Serine protease inhibitor Kazal-type (SPINK) is a skin keratinizing protease inhibitor, which was initially found in animal serum and is widely present in plants, animals, bacteria, and viruses, and they act as key regulators of skin keratinizing proteases and are involved in the regulation of keratinocyte proliferation and inflammation, primarily through the inhibition of deregulated tissue kinin-releasing enzymes (KLKs) in skin response. This process plays a crucial role in alleviating various skin problems caused by hyperkeratinization and inflammation, and can greatly improve the overall condition of the skin. Specifically, the different members of the SPINK family, such as SPINK5, SPINK6, SPINK7, and SPINK9, each have unique biological functions and mechanisms of action. The existence of these members demonstrates the diversity and complexity of skin health and disease. First, SPINK5 mutations are closely associated with the development of various skin diseases, such as Netherton’s syndrome and atopic dermatitis, and SPINK5 is able to inhibit the activation of the STAT3 signaling pathway, thereby effectively preventing the metastasis of melanoma cells, which is important in preventing the invasion and migration of malignant tumors. Secondly, SPINK6 is mainly distributed in the epidermis and contains lysine and glutamate residues, which can act as a substrate for epidermal transglutaminase to maintain the normal structure and function of the skin. In addition, SPINK6 can activate the intracellular ERK1/2 and AKT signaling pathways through the activation of epidermal growth factor receptor and protease receptor-2 (EphA2), which can promote the migration of melanoma cells, and SPINK6 further deepens its role in stimulating the migration of malignant tumor cells by inhibiting the activation of STAT3 signaling pathway. This process further deepens its potential impact in stimulating tumor invasive migration. Furthermore, SPINK7 plays a role in the pathology of some inflammatory skin diseases, and is likely to be an important factor contributing to the exacerbation of skin diseases by promoting aberrant proliferation of keratinocytes and local inflammatory responses. Finally, SPINK9 can induce cell migration and promote skin wound healing by activating purinergic receptor 2 (P2R) to induce phosphorylation of epidermal growth factor and further activating the downstream ERK1/2 signaling pathway. In addition, SPINK9 also plays an antimicrobial role, preventing the interference of some pathogenic microorganisms. Taken as a whole, some members of the SPINK family may be potential targets for the treatment of dermatological disorders by regulating multiple biological processes such as keratinization metabolism and immuno-inflammatory processes in the skin. The development of drugs such as small molecule inhibitors and monoclonal antibodies has great potential for the treatment of dermatologic diseases, and future research on SPINK will help to gain a deeper understanding of the physiopathologic processes of the skin. Through its functions and regulatory mechanisms, the formation and maintenance of the skin barrier and the occurrence and development of inflammatory responses can be better understood, which will provide novel ideas and methods for the prevention and treatment of skin diseases.

Eight compounds were isolated and purified from the ethyl acetate part of 70% acetone extract of Rehmannia glutinosa by various chromatographic techniques such as silica gel, MCI gel CHP-20, ODS, Toyopearl HW-40C, combined with TLC and semi-preparative HPLC. Their structures were elucidated by modern spectroscopy techniques (NMR, MS, UV, IR), and identified as neomartynoside A (1), osmanthuside B₆ (2), martynoside (3), isomartynoside (4), (E)-p-hydroxycinnamic acid (5), caffeic acid (6), ferulic acid (7), and methyl caffeate (8). Compound 1 is a new phenylethanol glycoside, which was identified as neomartynoside A. Compound 2 was isolated from Rehmannia glutinosa for the first time. In addition, compounds 2, 6 and 7 significantly increased relative glucose consumption, showing potential hypoglycemic activity.

Objective: This study aims to explore the influencing factors, formation mechanisms, and treatment methods of labial protuberance in the anterior maxilla during orthodontic treatment, providing a reference for clinical practice. Method: This study reports a case where the absence of upper anterior teeth 11 and 21, and the retraction tilting movement of teeth 12 and 22, resulted in labial protuberance and gingival hyperplasia. Alveolar osteoplasty and gingivoplasty were performed. The specific changes in the alveolar bone during the retraction of the anterior teeth and the characteristics of its remodeling were analyzed. Combined with relevant literature, the factors influencing the formation of labial protuberance in orthodontic patients, mechanisms, and methods for prevention and treatment were summarized. Results: After periodental surgery follow-up for 6 months, the gingival color and shape of teeth 12 and 22 were good, the labial alveolar bone was normal, and the overall condition was stable. A review of the literature showed that labial protuberance is more common in adult orthodontic patients, and the distance (>4 mm) and speed of retraction of anterior teeth are related to its formation, with the main mechanism likely being differential remodeling of the alveolar bone. In adult patients, the number of active osteoblasts and osteoclasts in the alveolar bone decreases, along with a reduction in metabolic activity and overall cellular activity, which diminishes the reactivity of the alveolar bone. After treatment of anterior teeth retraction, there is insufficient labial bone resorption. Moreover, the lack of mechanical stress-mediated periodontal ligament in the interdental space leads to reduced bone remodeling stimulation in this area, resulting in thickening of the labial alveolar bone of the upper anterior teeth. The remodeling rates of cortical and trabecular bone differ, with active trabecular bone proliferation near the tooth root surface and slow cortical bone resorption near the outer surface, which ultimately results in increased bone thickness at the labial cervical region. Specific case analysis indicates that the retraction distance of the upper anterior teeth in this case was about 6 mm. The alveolar bone at the missing sites of teeth 11 and 21, lacking periodontal ligament stimulation, showed less remodeling and absorption, likely appearing as hyperplasia. The prevention of labial bone protrusion mainly involves controlling the speed and distance of retraction of anterior teeth. Smaller labial protuberances generally do not require treatment, but those affecting function and aesthetics can be addressed with periodontal alveolar osteoplasty. Conclusion After the retraction of anterior teeth in orthodontics, a prominent, hard bone protuberance on the labial side can sometimes occur, which may be due to differential remodeling efficiency in different regions of the alveolar bone. For bone protuberance that influences aesthetics or function, periodontal alveolar osteoplasty can be a reliable option.

OBJECTIVE To analyze the impact of intergenerational substitution effect of the drugs with the same indication on fund expenditures for national medical insurance for this indication in China， taking national medical insurance negotiated drugs for non-small cell lung cancer （hereinafter referred to as “NSCLC national negotiation drugs”） as an example. METHODS The sales amounts of 15 types of NSCLC national negotiated drugs in secondary and tertiary public hospitals across seven sample provinces from 2017 to 2023 were collected from the Pharmaceutical Drug Database of the China National Pharmaceutical Industry Information Center. A sliding t-test and Mann-Kendall trend test were used to evaluate the trends in sales amounts and DDDs. Taking epidermal growth factor receptor（EGFR）-tyrosine kinase inhibitors （TKIs） and anaplastic lymphoma kinase （ALK）-TKIs as examples， the generational substitution characteristics of these drugs were analyzed. RESULTS The change points of sales amounts and DDDs differed slightly across provinces； the change points of sales amount were mostly concentrated between the first quarter of 2019 and the second quarter of 2020， while those for DDDs were primarily concentrated in the first to second quarters of 2021. In five provinces， i.e. Beijing， Heilongjiang， Jiangsu， Sichuan and Shaanxi， sales amounts showed no significant upward trend after the breakpoints （P＞0.05）， whereas in Guangdong and Hubei， both sales amounts and DDDs continued to rise significantly following the breakpoints （P＜0.05）. Since 2020， the growth in sales amounts of EGFR-TKIs had slowed. After 2021， the sales amounts and DDDs of first- and second-generation EGFR-TKIs declined， while third-generation EGFR-TKIs showed clear substitution effects. The sales amounts of ALK-TKIs continuedto grow. However， the sales amounts and DDDs of first-generation ALK-TKIs had declined year by year， with second-generation ALK-TKIs demonstrating a significant substitution effect on first-generation ones， while third-generation ALK-TKIs had not yet shown a clear substitution trend. CONCLUSIONS With the annual access to and renewal of drugs in national medical insurance negotiations， the overall expenditure trend for NSCLC negotiated drugs comes to a plateau. The intergenerational substitution relationships of drugs with the same indication achieve a relative balance in fund expenditures for negotiated drugs with the same indication. It is recommended that pharmaceutical companies carefully consider their research pipelines， and that medical insurance authorities， during the renewal management process， pay attention to the impact of drug substitution effects on the overall actual expenditure of medical insurance funds for that specific target or the same indication， and scientifically evaluate the extent of price reductions during contract renewals.

Objective To evaluate the pharmacokinetic characteristics and safety of single and multiple oral azvudine tablets in healthy young and elderly Chinese subjects.Methods This was a open-label and parallel-group study.The trial consisted of two groups:healthy young subjects group and healthy elderly subjects group,with 12 subjects in each group.Enrolled subjects were first given a single dose,fasting oral azvudine tablet 5 mg,after a 3-day cleansing period entered the multiple dose phase,fasting oral azvudine tablet 5 mg·d-1 for 7 days.Results After a single dose of azvudine 5 mg,Cmax and AUC0-∞ were(4.76±2.12)ng·mL-1,(6.53±2.20)ng·mL-1·h,and Tmax,t1/2 were 0.75,1.87 h in young subjects;Cmax and AUC0-∞ were(6.40±3.25)ng·mL-1,(9.50±3.70)ng·mL-1·h,and Tmax,t1/2 were 0.63,2.66 h in elderly subjects.After a multiple dose of azvudine 5 mg·d-1 for 7 d,Cmax and AUC0-∞ were(3.26±1.61)ng·mL-1,(5.38±2.19)ng·mL-1·h,and Tmax,ss,t1/2,ss were 0.88,2.13 h in young subjects;Cmax,ss and AUC0-∞,ss were(3.97±2.09)ng·mL-1,(6.71±3.26)ng·mL-1·h,and Tmax,ss,t1/2,ss were 0.75,2.56 h in elderly subjects.Elderly/young geometric mean ratios and 90％CIs were 128.37％(88.23％-186.76％),139.93％(105.42％-185.72％),140.03％(106.33％-184.41％)for azvudine Cmax,AUC0-t,AUC0-∞ after a single dose,and were 118.66％(80.83％-174.20％),118.41％(83.60％-167.69％),118.95％(84.78％-166.89％)for azvudine Cmax,AUC0-t,AUC0_∞ after a multiple dose of azvudine 5 mg·d-1 for 7 d.Conclusion After single and multiple oral administration of azvudine tablets,systemic exposure to azvudine was higher in healthy elderly subjects compared with healthy young subjects.After taking azvudine tablets,the types,severity and incidence of adverse events and adverse drug reactions in healthy elderly people were not significantly different from those in healthy young subjects.Azvudine was found to be safe and well tolerated in healthy elderly subjects.

ObjectiveThe scale of microalgae farming industry is huge. During farming, it is easy for microalgae to be affected by miscellaneous bacteria and other contaminants. Because of that, periodic test is necessary to ensure the growth of microalgae. Present microscopy imaging and spectral analysis methods have higher requirements for experiment personnel, equipment and sites, for which it is unable to achieve real-time portable detection. For the purpose of real-time portable microalgae detection, a real-time microalgae detection system of low detection requirement and fast detection speed is needed. MethodsThis study has developed a microalgae detection system based on deep learning. A microscopy imaging device based on bright field was constructed. With imaged captured from the device, a neural network based on YOLOv3 was trained and deployed on microcomputer, thus realizing real-time portable microalgae detection. This study has also improved the feature extraction network by introducing cross-region residual connection and attention mechanism and replacing optimizer with Adam optimizer using multistage and multimethod strategy. ResultsWith cross-region residual connection, the mAP value reached 0.92. Compared with manual result, the detection error was 2.47%. ConclusionThe system could achieve real-time portable microalgae detection and provide relatively accurate detection result, so it can be applied to periodic test in microalgae farming.

OBJECTIVE: To evaluate the effect of manual acupuncture on endometrial blood flow parameters by three-dimensional (3D) power Doppler ultrasound in women undergoing in vitro fertilization embryo transfer (IVF-ET). METHODS: Seventy patients undergoing IVF-ET were equally randomized into traditional or sham acupuncture treatment group for totally 4 days (from the day of oocyte aspiration to the day of embryo transfer) of treatment by random envelope method at the Reproductive Medicine Center and Outpatient Department of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medicine College, Huazhong University of Science and Technology from January 2013 to December 2015. Patients in the traditional acupuncture group accepted traditional acupuncture methods with manual acupuncture, and Zhongji (CV3), Qihai (CV 6), Sanyinjiao (SP6), Taichong (LR 3), Tianshu (ST 25), Guilai (ST 29) and Zusanli (ST 36) were chosen. Patients at the sham acupuncture group accepted shallow acupuncture methods at 4 non-meridian points at each shoulder and upper arm. Outcome measures included endometrial ultrasonic indices such as vascularization index (VI), flow index (FI) and vascularization flow index (VFI), endometrial thickness and volume, subendometrial VI (sVI), subendometrial FI (sFI), subendometrial VFI (sVFI), implantation rate, clinical pregnancy rate, abortion rate, live birth rate and number of live births. RESULTS: Finally, 34 patients in the traditional acupuncture group and 35 in the sham acupuncture group completed this trial. VI, FI and VFI of the traditional acupuncture group were significantly higher than those in the sham acupuncture group (P<0.05). No significant differences were found in endometrial thickness, endometrial volume, sVI, sFI, sVFI, implantation rate, clinical pregnancy rate, abortion rate, live birth rate and number of live births (P>0.05). CONCLUSIONS Manual acupuncture performed after oocyte aspiration and before transplantation improved the endometrial blood flow parameters VI, RI and VFI in women who underwent IVF-ET, instead of sVI, sFI and sVFI. Therefore, acupuncture might be beneficial in women undergoing IVF-ET by increasing endometrial blood flow and endometrial receptivity. (Registration No. ChiCTR2100053354).
Pregnancy ; Humans ; Female ; Fertilization in Vitro/methods* ; Single-Blind Method ; Embryo Transfer ; Pregnancy Rate ; Acupuncture Therapy ; Endometrium/blood supply*

The excipient processing is an essential part of traditional Chinese medicine processing, and understanding its scientific connotations is a critical scientific issue that urgently needs resolution. Building upon a foundation where the composition of traditional Chinese medicine substances is fundamentally clear, this paper applies the techniques and methods of chemoinformatics to the study of the excipient processing mechanism. Relevant information on traditional Chinese medicines processed with four kinds of excipients (wine, vinegar, salt and honey) was collected, including properties, taste, meridian tropism, chemical components, etc. Molecular descritors and skeletons corresponding to each chemical component were calculated using chemoinformatics to characterize the properties and structural features of the components. Characteristic components associated with the four excipients (wine, vinegar, salt and honey) were explored through multivariate statistical analysis and Murcko skeleton analysis. Further analysis, taking honey-processed Astragali Radix as an example, the focus was on the impact of the processing excipient honey on the solubility and permeability of its characteristic pharmacologically active components (isoflavones). It was discovered that the excipient honey can increase their solubility and permeability, emphasizing that the impact of processing excipients on the pharmacological classification properties is a key breakthrough in elucidating the mechanism of excipient processing. In summary, this study analyzed the characteristic components associated with the processing excipients "wine, vinegar, salt and honey" based on their composition characteristics, providing data support for the research on the mechanism of excipient processing from a biopharmaceutical perspective.

Macroporous adsorption resin, MCI, Toyopearl HW-40C and silica gel column chromatography combined with the semi-preparative HPLC were used to isolate and purify the water extract of Cornus officinalis. And the structures of compounds were identified by HRESIMS, NMR, IR, UV and ECD. A total of twelve compounds were isolated from the fruits of Cornus officinalis. They were identified as neolignan B (1), 2,3-dihydro-7-methoxy-2-(4′-hydroxy-3′-methoxyphenyl)-3a-O-β-D-xylopyranosyloxymethyl-5-benzofuranpropanol (2), cornucadinoside A (3), 3,4-dihydroxyacetophenone (4), n-butyl gallate (5), 3-hydroxybenzoic acid (6), n-butyl quininate (7), 5-hydroxymaltol (8), 2-furolic acid (9), 5-hydroxymethylfurfural (10), 5-(methoxycarbonyl)-2-pyrrolidone (11), and dimethyl malate (12). Compound 1 is a new biphenyl lignan, named as neolignan B. Compounds 2, 4, 5, 7-9 and 11 were isolated from Cornus officinalis for the first time.

A precursor ion selection (PIS) based ultra high performance liquid chromatography-quadrupole time of flight mass spectrometry (UHPLC-Q-TOF-MS) analytical method was used to screen the chemical components in Jiawei Dingzhi pills (JWDZP) comprehensively and rapidly. To compile the components of the compound medicine, a total of 1 921 components were found utilizing online databases and literature. After verifying the sources, unifying the component names, merging the multi-flavor attributed components, and removing the weak polar molecules, 450 components were successfully retained. The Acquity UPLC HSS T3 column (100 mm × 2.1 mm, 1.8 μm) was used, with a 0.1% formic acid water (A)-acetonitrile (B) as the mobile phase. The flow rate was 0.35 mL·min^-1, the column temperature was 35 ℃, and an electrospray ion source was used. Data was collected with the PIS strategy in both positive and negative ion modes. Compounds were screened through matching accurate molecular weight of the database, and identified according to MS/MS data (characteristic fragment ions and neutral loss), with comparison of reference. Some compounds were confirmed using standard products. A total of 176 compounds were screened out in the extract of JWDZP, among which 26 compounds were confirmed by standard products. These compounds include 96 components from the sovereign drug, and 34 coefflux components with low ion intensity. The PIS-UHPLC-Q-TOF-MS/MS method established in this study can quickly and comprehensively screen the chemical components of JWDZP, which enhanced the screening rate of components with co-elution compounds of low ion intensities and provided a basis for the study of the material foundation of JWDZP.