Efficacy and safety evaluation of three medicated eye patches in Demodex blepharitis: a multicenter, double-blind, randomized controlled clinical trial / 中华实验眼科杂志

Objective:To evaluate and compare the clinical efficacy and safety of three different medicated eye patches in the treatment of Demodex blepharitis. Methods:A multicenter, randomized, double-blind, parallel-controlled clinical trial was conducted.A total of 140 patients (280 eyes) with Demodex blepharitis were recruited in Shanghai Jing'an District Shibei Hospital, Xi'an Fourth Hospital and Kunming First People's Hospital from July 2021 to December 2022.The affected eyes were randomly divided into tea tree oil group, okra oil group, basal fluid control group and metronidazole group by the random number table method.Eye patches containing 20% tea tree oil, 1% okra oil, prepared base solution and 2% metronidazole were applied to the eyes for 28 days by the double-blind method.The count of Demodex was evaluated before treatment and on days 14 and 28 of treatment.Ocular surface symptoms were scored according to Ocular Surface Disease Index (OSDI). The degree of congestion at the eyelid margin and cylindrical dandruff at the root of eyelashes were scored under a slit lamp microscope.The effective rate was calculated according to the comprehensive scores above, and the adverse reactions of the subjects were observed.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Shanghai Jing'an District Shibei Hospital (No.YL-20200320-05). All the subjects were informed of the significance, purpose and method of the study.Written informed consent was obtained from each subject before any medical examination. Results:All subjects completed the treatment and follow-up, and the loss to follow-up rate was 0%.After 14 and 28 days of treatment, the Demodex count was significantly decreased in all groups compared with before treatment (all at P<0.05). After 28 days of treatment, the number of Demodex in tea tree oil group, okra oil group and metronidazole group were significantly lower than that in basal fluid control group, with statistically significant differences (all at P<0.05). The OSDI score, palpebral margin congestion score and cylindrical dandruff score on 14 and 28 days after treatment in tea tree oil group, okra oil group and metronidazole group were significantly lower than before treatment, showing statistically significant differences (all at P<0.05). After 28 days of treatment, the effective rates of tea tree oil group, okra oil group and metronidazole group were 71.4%, 71.4% and 62.9%, respectively, which were significantly higher than 25.7% in basal solution control group.No serious local or systemic adverse reactions were found during the treatment and follow-up. Conclusions:Eye patches containing tea tree oil, okra oil and metronidazole have significant effects on the treatment of Demodex blepharitis, which can improve the biological environment of the palpebral margin and eliminate the inflammation related to blepharitis.

Association of peripheral axial length, retinal curvature with refraction in school-aged children / 中华实验眼科杂志

Objective:To investigate the association of peripheral axial lengths and retinal curvatures with refractive status.Methods:A cross-sectional study was conducted out.Two hundred and eighty-seven eyes of 287 consecutive children aged 6-15 years old who recieved eye examinations at Beijing Tongren Hospital from July to October 2021 were enrolled, including 154 males and 133 females.Uncorrected and best corrected visual acuity were tested with a standard logarithmic visual acuity chart.Spherical equivalent (SE) was measured via an auto refractometer after cycloplegia with tropicamide.The hyperopic, emmetropic and myopic groups were defined with a SE >+ 0.5 D, SE >-0.5 D to ≤+ 0.5 D and SE≤-0.5 D, respectively.Central and 30° peripheral eye lengths (nasal, temporal, superior, inferior) were obtained using the Lenstar LS900.Retinal coordinates were derived from partial coherence interferometry modeling and converted to retinal curvatures.According to the median horizontal peripheral eye length differences (absolute difference between nasal and temporal), participants were assigned to H1 group (absolute difference <0.35 mm) or H2 group (absolute difference ≥0.35 mm). According to the median vertical peripheral eye length differences (absolute difference between superior and inferior), participants were assigned to V1 group (absolute difference <0.32 mm) or V2 group (absolute difference ≥0.32 mm). Four groups of V1H1, V1H2, V2H1 and V2H2 were constructed according to the grouping methods in both directions above.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Beijing Tongren Hospital, Capital Medical University (No.TRECKY2021-162). Written informed consent was obtained from guardians of each subject prior to any medical examination.Results:The central axial length was 23.53(22.93, 24.10)mm.Peripheral eye lengths of temporal, nasal, superior and inferior were 22.75(22.11, 23.22)mm, 22.99(22.32, 23.45)mm, 23.24(22.58, 23.75)mm and 23.12(22.52, 23.56)mm, respectively.Temporal eye length was shorter than nasal, showing a statistically significant difference ( Z=-3.58, P<0.01). Compared with H2 group, H1 group had shorter central, nasal, superior and inferior eye lengths, showing statistically significant differences (all at P<0.05). Compared with V2 group, V1 group had shorter central, nasal and superior eye lengths, showing statistically significant differences (all at P<0.05). SE of H1 group was + 0.06 (-1.06, + 0.75) D, which was significantly greater than -0.32 (-1.64, + 0.56) D of H2 group ( Z=-2.10, P=0.04). SE of V1 group was + 0.13 (-0.81, + 0.80) D, which was significantly greater than -0.56 (-1.83, + 0.48) D of H2 group ( Z=-3.39, P<0.01). The myopia ratio of V1 group was 33.5% (58/173), which was significantly lower than 50.5% (53/105) of V2 group ( χ2=7.83, P<0.01). There was a significant overall difference in SE among VIH1, V1H2, V2H1 and V2H2 groups ( H=24.79, P<0.01). SE was greater in V1H1 group than V1H2, V2H1 and V2H2 groups (all at P<0.01). There was a significant difference in both horizontal and vertical retinal curvatures among different refractive groups ( H=22.34, 19.30; both at P<0.01). The retical curvature in both directions of hyperopic and emmetropic groups were significantly larger than those of myopic group (both at P<0.01). Conclusions:Peripheral eye lengths are asymmetric in school-aged children.Higher asymmetry is associated with myopic shifts.Myopic children have a steeper retina than the hyperopic and emmetropic children.

Influencing factors of textbook outcomes in liver surgery after radical resection of gallbladder carcinoma: a national multicenter study / 中华消化外科杂志

Objective:To investigate the influencing factors of textbook outcomes in liver surgery (TOLS) after radical resection of gallbladder carcinoma.Methods:The retrospective case-control study was conducted. The clinicopathological data of 530 patients who underwent radical resection of gallbladder carcinoma in 15 medical centers, including the First Affiliated Hospital of Army Medical University et al, from January 2014 to January 2020 were collected. There were 209 males and 321 females, aged (61±10)years. Patients underwent radical resection of gallbladder carcinoma, including cholecystectomy, hepatectomy, invasive bile duct resection, and lymph node dissection. Observation indicators: (1) situations of TOLS; (2) influencing factors of TOLS. Measure-ment data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. Comparison of ordinal data between groups was conducted using the Mann-Whitney U test. The univariate analysis was conducted using the corresponding statistical methods based on data type, and variables with P<0.10 were included in multivariate analysis. Multivariate analysis was conducted using the Logistic stepwise regression model. Results:(1) Situations of TOLS. All 530 patients underwent radical resection of gallbladder carcinoma, and there were 498 cases achieving R 0 resection, 508 cases without ≥grade 2 intra-operative adverse events, 456 cases without postoperative grade B and grade C biliary leakage, 513 cases without postoperative grade B and grade C liver failure, 395 cases without severe com-plications within postoperative 90 days, 501 cases did not being re-admission caused by severe com-plications within postoperative 90 days. Of the 530 patients, 54.53%(289/530) of patients achieved postoperative TOLS, while 45.47%(241/530) of patients did not achieve postoperative TOLS. (2) Influencing factors of TOLS. Results of multivariate analysis showed that American Society of Anesthesiologists classification >grade Ⅱ, preoperative jaundice, T staging as T3?T4 stage, N staging as N2 stage, liver resection as right hemi-hepatectomy, and neoadjuvant therapy were independent factors influencing TOLS in patients undergoing radical resection of gallbladder carcinoma ( odds ratio=2.65, 1.87, 5.67, 5.65, 2.55, 3.34, 95% confidence interval as 1.22?5.72, 1.18?2.95, 2.51?12.82, 2.83?11.27, 1.41?4.63, 1.88?5.92, P<0.05). Conclusion:American Society of Anesthesiologists classification >grade Ⅱ, preoperative jaundice, T staging as T3?T4 stage, N staging as N2 stage, liver resection as right hemi-hepatectomy, and neoadjuvant therapy are independent factors influencing TOLS in patients undergoing radical resection of gallbladder carcinoma.

Incidence and prognosis of olfactory and gustatory dysfunctions related to infection of SARS-CoV-2 Omicron strain: a national multi-center survey of 35 566 population / 中华耳鼻咽喉头颈外科杂志

Objective: This cross-sectional investigation aimed to determine the incidence, clinical characteristics, prognosis, and related risk factors of olfactory and gustatory dysfunctions related to infection with the SARS-CoV-2 Omicron strain in mainland China. Methods: Data of patients with SARS-CoV-2 from December 28, 2022, to February 21, 2023, were collected through online and offline questionnaires from 45 tertiary hospitals and one center for disease control and prevention in mainland China. The questionnaire included demographic information, previous health history, smoking and alcohol drinking, SARS-CoV-2 vaccination, olfactory and gustatory function before and after infection, other symptoms after infection, as well as the duration and improvement of olfactory and gustatory dysfunction. The self-reported olfactory and gustatory functions of patients were evaluated using the Olfactory VAS scale and Gustatory VAS scale. Results: A total of 35 566 valid questionnaires were obtained, revealing a high incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain (67.75%). Females(χ2=367.013, P<0.001) and young people(χ2=120.210, P<0.001) were more likely to develop these dysfunctions. Gender(OR=1.564, 95%CI: 1.487-1.645), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), oral health status (OR=0.881, 95%CI: 0.839-0.926), smoking history (OR=1.152, 95%CI=1.080-1.229), and drinking history (OR=0.854, 95%CI: 0.785-0.928) were correlated with the occurrence of olfactory and taste dysfunctions related to SARS-CoV-2(above P<0.001). 44.62% (4 391/9 840) of the patients who had not recovered their sense of smell and taste also suffered from nasal congestion, runny nose, and 32.62% (3 210/9 840) suffered from dry mouth and sore throat. The improvement of olfactory and taste functions was correlated with the persistence of accompanying symptoms(χ2=10.873, P=0.001). The average score of olfactory and taste VAS scale was 8.41 and 8.51 respectively before SARS-CoV-2 infection, but decreased to3.69 and 4.29 respectively after SARS-CoV-2 infection, and recovered to 5.83and 6.55 respectively at the time of the survey. The median duration of olfactory and gustatory dysfunctions was 15 days and 12 days, respectively, with 0.5% (121/24 096) of patients experiencing these dysfunctions for more than 28 days. The overall self-reported improvement rate of smell and taste dysfunctions was 59.16% (14 256/24 096). Gender(OR=0.893, 95%CI: 0.839-0.951), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), history of head and facial trauma(OR=1.180, 95%CI: 1.036-1.344, P=0.013), nose (OR=1.104, 95%CI: 1.042-1.171, P=0.001) and oral (OR=1.162, 95%CI: 1.096-1.233) health status, smoking history(OR=0.765, 95%CI: 0.709-0.825), and the persistence of accompanying symptoms (OR=0.359, 95%CI: 0.332-0.388) were correlated with the recovery of olfactory and taste dysfunctions related to SARS-CoV-2 (above P<0.001 except for the indicated values). Conclusion: The incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain is high in mainland China, with females and young people more likely to develop these dysfunctions. Active and effective intervention measures may be required for cases that persist for a long time. The recovery of olfactory and taste functions is influenced by several factors, including gender, SARS-CoV-2 vaccination status, history of head and facial trauma, nasal and oral health status, smoking history, and persistence of accompanying symptoms.

Effects of different intensity of exercise combined with dietary intervention on body composition, lipid metabolism and gut microbiota in obese nonalcoholic fatty liver disease female college students / 中国学校卫生

Objective@#To understand the effects of different intensity of exercise combined with dietary intervention on body composition, lipid metabolism and gut microbiota in obese (nonalcoholic fatty liver disease,NAFLD) college students, so as to provide a theoretical reference for improving the health of the obese NAFLD female college students. @*Methods@#From March to Aprial 2022, 43 NAFLD female college students were recruited and randomly divided into HIIT group ( n =22) and MICT group( n =21). Subsequently, HIIT group received HIIT combined with diet intervention for 8 weeks and MICT group received MICT combined with diet intervention for 8 weeks, the changes of body composition, lipid metabolism and gut microbiota in NAFLD female college students were compared before and after intervention.@*Results@#Compared with that before the experiment, after 8 weeks of HIIT and MICT combined with dietary intervention, the weight, BMI, body fat mass, trunk fat mass, waist hip ratio and visceral fat area significantly decreased ( t = 15.56, 15.48, 15.74, 13.92, 6.51, 11.55; 13.64, 13.48, 15.82, 6.53, 4.40, 9.53), the levels of cholesterol and triglyceride and low density lipoprotein, bacillus coli and enterococcus significantly decreased ( t =6.75, 2.16, 6.86 , 3.06, 7.85; 3.55, 2.36, 4.00 , 3.32, 5.94); lactobacillus and bifidobacterium increased significantly ( t =6.64, 5.89; 5.11, 4.71); however, only HIIT group had a significant increase in the level of high density lipoprotein( t =5.08)( P <0.05). Compared with MICT group, body fat mass, trunk fat mass, visceral fat area and cholesterol level in HIIT group were significantly lower than those in MICT group ( t=2.20 , 2.10, 2.15, 2.26, P <0.05). There were no significant differences in other indicators between the two groups ( P >0.05).@*Conclusion@#The results show that HIIT and MICT have benefical effects on body composition, lipid metabolism and gut microbiota in obese NAFLD female college students , but HIIT is superior to MICT intervention in reducing body fat mass, visceral fat and improving lipid metabolism.

Effects of phacoemulsification with steep meridian transparent corneal incision on visual function, corneal astigmatism and tear film changes / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the effect of phacoemulsification with steep meridian transparent corneal incision on visual function, corneal astigmatism and tear film changes.METHODS: A total of 106 cataract patients(106 eyes)who underwent phacoemulsification in our hospital from January 2019 to December 2020 were selected as research objects, and they were divided into observation group and control group according to the operation mode: with 51 patients in the observation group who were treated with steep meridian transparent corneal incision, and 55 patients in the control group who were treated with transnasal transparent corneal incision. The changes of visual function, corneal astigmatism and tear film between the two groups were compared before operation and at 1wk, 1 and 3mo after operation.RESULTS: There was no statistical difference between the operation of two groups(all P&#x0026;#x003E;0.05). The visual acuity was significantly improved at 1wk, 1 and 3mo after operation, and it was better in the observation group than that in the control group. Mean defect(MD)of visual field was significantly lower, and it was significantly lower in the control group(all P&#x0026;#x003C;0.05); The corneal astigmatism AKP(+0)of the two groups was significantly lower at 3mo after operation, and the observation group was significantly lower than the control group(P&#x0026;#x003C;0.05). There was no statistical difference in corneal astigmatism AKP(+45)(P&#x0026;#x003E;0.05); Schirmer Ⅰ test(SⅠt)value increased first and then decreased, and the valley value was at 1wk after operation; Tear film break-up time(BUT)decreased first and then increased, and the valley value was at 1wk after operation. SⅠt in the observation group was lower than that in the control group at each time point(all P&#x0026;#x003C;0.05), while BUT in the observation group was higher than that in the control group at each time point(all P&#x0026;#x003C;0.05).CONCLUSION: Steep meridian transparent corneal incision phacoemulsification surgery is beneficial to improve the postoperative visual function of patients, reduce postoperative corneal astigmatism, reduce the damage to the patient's tear film function, and promote its recovery.

Bacteriological analysis of nasal secretions in patients with nasal lymphoma / 临床耳鼻咽喉头颈外科杂志

Objective:To investigate the etiological characteristics of nasal bacterial infection in patients with nasal lymphoma. Methods:The results of bacterial culture of nasal secretions from 39 healthy people and 86 patients with nasal lymphoma in the Affiliated Hospital of Qingdao University from January 2019 to June 2022 were retrospectively analyzed, and the differences in nasal bacteria distribution between nasal lymphoma and healthy people were analyzed and compared. Results:Corynebacterium（38.90%） was the most common bacteria in the nasal cavity of healthy people, followed by coagulase-negative Staphylococcus（31.95%）, Staphylococcus epidermidis（15.28%） and Staphylococcus aureus（6.95%）. The most common bacteria in nasal lymphoma patients was Staphylococcus aureus（30.37%）, followed by Corynebacterium（9.63%）, Staphylococcus epidermidis（7.41%） and coagulase negative Staphylococcus（6.67%）. A total of 81 nasal lymphoma patients were detected with bacteria, positive rate is as high as 94.19%（81/86）. Conclusion:Staphylococcus aureus is the main pathogenic bacteria in nasal secretion of patients with nasal lymphoma, which provides guiding significance for the clinical prevention and treatment of nasal lymphoma complicated with infection or not.

Independent prognostic value of the congestion and renal index in patients with acute heart failure / 老年心脏病学杂志（英文版）

BACKGROUND@#Clinical outcomes are poor if patients with acute heart failure (AHF) are discharged with residual congestion in the presence of renal dysfunction. However, there is no single indication to reflect the combined effects of the two related pathophysiological processes. We, therefore, proposed an indicator, congestion and renal index (CRI), and examined the associations between the CRI and one-year outcomes and the incremental prognostic value of CRI compared with the established scoring systems in a multicenter prospective cohort of AHF.@*METHODS@#We enrolled AHF patients and calculated the ratio of thoracic fluid content index divided by estimated glomerular filtration rate before discharge, as CRI. Then we examined the associations between CRI and one-year outcomes.@*RESULTS@#A total of 944 patients were included in the analysis (mean age 63.3 ± 13.8 years, 39.3% women). Compared with patients with CRI ≤ 0.59 mL/min per kΩ, those with CRI > 0.59 mL/min per kΩ had higher risks of cardiovascular death or HF hospitalization (HR = 1.56 [1.13-2.15]) and all-cause death or all-cause hospitalization (HR = 1.33 [1.01-1.74]). CRI had an incremental prognostic value compared with the established scoring system.@*CONCLUSIONS@#In patients with AHF, CRI is independently associated with the risk of death or hospitalization within one year, and improves the risk stratification of the established risk models.

Patent application of intelligent quality control technology in traditional Chinese medicine production process: a review / 中国中药杂志

In the new stage for intelligent manufacturing of traditional Chinese medicine(TCM) from pilot demonstration to in-depth application and comprehensive promotion, how to raise the degree of intelligence for the process quality control system has become the bottleneck of the development of TCM production process control technology. This article has sorted out 226 TCM intelligent manufacturing projects that have been approved by the national and provincial governments since the implementation of the "Made in China 2025" plan and 145 related pharmaceutical enterprises. Then, the patents applied by these pharmaceutical enterprises were thoroughly retrieved, and 135 patents in terms of intelligent quality control technology in the production process were found. The technical details about intelligent quality control at both the unit levels such as cultivation, processing of crude herbs, preparation pretreatment, pharmaceutical preparations, and the production workshop level were reviewed from three aspects, i.e., intelligent quality sensing, intelligent process cognition, and intelligent process control. The results showed that intelligent quality control technologies have been preliminarily applied to the whole process of TCM production. The intelligence control of the extraction and concentration processes and the intelligent sensing of critical quality attributes are currently the focus of pharmaceutical enterprises. However, there is a lack of process cognitive patent technology for the TCM manufacturing process, which fails to meet the requirements of closed-loop integration of intelligent sensing and intelligent control technologies. It is suggested that in the future, with the help of artificial intelligence and machine learning methods, the process cognitive bottleneck of TCM production can be overcome, and the holistic quality formation mechanisms of TCM products can be elucidated. Moreover, key technologies for system integration and intelligent equipment are expected to be innovated and accelerated to enhance the quality uniformity and manufacturing reliability of TCM.

Manufacturing classification system for oral solid dosage forms of traditional Chinese medicines (Ⅱ): classification of tablets disintegration behavior / 中国中药杂志

In this paper, 50 batches of representative traditional Chinese medicine tablets were selected and the disintegration time was examined with the method in Chinese Pharmacopoeia. The disintegration time and disintegration phenomenon were recorded, and the dissolution behaviors of water-soluble and ultraviolet-absorbent components during the disintegration process of tablets were characterized by self-control method. The results revealed that coating type and raw material type influenced the disintegration time of tablets. It was found that only 4% of traditional Chinese medicine tablets had obvious fragmentation during the disintegration process, while 96% of traditional Chinese medicine tablets showed gradual dissolution or dispersion. Furthermore, according to the disintegration speed, disintegration phenomenon, and whether the cumulative dissolution of measured components was > 90% at complete disintegration, a disintegration behavior classification system(DBCS) was created for the regular-release traditional Chinese medicine tablets. As a result, the disintegration behaviors of 50 batches of traditional Chinese medicine tablets were classified into four categories, i.e. ⅠA_2, ⅠB_1, ⅡB_1, and ⅡB_2. traditional Chinese medicine tablets(Class I) with disintegration time ≤ 30 min were defined to be rapid in disintegration, which can be the objective of optimization or improvement of Chinese herbal extract(semi extract) tablets. Different drug release models were used to fit the dissolution curve of traditional Chinese medicine tablets with gradual dissolution or dispersion phenomenon(i.e. Type B tablets). The results showed that the dissolution curves of water-soluble components in the disintegration process conformed to the zero order kinetics and the Ritger-Peppas model. It could be inferred that the disintegration mechanisms of type B tablets were a combination of dissolution controlled and swelling controlled mechanisms. This study contributes to understanding the disintegration behavior of traditional Chinese medicine tablets, and provides a reference for the design and improvement of disintegration performance of traditional Chinese medicine tablets.

Manufacturing classification system for oral solid dosage forms of traditional Chinese medicines(Ⅰ): classification of processing routes / 中国中药杂志

Oral solid dosage(OSD) occupies a key position in the market of Chinese patent medicines and new traditional Chinese medicines. Processing route is the foundation for the research and development of traditional Chinese medicine OSDs. On the basis of prescriptions and preparation methods of 1 308 traditional Chinese medicine OSDs recorded in the Chinese Pharmacopoeia, we summarized the patterns of processing routes of both modern dosage forms(tablets, granules, and capsules) and traditional dosage forms(pills and powder) and constructed a manufacturing classification system(MCS) based on the processing routes. Based on the MCS, statistical analyses were conducted respectively on medicinal materials, pharmaceutical excipients, extraction solvents in the pretreatment process, crushed medicinal materials, methods of concentration and purification, and methods of drying and granulation, aiming to uncover the process features. The results showed that each dosage form can be prepared via different routes with different processing methods of decoction pieces and raw materials for dosage preparation. The raw materials for dosage form preparation of traditional Chinese medicine OSDs included total extract, semi-extract, and total crushed powder, which accounted for different proportions. The raw materials for traditional dosage forms are mainly decoction pieces powder. Semi-extracts are the main raw materials for tablets and capsules, which account for 64.8% and 56.3%, respectively. Total extracts are the main raw materials for granules, with a proportion of 77.8%. Compared with tablets and capsules, traditional Chinese medicine granules with dissolubility requirements had a larger proportion of water extraction process, a higher proportion of refining process(34.7%), and a lower proportion of crushed medicinal mate-rials in semi-extract granules. There are four ways to add volatile oil to the modern dosage forms of traditional Chinese medicine. In addition, some new technologies and processes have been used in concentration, filtration, and granulation processes of traditional Chinese medicine OSDs, and the application of pharmaceutical excipients is diversified. The results of this study are expected to provide reference for the processing route design and upgrading of OSDs for new traditional Chinese medicines.

Research progress and maturity assessment of continuous manufacturing of traditional Chinese medicine / 中国中药杂志

The pharmaceutical manufacturing model is gradually changing from intermittent manufacturing to continuous manufacturing and intelligent manufacturing. This paper briefly reviewed the supervision and research progress in continuous pharmaceutical manufacturing in China and abroad and described the definition and advantages of continuous pharmaceutical manufacturing. The continuous manufacturing of traditional Chinese medicine(TCM) at the current stage was summarized in the following three terms: the enhancement of the continuity of intermittent manufacturing operations, the integration of continuous equipment to improve physical continuity between units, and the application of advanced process control strategies to improve process continuity. To achieve continuous manufacturing of TCM, the corresponding key technologies, such as material property characterization, process modeling and simulation, process analysis technology, and system integration, were analyzed from the process and equipment, respectively. It was proposed that the continuous manufacturing equipment system should have the characteristics of high speed, high response, and high reliability, "three high(H~3)" for short. Considering the characteristics and current situation of TCM manufacturing, based on the two dimensions of product quality control and production efficiency, a maturity assessment model for continuous manufacturing of TCM, consisting of operation continuity, equipment continuity, process continuity, and quality control continuity, was proposed to provide references for the application of continuous manufacturing technology for TCM. The implementation of continuous manufacturing or the application of key continuous manufacturing technologies in TCM can help to systematically integrate advanced pharmaceutical technology elements and promote the uniformity of TCM quality and the improvement of production efficiency.

Four critical engineering and technical problems in manufacturing measurement of traditional Chinese medicine / 中国中药杂志

Focusing on the development and quality improvement strategy of the traditional Chinese medicine(TCM) industry, the scientific and technological innovation of the new engineering of TCM should be paid attention to solve the "stuck neck" dilemma. Under the background of the ecological and industrial revolution of the scientific and technological innovation system, the super-scale information interaction and multi-dimensional integration will inevitably lead to profound changes in the manufacturing mode of TCM. Manufacturing measurement of TCM is formed on the basis of the reliability engineering theory of process control of TCM production. It is the development extension of system theory and system science ideas and a cross-fertilization discipline that combines theory with practice and adheres to the "four-oriented" re-epistemology improvement of the TCM discipline. In response to the problems of complex raw material sources, coarse process technology, unclear material basis, and poor applicability of equipment and technology in the manufacture of TCM, the transformation research mode of "aiming at the integration of pharmaceutical industry-developing intelligent production line-enabling industrial transformation" has been developed. This paper proposed the four key engineering technical problems, i.e., the identification of critical quality attributes(CQA) in the manufacture of TCM, the quality by design(QbD) and product development of the manufacturing process of TCM, the quality transfer principle and multivariate process capability index of TCM manufacturing, and the development of measurement technology and equipment of the manufacturing measurement of TCM, to achieve the systematization of quality control indicators, real-time process control, digitalization of manufacturing process, transparency of quality transfer, and intelligent whole-process control. In this paper, the new concepts, new theories, and new technologies provide a reference for the industrialization of TCM.

Immune regulation mechanism of Saposhnikoviae Radix polysaccharide based on zebrafish model / 中国中药杂志

The immunomodulatory effect of Saposhnikoviae Radix polysaccharide(SRP) was evaluated based on the zebrafish mo-del, and its mechanism was explored by transcriptome sequencing and real-time fluorescence-based quantitative PCR(RT-qPCR). The immune-compromised model was induced by navelbine in the immunofluorescence-labeled transgenic zebrafish Tg(lyz: DsRed), and the effect of SRP on the density and distribution of macrophages in zebrafish was evaluated. The effect of SRP on the numbers of macrophages and neutrophils in wild-type AB zebrafish was detected by neutral red and Sudan black B staining. The content of NO in zebrafish was detected by DAF-FM DA fluorescence probe. The content of IL-1β and IL-6 in zebrafish was detected by ELISA. The differentially expressed genes(DEGs) of zebrafish in the blank control group, the model group, and the SRP treatment group were analyzed by transcriptome sequencing. The immune regulation mechanism was analyzed by Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment, and the expression levels of key genes were verified by RT-qPCR. The results showed that SRP could significantly increase the density of immune cells in zebrafish, increase the number of macrophages and neutrophils, and reduce the content of NO, IL-1β, and IL-6 in immune-compromised zebrafish. The results of transcriptome sequencing analysis showed that SRP could affect the expression level of immune-related genes on Toll-like receptor pathway and herpes simplex infection pathway to affect the release of downstream cytokines and interferon, thereby completing the activation process of T cells and playing a role in regulating the immune activity of the body.

Application of high-density polyethylene implants in adult cleft lip and palate nasal deformity and dysfunction / 中华耳鼻咽喉头颈外科杂志

Objective: Through the use of high-density polyethylene implants in adults with cleft lip and palate nasal deformities and abnormal functions, to evaluate the clinical effect of postoperative patients on improving nasal shape and symptoms. Methods: A retrospective study of 12 patients with nasal deformities after cleft lip and palate surgery in the Shanghai Ninth People's Hospital Affiliated to Shanghai JiaoTong University School of Medicine from January 2018 to January 2022 was completed, including 7 males and 5 females, with the age ranging from 18 to 29 years. All the patients underwent nasal deformity correction, and nasal septum correction was performed if necessary. High-density polyethylene implants (MEDPOR/Su-Por) were used intraoperatively. Follow-up for at least 6 months was performed to measure the relevant appearance indicators and subjective Visual Analog Scale (VAS) scores, and to compare the clinical effects before and after surgery. SPSS 22.0 software was used for statistical analysis. Results: Before and after surgery, the average VAS score of nasal obstruction decreased by (4.83±0.94) points; the average VAS score of appearance satisfaction increased by (3.92±1.08) points; the height of nasal columella was increased by (1.79±0.78)mm; the height of nasal tip was increased by (2.79±1.50)mm; the height of ipsilateral nostril was increased by (1.83±0.62)mm; the width of the ipsilateral nasal floor was reduced by (0.42±0.47)mm. All of above were statistically significant (all P<0.05). Conclusion: High-density polyethylene implants can effectively improve the shape and function of the nose in operations related to cleft lip and palate nasal deformity and abnormal functions, and are an ideal synthetic material.

Deep neck space infections: a retrospective cohort study of surgical risk factors / 中华耳鼻咽喉头颈外科杂志

Objective: To explore risk factors affecting treatment for deep neck space infections (DNSIs) so as to provide guidance for appropriate early managements. Methods: A retrospective cohort study was conducted on inpatients with DNSIs admitted to the Department of Otolaryngology, Head and Neck Surgery, Affiliated Hospital of Qingdao University from March 2013 to February 2021. Patients were divided into surgical and non-surgical groups based on whether they had surgery or not. Information collected included demographic data, disease-related signs and symptoms, treatment history, systemic comorbidities, imaging data and laboratory indicators. Hypothesis testing, univariate Logistic regression and multivariate Logistic regression were used for data processing. Resuts A total of 61 patients were included, including 37 males and 24 females, aged 6-96 years. There were 35 cases (57.4%) in the surgical group and 26 cases (42.6%) in the non-surgical group. Multivariate analysis showed that risk factors for surgery as followings: neck dyskinesia (OR=0.03, 95%CI: 0.00-0.24), dysphagia (OR=0.10, 95%CI: 0.02-0.72), serum white blood cell count≥16.74×109/L (OR=1.18, 95%CI: 1.01-1.39) and interspace gas (OR=0.03, 95%CI: 0.00-0.30). Conclusion: Clinicians should be alert to these risk factors for surgery in the course of treatment and timely surgical treatment for patients who meet the conditions.

Guanxin Danshen Dripping Pills Improve Quality of Life and Cardiovascular Prognoses of CHD Patients after PCI with Anxiety or Depression (GLAD Study): A Randomized Double-Blind Placebo-Controlled Study / 中国结合医学杂志

OBJECTIVE@#To assess the efficacy and safety of Guanxin Danshen Dripping Pills (GXDS) in the treatment of depression or anxiety in patients with coronary heart disease (CHD) after percutaneous coronary intervention (PCI).@*METHODS@#From September 2017 to June 2019, 200 CHD patients after PCI with depression and anxiety were included and randomly divided into GXDS (100 cases) and placebo control groups (100 cases) by block randomization and a random number table. Patients in the GXDS and control groups were given GXDS and placebo, respectively, 0.4 g each time, 3 times daily for 12 weeks. The primary outcomes were scores of Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Scale (GAD-7) and the Seattle Angina Pectoris Scale (SAQ). The secondary outcomes included 12 Health Survey Summary Form (SF-12) scores and the first onset time and incidence of major adverse cardiovascular events (MACEs). Other indices including blood pressure, blood lipids, microcirculation and inflammatory-related indices, etc. were monitored at baseline, week 4, and week 12.@*RESULTS@#In the full analysis set (200 cases), after treatment, the PHQ-9 and GAD-7 scores in the GXDS group were considerably lower than those in the control group (P<0.05). Compared with the baseline, the total PHQ-9 scores of the experimental and control groups decreased by 3.97 and 1.18, respectively. The corrected mean difference between the two groups was -2.78 (95% CI: -3.47, -2.10; P<0.001). The total GAD-7 score in the GXDS group decreased by 3.48% compared with the baseline level, while that of the placebo group decreased by 1.13%. The corrected mean difference between the two groups was -2.35 (95% CI: -2.95, -1.76; P<0.001). The degree of improvement in SAQ score, SF-12 score, endothelin and high-sensitive C-reactive protein levels in the GXDS group were substantially superior than those in the placebo group, and the differences between the two groups were statistically significant (P<0.05). Similar results were obtained in the per protocol population analysis of 177 patients. Three cases of MACES were reported in this study (1 in the GXDS group and 2 in the placebo group), and no serious adverse events occurred.@*CONCLUSIONS@#GXDS can significantly alleviate depression and anxiety, relieve symptoms of angina, and improve quality of life in patients with CHD after PCI. (Registration No. ChiCTR1800014291).

Clinical features and genetic analysis of a child with acute form of Tyrosinemia type I due to a novel variant of FAH gene / 中华医学遗传学杂志

OBJECTIVE@#To analyze the clinical phenotype and genetic basis for a child with acute form of tyrosinemia type I (TYRSN1).@*METHODS@#A child with TYRSN1 who presented at the Gansu Provincial Maternal and Child Health Care Hospital in October 2020 was selected as the subject. The child was subjected to tandem mass spectrometry (MS-MS) and urine gas chromatography-mass spectrometry (GC-MS) for the detection of inherited metabolic disorders, in addition with whole exome sequencing (WES). Candidate variants were validated by Sanger sequencing.@*RESULTS@#The child's clinical features included abdominal distension, hepatomegaly, anemia and tendency of bleeding. By mass spectrometry analysis, her serum and urine tyrosine and succinylacetone levels have both exceeded the normal ranges. WES and Sanger sequencing revealed that she has harbored c.1062+5G>A and c.943T>C (p.Cys315Arg) compound heterozygous variants of the FAH gene, which were inherited from her father and mother, respectively. Among these, the c.943T>C was unreported previously.@*CONCLUSION@#Considering her clinical phenotype and result of genetic testing, the child was diagnosed with TYRSN1 (acute type). The compound heterozygous variants of the FAH gene probably underlay the disease in this child. Above finding has further expanded the spectrum of FAH gene variants, and provided a basis for accurate treatment, genetic counseling and prenatal diagnosis for her family.

Genetic features of a case with mosaic ring chromosome 4 and a review of the literature / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis, clinical phenotype and pathogenesis for a child with mosaicism ring chromosome 4.@*METHODS@#Clinical data of the child was collected. Peripheral blood chromosomal karyotype G banding analysis, chromosomal microarray analysis (CMA), fluorescence in situ hybridization (FISH) were carried out for the child, in addition with a review of the literature.@*RESULTS@#The child was born full-term with low birth weight, facial dysmorphism, patent ductus arteriosus and ventricular septal defect. His karyotype was determined as mos46,XY,r(4)(p16.3q35.2)[259]/45,XY,-4[25]/47,XY,r(4)(p16.3q35.2), +r(4)(p16.3q35.2)[8]/46,XY,der(4)del(4)(p16.3)inv(4)(p16.3q31.1)[6]/46,XY,dic?r(4;4)(p16.3q35.2;p16.3q35.2)[4]/48,XY,r(4)(p16.3q35.2),+r(4)(p16.3q35.2)×2[3]/46,XY,r(4)(p1?q2?)[2]; CMA result was arr[GRCH37]4p16.3(68 345-2 981 614)×1; FISH result was 45,XY,-4[12]/45,XY,-4×2,+mar1.ish r1(4)(WHS-,D4Z1+)[1]/ 46,XY,-4,+mar1.ishr1(4)(WHS-,D4Z1+)[73]/46,XY,-4,+mar2.ishr2(4)(WHS-,D4Z1++)[1]/47,XY,-4,+mar1×2.ishr1(4) (WHS-, D4Z1+)×2[4]/46,XY,del(4)(p16.3).ish del(4)(p16.3)(WHS-,D4Z1+)[9].@*CONCLUSION@#In this case, the ring chromosome 4 as a de novo variant has produced a number of cell lines during embryonic development and given rise to mosaicism. The clinical phenotype of ring chromosome 4 is variable. The instability of the ring chromosome itself, presence of mosaicism, chromosome breakpoint and range of deletion and/or duplication may all affect the ultimate phenotype.

Echinacoside hampers malignant progression of breast cancer MCF-7 cells by modulating AKR1B10/ERK signal transduction / 中国中药杂志

This study analyzes the impact of echinacoside(ECH) in the proliferation, metastasis and adriamycin(ADR) resistance of breast cancer(BC) MCF-7 cells via the modulation of aldo-keto reductase family 1 member 10(AKR1B10)/extracellular signal-regulated kinase(ERK) pathway. The chemical structure of ECH was firstly confirmed. MCF-7 cells were treated with different concentration(0, 10, 20, 40 μg·mL~(-1)) of ECH for 48 h. Western blot was used to analyze expression of AKR1B10/ERK pathway-associated proteins and cell counting kit-8(CCK-8) assay to determine cell viability. MCF-7 cells were collected and classified into control group, ECH group, ECH + Ov-NC group, and ECH + Ov-AKR1B10 group. Then Western blot was employed to analyze the expression of AKR1B10/ERK pathway-associated proteins. CCK-8 and 5-ethynyl-2'-deoxyuridine(EdU) assay were used to examine cell proliferation. Cell migration was appraised with scratch assay, Transwell assay, and Western blot. Eventually, MCF-7 cells were treated with ADR for 48 h to induce ADR resistance. Cell viability was tested by CCK-8 assay and cell apoptosis was estimated based on terminal-deoxynucleoitidyl transferase mediated nick end labeling(TUNEL) assay and Western blot. Based on Protein Data Bank(PDB) and molecular docking, the binding affinity of ECH to AKR1B10 was assessed. Various doses of ECH decreased the expression of AKR1B10/ERK pathway-associated proteins in a dose-dependent manner and declined cell viability compared with the control group. Compared with the control group, 40 μg·mL~(-1) ECH blocked the AKR1B10/ERK pathway in MCF-7 cells and inhibited the proliferation, metastasis and ADR resistance of the cells. Compared with the ECH + Ov-NC group, ECH + Ov-AKR1B10 group showed the recovery of some biological behaviors of MCF-7 cells. ECH also targeted AKR1B10. ECH can inhibit the proliferation, metastasis, and ADR resistance of BC cells by blocking AKR1B10/ERK pathway.