The prescription Mahuang Shengmatang in the Treatise on Cold Damage （《伤寒论》） has sparked considerable debate among medical practitioners throughout history， with varying opinions on its indications， pathogenesis described in the text， principle of compatibility， and clinical applications. Both ancient and modern interpreters of Mahuang Shengmatang often focus on herbal compatibility as a primary approach to deduce the pathogenesis and treatment methods. Building upon this foundation， this paper utilizes herbal dosage as a clue to discern the primary and secondary herbs in the prescription. It further analyzes the principle of compatibility based on herbal indications， summarizing the indications and therapeutic principles of this prescription. Ultimately， it reveals the underlying pathogenesis reflected in the text. The internal closure of heat and toxin leads to the stagnation of Qi， preventing Yang Qi from reaching the extremities and causing cold hands and feet. When the pathogenic Qi finds no outlet， it floods both the upper and lower regions of the body， attacking the throat and causing cough with expectoration of pus and blood， and descending to the large intestine to consume Yin fluids， resulting in persistent diarrhea. Based on this pathogenesis， the paper expands the scope of symptoms and signs associated with the prescription， providing a more detailed portrayal of the applicable patient population and enhancing the basis for clinical prescription references. Additionally， the paper presents considerations on several controversial topics， suggesting that the "lower pulse" described in the text refers to the lower limb arterial pulsation， and the symptoms and signs resemble those of septic shock in modern medicine. Therefore， Mahuang Shengmatang should be categorized as a prescription for treating warm diseases and it is not developed by ZHANG Zhongjing. By employing a detailed discussion on the syndrome， pathogenesis， and clinical application in the texts of Mahuang Shengmatang from the dosage， principle of compatibility， and herbal indications， this paper not only enriches the theoretical foundation of Mahuang Shengmatang but also provides a comprehensive perspective and fresh ideas for understanding its clinical application.

ObjectiveBased on ultra performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS/MS）， the combination of serum pharmacochemistry， response profile of absorbed components in serum， network pharmacology and drug-likeness prediction was used to screen the potential active ingredients of Yanghetang against breast cancer. MethodsUPLC-Q-TOF-MS/MS was used to identify the main components in different solvent extracts of Yanghetang， and serum pharmacochemistry was applied to analyze the absorbed components from the serum of female SD rats after 0.5， 1， 2 h of administration. Combined with the response characteristic values of serum drug components obtained from UNIFI 1.8.2， the absorbed prototype components and metabolites were screened to get the absorbed components of Yanghetang with a significant patterns of elimination and growth. Network pharmacology was applied to construct a drug-component-pathway-target-disease network， and molecular docking was performed between absorbed components and key targets of breast cancer， and the drug similarity was analyzed by SwissADME. ResultsForty-two compounds were identified in Yanghetang samples extracted with different solvents， of which 16 compounds were common to the three different extraction solvents（methanol， 50% methanol and water）. The results of drug-containing serum analysis showed that there were 16 absorbed components in serum， including 5 prototypes and 11 metabolites. Network pharmacology results showed that Yanghetang against breast cancer involved 15 key targets such as proto-oncogene tyrosine-protein kinase Src（SRC）， epidermal growth factor receptor（EGFR） and phosphoinositide 3 kinase catalytic alpha polypeptide（PIK3CA）. Molecular docking results showed that 16 potential active ingredients were well combined with the predicted targets. Combined with drug likenesses， 12 compounds in the absorbed components of Yanghetang were considered to have potential for anti-breast cancer activity， mainly including α-pinene and γ-eudesmol and their metabolites， of which one was from Ephedrae Herba， one was from Rehmanniae Radix， and eight were from Cinnamomi Cortex. ConclusionThe chemical components of Yanghetang mainly include polysaccharides， monoterpene glycosides and coumarins， and its prototype components mainly undergo oxidation， hydrolysis and acetylation after entering the blood. Its anti-breast cancer mechanism may be related to the regulation of signaling pathways such as the mitogen-activated protein kinase（MAPK） and phosphatidylinositol 3-kinase/protein kinase B（PI3K/Akt）. The results of this study can lay a foundation for further exploration of Yanghetang in the treatment of breast cancer.

Osteoporosis （OP） is a systemic metabolic disease with a strong correlation with age. The prevalence of osteoporosis is rising annually as a consequence of the growing issue of population ageing. The current treatments for OP have numerous shortcomings. In contrast， traditional Chinese medicine has a long history and a rich species diversity. Furthermore， recent years have seen an increase in the number of studies examining the anti-OP properties of traditional Chinese medicine. This may provide a safe and effective alternative strategy for the treatment of OP. The zebrafish， due to its favourable optical transparency and high homology with human genes， has been extensively employed as an animal research model in the investigation of human skeletal-related disease mechanisms and drug screening. This paper presents a review of anti-osteoporosis studies of traditional Chinese medicine using zebrafish as a model for osteoporosis. It also provides a summary of the experimental evaluation methods involved in such studies， an analysis of the current status of traditional Chinese medicine in the treatment of osteoporosis using zebrafish as a model， and a summary of the mechanism of action and the signalling pathways involved in traditional Chinese medicine in the anti-osteoporosis treatment of zebrafish. The current research status of Chinese medicine in the treatment of OP was analysed， as well as the mechanism of action of Chinese medicine against OP and the signalling pathways involved. Furthermore， the advantages and disadvantages of various zebrafish modelling methods of OP were compared with those of traditional animal models. The objective of this study is to provide a reference for the evaluation method of the zebrafish model in the study of bone-related diseases， as well as for the study of the mechanism of action of traditional Chinese medicine against OP and for the reference of the research and development of new drugs.

Objective To analyze the economic cost of self-monitoring of gestational diabetes mellitus, and provide a basis for measuring the economic burden of gestational diabetes mellitus, and to provide a reference for the formulation of intervention development and the adjustment of resource allocation. Methods The individual economic cost of self-monitoring for gestational diabetes mellitus was measured based on a decision tree model, and the total economic cost of self-monitoring for gestational diabetes mellitus in Beijing was estimated. The uncertainty of the model parameters was analyzed using one-way sensitivity analysis. Results The average individual economic cost of gestational diabetes self-monitoring was 1184 RMB, and the individual cost incurred by choosing different types of blood glucose meters ranged from 403 to 18 000 RMB. The average individual economic cost of finger-stick blood glucose monitoring was 606 RMB and the average individual economic cost of continuous glucose monitoring was 2 374 RMB. The total economic cost of gestational diabetes self-monitoring in Beijing was 23.818 0 million RMB, and the total economic cost incurred by choosing different types of blood glucose meters ranged from 0.292 5 to 9.027 9 million RMB. The proportion of the finger-stick blood glucose monitoring had the greatest impact on the robustness of the results. Conclusion Finger-stick blood glucose monitoring is still the dominant self-monitoring method and is less costly than continuous glucose monitoring. Self-monitoring of pregnant women with gestational diabetes mellitus incurs certain economic cost and causes an economic burden on society.

Objective To observe the effect of comorbidity for patients with non-small cell lung cancer (NSCLC) on exercise tolerance and cardiopulmonary function. Methods NSCLC patients who underwent cardiopulmonary exercise testing (CPET) before surgery were retrospectively included. According to the Charlson comorbidity index (CCI) score, patients were divided into two groups: a CCI≥3 group and a CCI＜3 group. The patients were matched with a ratio of 1 : 1 by propensity score matching according to the age, body mass index, sex, smoking history, exercise habits, pathological stage and type of surgery. After matching, CPET indexes were compared between the two groups to explore the differences in exercise tolerance and cardiopulmonary function. Results A total of 276 patients were included before matching. After matching, 56 patients were enrolled with 28 patients in each group, including 38 (67.9%) males and 18 (32.1%) females with an average age of (70.7±6.8) years. Compared with the CCI＜3 group, work rate at peak (WR peak), WR peak/predicted value (WR peak%), kilogram oxygen uptake at anaerobic threshold (VO2/kg AT), VO2/kg peak, VO2/kg peak%, peak carbon dioxide output, the minute ventilation to carbon dioxide production slope, O2 pulse peak and O2 pulse peak% of CCI≥3 group were statistically different (P＜0.05). Among them, the rate of postoperative pulmonary complication in the CCI≥3 group was higher than that in the CCI＜3 group (60.7% vs. 32.1%, P=0.032). Conclusion In the NSCLC patients, exercise tolerance and cardiopulmonary function decreased in patients with CCI≥3 compared with those with CCI<3. CPET can provide an objective basis for risk assessment in patients with comorbidity scored by CCI for pulmonary resection.

Studies have suggested that the nucleus accumbens (NAc) is implicated in the pathophysiology of major depression; however, the regulatory strategy that targets the NAc to achieve an exclusive and outstanding anti-depression benefit has not been elucidated. Here, we identified a specific reduction of cyclic adenosine monophosphate (cAMP) in the subset of dopamine D1 receptor medium spiny neurons (D1-MSNs) in the NAc that promoted stress susceptibility, while the stimulation of cAMP production in NAc D1-MSNs efficiently rescued depression-like behaviors. Ketamine treatment enhanced cAMP both in D1-MSNs and dopamine D2 receptor medium spiny neurons (D2-MSNs) of depressed mice, however, the rapid antidepressant effect of ketamine solely depended on elevating cAMP in NAc D1-MSNs. We discovered that a higher dose of crocin markedly increased cAMP in the NAc and consistently relieved depression 24 h after oral administration, but not a lower dose. The fast onset property of crocin was verified through multicenter studies. Moreover, crocin specifically targeted at D1-MSN cAMP signaling in the NAc to relieve depression and had no effect on D2-MSN. These findings characterize a new strategy to achieve an exclusive and outstanding anti-depression benefit by elevating cAMP in D1-MSNs in the NAc, and provide a potential rapid antidepressant drug candidate, crocin.

Background At present, the practice of pulmonary rehabilitation for pneumoconiosis in China is in a primary stage. The basis for formulating an individualized comprehensive pulmonary rehabilitation plan is still insufficient, which is one of the factors limiting the development of community-level rehabilitation work. Objective To formulate an exercise prescription based on maximum heart rate measured by cardiopulmonary exercise test (CPET), conduct an individualized comprehensive pulmonary rehabilitation program with the exercise prescription for patients with stable pneumoconiosis, and evaluate its role in improving exercise endurance and quality of life, thus provide a basis for the application and promotion of pulmonary rehabilitation. Methods A total of 68 patients were recruited from the Occupational Disease Prevention Hospital of Jinneng Holding Coal Industry Group Co., Ltd. from April to August 2022 , and were divided into an intervention group and a control group by random number table method, with 34 cases in each group. All the pneumoconiosis patients participated in a baseline test. The control group was given routine drug treatment, while the intervention group received multidisciplinary comprehensive pulmonary rehabilitation treatment on the basis of routine drug treatment, including health education, breathing training, exercise training, nutrition guidance, psychological intervention, and sleep management, whose exercise intensity was determined according to the maximum heart rate provided by CPET. The rehabilitation training lasted for 24 weeks. Patients were evaluated at registration and the end of study respectively. CPET was used to measure peak oxygen uptake per kilogram (pVO₂/kg), anaerobic threshold (AT), carbon dioxide equivalent of ventilation (EqCO₂), maximum metabolic equivalent (METs), and maximum work (W_max). The modified British Medical Research Council Dyspnea Questionnaire (mMRC), Self-rating Anxiety Scale (SAS), Self-rating Depression Scale (SDS), Pittsburgh Sleep Quality Index (PSQI), Chronic Obstructive Pulmonary Disease Assessment Test (CAT), and Short Form of Health Survey (SF-36) were used to evaluate the potential effect of the comprehensive pulmonary rehabilitation program. Results Among the included 68 patients, 63 patients were having complete data, then 31 cases were assigned in the control group and 32 cases in the interventional group. Before the intervention, there was no significant difference in pVO₂/kg, AT, EqCO₂, METs, or W_max between the two groups (P>0.05). At the end of the trail, the indicators like pVO₂/kg [(19.81±2.38) mL·(min·kg)⁻¹], AT [(14.48±2.33) mL·(min·kg)⁻¹], METs (5.64±0.69), and W_max [(85.25±14) W] of patients in the intervention group were all higher than those [(13.90±2.37) mL·(min·kg)⁻¹, (11.70±1.94) mL·(min kg)⁻¹, (3.97±0.70), and (61.77±14.72) W, respectively] in the control group (P<0.001); there was no significant difference in EqCO₂ between the two groups (P=0.083). Before the trial, there was no significant difference in mMRC, SAS, SDS, PSQI, or CAT scores between the two groups (P>0.05). At the end of the trail, the mMRC score (1.16±0.57), SAS score (27.93±2.12), SDS score (26.48±1.44), PSQI score (1.08±0.88), and CAT score (4.34±3.28) of patients in the intervention group were lower than those [(2.03±0.83), (35.87±6.91), (34.23±6.65), (5.37±3.03), and (13.87±7.53), respectively] in the control group (P<0.001). The SF-36 scores of bodily pain (94.13±10.72), general health (87.50±5.68), vitality (95.31±5.53), mental health (99.88±0.71), and health changes (74.22±4.42) in the intervention group were higher than those [(71.87±32.72), (65.81±15.55), (74.52±16.45), (86.97±16.56), and (29.84±13.50), respectively] in the control group (P<0.001), and no significant difference was found in social functioning and role emotional scores (P>0.05). Conclusion Comprehensive pulmonary rehabilitation can increase the oxygen intake and exercise endurance of pneumoconiosis patients, ameliorate dyspnea symptoms, elevate psychological state and sleep quality, and improve the quality of life.

Background It is a research hotspot to study the changes of metabolites and metabolic pathways in the process of coal worker's pneumoconiosis (CWP) by metabonomics and to explore its pathogenesis. Objective To study the change of metabolites in bronchoalveolar lavage fluid (BALF) of patients with CWP and explore the metabolic regulation mechanism of the disease. Methods Patients with CWP who met the national diagnostic criteria according to Diagnosis of occupational pneumoconiosis (GBZ 70-2015) and underwent massive whole lung lavage were selected as the case group, and patients with tracheostenosis who underwent bronchoscopy were selected as the control group. BALF samples were collected from the cases and the controls. After filtering out large particles and mucus, the supernatant was stored in a −80 ℃ refrigerator. The samples were detected and analyzed by liquid chromatography-mass spectrometry after adding extraction solution, cold bath ultrasonication, and high-speed centrifugation, and the metabolic profiles and related data of CWP patients were obtained. The differential metabolites related to the occurrence and development of CWP were screened by multiple statistical analysis; furthermore, we searched the Kyoto Encyclopedia of Genes and Genomes (KEGG) database for potential metabolic pathways involved in the progression. Results There was no significant difference in the general conditions of the subjects, such as weight, height, age, and length of service among the stage I group, the stage II group, the stage III group, and the control group (P˃0.05). When comparing the CWP stage I group with the control group, 48 differential metabolites were screened out, among which 14 were up-regulated and 34 were down-regulated. A total of 66 differential metabolites were screened out between the patients with CWP stage II and the controls, 14 up-regulated and 52 down-regulated differential metabolites. Compared with the control group, 63 differential metabolites were screened out in the patients with CWP stage III, including 11 up-regulated and 52 down-regulated differential metabolites. There were 36 differential metabolites that may be related to the occurrence of CWP, among which 11 differential metabolites were up-regulated, and 25 were down-regulated. Four significant differential metabolic pathways were identified through KEGG database query: linoleic acid metabolic pathway, alanine metabolic pathway, sphingolipid metabolic pathway, and glycerophospholipid metabolic pathway. Conclusion The metabolomic study of BALF show that there are 36 different metabolites in the occurrence and development of CWP, mainly associating with linoleic acid metabolism, alanine metabolism, sphingolipid metabolism, and glycerophospholipid metabolism pathways.

Background Pneumoconiosis is a widespread occupational disease in China at present. As a type of lung diseases, its pathological damage is mainly irreversible fibrotic changes in the lungs. Several studies have shown that the occurrence and development of lung diseases such as coal workers' pneumoconiosis are closely related to intestinal flora. Objective To observe intestinal flora of coal workers' pneumoconiosis patients based on the results of 16SrDNA high-throughput sequencing and evaluate the changes of intestinal flora after treatment with tetrandrine tablets. Methods A total of 80 patients with coal workers' pneumoconiosis attending the outpatient clinic of the Department of Occupational Diseases of the Emergency General Hospital from April to July 2022 were enrolled. All patients were treated with tetrandrine tablets for 4 weeks, with group A before the treatment of tetrandrine tablets and group B after the treatment. In the same period, 24 healthy controls (group C) were set up. Stool samples were collected before and after the treatment. Using 16SrDNA high-throughput sequencing, gene V3-V4 sequencing technology, and bioinformatic analysis platform, we evaluated the intestinal flora after treatment by groups. Results The dominant flora at the phylum level and genus level were the same across three groups. The relative abundances of phylum Bacteroidetes, Bifidobacterium, Bacteroides, and Facealibacterium in groups B and C were higher than those in group A, and the relative abundances of phy-lum Actinobacteria, genus Blautia, and genus Romboutsia in groups B and C were lower than those in group A (P＜0.05). The relative abundances of genus Clostridium, genus Megamonas, and genus Lactobacillus in group C was lower than that in groups A and B (P＜0.05). The alpha diversity analysis showed that the Chao1 index was higher in group A than in group C (P＜0.01). Compared with group A, the Shannon index was higher in group B, and the increases of Simpson index were all statistically significant in stage I patients (P＜0.05), but the differences in Chao1 index were not statistically significant (P＞0.05). The differences in the values of Chao1 index, Shannon index, and Simpson index in stage Ⅱ and stage III patients were not statistically significant (P＞0.05). The beta diversity analysis showed that the difference in flora structure between group A and group C was statistically significant (P＜0.05); the differences in flora structure before and after treatment in the same stage patients were statistically significant (P＜0.05). The partial least squares discriminant analysis (PLS-DA) showed that there were significant differences between group A and group C, and between group A and group B. The LEfSe analysis showed that the significant markers contributing to the differences were basically the same in stage I, stage Ⅱ, and stage Ⅲ after treatment, which were mainly phylum Bacteroidetes and its subordinate groups, class Negativicutes, or-der Selenomonas, and genus Facealibacterium. Conclusion There are differences in the distribution of flora between coal workers' pneumoconiosis patients and healthy individuals, and the structure and relative abundance of intestinal flora are changed and the number of beneficial flora is increased after treatment with tetrandrine tablets.

Background Multi-slice spiral computerized tomography (MSCT) can be used as an auxiliary diagnosis of chest radiography in diagnosis of pneumoconiosis, but there are few studies on the correlations between interstitial images and stage classification of coal workers' pneumoconiosis in the existing literature. Objective To present MSCT imaging manifestations and distribution characteristics of coal workers' pneumoconiosis and complications, evaluate correlations between coal workers' pneumoconiosis stages and pulmonary interstitial lesions, and provide a reliable imaging diagnosis basis for pneumoconiosis interstitial lesions. Methods From June 2022 to June 2023, a total of 1002 patients with coal workers' pneumoconiosis confirmed by the pneumoconiosis diagnostic and identification group in the Department of Occupational Diseases of the Emergency General Hospital were enrolled. MSCT was used to observe the abnormal imaging manifestations of the lungs of coal workers' pneumoconiosis patients and the diseases of pulmonary fibrosis related to their own diseases (thickening of the interlobular septum, bronchial perivascular interstitial mass thickening, parenchymal banding, subpleural line, intralobular interstitial thickening, honeycomb, and subpleural interstitial thickening), the occurrence of coal workers' pneumoconiosis and complications (old tuberculosis, active tuberculosis, pneumonia, atelectasis, lung cancer, bronchiectasis), and the density, size, and location of pneumoconiosis nodules. Imaging data were analyzed and statistically processed. Results All 1002 patients were male, with an average age of (60.71±6.87) years and an average dust exposure time of (23.01±7.80) years. Among them, there were 470 patients with stage I, 422 patients with stage II, and 110 patients with stage III. There were significant differences in the distribution of thickening of the interlobular septum, bronchial perivascular interstitial mass thickening, parenchymal banding, intralobular interstitial thickening, subpleural interstitial thickening, and honeycomb across different stages (P<0.05). Statistically significant differences in p, q, and r subsets of round nodules were found in patients with pneumoconiosis at different stages (P<0.05). Observed nodule types included solid nodules, pure ground-glass shadow nodules, and partial solid nodules. There were statistically significant differences in pulmonary tuberculosis and bronchiectasis among different stages of coal workers' pneumoconiosis (P<0.05). There were statistically significant differences in interstitial shadows and patches combined with interstitial shadows among different stages of pneumoconiosis complicated with pneumonia (P<0.05). Conclusion MSCT provides images of the progression of coal workers' pneumoconiosis and have a certain relationship with the stages of coal workers' pneumoconiosis, which is conducive to the formulation of reasonable treatment plans in the early clinical stage. Therefore, in the diagnosis and treatment of pneumoconiosis, a great attention should be paid to the imaging technology of chest computerized tomography, especially the use of MSCT examination.