Osteoporotic fractures(OPF) refer to the fractures caused by minor violence in the state of osteoporosis, seriously threatening the life and health of elderly patients. Drug and surgical therapies have limitations such as single targets, diverse adverse reactions, and poor prognosis. Kidney-tonifying traditional Chinese medicine(TCM) has good potential in the treatment of OPF. TCM can promote the healing of OPF by promoting angiogenesis in the early stage of bone healing, promoting osteogenic differentiation of bone marrow mesenchymal stem cells in the stage of bone repair, maintaining the balance of osteogenic and osteoclastic system in the stage of bone remodeling, and regulating the oxidative stress responses throughout the process of OPF healing. TCM can alleviate the pathological state of osteoporosis and promote fracture healing in OPF patients via multiple pathways and targets, demonstrating the advantages and potential of biphasic regulation.
Humans ; Drugs, Chinese Herbal/therapeutic use* ; Osteoporotic Fractures/metabolism* ; Animals ; Fracture Healing/drug effects* ; Medicine, Chinese Traditional ; Kidney/metabolism* ; Osteogenesis/drug effects*

Objective:To evaluate the effect of preemptive analgesia with ibuprofen on postoperative pain following single posterior tooth implantation, aiming to provide a clinical reference for its application.Methods:A multicenter, randomized, double-blind, placebo-controlled parallel-group trial was conducted. A total of 82 participants were included in the trial, meeting the eligibility criteria from April 2022 to April 2024 at the Capital Medical University School of Stomatology (40 cases), Beijing TianTan Hospital, Capital Medical University (22 cases), Beijing Chao-Yang Hospital, Capital Medical University (20 cases). Participants were randomly assigned in a 1∶1 ratio to either the ibuprofen group or the control group, with each group comprising 41 individuals. Participants in the ibuprofen group received 300 mg of sustained-release ibuprofen capsules orally 15 min before surgery, while the control group received a placebo. Both groups received the same postoperative analgesic regimen for 3 days. Pain scores were assessed using the numerical rating scale at 30 min, 4 h, 6 h, 8 h, 24 h, 48 h, and 72 h postoperatively, and the additional use of analgesic medication was recorded from days 4 to 6 postoperatively.Results:A total of 82 participants were initially enrolled in the study, with 7 dropouts (4 from the control group and 3 from the ibuprofen group), resulting in 75 participants (37 in the control group and 38 in the ibuprofen group) completing the trial. There were no reports of adverse events such as nausea or vomiting among the participants. The ibuprofen group exhibited significantly lower pain scores at 4 h, 6 h and 8 h [1.0 (0.0, 2.0), 1.0 (0.0, 2.0), 1.5 (0.0, 3.0) ] postoperatively compared to the control group 4 h, 6 h and 8 h [2.0 (1.0, 3.0), 3.0 (1.5, 4.0), 2.0 (1.0, 4.0)] ( Z=-1.99, P=0.047; Z=-3.01, P=0.003; Z=-2.10, P=0.036). The proportions of patients requiring additional analgesic medication between days 4 and 6 post-surgery were 18.4% (7/38) in the ibuprofen group and 27.0% (10/37) in the control group, with no significant difference (χ 2=0.79, P=0.373). The median additional medication usage postoperatively was [0.0 (0.0, 0.0) pills] in the ibuprofen group and [0.0 (0.0, 1.0) pills] in the control group, with no significant difference ( Z=-0.78, P=0.439). Conclusions:Preemptive analgesia with ibuprofen effectively reduces postoperative pain following tooth implantation, representing a safe and effective perioperative pain management strategy.

Objective To evaluate the efficiency of fluorescent PCR melting curve method in early diag-nosis of fluoroquinolones (FQs) resistance in the patients with tuberculosis,and to analyze the situation and characteristics of FQs resistance,so as to provide a basis for the standardized diagnosis and treatment of rifam-picin resistance/multidrug resistant tuberculosis (RR/MDR-TB) and pre-extensively drug resistant tuberculo-sis (pre-XDR-TB).Methods A total of 1094 smear positive samples from the outpatients and inpatients of Guiyang Municipal Public Health Treatment Center from January 2021 to August 2022 were collected and conducted the Roche solid culture method and bacterial species identification.Finally,589 cases of tuberculosis conducted the phenotypic drug sensitivity test and fluorescent PCR melting curve method for detecting rifam-picin (RFP),isoniazid(INH),ethambutol(EMB) and FQs resistance.The phenotypic drug sensitivity test served as the standard to evaluated the diagnostic efficiency of the fluorescent PCR melting curve method;the relationship between the patients' FQs resistance and clinical characteristics was analyzed according to the phenotypic drug sensitivity results.Results The sensitivity,specificity,coincidence rate and Kappa value of fluorescence PCR melting curve method for detecting FQs drug resistance were 91.30％,97.69％,96.94％ and 0.86 respectively;the area under the curve (AUC) was 0.945,which was higher than 0.924,0.923 and 0.850 of RFP,INH and EMB.The drug resistance rate of FQs in the patients with RR/MDR-TB was 22.80％,the Kappa value of fluorescence PCR melting curve method for detecting the patients' FQs drug re-sistance was 0.83,the consistency was good,AUC was 0.936.There was no statistically significant difference in sensitivity,specificity and coincidence rate of FQs resistance in TB patients with different bacterial loads by fluorescence PCR fusion curve (P>0.05).The treatment type,history of anti-tuberculosis,pulmonary cavity and MDR-TB were related with FQs resistance (P<0.05).Conclusion The fluorescent PCR melting curve method has good diagnostic efficiency for FQs resistance in the patients with tuberculosis.

Objective:To screen for preoperative frailty risk factors in elderly patients with spinal degenerative diseases and construct a risk prediction model.Methods:From September 2021 to August 2022, convenience sampling was used to select 324 elderly patients who underwent spinal surgery in the Department of Neurosurgery at Xuanwu Hospital, Capital Medical University as research subjects. The patients were surveyed using the General Information Questionnaire, Barthel Index, Nutritional Risk Screening 2002, Mini-mental State Examination, Geriatric Depression Scale-15, Generalized Anxiety Disorde-7, Athens Insomnia Scale, Charlson Comorbidity Index (CCI), and Modified Frailty Index. Binary Logistic regression analysis was used to explore the influencing factors of preoperative frailty in elderly patients with spinal degenerative diseases and establish a risk prediction model. Receiver Operating Characteristic (ROC) curve was used to assess the discriminative power of the model, and Hosmer-Lemeshow test was used to evaluate the goodness of fit of the model.Results:A total of 324 questionnaires were distributed, and 308 valid questionnaires were collected, with a valid response rate of 95.06% (308/324). Among 308 elderly patients with degenerative spinal diseases, 56 patients experienced preoperative frailty. Binary Logistic regression analysis showed that falls within one year, CCI, serum albumin, activities of daily living, and self-rated health status were the influencing factors for preoperative frailty in elderly patients with spinal degenerative diseases ( P<0.05). The area under the ROC curve of the prediction model was 0.851, with a sensitivity of 0.786 and a specificity of 0.778. Hosmer Lemeshow test indicated that the predictive model had a good fit (χ 2=3.764, P=0.709) . Conclusions:Falls within one year, CCI, serum albumin, activities of daily living, and self-rated health status are influencing factors for preoperative frailty in elderly patients with spinal degenerative diseases. The risk prediction model constructed can identify preoperative frailty early and has good predictive performance, which is worthy of clinical promotion.

OBJECTIVE: To evaluate the efficacy and safety of Wuda Granule (WDG) on recovery of gastrointestinal function after laparoscopic bowel resection in the setting of enhanced recovery after surgery (ERAS)-based perioperative care. METHODS: A total of 108 patients aged 18 years or older undergoing laparoscopic bowel resection with a surgical duration of 2 to 4.5 h were randomly assigned (1:1) to receive either WDG or placebo (10 g/bag) twice a day from postoperative days 1-3, combining with ERAS-based perioperative care. The primary outcome was time to first defecation. Secondary outcomes were time to first flatus, time to first tolerance of liquid or semi-liquid food, gastrointestinal-related symptoms and length of stay. Subgroup analysis of the primary outcome according to sex, age, tumor site, surgical time, histories of underlying disease or history of abdominal surgery was undertaken. Adverse events were observed and recorded. RESULTS: A total of 107 patients [53 in the WDG group and 54 in the placebo group; 61.7 ± 12.1 years; 50 males (46.7%)] were included in the intention-to-treat analysis. The patients in the WDG group had a significantly shorter time to first defecation and flatus [between-group difference -11.01 h (95% CI -20.75 to -1.28 h), P=0.012 for defecation; -5.41 h (-11.10 to 0.27 h), P=0.040 for flatus] than the placebo group. Moreover, the extent of improvement in postoperative gastrointestinal-related symptoms in the WDG group was significantly better than that in the placebo group (P<0.05). Subgroup analyses revealed that the benefits of WDG were significantly superior in patients who were male, or under 60 years old, or surgical time less than 3 h, or having no history of basic disease or no history of abdominal surgery. There were no serious adverse events. CONCLUSION The addition of WDG to an ERAS postoperative care may be a viable strategy to enhance gastrointestinal function recovery after laparoscopic bowel resection surgery. (Registry No. ChiCTR2100046242).
Humans ; Laparoscopy/adverse effects* ; Male ; Female ; Middle Aged ; Double-Blind Method ; Recovery of Function ; Drugs, Chinese Herbal/adverse effects* ; Treatment Outcome ; Gastrointestinal Tract/physiopathology* ; Defecation ; Aged ; Intestines/physiopathology*

Objective:To study the efficacy and safety of laparoscopic surgery in treatment of recurrent hepatocellular carcinoma.Methods:The clinical data of 58 patients with recurrent hepatocellular carcinoma who underwent surgical treatment from January 2010 to January 2018 at Hunan Provincial People’s Hospital were retrospectively analyzed. There were 50 males and 8 females, ranging in age from 28 to 78 (53.0±10.8) years old. Patients were divided into laparoscopic group ( n=27) and laparotomy group ( n=31) according to different surgical procedures. The differences in operative time, intraoperative blood loss, hospital stay, postoperative anal exhaustion time, postoperative complications and prognosis between the two groups were compared. Results:The intraoperative blood loss of laparoscopy group and laparotomy group were 100.0(50.0, 400.0) ml vs 300.0(100.0, 500.0) ml, the postoperative anal exhaustion time were (2.7±0.6) d vs (3.3±0.6) d, the hospital stay were (14.8±3.8) d vs (21.4±6.3) d, and these differences were statistically significant (all P<0.05). The operative time of the two groups were (243.4±27.2) min vs (217.5±34.7) min, with no statistical significance ( t=0.59, P=0.344). There were no significant differences between the two groups in postoperative complications (bile leakage, abdominal infection, hemorrhage, pleural effusion and hepatic encephalopathy) (all P>0.05); thetumor free survival, 1-year, and 3-year overall survival rates of the two groups were also not significantly different (both P>0.05). Conclusion:Laparoscopic surgery is safe and effective in the treatment of recurrent hepatocellular carcinoma, and its prognosis is similar to laparotomy, its complications are not significantly increased, which is worthy of promotion in clinic.

Objective: To understand the current status of diagnosis and treatment of chronic lymphocytic leukemia (CLL) /small lymphocytic lymphoma (SLL) among hematologists, oncologists, and lymphoma physicians from hospitals of different levels in China. Methods: This multicenter questionnaire survey was conducted from March 2021 to July 2021 and included 1,000 eligible physicians. A combination of face-to-face interviews and online questionnaire surveys was used. A standardized questionnaire regarding the composition of patients treated for CLL/SLL, disease diagnosis and prognosis evaluation, concomitant diseases, organ function evaluation, treatment selection, and Bruton tyrosine kinase (BTK) inhibitor was used. Results: ①The interviewed physicians stated that the proportion of male patients treated for CLL/SLL is higher than that of females, and the age is mainly concentrated in 61-70 years old. ②Most of the interviewed physicians conducted tests, such as bone marrow biopsies and immunohistochemistry, for patient diagnosis, in addition to the blood test. ③Only 13.7% of the interviewed physicians fully grasped the initial treatment indications recommended by the existing guidelines. ④In terms of cognition of high-risk prognostic factors, physicians' knowledge of unmutated immunoglobulin heavy-chain variable and 11q- is far inferior to that of TP53 mutation and complex karyotype, which are two high-risk prognostic factors, and only 17.1% of the interviewed physicians fully mastered CLL International Prognostic Index scoring system. ⑤Among the first-line treatment strategy, BTK inhibitors are used for different types of patients, and physicians have formed a certain understanding that BTK inhibitors should be preferentially used in patients with high-risk factors and elderly patients, but the actual use of BTK inhibitors in different types of patients is not high (31.6%-46.0%). ⑥BTK inhibitors at a reduced dose in actual clinical treatment were used by 69.0% of the physicians, and 66.8% of the physicians had interrupted the BTK inhibitor for >12 days in actual clinical treatment. The use of BTK inhibitors is reduced or interrupted mainly because of adverse reactions, such as atrial fibrillation, severe bone marrow suppression, hemorrhage, and pulmonary infection, as well as patients' payment capacity and effective disease progression control. ⑦Some differences were found in the perceptions and behaviors of hematologists and oncologists regarding the prognostic assessment of CLL/SLL, the choice of treatment options, the clinical use of BTK inhibitors, etc. Conclusion: At present, a gap remains between the diagnosis and treatment of CLL/SLL among Chinese physicians compared with the recommendations in the guidelines regarding the diagnostic criteria, treatment indications, prognosis assessment, accompanying disease assessment, treatment strategy selection, and rational BTK inhibitor use, especially the proportion of dose reduction or BTK inhibitor discontinuation due to high adverse events.
Female ; Humans ; Male ; Aged ; Middle Aged ; Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy* ; Prognosis ; Lymphoma, B-Cell ; Immunohistochemistry ; Immunoglobulin Heavy Chains/therapeutic use*

To investigate the effect and the mechanism of ppk1 gene deletion on the drug susceptibility of uropathogenic Escherichia coli producing extended-spectrum beta-lactamases (ESBLs-UPEC). The study was an experimental study. From March to April 2021, a strain of ESBLs-UPEC (genotype was TEM combined with CTX-M-14) named as UE210113, was isolated from urine sample of the patient with urinary tract infection in the Laboratory Department of Guangzhou Eighth People's Hospital, meanwhile its ppk1 gene knock-out strain Δpk1 and complemented strain Δpk1-C were constructed by suicide plasmid homologous recombination technique, which was used to study the effect of ppk1 gene on ESBLs-UPEC drug sensitivity and its mechanism. The drug susceptibility of UE210113, Δpk1, and Δpk1-C were measured by Vitek2 Compact System and broth microdilution method. The quantitative expression of ESBLs, outer membrane protein and multidrug efflux systems encoding genes of UE210113, Δpk1 and Δpk1-C were performed by using qRT-PCR analysis. By using two independent sample Mann-Whitney U test, the drug susceptibility results showed that, compared with UE210113 strain, the sensitivities of Δpk1 to ceftazidime, cefepime, tobramycin, minocycline and cotrimoxazole were enhanced (Z=-2.121,P<0.05;Z=-2.236,P<0.05;Z=-2.236,P<0.05;Z=-2.121,P<0.05), and the drug susceptibility of Δpk1-C restored to the same as which of UE210113 (Z=0,P>0.05). The expression levels of ESBLs-enconding genes bla_TEM and bla_CTX-M-14 in Δpk1 were significantly down-regulated compared with UE210113, but the expression was not restored in Δpk1-C. The expression of outer membrane protein gene omp F in Δpk1 was significantly up-regulated, while the expression of omp A and omp C were down-regulated. The results showed that the expression of multidrug efflux systems encoding genes tol C, mdt A and mdtG were down-regulated in Δpk1 compared with UE210113. The expression of all of the outer membrane protein genes and the multidrug efflux systems genes were restored in Δpk1-C. In conclusion,the lost of ppk1 gene can affect the expression of the outer membrane protein and multidrug efflux systems encoding genes of ESBLs-UPEC, which increase the sensitivity of ESBLs-UPEC to various drugs.
Humans ; beta-Lactamases/metabolism* ; Uropathogenic Escherichia coli/metabolism* ; Urinary Tract Infections ; Plasmids ; Membrane Proteins/genetics* ; Escherichia coli Infections ; Microbial Sensitivity Tests ; Anti-Bacterial Agents/pharmacology*

OBJECTIVE: To establish a visual reporting system for evaluating the activity of collagen Ⅰ α 1 chain (COL1A1) gene promoter in immortalized human hepatic stellate cells, so as to estimate the activation status of the cells and provide a new cell model for the screening and study of anti-hepatic fibrosis drugs. METHODS: The promoter sequence of human COL1A1 was amplified from the genomic DNA of human hepatocarcinoma cell line HepG2. Based on the pLVX-AcGFP1-N1 plasmid, the recombinant plasmid pLVX-COL1A1-enhanced green fluorescent protein (EGFP) was constructed, in which the enhanced green fluorescent protein gene expression was regulated by the COL1A1 promoter. The monoclonal cell line was acquired by stably transfecting pLVX-COL1A1-EGFP into the immortalized human hepatic stellate cell line LX-2 by the lentivirus packaging system and screening. The cell line was treated with transforming growth factor-β1 (TGF-β1) or co-treated with TGF-β1 and drugs with potential anti-hepatic fibrosis effects. The EGFP fluorescence intensity in cells was analyzed by the fluorescence microscope and ImageJ 1.49 software using a semi-quantitative method. The COL1A1 and EGFP mRNA were detected by reverse transcription real-time quantitative PCR (RT-qPCR), and corresponding proteins were detected by Western blot. RESULTS: The recombinant plasmid pLVX-COL1A1-EGFP with the expression of EGFP regulated by COL1A1 promoter was successfully constructed. Kozak sequence was added to enhance the expression of EGFP, which was identified by double digestion and sequencing. The LX-2 monoclonal cell line LX-2-CE stably transfected with pLVX-COL1A1-EGFP was obtained. After co-treatment with TGF-β1 and 5 μmol/L dihydrotanshinone Ⅰ with potential anti-hepatic fibrosis effect for 24 h, the total fluorescence intensity and the average fluorescence intensity of LX-2-CE were lower than those in TGF-β1 single treatment group (P < 0.05), the intracellular mRNA and protein levels of COL1A1 and EGFP were also lower than those in the TGF-β1 single treatment group (P < 0.05). CONCLUSION A reporter system for estimating activation of hepatic stellate cells based on COL1A1 promoter regulated EGFP expression is successfully constructed, which could visually report the changes in COL1A1 expression, one of the activation-related markers of hepatic stellate cells, in vitro. It provides a new cell model for the screening and study of anti-hepatic fibrosis drugs.
Humans ; Transforming Growth Factor beta1/pharmacology* ; Hepatic Stellate Cells/pathology* ; Liver Cirrhosis/genetics* ; Collagen Type I/pharmacology* ; RNA, Messenger/metabolism*

BACKGROUND/OBJECTIVES: Previous research has shown maternal betaine supplementation alleviates fetal-derived hepatic steatosis. Therefore, this study examined the anti-inflammatory effect of maternal betaine intake in offspring mice and its mechanism.MATERIALS/METHODS: Female C57BL/6J mice and their offspring were randomly divided into 3 groups according to the treatment received during gestation and lactation: control diet (CD), fatty liver disease (FLD), and fatty liver disease + 1% betaine (FLD-BET). The FLD group was given a high-fat diet and streptozotocin (HFD + STZ), and the FLD-BET group was treated with HFD + STZ + 1% betaine. After weaning, the offspring mice were given a normal diet for 5 weeks and then dissected to measure the relevant indexes. RESULTS: Compared to the CD group, the offspring mice in the FLD group revealed obvious hepatic steatosis and increased serum levels of alanine aminotransferase, interleukin (IL)-6, and tumor necrosis factor (TNF)-α; maternal betaine supplementation reversed these changes. The hepatic mRNA expression levels of IL-6, IL-18, and Caspase-1 were significantly higher in the FLD group than in the CD group. Maternal betaine supplementation reduced the expression of IL-1β, IL-6, IL-18, and apoptosis-associated speck-like protein containing C-terminal caspase recruitment domain (ASC). Maternal betaine supplementation also reversed the increasing protein expressions of nitric oxide dioxygenase-like receptor family pyrin domain containing 3 (NLRP3), ASC, Caspase-1, IL-1β, and IL-18 in offspring mice exposed to HFD + STZ. Maternal betaine supplementation decreased the homocysteine (Hcy) and s-adenosine homocysteine (SAH) levels significantly in the livers. Furthermore, the hepatic Hcy concentrations showed significant inverse relationships with the mRNA expression of TNF-α, NLRP3, ASC, and IL-18. The hepatic SAH concentration was inversely associated with the IL-1β mRNA expression. CONCLUSIONS The lipotropic and anti-inflammatory effect of maternal betaine supplementation may be associated with the inhibition of NLRP3 inflammasome in the livers of the offspring mice.