This study aims to explore the medication rules and mechanisms of treating chronic renal failure(CRF) by Jinling medical school based on data mining, network pharmacology, and experimental validation systematically and deeply. Firstly, the study selected the papers published by the inherited clinicians in Jinling medical school in Chinese journals using the subject headings named "traditional Chinese medicine(TCM) + chronic renal failure", "TCM + chronic renal inefficiency", or "TCM + consumptive disease" in China National Knowledge Infrastructure, Wanfang, and VIP Chinese Science and Technology Periodical Database and screened TCM formulas for treating CRF according to inclusion and exclusion criteria. The study analyzed the frequency of use of single TCM and the four properties, five tastes, channel tropism, and efficacy of TCM used with high frequency and performed association rule and clustering analysis, respectively. As a result, a total of 215 TCM formulas and 235 different single TCM were screened, respectively. The TCM used with high frequency included Astragali Radix, Rhei Radix et Rhizoma, Salviae Miltiorrhizae Radix et Rhizoma, Poria, and Atractylodis Macrocephalae Rhizoma(top 5). The single TCM characterized by "cold properties, sweet flavor, and restoring spleen channel" and the TCM with the efficacy of tonifying deficiency had the highest frequency of use, respectively. Then, the TCM with the rules of "blood-activating and stasis-removing" and "diuretic and dampness-penetrating" appeared. In addition, the core combination of TCM [(Hexin Formula, HXF)] included "Astragali Radix, Rhei Radix et Rhizoma, Poria, Salviae Miltiorrhizae Radix, and Angelicae Sinensis Radix". The network pharmacology analysis showed that HXF had 91 active compounds and 250 corresponding protein targets including prostaglandin-endoperoxide synthase 2(PTGS2), PTGS1, sodium voltage-gated channel alpha subunit 5(SCN5A), cholinergic receptor muscarinic 1(CHRM1), and heat shock protein 90 alpha family class A member 1(HSP90AA1)(top 5). Gene Ontology(GO) function analysis revealed that the core targets of HXF predominantly affected biological processes, cellular components, and molecular functions such as positive regulation of transcription by ribonucleic acid polymerase Ⅱ and DNA template transcription, formation of cytosol, nucleus, and plasma membrane, and identical protein binding and enzyme binding. Kyoto Encyclopedia of Genes and Genomes(KEGG) analysis revealed that CRF-related genes were involved in a variety of signaling pathways and cellular metabolic pathways, primarily involving "phosphatidylinositol 3-kinase(PI3K)-protein kinase B(Akt) pathway" and "advanced glycation end products-receptor for advanced glycation end products". Molecular docking results showed that the active components in HXF such as isomucronulatol 7-O-glucoside, betulinic acid, sitosterol, and przewaquinone B might be crucial in the treatment of CRF. Finally, a modified rat model with renal failure induced by adenine was used, and the in vivo experimental confirmation was performed based on the above-mentioned predictions. The results verify that HXF can regulate mitochondrial autophagy in the kidneys and the PI3K-Akt-mammalian target of rapamycin(mTOR) signaling pathway activation at upstream, so as to alleviate renal tubulointerstitial fibrosis and then delay the progression of CRF.
Data Mining ; Drugs, Chinese Herbal/chemistry* ; Network Pharmacology ; Humans ; Kidney Failure, Chronic/metabolism* ; Medicine, Chinese Traditional ; China

The traditional Chinese medicine(TCM) industry is a crucial part of China's pharmaceutical sector and plays a strategic role in ensuring public health and promoting economic and social development. In response to the practical demand for high-quality development of the TCM industry, this paper focused on the bottlenecks encountered during the digital and intelligent transformation of TCM production systems. Specifically, it explored technical strategies and methodologies for constructing the best TCM production mode. An innovative artificial intelligence(AI)-centered technical architecture for TCM production was proposed, focusing on key aspects of production management including process modeling, state evaluation, and decision optimization. Furthermore, a series of critical technologies were developed to realize the best TCM production mode. Finally, a novel AI-driven TCM production mode characterized by a closed-loop system of "measurement-modeling-decision-execution" was presented through engineering case studies. This study is expected to provide a technological pathway for developing new quality productive forces within the TCM industry.
Artificial Intelligence ; Drugs, Chinese Herbal ; Medicine, Chinese Traditional/methods* ; Humans

Panax notoginseng is the dried root and rhizome of Panax notoginseng(Burk.)F.H.Chen,a perennial erect herb of the genus Ginseng of the family Wujiaceae.As a traditional Chinese medicine in our country,Panax notoginseng has a good tonic effect,and the Dictionary of Traditional Chinese Medicines has the words that Panax notoginseng is used to tonify the blood,remove the blood stasis and damage,and stop epistaxis.It can also be used to pass the blood and tonify the blood with the best efficacy,and it is the most precious one of the prescription med-icines.Eaten raw,it removes blood stasis and generates new blood,subdues swelling and stabilizes pain,stops bleeding with-out leaving stasis,and promotes blood circulation without hurting the new blood;taken cooked,it can be used to replenish and strengthen the body.Notoginsenoside R1 is a characteristic com-pound in the total saponin of Panax ginseng.In recent years,China's aging has been increasing,and the incidence of neuro-logical disorders has been increasing year by year.Meanwhile,reports on notoginsenoside R1 in the treatment of neurological disorders are increasing,and its neuroprotective effects have been exerted with precise efficacy.The purpose of this paper is to review the treatment of neurological diseases and the mecha-nism of action of notoginsenoside R1,so as to provide a certain theoretical basis for clinical use and new drug development.

Background: Intrahepatic cholangiocarcinoma (ICC) is a highly desmoplastic tumor with poor prognosis even after curative resection. We investigated the associations between the composition of the ICC stroma and immune cell infiltration and aimed to develop a stromal-immune signature to predict prognosis in surgically treated ICC. Patients and methods: We recruited 359 ICC patients and performed immunohistochemistry to detect α-smooth muscle actin (α-SMA), CD3, CD4, CD8, Foxp3, CD68, and CD66b. Aniline was used to stain collagen deposition. Survival analyses were performed to detect prognostic values of these markers. Recursive partitioning for a discrete-time survival tree was applied to define a stromal-immune signature with distinct prognostic value. We delineated an integrated stromal-immune signature based on immune cell subpopulations and stromal composition to distinguish subgroups with different recurrence-free survival (RFS) and overall survival (OS) time. Results: We defined four major patterns of ICC stroma composition according to the distributions of α-SMA and collagen: dormant (α-SMAlow/collagenhigh), fibrogenic (α-SMAhigh/collagenhigh), inert (α-SMAlow/collagenlow), and fibrolytic (α-SMAhigh/collagenlow). The stroma types were characterized by distinct patterns of infiltration by immune cells. We divided patients into six classes. Class I, characterized by high CD8 expression and dormant stroma, displayed the longest RFS and OS, whereas Class VI, characterized by low CD8 expression and high CD66b expression, displayed the shortest RFS and OS. The integrated stromal-immune signature was consolidated in a validation cohort. Conclusion We developed and validated a stromal-immune signature to predict prognosis in surgically treated ICC. These findings provide new insights into the stromal-immune response to ICC.

This study explored the growth-promoting effect and mechanism of the endophytic bacterium Kocuria rosea on Rehmannia glutinosa, aiming to provide a scientific basis for the development of green bacterial fertilizer. R. glutinosa 'Jinjiu' was treated with K. rosea, and the shoot parameters including leaf length, leaf width, plant width, and stem diameter were measured every 15 days. After 120 days, the shoots and roots were harvested. The root indicators(root number, root length, root diameter, root fresh weight, root dry weight, root volume, and root vitality) and secondary metabolites(catalpol, rehmannioside A, rehmannioside D, verbascoside, and leonuride) were determined. The R. glutinosa growth-promoting mechanism of K. rosea was discussed from the effect of K. rosea on the nutrient element content in R. glutinosa and rhizosphere soil and the genome information of this plant. After application of K. rosea, the maximum increases in leaf length, leaf width, plant width, and stem diameter were 35.67%(60 d), 25.39%(45 d), 40.17%(60 d), and 113.85%(45 d), respectively. The root number, root length, root diameter, root volume, root fresh weight, root dry weight, and root viability increased by 41.71%, 45.10%, 48.61%, 94.34%, 101.55%, 147.61%, and 42.08%, respectively. In addition, the content of rehmannioside A and verbascoside in the root of R. glutinosa increased by 76.67% and 69.54%, respectively. K. rosea promoted the transformation of nitrogen(N), phosphorus(P), and potassium(K) in the rhizosphere soil into the available state. Compared with that in the control, the content of available N(54.60 mg·kg~(-1)), available P(1.83 μmol·g~(-1)), and available K(83.75 mg·kg~(-1)) in the treatment with K. rosea increased by 138.78%, 44.89%, and 14.34%, respectively. The content of N, P, and K in the treatment group increased by 293.22%, 202.63%, and 23.80% in the roots and by 23.60%, 107.23%, and 134.53% in the leaves of R. glutinosa, respectively. K. rosea carried the genes related to colonization(rbsB, efp, bcsA, and gmhC), N, P, and K metabolism(narG, narH, narI, nasA, nasB, GDH2, pyk, aceB, ackA, CS, ppa, ppk, ppk2, pstS, pstA, pstB, and pstC), and indole-3-acetic acid and zeatin synthesis(iaaH and miaA). Further studies showed that K. rosea could colonize the roots of R. glutinosa and secrete indole-3-acetic acid(3.85 μg·mL~(-1)) and zeatin(0.10 μg·mL~(-1)). In summary, K. rosea promotes the growth of R.ehmannia glutinosa by enhancing the nutrient uptake, which provides a theoretical basis for the development of plant growth-promoting microbial products.
Rehmannia/metabolism* ; Endophytes/metabolism* ; Plant Roots/growth & development* ; Micrococcaceae/genetics* ; Data Mining ; Plant Leaves/metabolism* ; Genomics ; Rhizosphere

Objective: To explore the intraseasonal variation in mortality risk from cold temperature exposure in Shandong Province. Methods: Mortality data in Shandong province from 2013 to 2018 were collected from the cause of death surveillance system of Shandong Center for Disease Control and Prevention. The basic information mainly included the date of death, age, gender, education level, cause of death, home address, etc. The daily meteorological data from China Meteorological Data Network mainly included the grid coordinate data of 0.01°×0.01° latitude and longitude, such as daily average temperature (℃) and daily average relative humidity (%). The cold season was from November to February. The first two months were the early cold season and the last two months were the late cold season. The extreme cold temperature was defined as the 10^th percentile of the temperature range of cold season. Time-stratified case crossover design with distributed lag non-linear model analyzed the association between temperature and mortality and the association between extreme low temperature and mortality in different lag days in the cold season, and compared the intraseasonal differences between early (November-December) and late (January-February) cold season. Results: The temperature ranged from -17.3 ℃ to 18.6 ℃ in Shandong Province during the cold season from 2013 to 2018, and the P₁₀ (extreme low temperature) was -13.7 ℃. The average daily temperature in the early cold season was (3.63±4.66) ℃. The temperature in the late cold season was (-0.09±3.70) ℃. The average daily relative humidity was (63.89±14.75) % in the early cold season and (62.27±14.19) % in the late cold season. This study included 1 473 300 deaths in the cold season in Shandong Province between 2013 and 2018. There were 824 601 (55.97%) males and 349 824 (23.75%) cases aged<65 years. There were 803 691 (54.55%) deaths due to circulatory diseases and 140 415 (9.53%) deaths due to respiratory diseases. The results of DLNM showed that the cumulative OR of extreme low temperature in the four months of cold season was 1.74 (95%CI: 1.63, 1.86) with the optimal temperature of 18.6 ℃ as the reference. The cumulative OR values of early and late cold season were 1.50 (95%CI: 1.32, 1.71) and 2.56 (95%CI: 2.12, 3.09), respectively (P<0.001). The lag effect lasted for 12 d. Conclusion: There is an intraseasonal variation of the association between cold temperature and mortality risk in Shandong Province. The mortality risk related to cold temperature in the late cold season is higher than that in the early cold season.
Female ; Humans ; Male ; China/epidemiology* ; Cold Temperature ; Cross-Over Studies ; Hot Temperature ; Mortality ; Seasons ; Temperature ; Middle Aged ; Aged

OBJECTIVE: To conduct qualitative and quantitative analyses of Tripterygium hypoglaucum in Yinning Tablets, a compound preparation of traditional Chinese herbal medicine. METHODS: Thin-layer chromatography (TLC) was used for qualitative analysis of Tripterygium hypoglaucum in Yining Tablets and the analytical protocols were optimized. High-performance liquid chromatography (HPLC) was used to quantitatively analyze the content of triptolide (the main active ingredient of Tripterygium hypoglaucum) in Yinning Tablets. RESULTS: The results of TLC analysis showed that the test sample of Yinning Tablets and the positive control samples both produced clear, well separated spots without obvious interference in the blank samples. Assessment of the influences of the thin-layer plates from different manufacturers, temperature and humidity on the test results demonstrated good durability of the test. HPLC analysis of triptolide showed a good linear relationship within the concentration range of 1-100 μg/mL (regression equation: A=22.219C-19.165, r=0.9999); the contents of triptolide in 3 batches of Yinning tablets were 0.34, 0.34, and 0.28 μg per tablet, all within the range of 0.28-0.34 μg per tablet. It was finally determined that each Yinning tablet should not contain more than 0.6 μg of triptolide. CONCLUSION TLC and HPLC are simple, accurate, durable and specific for qualitative and quantitative analyses of Tripterygium hypoglaucum in Yinning Tablets.
China ; Chromatography, High Pressure Liquid/methods* ; Plant Preparations ; Tablets ; Tripterygium/chemistry*

Objective: To verify the accuracy and effectiveness of Goldengate high-throughput deafness gene chip in detecting the patients with enlarged vestibular aqueduct syndrome(EVAS), and to provide a reference for genetic detection strategy of EVAS. Methods: From August 2016 to February 2018, 15 patients with EVAS and 60 normal controls were detected by Goldengate high-throughput deafness detection chip developed by our team, and the results were verified by Sanger sequencing. SLC26A4 gene sequencing was carried out in all the patients with EVAS. Results: 12/15 of patients with EVAS were detected mutations of SLC26A4 gene. Nine mutations were detected by chip detection and SLC26A4 gene direct sequencing, seven of which were detected by both methods. The chip could detect 93.33%(28/30) of the allele information provided by SLC26A4 gene direct sequencing. In addition to SLC26A4 gene, mutations of GJB2, PCDH15, TMC1, MYO6 and mitochondrial genes were detected in 15 patients with EVAS. These results were verified by Sanger sequencing. Conclusion: Goldengate high-throughput deafness gene chip possesses the traits of wide coverage and high accuracy, which can be used as a preliminary detection method for patients with EVAS.

Objective To evaluate the clinical efficacy and safety of Kanglaite injection combined with emcitabine injection and tegafur-gimeracil-oteracil potassium capsule in the treatment of advanced pancreatic cancer(PC).Methods A total of 45 patients with advanced pancreatic cancer were randomly divided into treatment group (n =23) and control group (n =22).The control group was given gemcitabine (1000 mg · m2,iv gtt,at day 1 and day 8) and tegafur-gimeracil-oteracil potassium capsule (1.25 m2 ≤ body surface area ＜ 1.5 m2,40 mg,bid;body surface area≥ 1.5 m2,50 mg,bid,day 1-day 14).The treatment group was treated with Kanglaite (20 g,qd,day 1-day 14) on the basis of control group.Both groups were treated for more than 4 cycles.The clinical benefit rate (CBR),overall survival (OS) and the adverse drug reactions (ADRs) were evaluated between the two groups.Results The CBR of treatment group and control group were 78.26％ (18 cases/23 cases) and 50.00％ (11 cases/22 cases) respectively,with significant difference (P ＜ 0.05).The median OS of treatment group and control group were 6.67 months and 5.60 months,respectively,with significant difference (P ＜ 0.05).The ADRs in the treatment group and control group were bone marrow depression,fatigue,gastrointestinal reaction,abnormal liver and kidney function and skin reaction,and there was no significant difference in the incidence of ADRs reactions between the two groups (P ＞ 0.05).Conclusion Kanglaite combined gemcitabine and tegafur-gimeracil-oteracil potassium is effective and safe in the treatment of advanced pancreatic cancer,with a longer OS,a higher incidence of clinical benefit and less ADRs.

OBJECTIVETo search for an effective method of reducing intraoperative blood loss in radical retropubic prostatectomy (RRP).

METHODSWe performed RRP for 100 patients with prostate cancer, 50 (group A) with the Walsh or Poor method for handling the dorsal venous complex (DVC), and the other 50 (group B) through the following three additional procedures for hemostasis: first placing a #7 prophylactic suture in the distal position of DVC, then ligating the vascular bundle of the prostatic apex with continuous 4-0 Vicryl sutures, and lastly placing a 4-0 absorbable suture followed by freeing the neurovascular bundle (NVB) or freeing NVB before suturing the remained levator ani myofascia and the deep layer of Denovilliers' fascia above the rectal serosa with 4-0 Vicryl. We assessed the effects of the three hemostatic methods in RRP by comparing the volumes of intraoperative blood loss and transfusion, operation time and perioperative levels of hemoglobin.

RESULTSThere were no significant differences between groups A and B in age, PSA, Gleason score, clinical stage, prostate volume, operation time and perioperative hemoglobin levels (P>0.05). The volumes of intraoperative blood loss and transfusion were markedly higher in group A ([1103.00 +/- 528.03] ml and [482.00 +/- 364.60] ml) than in B ([528.00 +/- 258.96] ml and [140.00 +/- 266.28] ml) (P<0.05).

CONCLUSIONIntraoperative blood loss in RRP could be significantly decreased by placing a prophylactic hemostatic suture in the distal position of DVC, continuous suture of the vascular bundle of the prostatic apex after cutting off the urethra, and placing a fine absorbable suture above NVB or continuous suture of the remained levator ani mony fascia and the deep layer of Denovilliers'fascia above the rectal serosa with absorbable sutures after freeing NVB.

Aged ; Blood Loss, Surgical ; prevention & control ; Hemostatic Techniques ; Humans ; Male ; Middle Aged ; Prostatectomy ; methods ; Prostatic Neoplasms ; surgery