Preparation and in vivo Distribution of Essential Oil from Alpinia zerumbet Fructus Encapsulated Nanoemulsions / 中国实验方剂学杂志

ObjectiveTo prepare oral nanoemulsions encapsulating essential oil from Alpinia zerumbet fructus（EOFAZ） and to investigate its pro-absorption effect in vitro and distribution in vivo. MethodThe proteoglycan conjugate polysaccharides of vinegar-processed Bupleuri Radix-bovine serum albumin（VBCP-BSA） was prepared by Maillard reaction of VBCP and BSA. Taking VBCP-BSA as emulsifier， vitamin B12（VB12） as absorption enhancer， and medium chain triglycerides mixed with EOFAZ as oil phase， the nanoemulsions loaded with EOFAZ was prepared by high energy emulsification method. The particle size， particle size distribution， surface Zeta potential， EOFAZ content and appearance and morphology of the nanoemulsions were characterized， and fluorescein tracer method was used to investigate the absorption effect of fluorescein-labeled EOFAZ nanoemulsions in vitro and their distribution in vivo. ResultVBCP-BSA was formed by Maillard reaction for 48 h with high grafting rate. Using VBCP-BSA as emulsifier， the homogeneous pink nanoemulsions was prepared and denoted as EOFAZ@VBCP-BSA/VB12. The particle size of the nanoemulsions was less than 100 nm and the particle size distribution was uniform. The surface of the nanoemulsions was a weak negative charge， and the shape was spherical. The encapsulation rate of the nanoemulsions for EOFAZ was greater than 80%， which had a good absorption effect in vitro and could enhance liver accumulation after oral administration. ConclusionThe designed proteoglycan nanoemulsions can effectively load EOFAZ， promote oral absorption and enhance liver distribution， which can provide experimental basis for the development of oral EOFAZ liver protection preparations.

Incidence and risk factors associated with negative postoperative behavioral changes in children undergoing painless gastroscopy.

OBJECTIVE: To investigate the incidence of and risk factors associated with negative postoperative behavioral changes (NPOBCs) in children undergoing painless gastroscopy. METHODS: Inclusion criteria: ASA I-II and outpatients aged 6-12 years undergoing painless gastroscopy. EXCLUSION CRITERIA: history of surgery or anesthesia, children with developmental or intellectual abnormalities, refusal to participate, preoperative abdominal pain score > 3 points, history of chronic abdominal pain of > 3 months duration, and serious intraoperative complications. On the 1st, 14th, and 30th day after the gastroscopy, the Post Hospitalization Behavior Questionnaire for Ambulatory Surgery (PHBQ-AS) was used to assess NPOBCs in children. RESULTS: A total of 1,670 children were included in this prospective observational cohort study. The incidence rates of NPOBCs were 14.13%, 4.55%, and 2.14% on the 1st, 14th, and 30th day after gastroscopy, respectively. The risk factors for the first day were female sex (OR 1.34, 95% CI 1.00-1.79), parental anxiety (OR 2.23, 95% CI 1.75-3.12), and severe anxiety in children (OR 2.83, 95% CI 1.96-4.07). The risk factors on the 14th day were parental anxiety (OR 3.71, 95% CI 2.19-6.29), a parental educational level above high school (OR 1.65, 95% CI 1.00-2.70), and severe anxiety in children (OR 11.87, 95% CI 5.85-24.07). The risk factors on the 30th day were female sex (OR 2.99, 95% CI 1.41-6.34), being an only child (OR 4.42, 95% CI 2.18-8.95), a parental educational level above high school (OR 2.66, 95% CI 1.27 NPOBCs 5.56), and severe anxiety in children (OR 6.84, 95% CI 2.84-16.49). CONCLUSION: In children undergoing painless gastroscopy, the incidence rates of NPOBCs on the 1st, 14th, and 30th day were 14.13%, 4.55%, and 2.14%, respectively. The risk factors for NPOBCs were severe anxiety in children, female sex, parental anxiety, and a parental educational level above high school. In particular, severe preoperative anxiety in children was a persistent risk factor for NPOBCs within 30 days.

Effects of transient receptor potential vanilloid 4 inhibitor HC067047 on anxiety-like behavior in mice induced by lipopolysaccharide / 解剖学报

Objective To investigate the effect of transient receptor potential vanilloid 4 (TRPV4) inhibitor HC067047 on anxiety-like behavior in mice induced by lipopolysaccharide (LPS). Methods Totally 48 male C57BL/6 mice were randomly divided into control group (NS), model group (LPS) and drug intervention group (HC + LPS). Anxiety mouse model was established by intraperitoneal injection of 0.83 mg/kg LPS. The HC + LPS group was intraperitoneally injected with HC067047 (10 mg/kg) 30 minutes before LPS injection, and the NS group and LPS group were injected with equal volume of normal saline. Open field test and social interaction experiments were used to detect anxiety-like behaviors in each group of mice; Immunohistochemical chemistry and Western blotting were used to detect the expression of TRPV4, inducible nitric oxide synthase (iNOS), neuronal nitric oxide synthase (nNOS) and endothelial nitric oxide synthase (eNOS) in the hippocampus. Results Immunohistochemical and Western blotting experiments showed that, compared with the NS group, the expression of TRPV4 in the hippocampus of the LPS group was significantly up-regulated (P<0.0001); In the open field test, compared with the NS group, the total distance (P < 0.0001), the distance in the central area (P<0.01) and the time of in the central area mice in the LPS group reduced significantly (P< 0.01). HC067047 intervention reversed the activities of LPS model mice total distance (P < 0.05), the distance of activities in the central area (P < 0.001) and the time of in the central area (P < 0.01); In the social interaction test, compared with the NS group, the interaction time the unfamiliar mice reduced significantly in LPS group (P<0.01), which was reversed by HC067047 treatment (P< 0.01); Western blotting detection revealed that the expression of hippocampal iNOS (P<0.05), nNOS (P < 0.001), and eNOS (P < 0.001) in the LPS group were significantly higher than the NS group, which reduced remarkably by HC067047 treatment (iNOS P < 0.05, nNOS P < 0.01 and eNOS P < 0.01). Conclusion Inhibiting the expression of TRPV4 can improve the anxiety-like behavior, and this process may be related to anti-oxidative stress.

Ginsenoside Rg1 attenuates palmitate-induced HMCs fibrosis by inhibiting NOX4/MAPK pathways / 中国药理学通报

Aim To investigate the inhibitory effect of ginsenoside Rg1 on sodium palmitate induced fibrosis in human glomerullar mesangial cells (HMCs) and its mechanism. Methods (1) HMCs were treated with different concentrations of PA for 24 h, the intracellular lipid accumulation was observed by oil red staining, and the intracellular ROS production was detected by H2DCFDA kit; (2) HMCs were divided into control, PA (160 μmol·L

Identification and verification of α-11 giardin-interacting protein / 中国血吸虫病防治杂志

Objective To identify and verify the interacting protein of α-11 giardin, so as provide the experimental evidence for studies on the α-11 giardin function. Methods The yeast two-hybrid cDNA library of the Giardia lambia C2 strain and the bait plasmid of α-11 giardin were constructed. All proteins interacting with α-11 giardin were screened using the yeast two-hybrid system. α-11 giardin and all screened potential interacting protein genes were constructed into pBiFc-Vc-155 and pBiFc-Vn-173 plasmids, and co-transfected into the breast cancer cell line MDA-MB-231. The interactions between α-11 giardin and interacting proteins were verified using bimolecular fluorescence complementation (BiFC). Results The yeast two-hybrid G. lambia cDNA library which was quantified at 2.715 × 107 colony-forming units (CFU) and the bait plasmid containing α-11 giardin gene without an autoactivation activity were constructed. Following two-round positive screening with the yeast two-hybrid system, two potential proteins interacting with α-11 giardin were screened, including eukaryotic translation initiation factor 5A (EIF5A), calmodulin-dependent protein kinase (CAMKL) and nicotinamide adenine dinucleotide phosphate-specific glutamate dehydrogenase (NADP-GDH), hypothetical protein 1 (GL50803_95880), hypothetical protein 2 (GL50803_87261) and a protein from Giardia canis virus. The α-11 giardin and EIF5A genes were transfected into the pBiFc-Vc-155 and pBiFc-Vn-173 plasmids using BiFC, and the recombinant plasmids pBiFc-Vc-155-α-11 and pBiFc-Vn-173-EIF5A were co-tranfected into MDA-MB-231 cells, which displayed green fluorescence under a microscope, indicating the interaction between α-11 giardin and EIF5A protein in cells. Conclusion The yeast two-hybrid cDNA library of the G. lambia C2 strain has been successfully constructed, and six potential protein interacting with α-11 giardin have been identified, including EIF5A that interacts with α-11 giardin in cells.

Diagnostic value of a combined serology-based model for minimal hepatic encephalopathy in patients with compensated cirrhosis / 中华检验医学杂志

Objective:To investigate the diagnostic accuracy of serological indicators and evaluate the diagnostic value of a new established combined serological model on identifying the minimal hepatic encephalopathy (MHE) in patients with compensated cirrhosis.Methods:This prospective multicenter study enrolled 263 compensated cirrhotic patients from 23 hospitals in 15 provinces, autonomous regions and municipalities of China between October 2021 and August 2022. Clinical data and laboratory test results were collected, and the model for end-stage liver disease (MELD) score was calculated. Ammonia level was corrected to the upper limit of normal (AMM-ULN) by the baseline blood ammonia measurements/upper limit of the normal reference value. MHE was diagnosed by combined abnormal number connection test-A and abnormal digit symbol test as suggested by Guidelines on the management of hepatic encephalopathy in cirrhosis. The patients were randomly divided (7∶3) into training set ( n=185) and validation set ( n=78) based on caret package of R language. Logistic regression was used to establish a combined model of MHE diagnosis. The diagnostic performance was evaluated by the area under the curve (AUC) of receiver operating characteristic curve, Hosmer-Lemeshow test and calibration curve. The internal verification was carried out by the Bootstrap method ( n=200). AUC comparisons were achieved using the Delong test. Results:In the training set, prevalence of MHE was 37.8% (70/185). There were statistically significant differences in AMM-ULN, albumin, platelet, alkaline phosphatase, international normalized ratio, MELD score and education between non-MHE group and MHE group (all P<0.05). Multivariate Logistic regression analysis showed that AMM-ULN [odds ratio ( OR)=1.78, 95% confidence interval ( CI) 1.05-3.14, P=0.038] and MELD score ( OR=1.11, 95% CI 1.04-1.20, P=0.002) were independent risk factors for MHE, and the AUC for predicting MHE were 0.663, 0.625, respectively. Compared with the use of blood AMM-ULN and MELD score alone, the AUC of the combined model of AMM-ULN, MELD score and education exhibited better predictive performance in determining the presence of MHE was 0.755, the specificity and sensitivity was 85.2% and 55.7%, respectively. Hosmer-Lemeshow test and calibration curve showed that the model had good calibration ( P=0.733). The AUC for internal validation of the combined model for diagnosing MHE was 0.752. In the validation set, the AUC of the combined model for diagnosing MHE was 0.794, and Hosmer-Lemeshow test showed good calibration ( P=0.841). Conclusion:Use of the combined model including AMM-ULN, MELD score and education could improve the predictive efficiency of MHE among patients with compensated cirrhosis.

Survey on status quo of psychosomatic medical service ability and training needs among general practice resident physicians / 中华全科医师杂志

Objective:To investigate the current status of psychosomatic medical service competence and training needs among general practice resident physicians.Methods:An online questionnaire survey was conducted from August to September 2021, among general practice resident physicians selected by cluster sampling from 4 affiliated hospitals of Tongji University. The questionnaire contained the basic information, the self-assessment and training needs of psychosomatic medical service competence of participants, and psychosomatic medical service requirements of patients in the community.Results:A total of 159 questionnaires were distributed, and 140 were collected (88.1%). The survey showed that 25.7% (36/140) of participants believed that 50% or more patients had physical symptoms accompanied by emotional problems; 29.3% (41/140) thought that 50% or more patients had sleep problems, but 60.0% (84/140) of them failed to provide appropriate treatment. The rate of "core knowledge and concepts of psychosomatic medicine" was 47.5% (665/1 400) and the correct rate of "common psychosomatic diseases" was (64.6±23.4)%. Merely 21.4% (30/140) participants reported satisfaction with the psychosomatic medical service competence; 62.8% (88/140) respondents believed that the coverage rate of the above-mentioned competence training in the current general practice residential training program was less than 50%, and 66.4% (93/140) supported that more psychosomatic training was "necessary". The acceptance rate of online training, workshops, MDT, and clinical practice ranged from 56.4% (79/140) to 63.4% (89/140).Conclusions:The survey indicates that there are large needs for psychosomatic medical services among patients in community, but the competence and confidence of general practice resident physicians to provide the service are significantly insufficient. Therefore, it is suggested to strengthen the training of psychosomatic medical service competence in the general practice residency training program.

Strategy of long-term anti-HBV treatment after liver transplantation for patients with HBV related liver disease / 中华普通外科杂志

Objective:To evaluate the risk of HBV recurrence after liver transplantation in patients with end-stage hepatitis B related liver disease, and to explore the indications for antiviral therapy withdrawal.Methods:The data of HBV DNA, cccDNA in liver puncture tissues and peripheral blood in 31 patients after liver transplantation was retrospectively analyzed.Results:Among the 31 patients, 15 (48%) had detectable and quantified HBV DNA in liver biopsy tissue, while their HBV related serological indicators were negative, suggesting an occult HBV infection in some patients. The study found 15 out of 19 cases who were taking Entecavir were cccDNA negative (78.9%), compared to 5 out of 12 cases (41.6%) in Lamivudine regiment ( P=0.03). Conclusions:Hidden HBV infection can be detected by amplifying cccDNA and HBV DNA in liver puncture tissue by using ddPCR. Entecavir is superior to lamivudine in the clearance of cccDNA.

Treatment of infected nonunion after internal fixation of subtrochanteric fracture with a reconstruction stent of external fixation / 中华创伤骨科杂志

Objective:To evaluate the treatment of infected nonunion after internal fixation of subtrochanteric fracture with a reconstruction stent of external fixation.Methods:A retrospective study was conducted to analyze the data of 5 male patients with infected nonunion after internal fixation of subtrochanteric fracture who had been treated and completely followed up at The Great Wall Orthopaedics and Hand Surgery Hospital from January 2017 to October 2022. The patients were (30.0±13.5) years old. Seinsheimer fracture types: ⅢA (1 case), ⅢB (1 case), Ⅳ (2 cases), and Ⅴ (1 case); original internal fixation: intramedullary system (4 cases) and plate fixation (1 case); the Cierny-Mader anatomical classification: type Ⅳ (diffuse type) for all. After complete debridement at stage one, 2 or 3 hydroxyapatite (HA) coated screws were placed at both fracture ends from the lateral side of the femur for unilateral reconstruction external fixation. Next, a hybrid external fixation scaffold was added with a 1/3 ring at the sagittal position and 1 or 2 HA screws in 4 cases while unilateral reconstruction external fixation was constructed at both sides by inserting 2 HA screws into both fracture ends from the anterior femur at the sagittal position in 1 case. Antibiotic bone cement was used to fill bone defects of (3.8±1.8) cm. At 6 to 8 weeks after debridement when infection did not recur, antibiotic bone cement was removed before autogenous iliac bone grafting was performed in 3 patients and osteotomy bone transport in 2 patients. Infection control, bone union time, time for removal of external fixation stent, complications, Sanders hip function score and Paley bone outcome score were recorded.Results:The 5 patients were followed up for (23.4±8.1) months after surgery. Infection at the fracture ends was controlled after 1 time of debridement in 3 patients and after 2 times of debridement in 2 patients. The loosening HA screws were replaced twice due to infection at the proximal nail tract, and autologous bone grafting was performed at the opposite fracture ends in 1 case; no complications occurred in the other 4 cases. Bony union was achieved at the extended segment and fracture ends in all patients. The time for imaging union after bone reconstruction was (10.2±3.4) months. The time for wearing a stent of external fixation was (18.0±4.5) months. There was no recurrent infection or lingering infection. According to the Sanders hip function score at the last follow-up, 4 cases were excellent and 1 case was good; according to the Paley bone outcome score, the curative effect was excellent in all.Conclusion:Application of a reconstruction stent of external fixation combined with antibiotic bone cement can control infection at the first stage and conduct bone reconstruction at the second stage to successfully treat the infected nonunion and preserve the hip function after internal fixation of subtrochanteric fracture.

Be alert to insidious fracture-related infections secondary to severe open fractures / 中华创伤骨科杂志

Objective:To report our experience in using the Ilizarov technique to treat bone defects secondary to Gustilo Ⅲb open tibial fractures with negative clinical signs and serological inflammatory markers.Methods:A retrospective study was performed to analyze the 19 patients with bone defects secondary to Gustilo Ⅲb open tibial fracture who had been treated at Department of Orthopaedics and Traumatology, Beijing Jishuitan Hospital between January of 2010 and June of 2021. They were 15 males and 4 females with an age of (41±11) years. Their inclusion criteria: undergoing treatment with Ilizarov technique (consecutive compression-distraction or bone transport), soft tissue coverage procedures resulting in wound closure and negative clinical infection signs for at least 3 months and normal serological inflammatory markers, and follow-up for more than 3 months after frame removal. Three-phase bone scan was performed for the patients before the present surgery. Debridement, sampling of deep tissues for bacterial culture, and external stabilization with a fixator were performed in the present surgery. Osteotomy for compression-distraction or bone transport technique was carried out at 1 stage or 2 stages. Systemic antibiotic therapy for 6 weeks was continued for those with positive microbiological analysis guided by antibiogram. Recorded were results of intra-operative pus detection around defects, microbiological findings, length of bone defect reconstructed, rate and time of infection recurrence during treatment, fracture union rate, bone healing index, bony and functional results.Results:The interval between primary injury to the present surgery was (10±8) months. The preoperative three-phase bone scan showed infection free in 8 cases, chronic osteomyelitis in 7 cases, and suspicious infection in 4 cases. No pus was found during intra-operative debridement in all. The intra-operative microbiological detection was positive in 1 sample in 1 patient (infection free indicated by bone scan), and in ≥2 samples in 3 patients (bone scan indicating non-infection, infection not excluded and osteomyelitis in 1 case each). The length of bone defect reconstructed was (8±3) cm. The follow-up after the present surgery was (37±15) months. Fracture union was achieved in all cases, with a bone healing index of (1.7±0.5) months/cm. Clinical infection signs were observed 1 (1, 1) month after the present surgery in 6 patients whose microbiological results were all negative. All the 6 patients ended up with no clinical recurrence after empirical use of systemic antibiotics in 5 and radical debridement in one. The bony results showed 16 excellent and 3 good cases while the functional results showed 10 excellent and 9 good cases.Conclusions:In treatment of bone defects secondary to Gustilo Ⅲb open tibial fractures with negative clinical signs and serological inflammatory markers, constant vigilance is needed against low-grade infection. Intra-operative multiple sampling of deep tissues with a standardized protocol and microbiological testing are extremely valuable for diagnosis of fracture-related infections.

Comparison of efficacy of modified single-incision and traditional double-incision for flexor hallucis longus tendon transfer in the treatment of Myerson type III chronic Achilles tendon ruptures in the middle-aged and elderly patients / 中华创伤杂志

Objective:To compare the efficacy of modified single-incision and traditional double-incision for flexor hallucis longus tendon transfer in the treatment of Myerson type III chronic Achilles tendon ruptures in the middle-aged and elderly patients.Methods:A retrospective cohort study was conducted to analyze the clinical data of 106 patients with Myerson type III chronic Achilles tendon ruptures admitted to Ningbo No.6 Hospital from January 2015 to May 2021, including 54 males and 52 females; aged 48-82 years [(67.2±8.4)years]. Flexor hallucis longus tendon transfer was assigned to 60 patients using modified single-incision (modified single-incision group) and to 46 patients using traditional double-incision (traditional double-incision group). The operation time, intraoperative blood loss as well as American foot and ankle society (AOFAS) ankle-hindfoot score, foot and ankle outcome score (FAOS), visual analogue score (VAS) before operation, at postoperative 12 months and at the last follow-up were compared between the two groups. Time to recover walking and self-care ability, and incidence of complications were compared as well.Results:All patients were followed up for 16-52 months [(37.4±9.5)months]. The operation time and intraoperative blood loss were (51.6±7.4)minutes and (16.6±3.9)ml in modified single-incision group compared to (72.8±7.5)minutes and (32.9±5.2)ml in traditional double-incision group (all P<0.01). There was no significant difference in the AOFAS ankle-hindfoot score, FAOS and VAS between the two groups before operation (all P>0.05). At postoperative 12 months and at the last follow-up, AOFAS ankle-hindfoot score and VAS were not significantly different between the two groups (all P>0.05), but FAOS in modified single-incision group [(112.6±3.0)points, (114.4±3.1)points] was improved significantly compared with traditional double-incision group [(110.8±4.1)points, (112.7±4.3)points] ( P<0.05 or 0.01). At postoperative 12 months and at the last follow-up, the AOFAS ankle-hindfoot score, FAOS and VAS in both groups were improved or decreased significantly compared with those before operation (all P<0.05). All patients recovered their pre-injury daily activities. The time to recover walking and self-care ability were (9.6±2.0)weeks and (12.7±1.7)weeks in modified single-incision group compared to (10.8±1.8)weeks and (13.7±1.9)weeks in traditional double-incision group (all P<0.01). In modified single-incision group, superficial incision infection ( n=1) was found and cured after oral antibiotics. In traditional double-incision group, superficial incision infection ( n=2), deep incision infection ( n=1), deep venous thrombosis ( n=1) and medial plantar nerve injury ( n=1) were found and cured after symptomatic internal medical therapy; claw toe deformity ( n=2) was found and relieved after wearing customized insoles and functional exercise. The incidence of complications was 1.7% (1/60) in modified single-incision group compared to 15.2% (7/46) in traditional double-incision group ( P<0.01). Conclusion:In contrast with traditional double-incision surgery, modified single-incision for flexor longus tendon transfer in the treatment of Myerson type III chronic Achilles tendon ruptures in the middle-aged and elderly patients has advantages such as shorter operation time, less intraoperative blood loss, better functional recovery, faster postoperative recovery and less complications.

Effectiveness on treatment of metacarpal avulsion fracture with Kirschner wire buckling combined with bone fixation / 中国修复重建外科杂志

OBJECTIVE@#To summarize the effectiveness of Kirschner wire buckling combined with bone fixation in the treatment of metacarpal avulsion fracture.@*METHODS@#The clinical data of 35 patients of metacarpal avulsion fracture admitted between March 2017 and June 2022 were retrospectively analyzed. There were 22 males and 13 females; the age ranged from 20 to 55 years, with an average of 31.6 years. There were 17 cases of the second metacarpal avulsion fracture, 6 cases of the fourth metacarpal avulsion fracture, and 12 cases of the fifth metacarpal avulsion fracture. The causes of injury included 21 cases of strangulation, 8 cases of sprain, and 6 cases of sports injury. X-ray film examination showed that the size of the avulsion fracture of metacarpal bone ranged from 0.30 cm×0.20 cm to 0.55 cm×0.45 cm. The total active motion (TAM) of the injured finger before operation was (154.00±17.38)°. The time from injury to operation was 3-10 days, with an average of 5.8 days. Follow-up regularly after operation, X-ray film and CT examination were performed to evaluate fracture healing and TAM of injured finger was measured. The finger function was evaluated by the trial standard of upper limb function evaluation of Hand Surgery Society of Chinese Medical Association.@*RESULTS@#All the incisions healed by first intention. All 35 patients were followed up 9-36 months, with an average of 28 months. All metacarpal avulsion fractures achieved bony healing, and the healing time was 4-6 weeks, with an average of 4.8 weeks. The metacarpophalangeal joint of the patient was stable, without stiffness, and the flexion and extension activities were good. At last follow-up, the TAM of the injured finger reached (261.88±6.23)°, which was significantly different from that before operation ( t=-35.351, P<0.001). The finger function was evaluated according to the trial standard of upper limb function evaluation of the Society of Hand Surgery of Chinese Medical Association, and 33 cases were excellent and 2 cases were good, with an excellent and good rate of 100%.@*CONCLUSION@#The treatment of metacarpal avulsion fracture with Kirschner wire buckling combined with bone fixation has the advantages of less trauma, firm fixation, and less interference to the soft tissue around metacarpophalangeal joints, which is a good alternative method for the metacarpal avulsion fracture.

Erratum: Author correction to "YPD-30, a prodrug of YPD-29B, is an oral small-molecule inhibitor targeting PD-L1 for the treatment of human cancer" Acta Pharmaceutica Sinica B 12 (2022) 2845-2858

[This corrects the article DOI: 10.1016/j.apsb.2022.02.031.].

Research advances on dihydrofolate reductase inhibitors in the treatment of tumors and bacterial infections / 药学学报

Dihydrofolate reductase (DHFR) is a well-known key target in the treatment of tumors, bacterial infections, and parasitic infections; and it plays a critical role in the biosynthesis of cellular DNA. DHFR inhibitors interfere with one-carbon metabolism by inhibiting substrate binding to DHFR, thereby inhibiting cell proliferation. Research on DHFR inhibitors has continued since the 1940s. To date, a variety of DHFR inhibitors have come into the market, primarily used for anti-tumor, antibacterial, antiparasitic, and anti-inflammatory therapy. This review summarizes the research progress of DHFR inhibitors with antitumor or antibacterial effects in recent years based on the classification of single-target and dual-target and looks forward to the opportunities and challenges faced by the work in this field.

Retrospective analysis of childcare center disinfection in some regions of Anhui Province during 2019-2022 / 中国学校卫生

Objective@#To understand the status of childcare center disinfection around the COVID-19 pandemic, the needs of professional technical support, so as to give advice for improvement measures.@*Methods@#Using multi stage stratified sampling method, one was selected from each area of northern and southern Anhui Province, with 3 counties/districts selected from each city. A total of 54, 58, 60 childcare institutions were selected. A questionnaire survey, as well as on site visits and data check were administered in these childcare centers in Anhui Province were implemented. Information regarding the three stage disinfection work from 2019 to 2022 and technical support needs were collected.@*Results@#A total of 54, 58, 60 childcare centers were investigated in 2019, 2020 and 2021-2022. Most of the childcare centers recorded disinfection work (96.3%, 96.6%, 98.3%), while few of them ( 26.4% , 26.3%, 58.3%) monitored disinfection factor intensity. The implementing rate of disinfection effect evaluation was 68.3% at the stage of normal prevention and control, the highest demand rate for professional technical support was guidance and training ( 95.0% ), and the highest demand rate for training content was disinfectant preparation method (81.7%). There were significant differences in the rate of disinfection tableware room allocation (A: 93.3%, B: 70.0%), and the rate of disinfection effect evaluation among different cities (A: 53.3%, B: 83.3%)( χ 2=6.24, 5.46, P <0.05).@*Conclusions@#From 2019 to 2022, childcare center disinfection has significantly improved, however, disinfection factor intensity monitoring and disinfection effect evaluation are neglected during the stage of normal prevention and control. The demand for professional technical institutions to provide disinfectant preparation method guidance and training is high.It is suggested to strengthen the monitoring and evaluation of disinfection and related technical guidance.

Path analysis on relationship among tested hearing thresholds, conscious hearing, and negative emotions in noise-exposed workers / 环境与职业医学

Background The correlation between noise exposure and negative emotions of noise-exposed workers has received increasing attention and related studies have been reported. However, there is a lack of research on the path and effect analysis of the relationship between noise exposure and negative emotions, which will contribute to a more comprehensive understanding of the health damage characteristics of noise in addition to hearing loss. Objective To explore the path and effects of cumulative noise exposure, tested hearing thresholds, and conscious hearing level of noise-exposed workers on negative emotions. Methods Using stratified random sampling, 312 noise-exposed workers from a machinery and equipment manufacturing enterprise were selected. Occupational history, negative emotions (including the feelings of stress, anxiety, and depression), and conscious hearing level of the workers were investigated using the Depression-Anxiety-Stress Scale (DASS-21) and a self-made questionnaire. The hearing threshold of the workers was measured by pure tone air conduction audiometry. Sound level meter was used to measure noise equivalent sound level at selected work sites. Individual cumulative noise exposure was estimated based on work site noise level and personal noise exposure history. Path analysis was used to analyze potential mediating effects of workers' hearing thresholds and conscious hearing levels on the relationship between noise exposure and negative emotions (including stress, anxiety, and depression). Results The positive rates of negative emotions among the 312 noise-exposed workers were 18.27% (57/312) for stress, 46.79% (146/312) for anxiety, and 28.53% (89/312) for depression; the cumulative noise exposure ranged from 101.0 to 136.1 dB(A)·d, with an average of 125.69 dB(A)·d. The distributions of tested hearing thresholds and conscious hearing levels among the workers exposed to noise were significantly inconsistent (P<0.001), with both unweighted and weighted Kappa values less than 0.4. The percentage of workers with conscious hearing levels higher than their hearing threshold levels was 16.0%, and the percentage of workers with conscious hearing levels lower than conscious hearing levels was 38.7%. The path analysis results showed that tested hearing thresholds had no mediating effect on the relationship between cumulative noise exposure and negative emotions. There was a partial mediating effect of conscious hearing level on the relationship between cumulative noise exposure and negative emotions, with a mediating effect value of 0.06 (95%CI: 0.03, 0.11) and a mediating effect ratio of 28.57%. Conclusion Conscious hearing plays a partial mediating role in the relationship between cumulative noise exposure and negative emotions of noise-exposed workers, while tested hearing thresholds do not.

Stilbene B10 induces apoptosis and tumor suppression in lymphoid Raji cells by BTK-mediated regulation of the KRAS/HDAC1/EP300/PEBP1 axis.

Lymphoma is a cancer of the lymphoid cells that originated in matured B or T cells. The bioactive natural compounds can efficiently treat this disease with lesser side effects. Thus, in this study, a natural stilbene B10 (3-methoxy 5-hydroxy stilbene) isolated from Cajanus cajan (Pigeon Pea) was screened for its anti-proliferative efficacy against 13 cancer cell lines. B10 showed a potential effect on the human lymphoma (Raji) cells. Cytotoxicity analysis of B10 has revealed IC50 concentrations in Raji cells at low doses (18 µM) than other cancer cell lines. The B10 could significantly cause dose and time-dependent inhibition in the proliferation of Raji cells triggering intrinsic apoptosis and S/G1 phase cellular arrest. There was an increased expression of phospho-γ-H2A.X and decreased expression of cyclin D1, causing DNA damage and cell cycle arrest, post- B10 treatments. The mitochondrial membrane potential (MMP) variations observed after B10 treatment led to changes in Bax/Bcl-2 ratio, cytochrome C release, and enhanced expression of cleaved caspase3, 9, PARP-1, and APAF-1. The B10 inhibited the proliferation of Raji cells by significantly downregulating the expression of KRAS, BTK, MDM2, P-JAK2, P-STAT3, PI3K, HDAC1/2, SIRT7, and EP300. The treatment upregulated the tumor suppressor genes PEBP1 and SAP18. Thus, the study could reveal the selective inhibitory effects of B10 on lymphoma, suggesting it as a probable innovative chemotherapeutic agent.

A prospective multicenter and real-world study on the diagnostic value of combination of number connection test-B and line tracing test in mild hepatic encephalopathy / 中华消化杂志

Objective:To investigate the diagnostic value of independent and combined subtests of the psychometric hepatic encephalopathy score (PHES) in mild hepatic encephalopathy(MHE) of patients with liver cirrhosis, so as to optimize the PHES.Methods:This was a prospective, multicenter and real-world study which was sponsored by the National Clinical Research Center of Infectious Diseases and the Portal Hypertension Consortium. Twenty-six hospitals from 13 provinces, autonomous regions and municipalities countrywide participated in this study, induding Tianjin Third Central Hospital, the Fourth People′s Hospital of Qinghai Province, the Second Affiliated Hospital of Baotou Medical College, the Third People′s Hospital of Taiyuan, the Fifth Medical Center of PLA General Hospital and so on. From October 2021 to February 2022, outpatients and hospitalized patients with liver cirrhosis and no obvious hepatic encephalopathy were consecutively enrolled. All patients received 5 PHES subjects in the same order: number connection test(NCT)-A, NCT-B, digit symbol test(DST), line tracing test(LTT) and serial dotting test(SDT), and the scores were calculated. The total score of PHES <-4 was taken as the cut-off value for diagnosing MHE. Compare the differences in each subtest between MHE group and non-MHE group. Receiver operating characteristic curve(ROC) and area under the curve(AUC) was performed to assess the diagnostic value of independent and combined subtests in MHE. Mann-Whitney U test and DeLong test were used for statistical analysis. Results:A total of 581 patients with liver cirrhosis were enrolled, 457 were diagnosed as MHE, and the incidence of MHE was 78.7%. The results of NCT-A, NCT-B, SDT, LTT, DST of MHE group were 60.00 s(47.01 s, 88.00 s), 90.45 s(69.32 s, 125.35 s), 74.00 s(57.65 s, 96.60 s), 74.72(60.00, 98.61) and 27.00(20.00, 36.00), respectively. Compared those of non-MHE group(34.00 s(29.15 s, 44.48 s), 50.00 s(40.98 s, 60.77 s), 50.00 s(41.07 s, 63.03 s), 46.23(38.55, 59.42) and 42.00(34.00, 50.75)), the differences were statistically significant( Z=12.37, 12.98, 9.83, 11.56, 10.66; all P<0.001). The AUC(95% confidence interval(95% CI)) of subtests of PHES NCT-B, NCT-A, LTT, DST and SDT alone in MHE diagnosis were 0.880(0.849 to 0.910), 0.862(0.828 to 0.896), 0.838(0.799 to 0.877), 0.812(0.772 to 0.851) and 0.788(0.743 to 0.832), respectively. The combination of 2 PHES subtests significantly increased the diagnostic efficacy. Among them the diagnostic efficacy of the combination of NCT-B and LTT was the best, the AUC(95% CI) was 0.924(0.902 to 0.947), the specificity was 91.9% and the sensitivity was 79.2%, which was better than a single PHES subtest (NCT-A, NCT-B, SDT, LTT and DST) and the combination of NCT-A and DST(AUC was 0.879, 95% CI0.847 to 0.910) which was recommended by guidelines on the management of hepatic encephalopathy in cirrhosis, the differences were statistically significant ( Z=3.78, 3.83, 5.57, 5.51, 5.38, 2.93; all P<0.01). Furthermore, compared between the combination of NCT-B and LTT and the combination of 3 subests of PHES, only the diagnostic efficacy of combination of NCT-B, LTT and SDT (AUC was 0.936, 95% CI 0.916 to 0.956) was better than that of the combination of NCT-B and LTT, the difference was statistically significant( Z=2.32, P=0.020). Conclusion:Based on the diagnostic efficacy and clinical feasibility of PHES subtests and their combinations, the combination of NCT-B and LTT is recommended for the diagnosis of MHE.

Diffusion-weighted imaging and fluid-attenuated inversion recovery mismatch guide intravenous thrombolysis in patients with ischemic stroke beyond a 4.5-h time window / 国际脑血管病杂志

Objective:To investigate the efficacy and safety of using diffusion-weighted imaging (DWI) and fluid-attenuated inversion recovery (FLAIR) mismatch to guide intravenous thrombolysis in patients with ischemic stroke beyond a 4.5-h time window.Methods:Patients with acute ischemic stroke received intravenous thrombolysis with alteplase in the Stroke Center of Hefei Second People's Hospital from July 2019 to June 2021 were retrospectively enrolled. According to the time of onset, they were divided into the time window group and the beyond time window group. The demographic and baseline clinical data of both groups were recorded and compared. The primary outcome measure was the clinical outcome assessed by the modified Rankin Scale (mRS) at 90 d after onset. 0-2 points were defined as good outcome, and >2 were defined as poor outcome. The secondary outcome measure was symptomatic intracranial hemorrhage (sICH). Multivariate logistic regression analysis was used to determine the independent risk factors for poor outcomes. Results:A total of 244 patients with acute ischemic stroke were enrollded, including 146 males (58.8%), aged 61.4±8.47 years. The median time from onset to thrombolysis was 142 min, and the median baseline National Institutes of Health Stroke Scale (NIHSS) score was 7. Thirty-six (14.8%) patients exceeded the 4.5 h time window, and 69 (28.3%) patients had poor outcomes. There were no significant differences in the good outcome rate (71.2% vs. 75.0%; χ2=0.224, P=0.636), any intracranial hemorrhage (9.6% vs. 13.9%; χ2=0.233, P=0.629) and the incidence of sICH (5.3% vs. 5.6%; χ2=0.000, P=1.000) between the time window group and the beyond time window group. Univariate analysis showed that the proportion of patients with atrial fibrillation or cardiogenic embolism and the baseline NIHSS score in the poor outcome group were significantly higher than those in the good outcome group (all P<0.05), while there was no statistical difference in the proportion of patients receiving intravenous thrombolysis beyond the time window. Multivariate logistic regression analysis showed that only the baseline NIHSS score was an independent risk factor for poor outcomes (odds ratio 1.681, 95% confidence interval 1.457-1.940; P<0.001). Conclusions:Compared with the patients who received intravenous thrombolysis within 4.5 h after onset, intravenous thrombolysis in patients with acute ischemic stroke beyond the 4.5 h time window guided by DWI-FLAIR mismatch results in similar clinical outcomes, and does not increase the incidence of intracranial hemorrhage.

Effect of gender difference on antigen induced Sjogren's syndrome model in mice / 中国药理学通报

Aim To study the effect of gender differences in C57BL / 6J mice on antigen induced Sjogren's syndrome(SS)model. Methods The submandibular gland protein of C57BL/6J female and male mice was extracted and mixed with the same amount of Freund's complete adjuvant(FCA)for the first three times, the antigen concentration was adjusted to 2.5 g·L-1, mixed with Freund's incomplete adjuvant(FIA)for the fourth time, and the same-sex mouse antigen was injected into the back of mice for a total of four times to induce the mouse SS model. The mouse SS model was induced by multi-point intradermal injection of antigen on the back of mice for four times,the body weight of female and male mice was measured every week, the general condition was observed, the saliva volume of mice was measured at the sixth week of modeling. After the mice were sacrificed, the pathological changes of submandibular gland and the changes of T and B lymphocyte subsets in spleen were detected, and the differences in SS model preparation between female and male mice were compared. Results The SS model of male and female mice was successfully established, and there was no significant difference in general condition, saliva volume, submandibular gland pathology, plasma cells and memory B cells between male and female SS mice. The success rate of SS model was 75% in female mice and 60% in male mice. Compared with normal mice of the same sex, the weight loss of female SS mice was earlier and more obvious than that of male SS mice; the submandibular gland index of male mice was significantly higher than that of female mice. Compared with normal mice of the same sex, the proportion of Th17 and Treg cells in spleen of female SS mice was more statistically significant than that of male SS mice. Conclusions The success rate of SS modeling in female mice is higher than that in male mice. Compared with male SS mice, female SS mice have more significant SS like manifestations and pathological manifestations, which can provide a reference basis for the selection of gender when establishing SS model.