ObjectiveTo investigate the therapeutic effects and mechanism of decoctions from four kinds of processed products of Aconiti Radix Lateralis Praeparata（ARLP） in deficiency-cold syndrome. MethodsA total of 36 SD rats were randomly divided into the control group， model group， Shengfupian（SFP） group， Paofuzi（PFZ） group， Heishunpian（HSP） group and Paofupian（PFP） group with 6 rats in each group. Except for the control group， rats in other groups were administered hydrocortisone sodium succinate via intramuscular injection to induce a cold deficiency syndrome model. After 14 consecutive days， each ARLP decoction pieces was administered via continuous gastric lavage at a dose of 12 g·kg^-1·d^-1 for 7 d， while the control and model groups received an equivalent volume of physiological saline. After the end of administration， body weight， spleen weight and thymus weight were measured for calculating the spleen and thymus indexes. Hematoxylin-eosin（HE） staining was used to observe the pathological morphology of adrenal tissue. The fully automatic biochemistry analyzer was used to measure the total cholesterol（TC）， triglyceride（TG）， lactic dehydrogenase（LDH） and lactate（LAC） levels in serum. Enzyme-linked immunosorbent assay（ELISA） was employed to measure the contents of 17-hydroxycorticosteroid（17-OHCS）， cortisol（CORT）， triiodothyronine（T₃）， thyroxine（T₄）， thyrotropin（TSH）， immunoglobulin（Ig） M， IgG， cyclic adenosine monophosphate（cAMP） and cyclic guanosine monophosphate（cGMP）. Western blot was used to measure the protein expression levels of protein kinase A（PKA）， cAMP response element-binding protein（CREB）， silent information regulator 1（Sirt1） and peroxisome proliferator-activated receptor γ coactivator-1α（PGC-1α）. And high performance liquid chromatography（HPLC） was used to determine the content of major alkaloids， followed by Pearson correlation analysis with pharmacodynamic indicators. ResultsAfter modeling， compare with the control group， the model rats exhibited symptoms such as lethargy and loose stools， mild abnormalities were observed in adrenal tissue structure， and both spleen and thymus indices were significantly reduced（P<0.01）. Thyroid， adrenal and immune system functions were suppressed， with decreased serum cAMP level and significantly elevated cGMP level（P<0.01）. Compared with the model group， the adrenal injury by hydrocortisone sodium succinate were repaired and the spleen index were increased significantly in all four ARLP groups（P<0.05， P<0.01）. The thymus index in SFP and PFZ groups were increased significantly（P<0.05）. The contents of T₃， TSH， 17-OHCS and CORT were increased significantly in SFP and PFZ groups（P<0.05）. In addition， the content of IgG in SFP， PFZ and PFP groups were increased significantly（P<0.01）， while the content of IgM in PFZ and HSP groups were also increased significantly（P<0.05）. Regarding the cyclic nucleotide system， PFZ significantly elevated cAMP level while reducing cGMP level（P<0.05）， exhibiting the most pronounced effect among the four decoction pieces. For energy metabolism indicators， PFZ significantly improved abnormal markers including TC， TG， LDH， and LAC（P<0.05）. HSP showed marked improvement effects on TG， LDH， and LAC（P<0.05）. Both PFZ and SFP significantly elevated the expression levels of PKA， CREB， Sirt1， and PGC-1α proteins（P<0.01）. Additionally， the diester alkaloids in ARLP showed a strong positive correlation with TG， IgG， and CORT， a strong negative correlation with LAC， a moderate positive correlation with T₄， and moderate negative correlations with cAMP and spleen index. Monomeric alkaloids showed strong positive correlations with TG and IgG， strong negative correlations with LAC， moderate positive correlations with CORT and T₄， and moderate negative correlations with cAMP and spleen index. However， the content of water-soluble alkaloids showed strong positive correlations with TC， LDH， 17-OHCS， T₃， TSH， and thymus index， moderate positive correlations with cAMP， CORT， T₄， and spleen index， and moderate negative correlation with cGMP. ConclusionAmong different processed ARLP decoction pieces， PFZ processed according to ZHANG Zhongjing's method exhibits the most potent warming and cold-dispelling effects. Its pharmacological actions are mediated through regulating the thyroid， adrenal， immune， cyclic nucleotide systems， and material-energy metabolism pathways. Among these， water-soluble alkaloids show strong or moderate correlations with more indicators of deficiency-cold syndrome and exhibit the highest content in PFZ. Therefore， PFZ processed according to ZHANG Zhongjing's method may exert its warming and cold-dispelling effects through water-soluble alkaloids.

ObjectiveTo investigate the protective effect of Rehmanniae Radix iridoid glycosides （RIG） on the kidney tissue of streptozotocin （STZ）-induced diabetic mice and explore the underlying mechanism. MethodsTwelve of 72 male C57BL/6J mice were randomly selected as the normal group， and the remaining 60 mice were fed with a high-fat diet for six weeks combined with injection of 60 mg·kg^-1 STZ for 4 days to model type 2 diabetes mellitus. The successfully modeled mice were randomized into model， metformin （250 mg·kg^-1）， catalpol （100 mg·kg^-1）， low-dose RIG （RIG-L， 200 mg·kg^-1） and high-dose RIG （RIG-H， 400 mg·kg^-1） groups （n=11）. Mice in each group were administrated with corresponding drugs， while those in the normal group and model group were administrated with the same dose of distilled water by gavage once a day. After 8 weeks of intervention， an oral glucose tolerance test （OGTT） was performed， and the area under the curve （AUC） was calculated. After mice were sacrificed， both kidneys were collected. The body weight， kidney weight， and fasting blood glucose （FBG） were measured. Biochemical assays were performed to measure the serum levels of triglycerides （TG）， total cholesterol （TC）， serum creatinine （SCr）， and blood urea nitrogen （BUN）. Enzyme-linked immunosorbent assay （ELISA） was employed to determine the serum level of fasting insulin （FINS）， and the insulin sensitivity index （ISI） and homeostatic model assessment for insulin resistance （HOMA-IR） were calculated. The pathological changes in kidneys of mice were observed by hematoxylin-eosin staining and Masson staining. The immunohistochemical method （IHC） was employed to assess the expression of interleukin-1 （IL-1）， interleukin-6 （IL-6）， tumor necrosis factor-α（TNF-α）， transforming growth factor-β₁ （TGF-β₁）， and collagen-3 （ColⅢ） in the kidney tissue. The protein levels of TGF-β₁， cell signal transduction molecule 3 （Smad3）， matrix metalloproteinase-9 （MMP-9）， and ColⅢ in kidneys of mice were determined by Western blot. ResultsCompared with the normal group， the model group showcased decreased body weight and ISI （P<0.01）， increased kidney weight， FBG， AUC， FINS， HOMA-IR， TC， TG， SCr， and BUN （P<0.01）， glomerular hypertrophy， capsular space narrowing， and collagen deposition in the kidney， up-regulated protein levels of IL-1， IL-6， TNF-α， TGF-β₁， ColⅢ， and Smad3 （P<0.01）， and down-regulated protein level of MMP-9 （P<0.01） in the kidney tissue. Compared with the model group， the treatment groups had no significant difference in the body weight and decreased kidney weight （P<0.05， P<0.01）. The FBG level declined in the RIG-H group after treatment for 4-8 weeks and in the metformin， catalpol， and RIG-L groups after treatment for 6-8 weeks （P<0.01）. The AUC in the RIG-L， RIG-H， and metformin groups decreased （P<0.05， P<0.01）. The levels of TC， SCr， and BUN in the serum of mice in each treatment group became lowered （P<0.05， P<0.01）. The level of TG declined in the RIG-L， RIG-H， and metformin groups （P<0.05， P<0.01）. The serum level of FINS declined in the catalpol， RIG-L， and metformin groups （P<0.01）. Compared with the model group， the treatment groups showed decreased HOMA-IR （P<0.01）， increased ISI （P<0.01）， alleviated pathological changes in the kidney tissue， and down-regulated expression of IL-1 and TGF-β₁. In addition， the protein levels of IL-6， TNF-α， and ColⅢ in the RIG-H and metformin groups and IL-6 and TNF-α in the RIG-L group were down-regulated （P<0.05， P<0.01）， and the protein levels of IL-6， TNF-α， and ColⅢ in the catalpol group and ColⅢ in the RIG-L group showed a decreasing trend without statistical difference. The protein levels of TGF-β₁， Smad3， and ColⅢ in the RIG-H and metformin groups were down-regulated （P<0.01）. Compared with that in the model group， the protein level of MMP-9 was up-regulated in each treatment group （P<0.01）. ConclusionRIG can improve the renal structure and function of diabetic mice by regulating the TGF-β₁/Smads signaling pathway.

ObjectiveTo clarify the anti-inflammatory and lung-protective effects of Yantiao prescription on lipopolysaccharide （LPS）-induced acute lung injury （ALI）， and to explore the impact of Yantiao prescription on the metabolic pathways of arachidonic acid （AA） in vivo. MethodsThirty male C57BL/6J mice were randomly divided into the following groups based on body weight： normal group， model group， dexamethasone group （2 mg·kg^-1）， low-dose Yantiao prescription group （18 g·kg^-1）， and high-dose Yantiao prescription group （36 g·kg^-1）， with 6 mice in each group. The ALI mouse model was established by intraperitoneal injection of LPS. The treatment groups received oral gavage once a day for 7 consecutive days， and serum and lung tissue were collected at the end of the experiment. The content of pro-inflammatory cytokines tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and interleukin-6 （IL-6） in serum was detected by enzyme-linked immunosorbent assay （ELISA）. Hematoxylin-eosin （HE） staining was used to assess lung tissue pathology. The wet/dry weight ratio （W/D） and myeloperoxidase （MPO） activity in lung tissue were measured. The content of AA metabolites in serum and lung tissue was measured by liquid chromatography triple quadrupole-mass spectrometry （LC-MS/MS）. ResultsCompared with the conditions in the normal group， the content of serum pro-inflammatory cytokines TNF-α， IL-1β， and IL-6 in the model group was significantly increased （P<0.01）. The alveolar structure in mice was severely damaged， with markedly thickened alveolar walls and extensive inflammatory cell infiltration. The W/D ratio and MPO activity in lung tissue were significantly increased （P<0.01）. The content of AA metabolites， including prostaglandin D₂ （PGD₂）， prostaglandin E₂ （PGE₂）， 11（S）-hydroxy-eicosatetraenoic acid ［11（S）-HETE］， and 5-hydroxy-eicosatetraenoic acid （5-HETE） in serum and lung tissue was significantly increased （P<0.05）， while the content of 11，12-epoxyeicosatrienoic acid （11，12-EET） and 14，15-epoxyeicosatrienoic acid （14，15-EET） in serum was significantly decreased （P<0.01）. Compared with the results in the model group， the content of serum pro-inflammatory cytokines TNF-α， IL-1β， and IL-6 in the dexamethasone group， low-dose Yantiao prescription group， and high-dose Yantiao prescription group was significantly reduced （P<0.05）. Mild thickening of alveolar walls， scattered inflammatory cell infiltration， and relatively intact tissue structure with improved alveolar architecture were observed. The W/D ratio and MPO activity in lung tissue were significantly reduced （P<0.01）. The content of AA metabolites PGD₂， PGE₂， 11（S）-HETE， and 5-HETE in serum from the dexamethasone group was significantly decreased （P<0.05）， while the content of 14，15-EET in serum significantly increased （P<0.01）， and the content of 5-HETE in lung tissue significantly decreased （P<0.01）. In the low-dose and high-dose Yantiao prescription groups， the content of AA metabolites PGD₂， PGE₂， 11（S）-HETE， and 5-HETE in serum and lung tissue was significantly decreased （P<0.05）， while the content of 11，12-EET in both serum and lung tissue was significantly increased （P<0.05）. ConclusionYantiao prescription has significant protective effects against LPS-induced ALI， which are related to its regulation of AA metabolic pathways in vivo.

Alzheimer's disease （AD）， a degenerative disease of the central nervous system， is characterized by progressive degradation of learning， memory， and cognitive functions. Currently， few drugs are available for treating AD， and their effects are limited. Berberine （BBR） is a natural isoquinoline （quaternary ammonium-like） with a wide range of pharmacological effects. Studies have proven that BBR has good potential in the treatment of AD. Specifically， BBR can inhibit the generation， aggregation， and neurotoxicity of amyloid-β and the hyperphosphorylation of Tau protein， promote the clearance of phosphorylated Tau protein， reduce the cholinesterase activity， neuroinflammation， and oxidative stress， regulate neuronal apoptosis， improve the mitochondrial function and glucose and lipid metabolism， suppress the monoamine oxidase activity， and modulate gut microbiota. In addition， researchers have ameliorated the low bioavailability of BBR. Probing into the potential targets is hoped to provide a reference for further research on the prevention and treatment of AD by BBR.

Liver cirrhosis is the terminal stage of various chronic liver diseases， with the main clinical manifestation of portal hypertension， which can lead to spontaneous portosystemic shunt （SPSS）. SPSS is very common in clinical practice and is closely associated with the prognosis of patients. This article summarizes the recent studies in the clinical significance of cirrhotic portal hypertension with SPSS， the controversies in studies， and the current status and future prospects and challenges of treatment， in order to provide a reference for the standardized diagnosis and treatment of portal hypertension.

ObjectiveTo explore the current situation of adverse medical behaviors in oncology patients and propose corresponding countermeasures to reduce the incidence of adverse medical behaviors in oncology patients， standardize their diagnosis and treatment order， and ensure the quality and safety of medical care. MethodsUsing the purposive sampling method， 16 oncology patients and caregivers from 3 communities in a city were selected for semi-structured and in-depth qualitative interviews from October to December 2023. Nvivo 12.0 software was used for data transcription and thematic analysis. ResultsThree themes were extracted. First， the adverse medical behaviors in oncology patients included overtreatment， non-standardized medication， and inaccurate recommendations of exorbitant examination items. Second， the influencing factors of adverse medical behaviors in oncology patients included limitations of the medical system and policy issues， difficulty in defending the rights of patients in a vulnerable position， as well as inadequacy of related ethical supervision and laws and regulations. Third， the countermeasures for adverse medical behaviours in cancer patients mainly encompassed improving the construction of medical systems and policies， optimizing the allocation of medical resources， enhancing the medical ethical literacy of medical personnel， standardizing the professional behaviour of medical personnel， strengthening medical ethical education for patients and enhancing their awareness of the protection of rights and interests， as well as strengthening ethical supervision and evaluation. ConclusionThe adverse medical behaviors in oncology patients are affected by tripartite factors， including medical staff， patients， and the system. The government， medical institutions， medical personnel， and patients should all adopt targeted countermeasures to deal with adverse medical behaviours， thus regulating diagnosis and treatment orders and ensuring the quality and safety of medical care.

Collagen is a major structural protein in the matrix of animal cells and the most widely distributed and abundant functional protein in mammals. Collagen’s good biocompatibility, biodegradability and biological activity make it a very valuable biomaterial. According to the source of collagen, it can be broadly categorized into two types: one is animal collagen; the other is recombinant collagen. Animal collagen is mainly extracted and purified from animal connective tissues by chemical methods, such as acid, alkali and enzyme methods, etc. Recombinant collagen refers to collagen produced by gene splicing technology, where the amino acid sequence is first designed and improved according to one’s own needs, and the gene sequence of improved recombinant collagen is highly consistent with that of human beings, and then the designed gene sequence is cloned into the appropriate vector, and then transferred to the appropriate expression vector. The designed gene sequence is cloned into a suitable vector, and then transferred to a suitable expression system for full expression, and finally the target protein is obtained by extraction and purification technology. Recombinant collagen has excellent histocompatibility and water solubility, can be directly absorbed by the human body and participate in the construction of collagen, remodeling of the extracellular matrix, cell growth, wound healing and site filling, etc., which has demonstrated significant effects, and has become the focus of the development of modern biomedical materials. This paper firstly elaborates the structure, type, and tissue distribution of human collagen, as well as the associated genetic diseases of different types of collagen, then introduces the specific process of producing animal source collagen and recombinant collagen, explains the advantages of recombinant collagen production method, and then introduces the various systems of expressing recombinant collagen, as well as their advantages and disadvantages, and finally briefly introduces the application of animal collagen, focusing on the use of animal collagen in the development of biopharmaceutical materials. In terms of application, it focuses on the use of animal disease models exploring the application effects of recombinant collagen in wound hemostasis, wound repair, corneal therapy, female pelvic floor dysfunction (FPFD), vaginal atrophy (VA) and vaginal dryness, thin endometritis (TE), chronic endometritis (CE), bone tissue regeneration in vivo, cardiovascular diseases, breast cancer (BC) and anti-aging. The mechanism of action of recombinant collagen in the treatment of FPFD and CE was introduced, and the clinical application and curative effect of recombinant collagen in skin burn, skin wound, dermatitis, acne and menopausal urogenital syndrome (GSM) were summarized. From the exploratory studies and clinical applications, it is evident that recombinant collagen has demonstrated surprising effects in the treatment of all types of diseases, such as reducing inflammation, promoting cell proliferation, migration and adhesion, increasing collagen deposition, and remodeling the extracellular matrix. At the end of the review, the challenges faced by recombinant collagen are summarized: to develop new recombinant collagen types and dosage forms, to explore the mechanism of action of recombinant collagen, and to provide an outlook for the future development and application of recombinant collagen.

OBJECTIVE To establish fingerprint， chemical pattern recognition and multi-component quantification analysis of Sanzi powder， and evaluate its quality. METHODS HPLC method was adopted. The fingerprints of 15 batches of Sanzi powder were established by using the Similarity Evaluation System for Chromatographic Fingerprint of Traditional Chinese Medicine （2012 edition）. Cluster analysis， principal component analysis and orthogonal partial least squares-discriminant analysis were also conducted. The variable importance in projection （VIP） value greater than 1 was used as the index to screen the differential markers， and the contents of the differential markers were determined by the same HPLC method. RESULTS A total of 21 common peaks in the HPLC fingerprints of 15 batches of Sanzi powder were calibrated， and the similarities of them were 0.994- 0.999； 6 common peaks were identified， including gallic acid （peak 3）， garminoside （peak 10）， corilagin （peak 11）， chebulinic acid （peak 16）， ellagic acid （peak 18）， crocin Ⅰ （peak 19）. According to the results of cluster analysis， YKD2024LH005，No.YKD2023LH062） principal component analysis and orthogonal partial least squares-discriminant analysis， 15 batches of samples could be clustered into two categories： S1， S5， S7， S9， S14 were clustered into one category； S2-S4， S6， S8， S10-S13， S15 were clustered into one category. VIP values of 11 differential components such as corilagin， chebulinic acid and ellagic acid were higher than 1. Among 15 batches of samples， the contents of corilagin， chebulinic acid and ellagic acid ranged 2.667-5.152， 9.506- 13.522， 0.891-1.811 mg/g. CONCLUSIONS Established HPLC fingerprint and multi-component quantification analysis of Sanzi powder are rapid and simple， and can be used for quality evaluation of Sanzi powder by combining with chemical pattern recognition. Eleven components such as corilagin， chebulinic acid and ellagic acid are differential markers affecting the quality of Sanzi powder.

ObjectiveTo observe the clinical efficacy and possible mechanisms of Xianglian Huazhuo Granules （香连化浊颗粒， XHG） in the treatment of chronic atrophic gastritis with intestinal metaplasia. MethodsA total of 140 patients with chronic atrophic gastritis and intestinal metaplasia were randomly divided into a treatment group and a control group， with 70 cases in each group. The treatment group received 12.5 g of XHG orally， twice daily. The control group received 12.5 g of placebo orally， twice daily. Both groups were treated for 6 months. The traditional Chinese medicine （TCM） symptom scores， pathological types， serum tumor markers of the digestive system， and serum bile acids （TBA）， interleukin-23 （IL-23）， and Dickkopf-related protein 1 （DKK-1） levels were observed before and after treatment. Safety indicators and adverse events were recorded. After treatment， TCM syndrome efficacy and pathological types were evaluated， and patients were followed up for 18 months with gastric endoscopy and pathological results， which were compared with the results after treatment finished. ResultsTwo patients dropped out in the control group， and a total of 168 cases were included in the final analysis， 70 in the treatment group and 68 in the control group. The treatment group showed a significant reduction in TCM symptom scores， serum TBA， IL-23， and DKK-1 levels， and a significant increase in alpha-fetoprotein （AFP）， carbohydrate antigen 125 （CA125）， carbohydrate antigen 199 （CA199） levels； in the control group， carcinoembryonic antigen （CEA）， CA125， CA199 levels significantly increased （P＜0.05 or P＜0.01）； and carbohydrate antigen 242 （CA242） level in both the treatment group and the control group decreased significantly （P＜0.01）. The treatment group had lower TCM symptom scores and lower levels of serum TBA， IL-23， and DKK-1 compared to the control group （P＜0.05）. The effective rate for TCM syndrome efficacy in the treatment group was 80.00% （56/70）， significantly higher than the 20.59% （14/68） in the control group （P < 0.05）. The effective rate for pathological classification in the treatment group was 72.73% （8/11） for mixed intestinal metaplasia， significantly better than 46.15% （6/13） in the control group （P＜0.05）. No adverse events were reported in either group. Among 40 patients who had a follow-up endoscopy after one year， 21 were from the treatment group， of whom 11 showed reduced intestinal metaplasia， 9 showed no significant changes， and 1 had worsened； while 19 patients in the control group had 4 with reduced intestinal metaplasia， 13 with no significant changes， and 2 with worsened conditions. No cancer was detected in either group. The treatment group showed significantly better improvement in intestinal metaplasia on follow-up gastric endoscopy pathology than the control group （P＜0.05）. ConclusionXHG can significantly improve the clinical symptoms in patients with chronic atrophic gastritis and intestinal metaplasia and reduce the degree of mixed intestinal metaplasia. The mechanism may involve lowering serum TBA， DKK-1， and IL-23 levles， thus delaying the progression from inflammation to cancer.

Background Diseases severely affect the efficiency of workers. Comorbidity refers to the coexistence of two or more chronic diseases or health problems in the same individual. Previous studies have primarily focused on occupational injuries caused by environmental exposures, while the analysis of the epidemiological characteristics of self-reported diseases and occupational injuries among manufacturing workers has been insufficient. Objective To analyze the distribution of self-reported diseases and occupational injuries among manufacturing workers, the strength of correlation between different diseases, and common disease combinations, and to preliminarily explore the relationship between self-reported diseases and occupational injuries. Methods A cross-sectional survey was conducted to investigate the occupational injuries of 2382 workers in 2 manufacturing enterprises over the past year, and 2355 questionnaires were valid after cleaning. The questionnaire included three parts: basic information, occupational injury occurrence, and disease prevalence. The self-reported diseases diagnosed by physicians included musculoskeletal diseases, cardiovascular diseases, respiratory diseases, mental health problems, neurological and sensory organ diseases, digestive organ diseases, reproductive and urinary organ diseases, skin diseases, tumors, endocrine and metabolic system diseases, blood diseases and birth defects, a total of 11 types. Log-binomial model was used to calculate the prevalence ratio (PR) value of the association between different diseases, and UpSet diagram was used to present the disease combination pattern. Results In total, 40.2% (946/2355) of the study participants reported at least one disease, while 8.6% (203/2355), 5.2% (122/2355), and 5.9% (140/2355) reported having two, three, and four or more diseases, respectively. A higher prevalence was observed for musculoskeletal diseases, neurological and sensory organ diseases, digestive organ diseases, and skin diseases, which accounted for 18.0% (423/2355), 13.8% (324/2355), 9.3% (218/2355), and 9.1% (214/2355), respectively. Workers with musculoskeletal disorders, cardiovascular diseases, or neurological and sensory organ diseases reported significantly higher incidence of occupational injuries compared with workers without the corresponding diseases (P<0.001, P=0.041, and P=0.006, respectively). Musculoskeletal diseases were strongly associated with comorbidities of neurological and sensory organ diseases (PR values were 1.86 and 1.98, respectively), and the other patters were musculoskeletal diseases and digestive organ diseases (PR and OR values were 1.57 and 2.35, respectively), and musculoskeletal diseases and cardiovascular diseases (PR and OR values were 1.46 and 2.22, respectively). The largest binomial comorbidity group involved musculoskeletal diseases and neurological and sensory organ diseases, accounting for 5.4% (25/465) of the comorbid workers. Conclusion Among the self-reported diseases of manufacturing workers, musculoskeletal diseases, neurological and sensory organ diseases, digestive organ diseases, and skin diseases are more common. Musculoskeletal diseases and neurological and sensory organ diseases are the most common in all comorbidities. Musculoskeletal diseases, cardiovascular diseases, and neurological and sensory organ diseases are associated with occupational injuries. In the prevention and control of occupational injuries, joint prevention strategies targeting multiple diseases should be strengthened.