Based on the theory of blood collateral， postoperative recurrence and metastasis of bladder cancer are considered to arise primarily from the binding of stasis and toxin， which accumulate and hide within the blood collaterals. Accordingly， treatment should focus on clearing and resolving the deeply concealed stasis toxin retained in the blood collaterals. The paired use of insect and vine medicinals may exert synergistic effects by simultaneously searching out and eliminating pathogenic factors， guiding the action of herbs to the channels， and unblocking the collaterals. Drawing on clinical practice， the stasis-toxin pathogenesis of postoperative recurrence and metastasis of bladder cancer can be divided into four stages including stagnation and astringent of collateral qi， formation of fixed stasis nests， transformation of persistent stasis into toxin， and deficiency of healthy qi with lingering toxin. Accordingly， four herb pairs are proposed for each stage based on conventional treatment， which are Dilong （Pheretima）-Daxueteng （Caulis Sargentodoxae）， Shuizhi （Hirudo）-Jixueteng （Caulis Spatholobi）， Wugong （Scolopendra）-Luoshiteng （Caulis Trachelospermi）， and Quanxie （Scorpio）-Qianjinteng （stephania）. Their potential modern pharmacological mechanisms are further discussed.

Helicobacter pylori is a bacterium that can cause chronic gastritis, peptic ulcers, and other gastrointestinal diseases. The World Health Organization has classified H. pylori as a group Ⅰ carcinogen. Antibiotics are the primary clinical approach for eradicating H. pylori. However, incomplete eradication of H. pylori by antibiotics can lead to persistent infection, which is a major risk factor for the high incidence of gastric cancer. The widespread use of antibiotics has led to the emergence of multidrug resistance in H. pylori, contributing to treatment failures of chronic gastric diseases and increasing the risk of spreading resistant strains. Multidrug-resistant H. pylori has become a serious challenge in the diagnosis and treatment of gastrointestinal diseases. This paper reviews the global trends in the development of multidrug resistance in H. pylori, the underlying mechanisms, the challenges it poses to clinical diagnosis, and its impact on drug development, drawing on relevant literature and the research findings from our group. It proposes using cgt expression as a novel method for determining viable bacteria, identifying intracellularization as a new form of resistance in H. pylori, and exploring the potential of O-glycans as a therapeutic approach against H. pylori to address multidrug resistance. It provides new insights into understanding the mechanisms of H. pylori multidrug resistance and its prevention strategies, offering promising directions for future clinical treatments and antimicrobial drug development.
Helicobacter pylori/genetics* ; Humans ; Drug Resistance, Multiple, Bacterial ; Helicobacter Infections/microbiology* ; Anti-Bacterial Agents/therapeutic use* ; Gastrointestinal Diseases/drug therapy*

Objective To establish a viable bacteria assay for Helicobacter pylori(H.pylori)by assessing the cgt gene expression,and to develop accordingly a rapid and novel testing method for clinical precision treatment.Methods Viable bacteria count was determined in bacterial cultures.The transcriptional expression level of cgt(hp0421),the conserved gene that encodes cholesterol-α-glucosyltransferase(CGT)in H.pylori,was measured by RT-PCR.The correlation between the number of colonies and cgt gene transcription expression was analyzed and the regression model was constructed.The linear range,sensitivity,and specificity of the new method were examined accordingly.The bactericidal action of clarithromycin was assessed using this method to verify the performance of the method in determining clinical bacterial drug resistance.Results The Ct values of cgt for H.pylori colony counts of 102,104,106,and 108 CFU/mL were 29.67±0.14,23.37±0.36,17.65±0.37,and 11.38±0.39,respectively.In the range of 101-108 CFU/mL,the regression equation for cgt gene expression and viable bacterial counts determined by RT-qPCR was y=-0.350 1x+12.49,with the correlation coefficient being R2=0.9992 and the sensitivity being 101 CFU/mL,showing no cross-reaction with 13 other bacteria.The lg values of live H.pylori bacteria treated with clarithromycin at 0,5,10,20,and 40 μg/mL for 12 h were 2.57±0.02,2.45±0.01,2.19±0.02,1.91±0.07,and 1.33±0.05,respectively.The corresponding cgt gene Ct values were 27.76±0.09,28.37±0.24,29.51±0.14,30.11±0.12,and 31.66±0.11.By applying the cgt gene expression in the equation,the estimated counts of viable bacteria were found to be 2.73±0.03,2.52±0.08,2.11±0.05,1.89±0.02,and 1.33±0.04,showing no significant difference in statistical analysis(P＞0.05).Conclusion The method for assessing viable bacteria account by evaluating cgt gene expression in H.pylori was successfully established,significantly reducing the time required to determine viable bacteria count and providing a new method for clinical viable bacteria testing.

Objective To evaluate the changes in the expression of isolectin B4 (IB4) and calcium gene-related peptide (CGRP) in neurons in dorsal root ganglion (DRG) of rats with neuropathic pain (NP).Methods Forty healthy male Sprague-Dawley rats,weighing 250-280 g,were divided into 2 groups (n =20 each) using a random number table method:solvent group (group S) and group NP.NP was induced by intraperitoneally injecting resiniferatoxin 210 μg/kg,and the solvent of resiniferatoxin was intraperitoneally injected in group S.The mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured in 5 rats selected before establishing the model and at 1,3,7 and 42 days after establishing the model.Five rats were sacrificed at 1,3,7 and 42 days after establishing the model,and the L4-6 segments of the DRGs were removed to determine the expression of CGRP and IB4 in neurons using immunofluorescence.Results Compared with the baseline before establishing the model,the MWT was signilicantly decreased at 3,7 and 42 days after establishing the model,and the TWL was prolonged at 1,3,7 and 42 days after establishing the model in group NP (P＜0.05).Compared with group S,the MWT was significantly decreased at 3,7 and 42 days after establishing the model,the TWL was prolonged at 1,3,7 and 42 days after establishing the model,and the expression of IB4 and CGRP in neurons in DRGs was down-regulated at 1,3,7 and 42 days after establishing the model in group NP (P＜0.05).Conclusion Down-regulated expression of IB4 expression in neurons in DRGs may be involved in the development and maintenance of mechanical hypersensitivity to pain,and down-regulated expression of CGRP may be involved in the development and maintenance of thermal analgesia in rats with NP.

Objective To observe the effects of sulfentanil with various doses on the Bispectral index and Narcotrend index without nociceptive stimulus under the sevoflurane anesthesia.Methods Forty-eight ASA Ⅰ or Ⅱ patients undergoing gynecological operations were randomly divided into four groups（n=12）.All patients were induced with sevoflurane,the end-tidal concentrations of sevoflurane in all groups were adjusted to 1.0 MAC after tracheal intubation. Fifteen minutes later,sufentanil was injected in groups of B,C,D with the doses of 0.25,0.5,1.0 μg/kg respectively. The observations were finished when the values of Bispectral index and the Narcotrend index reached the minimum over 5 min. The values of Bispectral index and the Narcotrend index were recorded every minutes after the sufentanil injection. Results Among all groups,the BIS,Narcotrend values and tmax produced no statistical difference. Compared with the time when conscious lost,BIS and Narcotrend values were significantly lower when sevoflurane anesthesia reached steady state in all groups. The values of BIS and Narcotrend were significant lower after the injection of sufentanil in the groups of B,C and D（P0.05）. Conclusion Under the sevoflurane anesthesia with the steady end-tidal concentration of 1.0MAC,sufentanil could reduce the values of BIS and Narcotrend index without nociceptive stimulus without distinction among different doses.