Objective:To analyze the evolution of ceftazidime/avibactam (CZA) resistance phenotyes and clinical features of 11 ST11-KL64 carbapenem-resistant Klebsiella pneumoniae (CRKP) isolates carrying bla KPC. Methods:Eleven CRKP isolates, designated K01 to K11, obtained from infected liver transplant patients from June to September 2024 were retrospectively studied. Broth microdilution method, whole genome sequencing (WGS) and plasmid conjugation assays were employed to investigate the antimicrobial susceptibility, resistance mechanisms, and genetic structural characteristics of these CRKP isolates. Clinical data were simultaneously collected and organized to analyze the correlation between bla KPC gene mutations and the clinical efficacy of antimicrobial therapy. Results:All eleven isolates of CRKP exhibited multidrug resistance phenotypes. Among them, K01-K09 and K11 were sensitive to CZA and resistant to carbapenems, while K10 was resistant to CZA and displayed sensitivity or intermediate resistance to carbapenems. WGS analysis showed that all 11 CRKP isolates belonged to the ST11-KL64 clonal type. Among these isolates, the K01-K09 and K11 isolates carry the bla KPC-2 gene, whereas the K10 isolate carries the bla KPC-33 gene. A single nucleotide mutation in bla KPC-2 (G532T) resulted in a substitution of tyrosine (Y) for aspartic acid (D) at Ambler position 179 (D179Y), causing resistance of CRKP to CZA and reduced sensitivity to Imipenem and Meropenem. The conjugative plasmid was successfully constructed, and compared to the parental strain, its minimum inhibitory concentration (MIC) to CZA increased 32 folds. Clinical data revealed that the patient developed the bla KPC-33 mutation after 51 days of CZA treatment. Conclusions:The bla KPC-33 mutation following CZA treatment for CRKP infection exhibits a considerable delay. It is essential to dynamically monitor the evolution of CRKP resistance to ensure timely adjustment of therapeutic strategies in case of the occurrence of mutations such as bla KPC-33.

Objective To investigate the current status of home medicine cabinet management and unmet needs for home-based pharmaceutical services among elderly hypertensive patients in Hubei Province,and to provide evidence for optimizing home pharmaceutical care models.Methods From July 2022 to March 2023,310 elderly hypertension patients across Hubei Province were enrolled.Pharmacists conducted home visits to administer structured questionnaires capturing demographics and blood pressure control rates,perform medication categorization and quality assessments of home medicine cabinets and document cabinet management issues in real-time.Results Among 290 valid questionnaires,binary logistic regression revealed better blood pressure control in non-working and non-smoking individuals.Medicine cabinet audits identified three critical issues:failure to separate Chinese and chemical medicines,duplicate medications with similar ingredients and missing original packaging.Post-intervention,all cabinets demonstrated proper medication categorization and storage compliance.Conclusions Significant medication safety hazards exist in elderly hypertensive patients'home medicine cabinets.Pharmacist-led home interventions effectively cleared substandard medications and improved medication safety.Future home pharmaceutical services should focus on optimizing cabinet management protocols,enhancing medication safety awareness and personalizing pharmaceutical care to ensure precise and effective home-based medication management.

Objective To investigate the current status of home medicine cabinet management and unmet needs for home-based pharmaceutical services among elderly hypertensive patients in Hubei Province,and to provide evidence for optimizing home pharmaceutical care models.Methods From July 2022 to March 2023,310 elderly hypertension patients across Hubei Province were enrolled.Pharmacists conducted home visits to administer structured questionnaires capturing demographics and blood pressure control rates,perform medication categorization and quality assessments of home medicine cabinets and document cabinet management issues in real-time.Results Among 290 valid questionnaires,binary logistic regression revealed better blood pressure control in non-working and non-smoking individuals.Medicine cabinet audits identified three critical issues:failure to separate Chinese and chemical medicines,duplicate medications with similar ingredients and missing original packaging.Post-intervention,all cabinets demonstrated proper medication categorization and storage compliance.Conclusions Significant medication safety hazards exist in elderly hypertensive patients'home medicine cabinets.Pharmacist-led home interventions effectively cleared substandard medications and improved medication safety.Future home pharmaceutical services should focus on optimizing cabinet management protocols,enhancing medication safety awareness and personalizing pharmaceutical care to ensure precise and effective home-based medication management.

Objective:To analyze the evolution of ceftazidime/avibactam (CZA) resistance phenotyes and clinical features of 11 ST11-KL64 carbapenem-resistant Klebsiella pneumoniae (CRKP) isolates carrying bla KPC. Methods:Eleven CRKP isolates, designated K01 to K11, obtained from infected liver transplant patients from June to September 2024 were retrospectively studied. Broth microdilution method, whole genome sequencing (WGS) and plasmid conjugation assays were employed to investigate the antimicrobial susceptibility, resistance mechanisms, and genetic structural characteristics of these CRKP isolates. Clinical data were simultaneously collected and organized to analyze the correlation between bla KPC gene mutations and the clinical efficacy of antimicrobial therapy. Results:All eleven isolates of CRKP exhibited multidrug resistance phenotypes. Among them, K01-K09 and K11 were sensitive to CZA and resistant to carbapenems, while K10 was resistant to CZA and displayed sensitivity or intermediate resistance to carbapenems. WGS analysis showed that all 11 CRKP isolates belonged to the ST11-KL64 clonal type. Among these isolates, the K01-K09 and K11 isolates carry the bla KPC-2 gene, whereas the K10 isolate carries the bla KPC-33 gene. A single nucleotide mutation in bla KPC-2 (G532T) resulted in a substitution of tyrosine (Y) for aspartic acid (D) at Ambler position 179 (D179Y), causing resistance of CRKP to CZA and reduced sensitivity to Imipenem and Meropenem. The conjugative plasmid was successfully constructed, and compared to the parental strain, its minimum inhibitory concentration (MIC) to CZA increased 32 folds. Clinical data revealed that the patient developed the bla KPC-33 mutation after 51 days of CZA treatment. Conclusions:The bla KPC-33 mutation following CZA treatment for CRKP infection exhibits a considerable delay. It is essential to dynamically monitor the evolution of CRKP resistance to ensure timely adjustment of therapeutic strategies in case of the occurrence of mutations such as bla KPC-33.

By organizing and studying on the original works of LI Wenrong， this paper aimed to explore his theories and methods for treating liver diseases. LI Wenrong believes that the liver is easily prone to physiological disturbances， difficult to pacify， and can be compared to a “chariot” that moves horizontally and vertically， acting as a “general” for both civil and military affairs. Pathologically， liver diseases tend to spread to other organs， resulting in ever-changing pathological changes， often affecting emotional health. In terms of therapeutic methods， LI Wenrong proposes ten methods including draining fire to calm the liver， nourishing water to moisten wood， clearing metal to calm the liver， calming gallbladder and harmonizing liver， subduing yang with shell-drug， treating liver diseases by supplementing spleen， soothing the liver with sweetness， astringing the liver with sourness， relieving the liver with spiciness， and draining the liver with excess-fire. These methods have great guidance and reference value for contemporary clinical practice in traditional Chinese medicine.

Objective:To investigate the relationship between serum fibrous gel protein-3 (ficolin-3) and serum alanine (ALA) levels and gestational diabetes (GDM) .Methods:A total of 98 pregnant women with GDM admitted to our hospital from Jan. 2020 to Aug. 2020 were selected as the observation group, and 98 healthy pregnant women undergoing physical examination during the same period were taken as the control group. The level of serum ficolin-3 was measured by enzyme-linked immunosorbent assay (ELISA) , and the level of serum ALA was measured by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) . The two groups were compared in terms of serum ficolin-3, ALA levels and biochemical indicators (hemoglobin (HbA1c) , total cholesterol (TC) , high-density lipoprotein cholesterol (HDL-C) , low-density lipoprotein cholesterol (LDL-C) , serum total protein (TP) , serum urea (SU) levels) , and pregnancy outcomes. Pearson method was used to analyze the correlation between serum ficolin-3 and ALA levels and various biochemical indexes. Univariate analysis and binary logistic regression analysis were used to investigate the risk factors of GDM.Results:Serum ficolin-3, HbA1c, and SU levels in the observation group were all higher than that in the control group. Serum ALA level was lower than that in the control group, and the difference was statistically significant ( P<0.05) . TC, HDL-C, LDL-C, TPT showed no significant difference between the two groups ( P>0.05) . In the observation group, serum ficolin-3 was positively correlated with HbA1c and Su, and serum ALA was negatively correlated with HbA1c and SU ( P < 0.05) . The incidence of adverse outcomes including gestational neonatal asphyxia, neonatal jaundice, giant size, and amniotic fluid contamination in the observation group (26.53%) was higher than that in the control group (12.24%) , The difference was statistical significant ( P<0.05) . The univariate analysis showed that GDM was associated with age, weight gain during pregnancy, serum ficolin-3, ALA, HbA1c, SU, family history of diabetes ( P<0.05) ; Binary logistics regression analysis found that age ≥28 years, weight gain≥ 14 kg, serum ficolin-3≥24ng/ml, HbA1c 6.0%, and a family history of diabetes were risk factors for GDM, while serum ALA≥1.9 μg/ml was a protective factor of GDM, ( P<0.05) . Conclusion:The increase of serum ficolin-3 and the decrease of ALA level in pregnant women are risk factors of GDM, and have an adverse impact on the final delivery outcome

Objective: Attentional biases toward emotional scenes may represent vulnerability and maintenance factors in depression. Antidepressant therapy may improve cognitive function and reduce depression, and is considered as the mechanism of action of antidepressants. Therefore, we conducted an eye-tracking test to examine whether selective serotonin re-uptake inhibitor (SSRI) antidepressants can reduce negative attentional biases and elicit clinical responses in depression. Methods: Twenty first-episode depressive patients freely viewed three types of pictures that depicted different emotional scenes (i.e., positive-control, neutral-control, and negative-control) for 4,000 ms while their eye movements were monitored. The attentional bias to different emotional scenes was assessed before and after eight weeks of SSRI treatment using the eye-tracking method. The control group included a group of healthy individuals. Results: The results revealed that first-episode depressive patients oriented their gaze more frequently to negative images and less to happy images, compared to controls. Importantly, the attentional bias in depressive patients was regulated after eight weeks of SSRI treatment. Patients showed an increased tendency to fixate on positive images and a decreased tendency to focus on negative images. Conclusion This suggests that SSRI antidepressants decrease vulnerability to negative images, while having an effect on attention in respect to positive images.

Managing the dysregulated host response to infection remains a major challenge in sepsis care. Chinese treatment guideline recommends adding XueBiJing, a five-herb medicine, to antibiotic-based sepsis care. Although adding XueBiJing further reduced 28-day mortality modulating the host response, pharmacokinetic herb-drug interaction is a widely recognized issue that needs to be studied. Building on our earlier systematic chemical and human pharmacokinetic investigations of XueBiJing, we evaluated the degree of pharmacokinetic compatibility for XueBiJing/antibiotic combination based on mechanistic evidence of interaction risk. Considering both XueBiJing‒antibiotic and antibiotic‒XueBiJing interaction potential, we integrated informatics-based approach with experimental approach and developed a compound pair-based method for data processing. To reflect clinical reality, we selected for study XueBiJing compounds bioavailable for drug interactions and 45 antibiotics commonly used in sepsis care in China. Based on the data of interacting with drug metabolizing enzymes and transporters, no XueBiJing compound could pair, as perpetrator, with the antibiotics. Although some antibiotics could, due to their inhibition of uridine 5'-diphosphoglucuronosyltransferase 2B15, organic anion transporters 1/2 and/or organic anion-transporting polypeptide 1B3, pair with senkyunolide I, tanshinol and salvianolic acid B, the potential interactions (resulting in increased exposure) are likely desirable due to these XueBiJing compounds' low baseline exposure levels. Inhibition of aldehyde dehydrogenase by 7 antibiotics probably results in undesirable reduction of exposure to protocatechuic acid from XueBiJing. Collectively, XueBiJing/antibiotic combination exhibited a high degree of pharmacokinetic compatibility at clinically relevant doses. The methodology developed can be applied to investigate other drug combinations.

Objective To investigate the optimal order of infantile touching. Methods In our hospital from February 1st to April 30th 2014 a total of 1248 newborn touching peoplefrom head to foot, used the traditional top-down massage manipulation (as control group); May 1st to July 31st 2014 newborn touching people a total of 1309 new born, with the improved techniques: from the foot end to bottom-up against the tentacle method (as experimental group). The success rate of neonatal touch were observed and compared between the two groups. Results The success rate of the experiment group neonatal massage was 87.2%,significantly higher than that in the control group (29.7%)(χ2=18.552, P<0.05). The infants more quiet, comfortable, little panic restless mood in test group compared with the control group, the difference was statistical significant(P<0.05). Conclusion The detection of neonatal from the foot to the touch than the ab initio down massagemore comfortable in the clinical work, not easy to be noisy.

Objective To investigate the effect of extract ofTangshen-HuazhuoRecipe(TSHZR) on the serum concentrations of transforming growth factorβ1(TGF-β1) and platelet derived growth factor(PDGF) in patients withⅣ stage of diabetic nephropathy(DN).Methods From June 2012 to December 2012, 98 patients ofⅣstage DN in our hospital outpatient were enrolled and randomly divided into treatment group(n=48) and control group(n=50) using random number table. All patients received conventional therapies of controlling blood sugar, lipid, blood pressure and anticoagulant therapy. On such basis, the control group was treated by irbesartan, 150 mg/d, and the treated group treated by TSHZR combined with irbesartan,150 mg/d, for 6 months. Serum TGF-β1 and PDGF were determined with ELISA before and after treatment,and urinary albumin excretion rate,HbA1c,serum creatinine,blood urea nitrogen and lipid profiles were examined as well. ResultsIn the treated group, the TGF-β1 was(172.5±31.3), (123.6±21.2)pg/ml, the PDGF was(860.9± 131.2), (500.6±130.2)pg/ml before the treatment and after the treatment, respectively. The TGF-β1 and PDGF after the treatment were significantly decreased than those before the treatment(P<0.01). After the treatment, TGF-β1 and PDGF in the treated group were statistically significant compared to the control group[TGF-β1 is(157.4±39.6)pg/ml, PDGF is(765.7±161.8)]pg/ml,P<0.01). After the treatment, the treatment group was superior to the control group in TG(1.72±0.25)mmol/L,(2.09±0.27)mmol/L,(P<0.01), TC(4.56± 0.64)mmol/L,(6.11±0.93)mmol/L, (P<0.01), HDL-C(1.56±0.50)mmol/L,(1.36±0.44)mmol/L, (P<0.01), LDL-C(2.46±1.08)mmol/L(3.32±0.87)mmol/L,(P<0.05)and UAER(100.73±204.24)μg/min, (226.24±396.38)μg/min, (P<0.01).Conclusion TSHZR can inhibit the progressive of IV stage of diabetic nephropathy by suppressing TGF-β1 and PDGF expression level.