissues were 99.5% and 100.0%, respectively. Conclusion: The IFNA and PTH detection in tissue eluate is a rapid, simple, and accurate procedure, which helps the surgeon to identify parathyroid tissue and to ensure the endocrine activity of preserved or autografted parathyroid tissue during parathyroidectomy.

POST1/C12ORF49 regulates the SREBP pathway by promoting site-1 protease maturation

Sterol-regulatory element binding proteins (SREBPs) are the key transcriptional regulators of lipid metabolism. The activation of SREBP requires translocation of the SREBP precursor from the endoplasmic reticulum to the Golgi, where it is sequentially cleaved by site-1 protease (S1P) and site-2 protease and releases a nuclear form to modulate gene expression. To search for new genes regulating cholesterol metabolism, we perform a genome-wide CRISPR/Cas9 knockout screen and find that partner of site-1 protease (POST1), encoded by C12ORF49, is critically involved in the SREBP signaling. Ablation of POST1 decreases the generation of nuclear SREBP and reduces the expression of SREBP target genes. POST1 binds S1P, which is synthesized as an inactive protease (form A) and becomes fully mature via a two-step autocatalytic process involving forms B'/B and C'/C. POST1 promotes the generation of the functional S1P-C'/C from S1P-B'/B (canonical cleavage) and, notably, from S1P-A directly (non-canonical cleavage) as well. This POST1-mediated S1P activation is also essential for the cleavages of other S1P substrates including ATF6, CREB3 family members and the α/β-subunit precursor of N-acetylglucosamine-1-phosphotransferase. Together, we demonstrate that POST1 is a cofactor controlling S1P maturation and plays important roles in lipid homeostasis, unfolded protein response, lipoprotein metabolism and lysosome biogenesis.

Real time release testing of disintegration time of uncoated Tianshu Tablets / 中国中药杂志

In this paper, a real time release testing(RTRT) model for predicting the disintegration time of Tianshu tablets was established on the basis of the concept of quality by design(QbD), in order to improve the quality controllability of the production process. First, 49 batches of raw materials and intermediates were collected. Afterwards, the physical quality attributes of all materials were comprehensively characterized. The partial least square(PLS) regression model was established with the 72 physical quality attributes of raw materials and intermediates as input and the disintegration time(DT) of uncoated tablets as output. Then, the variable screening was carried out based on the variable importance in the projection(VIP) indexes. Moisture content of raw materials(%HR), tapped density of wet masses(D_c), hygroscopicity of dry granules(%H), moisture content of milling granules(%HR) and Carr's index of mixed granules(IC) were determined as the potential critical material attributes(pCMAs). According to the effects of interactions of pCMAs on the performance of the prediction model, it was finally determined that the wet masses' D_c and the dry granules'%H were critical material attributes(CMAs). A RTRT model of the disintegration time prediction was established as DT=34.09+2×D_c+3.59×%H-5.29×%H×D_c,with R~2 equaling to 0.901 7 and the adjusted R~2 equaling to 0.893 3. The average relative prediction error of validation set for the RTRT model was 3.69%. The control limits of the CMAs were determined as 0.55 g·cm~(-3)<D_c<0.63 g·cm~(-3) and 4.77<%H<7.59 according to the design space. The RTRT model of the disintegration time reflects the understanding of the process system, and lays a foundation for the implementation of intelligent control strategy of the key process of Tianshu Tablets.

Predictive model for hygroscopicity of contents in Guizhi Fuling Capsules / 中国中药杂志

To control the risks of powder caking and capsule shell embrittlement of Guizhi Fuling Capsules, a predictive model for hygroscopicity of contents in Guizhi Fuling Capsules was built. A total of 90 batches of samples, including raw materials, intermediate powders and capsules, were collected during the manufacturing of Guizhi Fuling Capsules. According to the production sequence, 47 batches were used as the calibration set, and the properties of raw materials and the four intermediate powders were comprehensively characterized by the physical fingerprint. Then, the partial least squares(PLS) model was developed with the content hygroscopicity as the response variable. The variable importance in projection(VIP), variance inflation factor(VIF) and regression coefficients were used to screen out potential critical material attributes(pCMAs). As a result, five pCMAs from 54 physical parameters were screened out. Furthermore, different models were built by different combinations of pCMAs, and their predictive robustness of 43 batches was evaluated on the basis of the validation set. Finally, the tap density(D_c) of wet granules obtained from wet granulation and the angle of repose(α) of raw materials were identified as the critical material attributes(CMAs) affecting the hygroscopicity of the contents of Guizhi Fuling Capsules. The prediction model established with the two CMAs as independent variables had an average relative prediction error of 2.68% for samples in the validation set, indicating a good accuracy of prediction. This paper proved the feasibility of predictive modeling toward the control of critical quality attributes of Chinese medicine oral solid dosage(OSD). The combination of the continuous quality improvement, the industrial big data and the process modeling technique paved the way for the intelligent manufacturing of Chinese medicine oral solid preparations.

Identification of critical process parameters of Jinqing alcohol precipitation of Reduning Injection by big data / 中国中药杂志

Lonicerae Japonicae Flos and Artemisiae Annuae Herba(LA or Jinqing) alcohol precipitation has various process parameters and complex process mechanism, and is one of the key units for manufacturing Reduning Injection. In order to identify the critical process parameters(CPPs) affecting the weight of the extract produced from the alcohol precipitation process, 259 batches of historical production data from 2017 to 2018 were collected, with a total of 829 318 data points. These data showed characteristics of large data, such as a large data volume, a low value density, and diverse sources. The data cleaning and feature extraction were first performed, and 48 feature variables were selected. The original data points were reduced to 9 936. Then, a combination of Pearson correlation analysis and grey correlation analysis were used to screen out 15 potential critical process parameters(pCPPs). After that, the partial least squares(PLS) was used in prediction of the weight of the extract, proving that the performance of predictive model based on 15 pCMAs is equivalent to that of predictive model based on 48 feature variables. The variable importance in projection(VIP) index was used to identify 9 CPPs, including 2 alcohol precipitation supernatant volume parameters, 4 initial extract weight parameters and 3 added alcohol volume parameters. As a result, the number of data points was 1 863, accounting for 0.28% of the original data. The big data analysis approach from a holistic point of view can effectively increase the value density of the original data. The critical process parameters obtained can help to accurately describe the quality transfer mechanism of the Jinqing alcohol precipitation process.

Rapid Determination of Coating Film Thickness of Tianshu Tablets by Near Infrared Spectroscopy / 中国实验方剂学杂志

<b>Objective::To investigate the feasibility of near-infrared spectroscopy for detecting the coating film thickness of Tianshu tablets. <b>Method::Nine batches of Tianshu tablets were taken during the coating process. Then, their near-infrared diffuse reflection spectra were collected. The sample set was divided into calibration set and validation set by Kennard-Stone algorithm. The preprocessing method was selected. The synergy interval partial least squares (siPLS) and moving window partial least squares (mwPLS) were employed to screen the optimal spectral interval. And the corresponding quantitative calibration model of partial least squares (PLS) were established. Some evaluation parameters were adopted to assess the performance of the model. <b>Result::The method of first derivative and Norris Derivative smoothing combined with standard normal variate transformation was suitable for processing the spectra. The optimal PLS model was established in the preferred band interval of siPLS. The correlation coefficient between the predicted value and the measured value of calibration set was 0.966, and the correlation coefficient between the predicted value and the measured value of validation set was 0.991.Both root mean square error of calibration (RMSEC) and root mean square error of prediction (RMSEP) values were small, which showed the fitness and predictive performance of the model were favorable. <b>Conclusion::The near-infrared spectroscopy technique can be used to determine coating film thickness of Tianshu tablets with high accuracy, which provides technical supports for the in-line determination of coating thickness in the production process of traditional Chinese medicine tablets.

Efficacy of CO2 dot matrix laser combined with 595 nm pulsed dye laser on cesarean section skin scar / 中华医学美学美容杂志

Objective To investigate the clinical efficacy of CO2 lattice laser combined with 595 nm pulsed dye laser in the treatment of cesarean section skin scar.Methods A total of 60 patients with cutaneous scar after cesarean section in our hospital from June 2015 to October 2017 were enrolled.The patients were divided into observation group and control group according to the order of hospitalization.Each group had 30 cases.Both CO2 lattice and 595 nm pulsed dye lasers were used in study group.Only CO2 lattice laser was used in control group.Vancouver scar scale (VSS) and adverse reactions were analyzed after treatment in both groups.Results The two groups were compared at 3 months and 6 months after treatment.The VSS scores of the study group were (52.00± 1.31) and (3.81±1.38),which was significantly lower than that of the control group (6.30±1.21) and (5.00± 1.38).The difference was statistically significant (t =3.175,3.35,P ＜0.05).There were no significant differences in adverse reactions between the two groups (P＞0.05).Conclusions CO2 dot laser combined with 595 nm pulsed dye laser for the treatment of cesarean section skin scar is more effective than CO2 dot matrix laser alone.

5'-flanking regulatory sequence methylation of the Boule gene in the testis tissue of infertile men with Sertoli cell-only syndrome / 中华男科学杂志

<p><b>Objective</b>To investigate the 5'-flanking regulatory sequence methylation status of the Boule gene in the testis tissue of infertile men with Sertoli cell-only syndrome (SCOS).</p><p><b>METHODS</b>We collected biopsy samples of the testis tissue from 12 men with obstructive azoospermia (the control group) and 15 cases of SCOS, all without varicocele, cryptorchidism, or infectious disease. We extracted genomic DNA from the testis tissue of the SCOS patients, analyzed the characteristics of the 5'-flanking regulatory sequence of the Boule gene using the bioinformatics method, and detected the methylation status of the Boule gene by sodium bisulfite sequencing.</p><p><b>RESULTS</b>A CpG island was observed in the 5'-flanking regulation region of the Boule gene. The methylation level of the Boule gene was remarkably higher in the SCOS group than in the obstructive azoospermia controls (61.4% vs 21.7%, P<0.01), with significant differences in the methylation levels of 14 CpG sites, namely, －58 bp, －50 bp, －48 bp, －38 bp, －28 bp, －24 bp, －20 bp, －15 bp, －1 bp, +5 bp, +8 bp, +15 bp, +29 bp, and +58 bp.</p><p><b>CONCLUSIONS</b>The methylation level of the Boule gene is significantly higher in the SCOS patients than in the obstructive azoospermia males, which suggests that the changes in Boule methylation may be associated with spermatogenic dysfunction.</p>

Sedum sarmentosun bunge extraction ameliorated severe acute pancreatitis-induced lung injury: an experimental research / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To explore the effect of Sedum sarmentosum Bunge Extract (SSBE) on severe acute pancreatitis (SAP) induced acute lung injury (ALI) model rats and their excessive inflammatory reactions.</p><p><b>METHODS</b>Forty-two healthy adult male Sprague-Dawley (SD) rats were randomly divided into 3 groups, the sham-operated control group (C), the SAP group (SAP), and the SSBE treated group (SSBE), 14 in each group. SAP induced ALl rat model was induced by retrograde injection of 5% sodium taurocholate (1 mL/kg) into the pancreatic duct. SSBE (100 m/kg) was administrated subcutaneously after the establishment of the SAP model. Equal dose of SSBE was injected again 12 h later. Equal volume of normal saline was administrated in the same way for rats in the C group and the SAP group. Rats were sacrificed after successful modeling and samples taken at 12 and 24 h. Pathological changes in the pancreas and the lung tissue were observed under light microscope. The ascites, serum amylase (AMS), wet/dry proportion (W/D) of the lung tissue, activities of myeloperoxidase (MPO), interleukin-1 (IL-1), IL-6, and tumor necrosis factor-alpha (TNF-alpha) were also measured.</p><p><b>RESULTS</b>Ascites and serum AMS activities significantly increased; MPO, IL-1, IL-6, TNF-alpha contents, and W/D ratio also significantly increased in the SAP group, when compared with the C group (P<0.05). Compared with the SAP group, those parameters were all attenuated in the SSBE group at 12 and 24 h (P<0.05, P<0.01). Pathological changes in the pancreas and the lung tissue were alleviated in the SSBE group under light microscope. The injury degree ranged between that of the C group and the SAP group.</p><p><b>CONCLUSION</b>SSBE could relieve the ALl in SAP model rats, which could be achieved through alleviating inflammation responses of SAP rats.</p>

A novel pressure difference-induced perforation aortic stent-grafts system: an experimental study / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Most of endovascular stent-graft modifications to preserve side branch must be customized according to extensive pre-operative assessment, which may not be possible in many hospitals and emergency settings. The study was to develop a novel stent-grafts system that would allow in situ "fenestration", with less reliance on preoperative imaging.</p><p><b>METHODS</b>The magnitude of pressure difference (PD) between left subclavian artery (LSA) and aortic arch were measured in 12 experimental pigs. Changes of PD before and after LSA was covered were analyzed respectively. The novel stent graft was made by multi-dimensional and multiple textiles forming technology. According to the PD measurement in pigs, we evaluated the feasibility of the stent-graft in a mock circulation system.</p><p><b>RESULTS</b>In pigs, the blood pressure of aortic arch was significantly higher than that of LSA after it was covered (P < 0.001) and PD was (42.78 ± 5.17) mmHg. After target vessel was covered and when PD between the LSA and aorta reached the magnitude measured in pigs, contrast media oozed from the cranny of graft to the LSA, which was generated by sliding and deformation of yarns of novel stent-graft.</p><p><b>CONCLUSIONS</b>The study proposes the design of pressure difference-induced perforation aortic stent-grafts system and verifies that the PD between LSA and aortic arch is high enough to allow in situ "fenestration" by stent graft made by multi-dimensional and multiple textiles forming technology.</p>

Advances in the quantitative analytical methods of drug polymorphism / 药学学报

Polymorphism of drug is known to influence the stability, dissolution, bioavailability and other performance characteristics of the products. Therefore, the crystal form of the drug must be identified and determined in order to ensure consistent product performance. Even if the identification and characterization of crystal forms are performed thoroughly and the effective crystal form is selected for preparation, it is important to ensure that the effective crystal form in the final product remains unchanged. Therefore, it is essential to quantitate the content of the effective crystal form in the product to control the quality and performance of them. X-ray powder diffraction, FT-Raman, mid-IR, near-IR, terahertz pulsed spectroscopy, solid-state NMR spectroscopy, and DSC are the quantitative methods of crystal form used in the recent 10 years. This review briefly highlights the basic principles and the progress of these methods and discusses the perspective as they apply to pharmaceutical research and development.

Intercostal video-mediastinoscopy: a report of 701 cases / 中华外科杂志

<p><b>OBJECTIVE</b>To summarize the experience of intercostal video-mediastinoscopy (VMS) in treatment for mediastinal masses, malignant pleural effusion and palmar hyperhidrosis.</p><p><b>METHODS</b>The clinical data of 701 patients received intercostal VMS from November 2001 to June 2007 were summarized retrospectively. Forty-eight patients with mediastinal masses and 46 patients with suspected malignant pleural effusion underwent intercostal VMS pleural biopsy (39 cases with talc pleurodesis) and 607 patients with palmar hyperhidrosis underwent bilateral intercostals VMS thoracic sympathectomy.</p><p><b>RESULTS</b>No mortality and morbidity were reported in this group. Definitive pathologic diagnosis had been made through VMS mediastinal masses biopsy in mediastinal masses and pleural biopsy in pleura effusion. The efficiency of talc pleurodesis was 100% for 39 cases. The symptoms of sweating of hands in 607 patients with palmar hyperhidrosis disappeared completely, all patients' hands became dry with a 1.5 degrees C to 3.0 degrees C increase of the skin temperature immediately after operation. No recurrence occurred during the follow-up.</p><p><b>CONCLUSION</b>VMS is a simple, convenient and alternative procedure for the treatment of mediastinal masses, malignant pleural effusion and palmar hyperhidrosis.</p>