Objective To optimize the extraction process of Xuetong capsules and establish its quality control method. Methods The extraction process was optimized by orthogonal experiment using ethanol reflux method to investigate the effects of different factors on diphenylstilbene, aloin and extraction yield. The content of 5 anthraquinone compounds in Xuetong capsule was determined by HPLC. Results The optimal extraction process was to add 10 times ethanol, with an ethanol concentration of 70%, and extract 3 times, each time for 1 h; 5 components had a good linear relationship with peak area within a certain concentration range, r>0.999 7; The range of sample recovery rate was 93.66%-96.85%, RSD range of 1.48%-1.66%. The content determination results of the 5 components in three batches of Xuetong capsules were （0.632-0.641）, （0.660-0.681）, （1.968-1.991）, （2.547-2.580）, and （1.076-1.101） mg/g. Conclusion The method was accurate, reproducible, and highly feasible, which could be references for producing and improving the quality control standards of Xuetong capsules.

Liumotang comes from the Yuan dynasty's Effective Prescription Handed Down for Generations of Physicians. It is composed of six medicinal materials： Arecae Semen， Aquilariae Lignum Resinatum， Aucklandiae Radix， Linderae Radix， Rhei Radix et Rhizoma， and Aurantii Fructus. It is a classical formula for treating abdominal pain due to Qi stagnation and constipation accompanied by heat. This study systematically collated the records of Liumotang in ancient medical books and modern clinical literature and conducted in-depth analysis and textual research on its formula source， main diseases， composition， dosage， medical books， container capacity， processing， preparation method， usage， drug basis， formula meaning， and other key information， so as to provide a powerful reference for the development and clinical application of compound preparations of the classical formula Liumotang. The results show that Liumotang was first seen in Effective Prescription Handed Down for Generations of Physicians， and many medical books of the past dynasties have imitated this. In terms of drug basis， the dried and mature seeds of the palm plant Areca catechu， resin-containing wood of the Daphneaceae plant Aquilaria sinensis， the dried roots of the Asteraceae plant woody Aucklandia lappa， the dried tuber root of the Lauraceae plant Lindera aggregata， the dried roots and rhizomes of the knotweed plant， R. palmatum， R.tangutikum， and R. officinale， and the dried and unripe fruits of the citrus genus C. aurantium and its cultivated varieties from the family Rutaceae were selected. In terms of dosage， through the textual research on bowls in the Ming and Qing dynasties， combined with the conversion of medicines and bowl capacity in the Qing dynasty， it was estimated that the dosage of each drug in the Yuan dynasty was 10.86 g. In the Ming and Qing dynasties， the dosage of drugs was mostly equal， but the dosage of drugs was somewhat different. In terms of processing， preparation method， and usage， in the medical books of the past dynasties， the processing of drugs has slightly changed， but raw drugs are used in all preparations. The preparation method and usage did not change much during the Yuan， Ming， and Qing dynasties， except for certain differences in dosage. In terms of syndrome， Liumotang was first used to treat abdominal pain due to Qi stagnation and constipation accompanied by heat. Medical books of the past dynasties often omit the symptoms of heat. In modern clinical practice， Liumotang is mainly used in the digestive system and urinary system diseases and is mostly used to treat constipation-predominant irritable bowel syndrome， biliary reflux gastritis， functional constipation， slow transit constipation， and other diseases， with no adverse reactions found yet. The above results provide a reliable scientific basis for the development and clinical treatment of Liumotang compound preparations.

OBJECTIVE To establish the HPLC fingerprint of Xintong granules and the quantitative analysis of multi- components by single-marker method （QAMS） to determine the contents of 7 components， so as to provide a scientific basis for their quality control. METHODS HPLC method was used to establish the fingerprints for 10 batches of Xintong granules （No. S1- S10）， and similarity evaluation， cluster analysis （CA） and partial least squares-discriminant analysis （PLS-DA） were performed. At the same time， the contents of seven components， including puerarin， daidzin， calycosin-7-O- β -D-glucoside， stilbene glycoside， naringin， icariin and tanshinone ⅡA， were determined by QAMS method， and were compared with the results of external standard method. RESULTS A total of 18 common peaks were marked and 7 peaks were identified in the HPLC fingerprints for 10 batches of Xintong granules， namely puerarin （peak 4）， daidzin （peak 7）， calycosin-7-O-β-D-glucoside （peak 9）， stilbene glycoside （peak 10）， naringin （peak 12）， icariin （peak 17）， and tanshinone ⅡA （peak 18）； the similarities among them were more than 0.990， and CA and PLS-DA results showed that S4-S5，S8-S10，S1-S3 and S6-S7 were clustered into three categories， respectively. Using naringin as the internal standard， the contents of puerarin， daidzin， calycosin-7-O-β-D-glucoside， stilbene glycoside， icariin and tanshinone ⅡA were determined to be 7.868 1-10.181 2， 1.709 2-2.374 1， 0.285 2-0.326 3， 1.024 1- 1.523 9， 0.140 2-0.290 4， and 0.077 1-0.219 4 mg/g， respectively， by the QAMS. These results showed no significant differences compared to those obtained by the external standard method. CONCLUSIONS Established HPLC fingerprint and QAMS method are convenient， stable and accurate， which can provide a basis for the quality evaluation of Xintong granules.

The main protease (M^pro) of SARS-CoV-2 is an attractive target in anti-COVID-19 therapy for its high conservation and major role in the virus life cycle. The covalent M^pro inhibitor nirmatrelvir (in combination with ritonavir, a pharmacokinetic enhancer) and the non-covalent inhibitor ensitrelvir have shown efficacy in clinical trials and have been approved for therapeutic use. Effective antiviral drugs are needed to fight the pandemic, while non-covalent M^pro inhibitors could be promising alternatives due to their high selectivity and favorable druggability. Numerous non-covalent M^pro inhibitors with desirable properties have been developed based on available crystal structures of M^pro. In this article, we describe medicinal chemistry strategies applied for the discovery and optimization of non-covalent M^pro inhibitors, followed by a general overview and critical analysis of the available information. Prospective viewpoints and insights into current strategies for the development of non-covalent M^pro inhibitors are also discussed.

Aim To analyze the anti-A549 and HI299 lung ade-nocarcinoma activities via using examples of baicalin, astragalo-side, hesperidin and cisplatin based on real time cellular analysis (RTCA) technology, and to build a new strategy for EC50 e-valuation reflecting the time-dimensional characteristic. Methods Using RTCA Software Pro for data analysis and GraphPad Prism and Origin Pro plotting, the in vitro anti-A549 and H1299 lung adenocarcinoma activities of baicalin, astragaloside, hesperidin, and cisplatin were characterized using the endpoint method and time dimension, respectively. Results (X) There were significant differences in EC50 values of A549 and H1299 cells at 24 h and 48 h endpoint methods. (2) The correlation coefficient of the curve fitted with the four-parameter equation was > 0. 9, and the dynamic change of EC50 remained relatively stable (the linear fitting of EC50 at adjacent 4 points I slope 1^1) used to calculate the EC50 value within this time dimension. The EC50 of baicalin, astragaloside, hesperidin and cisplatin on A549 cells was 52. 97 ±1.75 плпо! • L~1(16~48 h) , 62.88 ± 2.91 ijunol • L"1 (32.25 -48 h) , 78.84 ±0.33 плпо1 • L"1 (21.5 -29.75 h), 13.57 ±1.54 плпо1 • L_1(27.5 -48 h), respectively; the EC50 of baicalin, astragaloside, hesperidin and cisplatin on H1299 cells was 43. 71 ± 1. 26 |лто1 • L_1 ( 19. 5 -48 h), 47.23 ±1. 19 |лто1 • L_1(14 -48 h) , 39.45 ±0.24 плпо1 • L"1 (12.75 -46.25 h), 25.97 ±4.76 плпо1 • L"1 (10. 25 -48 h) , respectively. The results showed that the time window for the anti-tumor effect of the test solution/drug was different. Conclusions Based on RTCA technology, it is more accurate and reasonable to select EC50 data that exhibit better fitting, stable changes, and time-dimensional characteristics for the evaluation of anti-tumor activity. In addition, this method of distinguishing different effective time of antitumor drugs can provide a reference for the timing of clinical combination drugs, and this approach will also provide a reference for further related studies.

Objective Hippocampal atrophy is a clinically important marker for the diagnosis of many psychiatric disorders such as Alzheimer’s disease‚ so accurate segmentation of the hippocampus is an important scientific issue. With the development of deep learning‚ a large number of advanced automatic segmentation method have been proposed. However‚ 3D hippocampal segmentation is still challenging due to the effects of various noises in MRI and unclear boundaries between various classes of the hippocampus. Therefore‚ the aim of this paper is to propose new method to segment the hippocampal head‚ body‚ and tail more accurately. Methods To overcome these challenges‚ this paper proposed two strategies. One was the spatial and frequency domain features adaptive fusion strategy‚ which reduced the influence of noise on feature extraction by automatically selecting the appropriate frequency combination through fast Fourier transform and convolution. The other was an inter-class boundary region enhancement strategy‚ which allowed the network to focus on learning the boundary regions by weighting the loss function of the boundary regions between each class to achieve the goal of pinpointing the boundaries and regulating the size of the hippocampal head‚ body and tail. Results Experiments performed on a 50-case teenager brain MRI dataset show that our method achieves state-of-the-art hippocampal segmentation. Hippocampal head‚ body and tail had been improved compared to the existing method. Ablation experiments demonstrated the effectiveness of our two proposed strategies‚ and we also validated that the network had a strong generalization ability on a 260-case Task04_Hippocampus dataset. It was shown that the method proposed in this paper could be used in more hippocampal segmentation scenarios. Conclusion The method proposed in this paper can help clinicians to observe hippocampal atrophy more clearly and accomplish more accurate diagnosis and follow-up of the condition.

This paper summarized professor WANG Xinlu's experience in clinical application of hongjingtian （Radix et Rhizoma Rhodiolae Crenulatae）. It is believed that hongjingtian is good at boosting qi and supplementing deficiency， moving qi and resolving constraint， invigorating blood and unblocking vessels， which can be widely used in various diseases caused by qi-blood disorders such as qi deficiency， qi constraint， and blood stasis. Hongjingtian is commonly used with jixueteng （Caulis Spatholobi） to boost qi and nourish blood， invigorate blood and unblock vessels， and together with yuzhizi （Fructus Akebiae） to regulate qi and invigorate blood， dissolve stasis and dissipate masses. According to the specific symptoms， hongjingtian can be flexibly combined with other medicinal herbs to prepare different experienced formulas， such as self-made Sanhong Yangxin Decoction （三红养心汤） for palpitation with qi deficiency and blood stasis syndrome， self-made Anfei Dingchuan Decoction （安肺定喘汤） for exacerbation of asthma with deficiency syndrome， self-made Honghu Jieyu Decoction （红胡解郁汤） for constraint syndrome of qi constraint and blood stasis， and self-made Shexue Chudian Decoction （摄血除癜汤） for idiopathic thrombocytopenic purpura with qi deficiency failing to contain syndrome. For severe cases of coronavirus disease 2019 （COVID-19） with qi-yin desertion syndrome， hongjingtian is commonly used together with modified Shengmai Powder and Tingli Dazao Xiefei Decoction （生脉散合葶苈大枣泻肺汤）， and for those with yang qi external desertion syndrome， hongjingtian combined with shanyurou （Fructus Corni） and Shenfu Decoction （参附汤） is recommended. Moreover， long COVID-19 with healthy qi deficiency and pathogen lingering syndrome can be treated with self-made Xinguan Fuyu Decoction （新冠复愈汤）.

Congenital cranial dysinnervation disorders(CCDDs)are a group of diseases with congenital non-progressive developmental abnormalities or absence of one or more cranial nerves, resulting in primary or secondary abnormalities of cranial nerves innervating the extraocular muscles. CCDDs can be sporadic or hereditary, and may be accompanied by systemic abnormalities. In recent years, with the research progress of neuropathology, neuroimaging, and genetics, it has not only been clarified that the cause of eye movement disorder in CCDDs is neurogenic, but also been found the pathogenic genes of CCDDs, including SALL4, HOXA1, KIF21A, PHOX2A, TUBB3, and HOXB1, etc. In this review, the relevant domestic and international literatures on the molecular genetics and neuroscience of CCDDs in recent years are reviewed, aiming to address how the causing gene mutations of CCDDs affect brain neural development and further lead to congenital abnormal cranial nerve innervation, in order to provide references for the clinical and basic research of CCDDs.

【Objective】 To establish a blood quality monitoring indicator system, in order to continuously improve blood quality and standardized management. 【Methods】 Based on the research of literature and standards, and guided by the key control points of blood collection and supply process, the blood quality monitoring indicator system was developed. Through two rounds of Delphi expert consultation, the indicator content was further revised and improved according to expert opinions after six months of trial implementation. The indicator weight was calculated by questionnaire and analytic hierarchy process. 【Results】 A blood quality monitoring indicator system covering the whole process of blood collection and supply was constructed, including five primary indicators, namely blood donation service, blood component preparation, blood testing, blood supply and quality control, as well as 72 secondary indicators, including definitions, calculation formulas, etc. Two rounds of expert consultation and two rounds of feasibility study meeting were held to revise 17 items and the weight of each indicator was obtained through the analytic hierarchy process. After partial adjustments, a blood quality monitoring indicator system was formed. 【Conclusion】 A blood quality monitoring indicator system covering the whole process of blood collection and supply has been established for the first time, which can effectively evaluate the quality management level of blood banks and coordinate blood quality control activities of blood banks in Shandong like pieces in a chess game, thus improving the standardized management level

【Objective】 To objectively evaluate the quality control level of blood testing process in blood banks through quantitative monitoring and trend analysis, and to promote the homogenization level and standardized management of blood testing laboratories in blood banks. 【Methods】 A quality monitoring indicator system covering the whole process of blood collection and supply, including blood donation service, blood component preparation, blood testing, blood supply and quality control was established. The questionnaire Quality Monitoring Indicators for Blood Collection and Supply Process with clear definition of indicators and calculation formulas was distributed to 17 blood banks in Shandong province. Quality monitoring indicators of each blood bank from January to December 2022 were collected, and 31 indicators in terms of blood testing were analyzed using SPSS25.0 software. 【Results】 The proportion of unqualified serological tests in 17 blood bank laboratories was 55.84% for ALT, 13.63% for HBsAg, 5.08% for anti HCV, 5.62% for anti HIV, 18.18% for anti TP, and 1.65% for other factors (mainly sample quality). The detection unqualified rate and median were (1.23±0.57)% and 1.11%, respectively. The ALT unqualified rate and median were (0.74±0.53)% and 0.60%, respectively. The detection unqualified rate was positively correlated with ALT unqualified rate (r=0.974, P<0.05). The unqualified rate of HBsAg, anti HCV, anti HIV and anti TP was (0.15±0.09)%, (0.05±0.04)%, (0.06±0.03)% and (0.20±0.05)% respectively. The average unqualified rate, average hemolysis rate, average insufficient volume rate and the abnormal hematocrit rate of samples in 17 blood bank laboratories was 0.21‰, 0.08‰, 0.01‰ and 0.02‰ respectively. There were differences in the retest concordance rates of four HBsAg, anti HCV and anti HIV reagents, and three anti TP reagents among 17 blood bank laboratories (P<0.05). The usage rate of ELISA reagents was (114.56±3.30)%, the outage rate of ELISA was (10.23±7.05) ‰, and the out of range rate of ELISA was (0.90±1.17) ‰. There was no correlation between the out of range rate, outrage rate and usage rate (all P>0.05), while the outrage rate was positively correlated with the usage rate (r=0.592, P<0.05). A total of 443 HBV DNA positive samples were detected in all blood banks, with an unqualified rate of 3.78/10 000; 15 HCV RNA positive samples were detected, with an unqualified rate of 0.13/10 000; 5 HIV RNA positive samples were detected, with an unqualified rate of 0.04/10 000. The unqualified rate of NAT was (0.72±0.04)‰, the single NAT reaction rate [(0.39±0.02)‰] was positively correlated with the single HBV DNA reaction rate [ (0.36±0.02) ‰] (r=0.886, P<0.05). There was a difference in the discriminated reactive rate by individual NAT among three blood bank laboratories (C, F, H) (P<0.05). The median resolution rate of 17 blood station laboratories by minipool test was 36.36%, the median rate of invalid batch of NAT was 0.67%, and the median rate of invalid result of NAT was 0.07‰. The consistency rate of ELISA dual reagent detection results was (99.63±0.24)%, and the median length of equipment failure was 14 days. The error rate of blood type testing in blood collection department was 0.14‰. 【Conclusion】 The quality monitoring indicator system for blood testing process in Shandong can monitor potential risks before, during and after the experiment, and has good applicability, feasibility, and effectiveness, and can facilitate the continuous improvement of laboratory quality control level. The application of blood testing quality monitoring indicators will promote the homogenization and standardization of blood quality management in Shandong, and lay the foundation for future comprehensive evaluations of blood banks.