OBJECTIVES: To explore the therapeutic effect of LuoFuShan Rheumatism Plaster (LFS) on neuropathic pain (NP) and its molecular mechanism. METHODS: Mouse models of sciatic nerve chronic constriction injury (CCI) were treated with low, medium, and high doses (2.2, 4.4, and 8.8 cm², respectively) of LFS by topical application for 14 consecutive days. The therapeutic effects were assessed by evaluating the mechanical withdrawal threshold (MWT), paw withdrawal latency (PWL), plasma IL-6 and TNF-α levels, and histopathology of the sciatic nerve. Network pharmacology and molecular docking were used to identify the key targets and signaling pathways. The key targets were verified by RT-qPCR and immunohistochemistry. The biosafety of LFS was evaluated by measuring the organ indices and damage indicators of the heart, liver, and kidneys. RESULTS: Compared with the CCI group, LFS dose-dependently increased MWT and PWL, reduced plasma IL-6 and TNF-α levels, and alleviated sciatic nerve inflammation in the mouse models. Network pharmacology identified 378 bioactive compounds targeting 279 NP-associated genes enriched in TLR and TNF signaling. Molecular docking showed that quercetin and ursolic acid in LFS could stably bind to TLR4 and TNF‑α. In the mouse models of sciatic nerve CCI, LFS significantly downregulated the mRNA expression levels of Tlr4 and Tnf-α in the spinal cord in a dose-dependent manner and lowered the protein expressions of TLR4 and TNF-α in the sciatic nerve. LFS treatment did not cause significant changes in the organ indices or damage indicators of the heart, liver and kidneys as compared with those in the CCI model group and sham-operated group. CONCLUSIONS LFS alleviates NP in mice by suppression of TLR4/TNF-α-mediated neuroinflammation with a good safety profile.
Animals ; Toll-Like Receptor 4/metabolism* ; Neuralgia/metabolism* ; Mice ; Signal Transduction/drug effects* ; Tumor Necrosis Factor-alpha/metabolism* ; Drugs, Chinese Herbal/pharmacology* ; Sciatic Nerve/injuries* ; Male ; Molecular Docking Simulation ; Disease Models, Animal ; Interleukin-6

Objective To observe the value of spectral CT for predicting regional lymph node metastasis of colorectal cancer(CRC).Methods Totally 73 patients with CRC confirmed by postoperative pathology were retrospectively enrolled and divided into positive group(n=29)and negative group(n=44)based on the presence or absence of regional lymph node metastasis.The lymph node short diameter,CT value of 120 kV conventional image(CT value120 kV),CT values of 40 keV and 70 keV virtual single energy images(CT value40 keV and CT value70keV),iodine density(ID),effective atomic number(Zeff)and spectral curve slope(λHU).The above parameters and clinical indicators were compared between groups.After excluding those with variance inflation factor greater than 10,model 1 was constructed based on carbohydrate antigen 19-9(CA19-9)and carcinoembryonic antigen(CEA),model 2 based on conventional CT parameters(lymph node short diameter,CT value120 kV),model 3 based on spectral CT parameters(CT value70 keV,ID,Zeff,λHU),and model 4 based on conventional CT parameters and spectral CT parameters.The efficacy of 4 models for predicting regional lymph node metastasis of CRC were analyzed.Results Significant differences in patients'gender,carbohydrate antigen 19-9(CA1 9-9),carcinoembryonic antigen(CEA),lymph node short diameter,CT value120 kV,CT value40 keV,CT value70 keV,ID,Zeff and λHU were found between 2 groups(all P＜0.05).The area under the curve(AUC)of model 1-4 for predicting regional lymph node metastasis of CRC was 0.734,0.752,0.996 and 0.995,respectively,and significant differences were found between model 1 and 3,model 1 and 4,model 2 and 3,as well as model 2 and 4(all P＜0.001).Conclusion Enhanced venous phase spectral CT could effectively predict regional lymph node metastasis of CRC.

ObjectiveTo investigate the clinical efficacy of Tenghuang Jiangu tablets （THJGT） combined with oral non-steroidal anti-inflammatory drugs （NSAIDs） in the treatment of osteoarthritis of the knee and its applicable stage based on real-world data， and provide a basis for the rational clinical use of THJGT. MethodA total of 218 cases treated with THJGT combined with oral NSAIDs included in the "THJGT for knee osteoarthritis case registry" from September 2019 to January 2021 were selected as the observation group， and 126 cases treated with oral NSAIDs alone as the control group （CG）. The data of gender， age， body mass index， Kellgren-Lawrence grading scale （K-L scale） score， visual analogue score （VAS score）， Western Ontario and McMaster Universities Osteoarthritis Index （WOMAC） score， swelling grade， joint fear of cold score， back pain and weakness score， and occurrence of adverse events/reactions of the patients in both groups were used for the evaluation of efficacy with full analysis set. The propensity score matching method was used to exclude the influence of confounding factors between groups， and the sub-data sets were established， with which the repeated measures analysis of variance （ANOVA） was carried out to evaluate the efficacy. Visit points were at registration， 4 weeks and 8 weeks after registration. The data were statistically analyzed in Excel 2019 and SPSS 23.0. ResultThe proportion of females in the observation group was 66.06% （144/218）， which was higher than that （58.73%， 74/126） in the control group （χ²=1.846）. The average age in the observation group was （61.12±7.01） years， which was higher than that ［（59.38±5.99） years］ in the control group （W=19 918.50， P<0.05）. The remission rate in the observation group was 98.17% （214/218）. In the observation group， the proportions of the patients at K-L grades Ⅱ and Ⅲ were 64.22% （144/218） and 25.23% （55/218）， respectively. The effect analysis of the whole data set for enrollment and treatment for 8 weeks showed that the VAS score of the experimental group decreased by （3.27±1.24） points on average， which was better than that of the control group [（2.75±1.20）， W=34 179.00， P<0.05]. The average WOMAC score decreased （23.43±11.46） points， which was better than that of the control group [（16.71±8.86）， W=32 387.00， P<0.05]. The average swelling grade decreased （0.63±0.64）， which was better than the control group [（0.33±0.59）， W=33 847.50， P<0.05]. The average score of joint chills decreased （1.90±1.84）， points， which was better than that of control group [（1.40±1.28）， W=35 165.00， P<0.05]. The average lumbar acid fatigue score decreased by （2.02±1.64） points, which was better than that of the control group [（1.10±1.28）， W=32 986.50， P<0.05]. Efficacy analysis of subdata sets for enrollment， 4 weeks of medication and 8 weeks of medication showed that VAS scores of both groups showed a downward trend after treatment， and the improvement of experimental group was more significant than that of control group at 4 weeks， with statistical significance （P<0.05）. After treatment， the total WOMAC score of both groups showed a downward trend， and the improvement of experimental groups was more significant at 4 weeks and 8 weeks （P<0.05）. After treatment， swelling， cold fear grade and lumbar acid fatigue score of both groups showed a decreasing trend,， and the improvement of experimental group was more significant at 8 weeks （P<0.05）. The therapeutic effect analysis of patients in the attack stage and remission stage of the experimental group showed that the total WOMAC score of the two groups showed a downward trend after treatment， and the trend was basically the same， and there was no statistical difference between the two groups at enrollment， 4 weeks after treatment， and 8 weeks after treatment （t=1.675， t=2.068， t=2.364）. The total WOMAC score of the patients in remission stage in the experimental group with K-L grading between grade 0 and grade Ⅲ had statistical significance at 4 weeks after treatment compared with the time of entry （P<0.05， P<0.01）. Group of adverse event rate was 4.13% （9/218）， lower than the control group 10.32% （13/126） （χ²= 5.109， P<0.05）. ConclusionThe population receiving THJGT combined with oral NSAIDs is mostly female， old， in remission， and with K-L grades Ⅱ and Ⅲ. THJGT can enhance the anti-inflammatory and analgesic effects of oral NSAIDs and keep the drug effect in improving joint function and alleviating fear of cold， swelling， and back pain and weakness. The drug combination can be applied to patients in both attack and remission， and the clinical application should take patient's disease stage and degree of osteoarthritis into account. Furthermore， the combination has the potential to reduce the incidence of adverse events caused by NSAIDs.

ObjectiveTo explore the medication characteristics and clinical efficacy of the Tenghuang Jiangu tablets in the treatment of knee osteoarthritis （KOA） in the remission stage in the real world，providing references for rational clinical use of this prescription. MethodBased on the "registration system of KOA treated with Tenghuang Jiangu tablets"，2 439 KOA cases in the remission stage were analyzed by SPSS 25.0，IBM SPSS Modeler18.0，and Apriori algorithm. To be specific，the age，body mass index （BMI），and course of treatment were described in the form of x̄±s. The information on gender，K-L grade，daily dose，and frequency of drug use was described by frequency analysis. The number of cases，course of treatment，daily dose，and drug use frequency of the single-use group and the combined-use group were described by frequency analysis，and the combination of drugs was described by frequency analysis and Apriori algorithm. Mann-Whitney U test was employed to compare the scores of Visual Analogue Scale （VAS），Western Ontario and McMaster Universities Osteoarthritis Index （WOMAC），pain，stiffness，and joint function between the single-use group and the combined-use group. ResultThe results of clinical treatment showed that 2 439 patients with KOA in the remission stage were treated with Tenghuang Jiangu tablets，with 1 432 （58.71%） in the single-use group and 1 007 （41.29%） in the combined-use group. The average daily dose of Tenghuang Jiangu tablets was （3.90±1.44） g，and the majority of the patients were at grade Ⅱ （54.47%）. The daily average daily dose of Tenghuang Jiangu tablets in the single-use group was （3.64±1.35） g，which was lower than that in the combined-use group ［（4.26±1.48） g，P<0.05］. In the combined use，the top three western medicines were glucosamine （270 times，14.68%），sodium hyaluronate （126 times，6.85%），and imrecoxib （116 times，6.31%），and the top three Chinese medicines were Huoxuezhitong capsules/tablets/ointments （31 times，1.69%），Biqi capsules （25 times，1.36%），and Maizhiling （23 times，1.25%）. As for the overall clinical efficacy，the VAS score was （5.13±0.93） score before treatment and （2.22±1.18） score after treatment （P<0.05），with an overall average decrease of （2.91±1.14） score， and the average decrease in the single-use group was （2.76±1.43） score， which was lower than that in the combined-use group ［（3.12±1.36） score，（P<0.01）］. The WOMAC score was （31.05±11.84） score before treatment and （13.55±9.91） score after treatment （P<0.05）. The overall average decrease was （17.50±11.79） score， and the average decrease in the single-use group and combined-use group was （16.39±11.14） score and （19.08±12.50） score，respectively （P<0.01）. The patients with KOA>grade Ⅱ accounted for 91.34%（1 308/1 432） and 93.55%（942/1 007） in the single-use group and combined-use group，respectively （χ²=80.026，P<0.05）. A total of 43.37%（621/1 432） of the patients in the single-use group had other complications，lower than that in the combined-use group ［54.92%（553/1 432），（χ²=20.087，P<0.01）］. ConclusionMore than half of the patients with KOA in the remission stage are treated with Tenghuang Jiangu tablets alone，and the combination therapy is mainly applied in patients with severe conditions or other complications. In relieving knee joint pain and improving joint stiffness and joint function，both the Tenghuang Jiangu tablets alone and the combination therapy are effective.

Nanoparticulate drug delivery systems (Nano-DDSs) have emerged as possible solution to the obstacles of anticancer drug delivery. However, the clinical outcomes and translation are restricted by several drawbacks, such as low drug loading, premature drug leakage and carrier-related toxicity. Recently, pure drug nano-assemblies (PDNAs), fabricated by the self-assembly or co-assembly of pure drug molecules, have attracted considerable attention. Their facile and reproducible preparation technique helps to remove the bottleneck of nanomedicines including quality control, scale-up production and clinical translation. Acting as both carriers and cargos, the carrier-free PDNAs have an ultra-high or even 100% drug loading. In addition, combination therapies based on PDNAs could possibly address the most intractable problems in cancer treatment, such as tumor metastasis and drug resistance. In the present review, the latest development of PDNAs for cancer treatment is overviewed. First, PDNAs are classified according to the composition of drug molecules, and the assembly mechanisms are discussed. Furthermore, the co-delivery of PDNAs for combination therapies is summarized, with special focus on the improvement of therapeutic outcomes. Finally, future prospects and challenges of PDNAs for efficient cancer therapy are spotlighted.

Objective:To investigate the molecular mechanism of the disease based on the clinical characterization and genetic mutation analysis in a family with intellectual disability.Methods:The proband with intellectual disability was diagnosed at Luohe Central Hospital in December 2019. Peripheral blood samples were collected from four family members. Whole exome sequencing (WES) was used to screen the pathological mutations. Then the PCR and Sanger sequencing were used to verify the selected mutations and combine the relevant database to analyze variation loci.Results:We infer that the ARX c.1162 A>G was co-segregated with the phenotype of the family based on the results of WES. The results of sanger sequencing and WES are consistent. The mother of the proband is the carrier of the mutation. There is no mutation frequency reported in the healthy population. The mutation of the ARX c.1162A>G is harmful inferred by a variety of bioinformatics software. Combined with the phenotypic analysis of OMIM database, we infer the phenotype caused by the mutation is consistent with the patients in the family.Conclusion:The mutation of the ARX c.1162 A>G may be the cause of the intellectual disability in the family affected. And the variant has not been reported in China.

Objective To choose a reasonable non-drug treatment program for women with postpartum breast pain. Methods Based on an adequate assessment of the patients′ condition, the clinical questions were proposed and the references were searched in a series of databases, such as Cochrane Library, PubMed, Ovid, CINAHL, CNKI, Wanfang, Weipu, CBM. Results A preliminary search of 484 articles on cabbage therapy for postpartum breast pain was carried. Through rigorous preliminary screening and screening, 11 articles were finally included, including 2 systematic reviews, 2 randomized controlled trials and 7 quasi-experiment. Through the analysis of the inclusion literature, the data was extracted, and the evidence and summary evidence were strictly evaluated.According to the results of evidence, based on the patients′ condition and the wishes of the family, the cold and hot cabbage leaves were alternately applied to the breast of 10 postpartum women with breast engorgement, the breast distended pain were improved. Conclusions The method of evidence-based nursing can provide safe and effective treatment for postpartum women with breast engorgement.

Total 732 subjects aged 30-60 years undergoing health check-up at Beijing Hospital Medical Examination Center in 2009,who had no history of non-alcoholic fatty liver disease (NAFLD) were recruited in the study.According to the quartile of hemoglobin (HGB) level,the subjects were divided into 4 groups:Q1:HGB ≤ 131 g/L (n =192),Q2:HGB ＞ 131 g/L and ≤ 140 g/L (n =178),Q3:HGB ＞ 140 g/L and ≤152 g/L (n =184),Q4:HGB ＞ 152 g/L (n =178).All participants were followed up for 4 years,the prevalence rates of NAFLD in groups Q1,Q2,Q3 and Q4 were 8.3％ (16/192),17.4％ (31/178),23.4％ (43/184) and 25.3％ (45/178),respectively (P ＜0.05).Logistic regression showed that the rates of NAFLD in groups Q2,Q3 and Q4 were 2.32 (1.22-4.41),3.36 (1.81-6.21) and 3.72(2.02-6.87) times higher as group Q1 (P ＜ 0.05).Multiple logistic regression analysis showed that the hemoglobin level,TG and BMI were the independent risk factors of NAFLD.

Objective To analyze the effect of Chinese diabetes risk score in health checkup of elderly population and to explore the risk factors of abnormal glucose metabolism in the elderly patients.Methods Chinese diabetes risk score(C-DRs)screening,glucose tolerance test(OGTT),blood biochemical parameters and history collection were performed in 1 181 elderly people participating the health checkup.The area under the ROC curve(AUC)was used to evaluate the accuracy of the screening method.The effect of different cumulative C-DRs on screening target population was reflected by the Gordon index.Multivariate logistic regression analysis was used to analyze relevant risk factors for the glucose metabolic abnormalities.Results The AUC of screening for diabetes was 0.749(95%CI:0.715-0.782),and the best cut-point value was 32.5 points.The sensitivity was 86.50%,the specificity was 60.84%,and the Gordon index was 0.47(P=0.000).The AUC of screening for the pre-diabetes was 0.760(95%CI:0.733-0.787),and the best cut-point was 33.5 points.The sensitivity was 70.89%,the specificity was 68.72%,and the Gordon index was 0.40(P=0.000).The AUC of screening for MS was 0.797(95% CI:0.772-0.823),and the best cut-point value was 32.5 points.The sensitivity was 83.62%,the specificity was 64.90%,and the Gordon index was 0.49(P=0.000).The AUC of screening for insulin resistance was 0.609(95%CI:0.645-0.734),and the best cut-point value was 30.5 points.The sensitivity was 81.25%,the specificity was 44.81%,and the Gordon index was 0.26(P=0.000).Multiple logistic regression analysis showed that age over 80 years,abdominal obesity(waist circumference,male ≥ 90 cm,female ≥ 85 cm),hypertension,hypertriglyceridemia,family history of diabetes were risk factors for abnormality of glucose metabolism in the elderly.The odd ratio values of the above were 1.557,1.543,1.495,1.569,1.625,1.715(all P<0.05).Conclusions Chinese diabetes risk score may be used to screen for diabetes,metabolic syndrome and insulin resistance in the elderly population.Old age,abdominal obesity,hypertension,hypertriglyceridemia and family history of diabetes are independent risk factors for abnormal glucose metabolism in the elderly population.

Objective To investigate the relationship between serum uric acid and the risk of nonalcoholic fatty liver disease.Methods A cohort study was performed among individuals who had physical examination at Beijing Hospital medical examination center during 2009.A total of 732 subjects without nonalcoholic fatty liver disease,30-60 years old,were selected.Subjects were divided into 4 groups (Q1,Q2,Q3,Q4) according to serum uric acid level.Theincidence of NAFLD in each group in 2013 were observed.Serum alanine aminotransferase,aspartate aminotransferase,triglycerides,total cholesterol,high density lipoprotein-cholesterol,low density lipoprotein-cholesterol,fasting plasma glucose,and imaging examinations were determined.Cumulative incidence ofNAFLD was compared between each group and effect of baseline serum uric acid on new-onset NAFLI was assessed by logistic regression analysis.Results The cumulative incidence of NAFLD increased irconjunction with the increase of baseline serum uric acid in 4 groups (Q1 8.70％,Q2 13.04％,Q3 19.23％,Q4 32.97％,x2=37.865,P＜0.05).Logistic regression showed that the incidence of nonalcoholic fattyliver disease was increased along with elevated levels of serum uric acid.Subjects in the Q2,Q3,Q4 groups showed an increased risk of NAFLD,relative risks were 1.575 (0.807-3.074);2.580 (1.329-54.701);5.164 (2.838-9.397),compared to those in Q1 group.Moreover,after adjustment for baseline factors (e.g.Age,sex),risk of NAFLD remained higher,with odds ratio at 1.234,and the difference was statistically significant.Conclusions Serum uric acid was found to be correlated with the prevalence of nonalcoholic fatty liver disease.Serum uric acid appeared to be an independent risk factor for NAFLD.