Identification and characterization of circadian clock genes in the head transcriptome of Conopomorpha sinensis Bradley.

Conopomorpha sinensis Bradley is the most detrimental pest to litchi and longan in China. Adult eclosion, locomotion, mating and oviposition of C. sinensis usually occur at night, regulated by a circadian rhythm. Nevertheless, our understanding of the linkages between adult circadian rhythms and clock genes remains inadequate. To address this gap, transcriptomic analysis was conducted on female and male heads (including antennae) of C. sinensis using the Illumina HiSeq 6000 platform to identify major circadian clock-related genes. The annotated sequences were analyzed by BLASTx, and candidate clock genes were classified based on conservation, predicted domain architectures, and phylogenetic analysis. The analysis revealed a higher conservation of these genes among the compared moths. Further, the expression profile analysis showed a significant spatiotemporal and circadian rhythmic accumulation of some clock genes during development. The candidate clock genes were predominantly expressed in the head, highlighting their crucial function in circadian rhythm regulation. Moreover, CsinPer, CsinTim1, and CsinCry1 displayed similar dynamic expressions with a peak expression level in the 4th age adults, suggesting their involvement in regulation of courtship and mating behaviors. The CsinPer and CsinTim1 mRNA oscillated strongly with a similar phase, containing a peak expression just before the female mating peak. This work will greatly contribute to understanding the circadian clock system of C. sinensis and provide valuable information for further studies of the molecular mechanisms involved in rhythmicity in fruit-boring pests.

Treatment progress of follicular lymphoma / 白血病·淋巴瘤

Follicular lymphoma (FL) is the most common indolent B-cell lymphoma. The 2023 American Society of Hematology (ASH) annual meeting announced the latest updates on newly diagnosed and relapsed/refractory FL, including the targeted therapy, bio-specific antibodies and chimeric antigen receptor T-cell (CAR-T) therapy. This review provides an overview of these updates.

Expression of CENPF and miR-1-3p in the serum of patients with advanced gastric cancer and their correla-tion with prognosis / 实用医学杂志

Objective To investigate the expression of centromeric protein F(CENPF)and microribonucleic acid 1-3p(miR-1-3p)in the serum of patients with advanced gastric cancer and their correlation with prognosis.Methods Sixty patients with advanced gastric cancer admitted to our hospital from March 2019 to March 2020 were collected as the study group,while 60 healthy volunteers who underwent physical examinations at our hospital's physical examination center during the same period were collected as the control group.Real-time fluorescence quantitative PCR(qRT-PCR)method was applied to detect the expression levels of serum CENPF and miR-1-3p in each group;Pearson method was applied to analyze the correlation between serum levels of CENPF and miR-1-3p;Kaplan-Meier method was applied to analyze the relationship between the expression of CENPF,miR-1-3p,and prognosis in patients with advanced gastric cancer;and COX regression was applied to analyze risk factors affecting the prognosis of patients with advanced gastric cancer.Results Compared with the control group,the CENPF level in the study group was obviously increased,while the miR-1-3p level was obviously reduced(P＜0.05).The correlation analysis results showed that there was a negative correlation between serum CENPF and miR-1-3p levels in patients with advanced gastric cancer(r =-0.650,P＜0.001).There were obvious differences in CENPF and miR-1-3p levels among different TNM stages and lymph node metastasis status(P＜0.05).The 3-year survival rate of patients in the high expression group of CENPF was 19/30(63.33%),which was obviously lower than that in the low expression group,28/30(93.33%)(χ2 = 7.954,P＜0.001);the 3-year survival rate of patients in high expression group of miR-1-3p was 29/30(96.67%),which was obviously higher than that in the low expression group,18/30(60.00%)(χ2 = 11.882,P = 0.001).Multivariate COX regression analysis showed that TNM staging,lymph node metastasis,CENPF,and miR-1-3p expression were risk factors affecting the prognosis of patients with advanced gastric cancer(P＜0.05).Conclusion The serum CENPF level in patients with advanced gastric cancer obviously increase,while miR-1-3p level obviously decrease,both of which are related to prognosis.

Development and validation of a method for quantitation of cefepime/avibactam in M-H broth: application to antibacterial activity using in vitro PK/PD Model / 中国临床药理学与治疗学

AIM: To establish a method for quantitation of cefepime and avibactam in M-H broth, and applicated in the in vitro dynamic PK/PD model. METHODS: The cefepime was also determined using the high-performance liquid chromatography method (HPLC), the avibactam was also determined using the liquid chromatography-mass spectrometry (LC-MS/MS), an in vitro dynamic PK/PD model was established to study the PK/PD relationship of cefepime/avibactam against carbapenem resistant Klebsiella pneumoniae (CRKP). RESULTS: The linear ranges of cefepime and avibactam were good at (0.5-20) and (0.1-25) μg/mL (r=0.999), and the lower limit concentrations were 0.5 and 0.1 μg/mL. The extraction recoveries of cefepime and avibactam in M-H broth were 88.0%-101.7% and 90.9%-95.2%, the relative standard deviation of intra-day precision and inter-day precision were less than 5.2%. The concentration-time curves were well simulated by the PK/PD model. All observed concentrations in each experiment were in the range of 20% of the targeted values. For the CRKP of MIC=8 μg/mL and MIC=16 μg/mL, the colony decreased to 2.783Log10 CFU/mL and 1.325Log10 CFU/mL at the cefepime/avibactam 2.5 g q8 h administration after 24 h. CONCLUSION: The determination method of cefepime and avibactam in broth established in this study has high sensitivity and good stability. For the CRKP with MIC≤8 μg/mL,cefepime/avibactam showed that good anti-CRKP activity under routine administration in vitro dynamic PK/PD model.

Influence of different depths of anesthesia under the guidance of anesthesia depth detector on awakening quality of elderly patients with colon cancer after laparoscopic surgery / 中国医学装备

Objective:To explore the influence of different depths of anesthesia under guidance of anesthesia depth detector on the awakening quality of elderly patients with colon cancer after laparoscopic surgery.Methods:A total of 96 elderly patients with colon cancer who underwent surgical resection and admitted to Beijing Changping District Hospital from February 2017 to June 2020 were selected.They were randomly divided into mild anesthesia group,moderate anesthesia group and deep anesthesia group according to the random sampling,with 32 in each group.The bispectral index(BIS)of deep anesthesia group was within 30-39 interval,and the BIS of moderate anesthesia group was within 40-49 interval,and the BIS of mild anesthesia group was within 50-60 interval.The Prince-Henry pain scale scores of patients with different depths of anesthesia under anesthesia depth detector were observed.The stress response-related indicators included adrenocorticotropic hormone(ACTH),cortisol(Cor)and interleukin-6(IL-6)of patients at three different time points:pre operation(S1),intra operation(S2)and post operation(S3)were monitored.Additionally,the differences of the incidences of complications and the cognitive function also were analyzed.Results:The postoperative Prince-Henry pain scores of the three groups of patients with colon cancer showed there were no statistically significant differences among anesthesia groups with different depths(P>0.05).The stress response indicators included ACTH,Cor and IL-6 appeared significant time-dependent changes among anesthesia groups with different depths.The stress response indicators of all groups significantly increased at S2 point,and the ACTH,Cor and IL-6 levels of mild anesthesia group were respectively(13.73±1.63)nmol/L,(269.24±31.46)nmol/L and(83.67±3.44)μg/L,and these of moderate anesthesia group were respectively(18.26±2.52)nmol/L,(242.56±36.75)nmol/L and(109.35±6.44)μg/L,and these of deep anesthesia group were respectively(19.42±2.42)nmol/L,(432.35±31.34)nmol/L and(132.42±2.31)μg/L.There were significant differences in these indicators in same group between S2 point and S1 point(tmild group=7.99,12.48,16.48,tmoderate group=2.19,6.82,3.03,tdeep group=14.21,5.11,20.14,P＜0.05),respectively.The differences of the incidence rates of complication between the mild anesthesia group and the moderate anesthesia group,and between the mild anesthesia and the deep anesthesia group were statistically significant(x2=6.342,5.238,P<0.05),respectively.The MMSE scores 24 hours after surgery indicated that the difference of that between mild anesthesia group and deep anesthesia group,and between moderate anesthesia group and deep anesthesia group were significant(t=4.74,3.77,P<0.05),respectively.Conclusion:The depth of anesthesia has a significant influence on postoperative recovery quality,stress response and cognitive function.Using anesthesia depth detector to adjust the different depth of anesthesia can help to improve the awakening quality of elderly patients with colon cancer post-surgery and reduce the incidence of adverse reactions.

High Toughness, Multi-dynamic Self-Healing Polyurethane for Outstanding Energy Harvesting and Sensing.

Triboelectric nanogenerators (TENGs) are an emerging class of energy harvesting devices with considerable potential across diverse applications, including wearable electronic devices and self-powered sensors. However, sustained contact, friction, and incidental scratches during operation can lead to a deterioration in the electrical output performance of the TENG, thereby reducing its overall service life. To address this issue, we developed a self-healing elastomer by incorporating disulfide bonds and metal coordination bonds into the polyurethane (PU) chain. The resulting elastomer demonstrated exceptional toughness, with a high value of 85 kJ m-3 and an impressive self-healing efficiency of 85.5%. Specifically, the TENG based on that self-healing PU elastomer generated a short circuit current of 12 µA, an open circuit voltage of 120 V, and a transfer charge of 38.5 nC within a 2 cm × 2 cm area, operating in contact-separation mode. With an external resistance of 20 MΩ, the TENG achieved a power density of 2.1 W m-2. Notably, even after self-healing, the electrical output performance of the TENG was maintained at 95% of the undamaged device. Finally, the self-healing TENG was employed to construct a self-powered noncontact sensing system that can be applied to monitor human motion accurately. This research may expand the application prospects of PU materials in future human-computer interaction and self-powered sensing fields.

Extensive emission tuning and characterization of highly efficient CuInS2 quantum dots for white light-emitting diodes.

Whole visible range emitting CuInS2/ZnS QDs were obtained with broad band-width and high luminous efficiency by altering the Cu/In ratio and coating ZnS layer. 1-Dodecanethiol (DDT) as a sulfur source in the ZnS coating process can inhibit the lattice defects caused by Zn2+ inter-diffusion, thus increasing the photoluminescence quantum yield (PL QY). Then the stability and lighting performance of white light-emitting diodes (WLEDs) based on these CuInS2/ZnS QDs were characterized. The optimized WLED device exhibited a moderate luminous efficacy (LE) (70.33 lm·W-1) and ultrahigh color qualities (CRI Ra = 92.7, R9 = 95.9, R13 = 96.3) with warm white at a correlated color temperature (CCT) of 4052 K.

Recent Advances in Tailored Fabrication and Properties of Biobased Self-Healing Polyurethane.

With the emergence of challenges in the environmental degradation and resource scarcity fields, the research of biobased self-healing polyurethane (BSPU) has become a prevailing trend in the technology of the polyurethane industry and a promising direction for developing biomass resources. Here, the production of BSPU from lignocellulose, vegetable oil, chitosan, collagen, and coumarin is classified, and the principles of designing polyurethane based on compelling examples using the latest methods and current research are summarized. Moreover, the impact of biomass materials on self-healing and mechanical properties, as well as the tailored performance method, are presented in detail. Finally, the applications of BSPU in biomedicine, sensors, coatings, etc. are also summarized, and the possible challenges and development prospects are explored to helpfully make progress in the development of BSPU. These findings demonstrate valuable references and practical significance for future BSPU research.

A robust microsatellite instability detection model for unpaired colorectal cancer tissue samples / 中华医学杂志(英文版)

BACKGROUND@#Microsatellite instability (MSI) is a key biomarker for cancer immunotherapy and prognosis. Integration of MSI testing into a next-generation-sequencing (NGS) panel could save tissue sample, reduce turn-around time and cost, and provide MSI status and comprehensive genomic profiling in single test. We aimed to develop an MSI calling model to detect MSI status along with the NGS panel-based profiling test using tumor-only samples.@*METHODS@#From January 2019 to December 2020, a total of 174 colorectal cancer (CRC) patients were enrolled, including 31 MSI-high (MSI-H) and 143 microsatellite stability (MSS) cases. Among them, 56 paired tumor and normal samples (10 MSI-H and 46 MSS) were used for modeling, and another 118 tumor-only samples were used for validation. MSI polymerase chain reaction (MSI-PCR) was performed as the gold standard. A baseline was built for the selected microsatellite loci using the NGS data of 56 normal blood samples. An MSI detection model was constructed by analyzing the NGS data of tissue samples. The performance of the model was compared with the results of MSI-PCR.@*RESULTS@#We first intersected the target genomic regions of the NGS panels used in this study to select common microsatellite loci. A total of 42 loci including 23 mononucleotide repeat sites and 19 longer repeat sites were candidates for modeling. As mononucleotide repeat sites are more sensitive and specific for detecting MSI status than sites with longer length motif and the mononucleotide repeat sites performed even better than the total sites, a model containing 23 mononucleotide repeat sites was constructed and named Colorectal Cancer Microsatellite Instability test (CRC-MSI). The model achieved 100% sensitivity and 100% specificity when compared with MSI-PCR in both training and validation sets. Furthermore, the CRC-MSI model was robust with the tumor content as low as 6%. In addition, 8 out of 10 MSI-H samples showed alternations in the four mismatch repair genes ( MLH1 , MSH2 , MSH6 , and PMS2 ).@*CONCLUSION@#MSI status can be accurately determined along the targeted NGS panels using only tumor samples. The performance of mononucleotide repeat sites surpasses loci with longer repeat motif in MSI calling.

Therapeutic effect of ursodeoxycholic acid-berberine supramolecular nanoparticles on ulcerative colitis based on supramolecular system induced by weak bond / 中国中药杂志

Ulcerative colitis(UC) is a recurrent, intractable inflammatory bowel disease. Coptidis Rhizoma and Bovis Calculus, serving as heat-clearing and toxin-removing drugs, have long been used in the treatment of UC. Berberine(BBR) and ursodeoxycholic acid(UDCA), the main active components of Coptidis Rhizoma and Bovis Calculus, respectively, were employed to obtain UDCA-BBR supramolecular nanoparticles by stimulated co-decocting process for enhancing the therapeutic effect on UC. As revealed by the characterization of supramolecular nanoparticles by field emission scanning electron microscopy(FE-SEM) and dynamic light scattering(DLS), the supramolecular nanoparticles were tetrahedral nanoparticles with an average particle size of 180 nm. The molecular structure was described by ultraviolet spectroscopy, fluorescence spectroscopy, infrared spectroscopy, high-resolution mass spectrometry, and hydrogen-nuclear magnetic resonance(H-NMR) spectroscopy. The results showed that the formation of the supramolecular nano-particle was attributed to the mutual electrostatic attraction and hydrophobic interaction between BBR and UDCA. Additionally, supramolecular nanoparticles were also characterized by sustained release and pH sensitivity. The acute UC model was induced by dextran sulfate sodium(DSS) in mice. It was found that supramolecular nanoparticles could effectively improve body mass reduction and colon shortening in mice with UC(P<0.001) and decrease disease activity index(DAI)(P<0.01). There were statistically significant differences between the supramolecular nanoparticles group and the mechanical mixture group(P<0.001, P<0.05). Enzyme-linked immunosorbent assay(ELISA) was used to detect the serum levels of tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6), and the results showed that supramolecular nanoparticles could reduce serum TNF-α and IL-6 levels(P<0.001) and exhibited an obvious difference with the mechanical mixture group(P<0.01, P<0.05). Flow cytometry indicated that supramolecular nanoparticles could reduce the recruitment of neutrophils in the lamina propria of the colon(P<0.05), which was significantly different from the mechanical mixture group(P<0.05). These findings suggested that as compared with the mechanical mixture, the supramolecular nanoparticles could effectively improve the symptoms of acute UC in mice. The study provides a new research idea for the poor absorption of small molecules and the unsatisfactory therapeutic effect of traditional Chinese medicine and lays a foundation for the research on the nano-drug delivery system of traditional Chinese medicine.

Establishment and validation of a multigene model to predict the risk of relapse in hormone receptor-positive early-stage Chinese breast cancer patients / 中华医学杂志(英文版)

BACKGROUND@#Breast cancer patients who are positive for hormone receptor typically exhibit a favorable prognosis. It is controversial whether chemotherapy is necessary for them after surgery. Our study aimed to establish a multigene model to predict the relapse of hormone receptor-positive early-stage Chinese breast cancer after surgery and direct individualized application of chemotherapy in breast cancer patients after surgery.@*METHODS@#In this study, differentially expressed genes (DEGs) were identified between relapse and nonrelapse breast cancer groups based on RNA sequencing. Gene set enrichment analysis (GSEA) was performed to identify potential relapse-relevant pathways. CIBERSORT and Microenvironment Cell Populations-counter algorithms were used to analyze immune infiltration. The least absolute shrinkage and selection operator (LASSO) regression, log-rank tests, and multiple Cox regression were performed to identify prognostic signatures. A predictive model was developed and validated based on Kaplan-Meier analysis, receiver operating characteristic curve (ROC).@*RESULTS@#A total of 234 out of 487 patients were enrolled in this study, and 1588 DEGs were identified between the relapse and nonrelapse groups. GSEA results showed that immune-related pathways were enriched in the nonrelapse group, whereas cell cycle- and metabolism-relevant pathways were enriched in the relapse group. A predictive model was developed using three genes ( CKMT1B , SMR3B , and OR11M1P ) generated from the LASSO regression. The model stratified breast cancer patients into high- and low-risk subgroups with significantly different prognostic statuses, and our model was independent of other clinical factors. Time-dependent ROC showed high predictive performance of the model.@*CONCLUSIONS@#A multigene model was established from RNA-sequencing data to direct risk classification and predict relapse of hormone receptor-positive breast cancer in Chinese patients. Utilization of the model could provide individualized evaluation of chemotherapy after surgery for breast cancer patients.

Key quality attributes of benchmark samples of famous classical formula Kaixin Powder / 中国中药杂志

We prepared 15 batches of Kaixin Powder benchmark samples with the decoction pieces of different batches. Further, we established the specific chromatograms and index component content determination method of Kaixin Powder benchmark samples and analyzed the peaks and similarity of the chromatograms. With sibiricose A5, sibiricose A6, polygalaxanthone Ⅲ, 3,6'-disinapoyl sucrose, ginsenoside Rb_1, β-asarone, α-asarone, and dehydropachymic acid as index components, the index component content determination method was established and 70%-130% of the mean content of each component was set as the range. The chromatograms of 15 batches of Kaixin Powder benchmark samples had a total of 22 characteristic peaks, among which 8 peaks were identified, which represented sibiricose A5, sibiricose A6, polygalaxanthone Ⅲ, 3,6'-disinapoyl sucrose, ginsenoside Rb_1, β-asarone, α-asarone, and dehydropachymic acid, respectively. The chromatograms shared the similarity of 0.992-0.999. The 15 batches of benchmark samples had sibiricose A5 of 0.34-0.55 mg·g~(-1), sibiricose A6 of 0.43-0.57 mg·g~(-1), polygalaxanthone Ⅲ of 0.12-0.19 mg·g~(-1), 3,6'-disinapoyl sucrose of 1.08-1.78 mg·g~(-1), ginsenoside Rb_1 of 0.33-0.62 mg·g~(-1), β-asarone of 2.34-3.72 mg·g~(-1), α-asarone of 0.11-0.22 mg·g~(-1), and dehydropachymic acid of 0.053-0.079 mg·g~(-1). This study established the specific chromatograms and index component content determination method of Kaixin Powder benchmark samples, and the method was simple, feasible, reproducible, and stable. This study provides a scientific basis for further research on the key chemical properties of the benchmark samples and preparations of Kaixin Powder.

Investigation of familial tendency of endometriosis / 中华妇产科杂志

Objective: To investigate the familial heritability of endometriosis and to compare the clinical characteristics of patients with or without a family history of endometriosis. Methods: From January 2020 to June 2022, 850 patients with endometriosis confirmed by laparotomy or laparoscopy in Peking University Third Hospital were included in this study. Clinical data were collected, family history was followed up, and the differences of clinical indicators between patients with and without family history of endometriosis were compared. Results: A total of 850 patients were enrolled, with an average age of (33.8±7.0) years old, 315 (37.1%, 315/850) patients in stage Ⅲ and 496 (58.4%, 496/850) patients in stage Ⅳ. There were 100 patients with family history of endometriosis, accounting for 11.8% (100/850). Most of the 113 relatives involved were mothers, daughters and sisters (76.1%, 86/113), 81.5% (22/27) of the second and third degree relatives were maternal relatives. The median ages of patients with and without family history of endometriosis were 30 and 33 years old respectively at the time of diagnosis. The unmarried rate of patients with family history was higher [42.0% (42/100) vs 26.3% (197/750)]. The percentage of dysmenorrhea patients with family history was higher [89.0% (89/100) vs 55.5% (416/750)]. The medians of dysmenorrhea score in patients with and without family history were 6 and 2, and the median durations of dysmenorrhea were 10 and 1 years. There were significant differences in age, marital status, percentage of dysmenorrhea, dysmenorrhea score and duration (all P<0.001). The median levels of serum cancer antigen (CA) 125 in patients with family history and patients without family history at the time of diagnosis were 57.5 and 46.9 kU/L respectively, with a statistically significant difference (P<0.05). However, there were no significant differences between the two groups in nationality, bady mass index, menarche age, menstrual cycle, menstrual period, menstrual volume, serum CA19-9 level, cyst location and size, stage, history of adverse pregnancy and childbirth, infertility, adenomyosis and deep infiltrating endometriosis (all P>0.05). By comparing the specific conditions of dysmenorrhea patients with and without family history of endometriosis, there were no significant differences between the two groups in terms of the age of onset of dysmenorrhea, duration of dysmenorrhea, primary and secondary dysmenorrhea, and progressive aggravation of dysmenorrhea (all P>0.05). The difference in the degree of dysmenorrhea in dysmenorrhea patients with family history of endometriosis was significant (P<0.001). Conclusions: The incidence of endometriosis has a familial tendency, and most of the involved relatives are the first degree relatives. Compared with patients without family history of endometriosis, endometriosis patients with family history are diagnosed at an earlier age, with higher percentage of dysmenorrhea, had more severe dysmenorrhea and higher serum CA125 level.

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.

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.

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.

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.

Treatment progress of relapsed/refractory follicular lymphoma / 白血病·淋巴瘤

Follicular lymphoma (FL) is the most common indolent B-cell lymphoma. The outcome of relapsed/refractory FL patients after multi-therapy is poor. The 64th American Society of Hematology annual meeting in 2022 announced the latest updates on relapsed/refractory FL, including targeted therapy, bio-specific antibodies and chimeric antigen receptor T-cell. This review provides an overview of these updates.

Changes of T lymphocyte subsets in peripheral blood of patients with diffuse large B-cell lymphoma and its clinical significance / 白血病·淋巴瘤

Objective:To investigate the changes of T lymphocyte subsets in peripheral blood of patients with diffuse large B-cell lymphoma (DLBCL) and its clinical significance.Methods:The clinical data of 99 DLBCL patients admitted to the First Affiliated Hospital of Xiamen University from January 2022 to January 2023 were retrospectively analyzed. T lymphocyte subsets in peripheral blood before and after treatment were detected by using flow cytometry. According to the disease status at the time of blood collection and detection, the patients were divided into the newly-diagnosed DLBCL group (28 cases), and the newly-treated remission DLBCL group (71 cases); and 40 healthy volunteers undergoing the physical examination during the same period were selected as the healthy control group. The proportion and absolute count differences of T lymphocytes and the related subsets in 3 groups were compared. Besides, the correlation among T lymphocyte subsets, the correlation of each subset with international prognostic index (IPI) score and treatment response in newly-diagnosed DLBCL patients were further analyzed.Results:The proportion of CD3 + T cells in newly-diagnosed DLBCL group was decreased compared with that in the healthy control group [(58±14)% vs. (67±7)%, P < 0.05]. The absolute count of CD3 + T cells in both newly-diagnosed group and the newly-treated remission group was reduced compared with that in the healthy control group [(875±483) /μl and (808±553) /μl vs. (1 374±279) /μl, P < 0.001]. The absolute count of CD4 + and CD8 + T cells in newly-diagnosed group was decreased compared with that in the healthy control group [(478±313) /μl vs. (695±154) /μl, (316±181) /μl vs. (525±193) /μl, all P < 0.001]. Both the proportion and absolute count of CD4 + T cells in the newly-treated remission DLBCL group were decreased compared with those in the newly-diagnosed DLBCL group and the healthy control group [(40±14)% vs. (53±14)% and (51±9)%, (313±247) /μl vs. (478±313) /μl and (695±154) /μl, all P < 0.05]. The porportion of CD8 + T cells was increased compared with that in the other two groups [(51±15)% vs. (37±12)% and (38±9)%, all P < 0.001]. Compared with the healthy control group, the effect/memory subsets proportion of regulatory T cell (Treg) and conventional T cell (Tcon) were increased in both newly-diagnosed DLBCL group and the newly-treated remission DLBCL group [(79±16)% and (84±12)% vs. (71±11)%,(72±16)% and (76±14)% vs. (62±13)%, all P < 0.05], and the proportion of CD127 + memory Tcon and CD8 + T cell subsets was reduced [(73±14)% and (66±20)% vs. (85±8)%,(39±15)% and (25±21)% vs. (62±16)%, all P < 0.05]. In newly-diagnosed DLBCL group, the absolute counts of CD3 + T and CD4 + T cells were negatively correlated with the proportion of effector Treg ( r = -0.379, P = 0.049; r = -0.384, P = 0.040, respectively). IPI score of DLBCL patients was correlated with the proportion of CD8 + T cells ( Eta2 = 0.15, P = 0.038). The proportion of CD127 + memory Tcon in patients with non-complete remission was increased compared with that in patients with complete remission after treatment ( P = 0.020). Conclusions:The proportion and absolute count of T lymphocyte cells in peripheral blood of newly-diagnosed DLBCL patients is decreased, and the differentiation state of T lymphocyte cells shows change trend, which is related to the clinical characteristics and treatment response of DLBCL patients. Even if DLBCL patients have achieved treatment remission, T lymphocyte cells are not completely return to the normal.

Intelligent co-design of material, process, and equipment for manufacturing high-quality traditional Chinese medicine preparations / 中国中药杂志

In the context of Pharma 4.0, the design tools that support the pharmaceutical Quality by Design(QbD) are iterating fast toward intelligent or smart design. The conventional development methods for traditional Chinese medicine(TCM) preparations have the limitations such as over dependence on experience, low dimensions for the designed experiment parameters, poor compatibility between the process and equipment, and high trial-and-error cost during process scale-up. Therefore, this paper innovatively proposed the intelligent co-design involving material, process, and equipment for manufacturing high-quality TCM preparations, and introduced the design philosophy, targets, tools, and applications with TCM oral solid dosage(OSD) as an example. In terms of design philosophy, the pharmaceutical design tetrahedron composed of critical material attributes, critical process parameters, critical equipment attributes, and critical quality attributes was developed. The design targets were put forward based on the product performance classification system. The design tools involve a design platform that contains several modules, such a as the iTCM material database, the processing route classification system, the system modeling and simulation, and reliability-based optimization. The roles of different modules in obtaining essential and universal design knowledge of the key common manufacturing units were introduced. At last, the applications of the co-design methodology involving material, process, and equipment in the high shear wet granulation process development and the improvement of the dissolving or dispersion capability of TCM formula granules are illustrated. The research on advanced pharmaceutical design theory and methodology will help enhance the efficiency and reliability of drug development, improve the product quality, and promote the innovation of high-end TCM products across the industry.