Acute pancreatitis （AP） is a common clinical acute abdominal disease， which is characterized by acute onset， rapid development， severe disease， many complications， and high mortality rate. It can progress to severe AP （SAP） if not treated promptly in the early stage. The pathogenesis of AP is complex and involves multiple cellular and molecular levels. It is now clear that oxidative stress and reactive oxygen species （ROS） production are involved in the physiopathological process of AP， which is associated with a low quantity and activity of antioxidant enzymes in pancreatic cells. Nuclear factor E₂-related factor 2 （Nrf2） serves as the ''golden key'' to maintain redox homeostasis in tissue cells and constitutes an important signaling pathway for antioxidant response and inflammation in vivo by collaborating with downstream antioxidant enzymes such as heme oxygenase-1 （HO-1）. Traditional Chinese medicine has unique efficacy in treating diseases due to its multi-component， multi-target， multi-drug delivery， and multi-formulation characteristics. Based on the concept of synergy between traditional Chinese and Western medicine， traditional Chinese medicine is becoming a new craze in the treatment of AP. The level of oxidative stress and Nrf2/HO-1 signaling pathway in AP pancreatic tissue are in a dynamic change process， and the intervention of traditional Chinese medicine can clean ROS production， affect the inflammatory pathway， and reduce oxidative stress damage， so as to protect against pancreatic injury. This suggests that this pathway plays an important role in AP. This article reviews the recent literature on the regulation of the Nrf2/HO-1 signaling pathway by traditional Chinese medicine for AP and summarizes that the monomers of traditional Chinese medicine targeting this pathway are mainly heat-clearing and detoxifying， blood-activating and blood-stasis-removing， and Qi benefiting and middle warming， and the compounds of traditional Chinese medicine include Yinchenhao Decoction and QingYi Ⅱ， so as to provide a new direction for the prevention and treatment of AP and further drug development.

OBJECTIVE To characterize paclitaxel nanoparticles （PTX-PLGA-NPs） and evaluate their in vitro inhibitory effect on Lewis lung cancer cells. METHODS The PTX-PLGA-NPs prepared by the emulsion-solvent evaporation method were characterized in terms of particle size， polydispersity index （PDI）， Zeta potential， microscopic morphology， encapsulation efficiency， drug loading， ultraviolet-visible absorption characteristics and stability. Using mouse Lewis lung cancer cells as the subjects and paclitaxel reference substance as the control， the cytotoxicity and in vitro killing activity of PTX-PLGA-NPs were detected using CCK-8 method and Calcein-AM/PI double staining method， respectively. The effects of PTX-PLGA-NPs on cell apoptosis and cell cycle were assessed by Annexin Ⅴ-FITC/PI staining method and PI staining method， respectively. RESULTS PTX-PLGA-NPs were spherical with an average particle size of （172.03±0.95） nm， PDI of 0.098±0.012， and Zeta potential of （－1.76±0.02） mV. The encapsulation efficiency and drug loading were （52.32±0.66）% and （7.07±0.18）%， respectively， and the ultraviolet-visible absorption characteristics were not affected by the carrier polylactic-co-glycolic acid. When stored in the dark at 4 °C for 7 days， no significant change was noted in particle size， and the average PDI （after 1， 2， 4 and 7 days of storage） was under 0.3. Compared with the paclitaxel reference substance group， the PTX-PLGA-NPs group had more cells in a state of death， the survival rate （at the PTX concentration of 11.2 μg/mL） was significantly decreased， and both the apoptosis rate and the proportion of G2 phase cells were significantly increased （P＜0.05）. CONCLUSIONS The prepared PTX-PLGA-NPs indicate homogeneity in particle size， uniform dispersion， stable properties， and stronger in vitro killing effect on lung cancer cells than PTX.

Objective:To analyze the clinical characteristics and influencing factors of vascular involvement in Beh?et′s Disease (BD) to improve and provideunderstanding of insights for clinicians to better understand this condition.Methods:Clinical data from 220 BD patients admitted to the First Affiliated Hospital of Guangxi Medical University from January 2012 to May 2022 were collected. Clinical manifestations and laboratory findings were compared between BD patients with and without vascular involvement, as well as between those with improved conditions and those with progressive conditions. Binary logistic regression was used to analyze the influencing factors.Results:①The average age of the 220 BD patients was 36.5±15.3 years. Among them, 23 patients (10.5%) had vascular involvement, including 20 males (87.0%).②Compared to BD patients without vascular involvement, those with vascular involvement had significantly higher rates of smoking [6.1%(12/197) vs.34.8%(8/23), χ2=17.19, P<0.001], cardiac involvement [1.5%(3/197) vs. 13.0%(9/23), χ2=6.42, P=0.011], and elevated C-reactive protein(CRP) levels (78.3% vs. 56.3%, χ2=4.08, P=0.043).③ Among BD patients with vascular involvement, 11 cases (47.8%) had venous lesions, and 20 cases (87.0%) had arterial lesions, with 8 cases (34.8%) having both venous and arterial involvement. The most common type of vascular involvement was arterial dilatation (11 cases), mainly aneurysms (10 cases), and deep venous thrombosis of the lower extremities (7 cases).④The 23 BD patients with vascular involvement were followed up for an average of 18.3 months. Among them, 16 patients (69.6%) showed stable improvement, while 7 patients (30.4%) experienced disease progression, including 4 deaths (1 male and 3 females). A total of 91.3% (21/23) of the patients received glucocorticoid therapy. Immunosuppressive therapy was administered to 82.6% (19/23) of the patients, with 65.2% (10/23) receiving with cyclophosphamide and 43.5% receiving with thalidomide. Additionally, 13% (3/23) of the patients were treated with cyclosporine and methotrexate, respectively, and 8.7% (2/23) were treated with received mycophenolate mofetil. Anticoagulant therapy was given to 21.7% (5/23) of the patients, using either warfarin or low molecular weight heparin. Biologic therapy was administered to 17.4% (4/23) of the patients, and surgical intervention was performed in 43.5% (10/23) of the patients. ⑤Binary logistic regression analysis identified male gender [ OR(95% CI)=5.70(1.60, 20.90), P=0.009] as an indepe-ndent risk factor for vascular involvement in BD. Conclusion:The incidence of vascular involvement in BD is 10.5%, with a higher prevalence in males. Arterial involvement is more common than venous involvement, with arterial aneurysms being the most common manifestation. Clinicians should pay attention to CRP and total cholesterol levels in BD patients.

Objective To enhance the understanding of the quality control of rubber closures and to promote pharmaceutical manufacturers'reasonable selection and effective management of rubber closures.Methods According to the performance needs of drug products for rubber closures,the impacts of the ingredients and manufacturing processes of rubber closures with other possible influence on drug products were analyzed.Complied with the requirements of pharmaceutical lifecycle management,the processes of selection and utilization of rubber closures were divided into three periods,including screening,validation and maintenance,and suggestions on the tasks and goals for these three periods were given.Results Though the actual performance of rubber closures was affected by multiple factors,the processability in the pharmaceutical manufacturing processes and the suitability in the periods of storage,transportation and clinical application could be confirmed by reasonable screening and scientific validation of rubber closures.And by the effective quality control of rubber closures,the suitability could be maintained across the lifecycle of drug products.Conclusion By means of the reasonable selection and effective quality control of rubber closures,it would be benefit for keeping drug safety,efficacy and quality controllability throughout the lifecycle.

Objective To establish methods for detection of water in rubber closures as one of the Chinese Pharmacopoeia series of standards for pharmaceutical packaging material.Methods The formulation process of determination of water in rubber closures was explained,the key contents of the standard were analyzed,and the determination results of water content by oven-drying method and Karl Fischer drying furnace-coulometric titration method were compared.Results The determination results of water content in multiple batches of rubber stopper samples by over-drying method were generally higher than that by Karl Fischer drying oven-Coulometric titration method.The latter method is highly specific and accurate,and can better reflect the true water content of rubber closures.Conclusion Two methods for determining water content in rubber closures have been developed.Enterprises can choose the appropriate method based on the intended use of their products and daily testing needs.

ObjectiveTo investigate the effect of Shouwuwan on the synaptic plasticity of hippocampal neurons in the rat model of D-galactose-induced aging via the mammalian target of rapamycin （mTOR） signaling pathway. MethodA total of 50 male SPF-grade SD rats were randomized into normal group， model group， vitamin E （0.018 g·kg^-1） group， and low- and high-dose （1.08，2.16 g·kg^-1， respectively） Shouwuwan groups. Except the normal group， the other four groups were treated with D-galactose （120 mg·kg^-1） for the modeling of aging. The rats were simultaneously administrated with corresponding agents by gavage. After six weeks of modeling， Morris water maze test was carried out to examine the behavioral changes. The whole brain and hippocampus samples were collected. The expression of postsynaptic density protein-95 （PSD-95） and synaptophysin （SYN） in the hippocampus was detected by immunohistochemistry. Golgi staining was employed to observe the changes in the morphology and function of neurons. Western blot and Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） were respectively employed to determine the mRNA and protein levels of mTOR， phosphorylated （p）-mTOR， p70 ribosome protein S6 kinase （p70S6K）， phosphorylated （p）-p70S6K， eukaryotic translation initiation factor 4E-binding protein 2 （4EBP2）， and phosphorylated （p）-4EBP2 in the hippocampus. ResultCompared with the normal group， the model group showed slow swimming （P<0.01）， extended total swimming distance （P<0.05）， prolonged latency （P<0.01）， and decreased crossing number （P<0.01）. The modeling inhibited the expression of PSD-95 and SYN in the CA1 region of the hippocampus （P<0.01）， with the weakest staining effect and the smallest region， decreased the intersections of hippocampal neuron dendrites with concentric circles at the concentric distance of 100， 140， 180， and 200 μm from the cell body （P<0.01）， and reduced the length and density of dendritic spine （P<0.01）. In addition， the modeling up-regulated the mRNA levels of mTOR and p70S6K and the protein levels of p-mTOR and p-p70S6K （P<0.01） and down-regulated the mRNA level of 4EBP2 and the protein levels of 4EBP2 and p-4EBP2 （P<0.01）. Compared with the model group， low- and high-dose Shouwuwan increased the average swimming speed （P<0.01）， shortened the latency （P<0.01）， increased the crossing number （P<0.01）， promoted the expression of PSD-95 and SYN in the hippocampal CA1 region （P<0.01）， increased the intersections between hippocampal neuronal dendrites and concentric circles at the concentric distance of 100， 140， 180，200 μm from the cell body （P<0.01）， and increased the number， length， and density of dendritic spine （P<0.01）. Furthermore， Shouwuwan down-regulated the protein levels of p-mTOR and p-p70S6K （P<0.01）， up-regulated the protein levels of 4EBP2 and p-4EBP2 （P<0.05，P<0.01）， down-regulated the mRNA levels of mTOR and p70S6K （P<0.01）， and up-regulated the mRNA level of 4EBP2 （P<0.01）. ConclusionShouwuwan can improve the learning and memory ability of rats exposed to D-galactose， promote the expression of proteins associated with synaptic plasticity， improve the morphology of neurons， repair neural function， reduce neuronal apoptosis， and inhibit mTOR signaling pathway to delay brain aging.

Objective: To perform an epidemiological survey of the first case with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in Pinghu City of Jiaxing City, Zhejiang Province on March 13, 2022, so as to provide insights into the management of coronavirus disease (COVID-19) epidemics. Methods: According to the requirements of the Protocol on Prevention and Control of COVID-19 (8th Edition), epidemiological investigations were performed among 39 cases with SARS-CoV-2 infections in Pinghu City from March 13 to 20, 2022. Cases' demographics, clinical symptoms, history of immunization and exposure were collected, and close contacts were identified. Pharyngeal swabs were sampled from infected cases for detection of SARS-CoV-2 nucleic acid and whole-genome sequencing, and the source of infection and transmission route were investigated. Results: The index case for this COVID-19 epidemic was an imported case from Shanghai Municipality, who infected 6 persons via aerosol transmission when playing in the badminton venue of Pinghu National Fitness Center on March 9; subsequently, one of these infected cases infected another 18 persons when playing in the badminton venue of Jiadian Village Resident's Fitness Center in Zhapu Township on March 12. Sixteen confirmed cases were reported, and all cases were mild; another 23 asymptomatic cases were diagnosed, with no death reported. This epidemic occurred from March 11 to 20, with 3 generations of spread and a median incubation period of 3 days. The SARS-CoV-2 infected cases had a median age of 33.5 (interquartile range, 12.0) years and included 36 cases with a history of COVID-19 vaccination. There were 16 cases with fever, cough, runny nose and sore throat, and 13 cases with imaging features of pneumonia. The effective reproductive number (Rt) of the COVID-19 epidemic was 7.73 at early stage, and was less than 1 since March 21. Whole-genome sequencing identified Omicron BA.2 variant among 33 cases, which had high homology with the index cases. Conclusion This epidemic was a cluster of COVID-19 caused by imported Omicron BA.2 variant infection from Shanghai Municipality, and the COVID-19 transmission was mainly caused by indoor aerosols.

Objective:To study the clinical characteristics of neonatal plesiomonas shigelloides (P. shigelloides) septicemia.Methods:The clinical data of a neonate with P.shigelloides septicemia admitted to the Department of Neonatology of our hospital were reviewed. Literature on this subject were searched in the following databases: CNKI, CQVIP database, Wanfang Database, SinoMed, PubMed and Web of Science (up to April 2022).The clinical characteristics of reported cases of neonatal P.shigelloides septicemia were analyzed.Results:Our patient was a full-term female neonate with symptoms of tachypnea, groaning, hypotension, septic shock and poor intestinal peristalsis. The cardiac and pulmonary ultrasound indicated pulmonary hypertension and right pleural effusion (empyema). The X-ray suggested pneumothorax. The blood culture showed P.shigelloides. Lumbar puncture and brain imaging showed no central nervous system involvement. After meropenem, penicillin and symptomatic treatment, the patient was cured and discharged without sequelae. In the literature review, 14 articles and 14 cases of neonatal P.shigelloides septicemia were found (a total of 15 cases including our case).All 15 cases had fever, 10 with convulsion/seizure, 8 had jaundice, 8 with respiratory distress/respiratory failure, 6 had feeding difficulty and 6 were irritable. Brain imaging features were hydrocephalus and panencephalitis. Antibiotics and symptomatic treatment were the main therapy. 8 cases died and 7 cases survived including 2 cases with neurological sequelae.Conclusions:Neonatal P.shigelloides septicemia has nonspecific manifestations, often involves multiple organs with significant neurological involvement and a high mortality rate.

OBJECTIVE: To develop a multiplex PCR method for a rapid detection of Y chromosome-specific sequences in patients with Turner syndrome. METHODS: Nine genes were selected from various regions of the Y chromosome for designing the primers, which included SRY, TBL1Y, TSPY on the short arm of the Y chromosome, DDX3Y, HSFY1, RPS4Y2 and CDY1 on the long arm of Y chromosome and SHOX in the short arm and SPRY3 in the long arm of the pseudoautosomal region (PAR) of X and Y chromosomes. A multiplex PCR method for the nine genes in Y chromosome was established and optimized. The sensitivity was tested by using different amounts of genomic DNA. A total of 36 patients with Turner syndrome and a patient with male dwarfism with karyotype of 46, X, +mar were examined by the multiplex PCR method for the existence of materials from the Y chromosome. RESULTS: The optimization results of the multiplex PCR reaction system (50 μL) showed that when the final concentration of upstream and downstream of each pair of primers was 0.1 μM, the multiplex PCR reaction of the 9 pairs of primers clearly amplified the target with the expected band size, and there was no non-specific amplification. The bands were clearly visible when the amount of genomic DNA in the multiple PCR reaction system was as low as 1 ng. By using the method, we have examined the 36 patients with Turner syndrome. One patient with Turner syndrome with karyotype of 45,X[40]/47XYY[21] amplified specific seven genes on Y chromosome, 35 patients with Turner syndrome amplified only two target genes SHOX and SPRY3, but not the other seven specific genes on the Y chromosome, which was in keeping with the clinical manifestations of such patients. CONCLUSION This study established a multiplex PCR reaction system with nine genes, which can quickly and accurately screen Y chromosome materials in patients with Turner syndrome. It has the advantages of low cost, simple operation, high specificity and rapid turn-around time, and can be used to detect Turner syndrome patients with Y chromosome material in time. The method has provided a diagnostic basis for preventive gonad resection to prevent malignant gonadal tumors.
Humans ; Male ; Turner Syndrome/genetics* ; Multiplex Polymerase Chain Reaction ; Y Chromosome ; Karyotyping ; DNA Primers ; DNA ; Chromosomes, Human, Y/genetics* ; Transducin/genetics* ; Minor Histocompatibility Antigens ; DEAD-box RNA Helicases/genetics*

ObjectiveTo investigate the effect of Shouwuwan on apoptosis of hippocampal neurons in D-galactose-induced aging rats through phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） pathway. MethodFifty male SD rats of SPF grade were randomly divided into normal group， model group， vitamin E group， and Shouwuwan medium- and high-dose groups. Except the normal group， the other four groups were given D-galactose （120 mg·kg^-1） to prepare aging model. Additionally， Shouwuwan was used to intervene in the Shouwuwan medium- and high-dose groups （1.08 and 2.16 g·kg^-1， respectively）， and vitamin E group （0.018 g·kg^-1） was given vitamin E by gavage. After 6 weeks of modeling， the whole brain and hippocampal tissue were taken and the morphological changes of hippocampal neurons were observed by Nissl staining. The apoptosis of hippocampal cells was detected by in situ end labeling ［TdT-mediated dUTP nick-end labeling （TUNEL）］. The protein expression levels of PI3K， phosphorylated （p）-PI3K， Akt， p-Akt， Caspase-3， forkhead box protein O3a （FoxO3a）， p-FoxO3a， B-cell lymphoma-2 （Bcl-2） and Bcl-2-associated X protein （Bax） were detected by Western blot. Real-time fluorescence quantitative PCR （Real-time PCR） was performed to determine the mRNA expression level of FoxO3a in hippocampus. ResultCompared with the conditions in the normal group， the apoptotic cells of hippocampal neurons in the model group were significantly increased， and the apoptosis index was elevated （P<0.01）. Nissl staining of the hippocampal CA1 region showed that hippocampal neurons were lost and sparse， and the number of Nissl bodies was reduced， with pyknosis and deep staining. The relative protein expression of p-PI3K， p-Akt， Caspase-3 and Bax， p-PI3K/PI3K ratio and p-Akt/Akt ratio were all increased （P<0.01）， while the relative protein expression of FoxO3a， p-FoxO3a and Bcl-2， and p-FoxO3a/FoxO3a ratio were decreased （P<0.01）. The mRNA expression of FoxO3a was lowered （P<0.01）. Compared with the conditions in the model group， after treatment with Shouwuwan， the apoptotic cells were markedly reduced， and the apoptosis index of each treatment group was decreased （P<0.01）. Nissl staining of the hippocampal CA1 region demonstrated that the loss of neurons in each treatment group was improved， and Nissl bodies were increased and densely arranged. There was no statistically significant difference in the relative protein expression of PI3K and Akt in each group. In Shouwuwan medium- and high-dose groups， the relative protein expression of p-PI3K， p-Akt， Caspase-3 and Bax， p-PI3K/PI3K ratio and p-Akt/Akt ratio were decreased， while the relative protein expression of FoxO3a andp-FoxO3a， and Bcl-2， and p-FoxO3a/FoxO3a ratio were increased （P<0.01）. The mRNA expression of FoxO3a was up-regulated （P<0.01）. ConclusionShouwuwan could improve the structure of hippocampal neurons， inhibit PI3K/Akt signal pathway， down-regulate Caspase-3 and Bax， activate FoxO3a， and up-regulate Bcl-2 and Bcl-2/Bax ratio， to reduce neuronal apoptosis.