ObjectiveTo investigate the mechanisms by which the combination of berberine （BBR） and baicalin （BAI） ameliorates type 2 diabetes mellitus （T2DM） due to internal accumulation of dampness-heat from the perspectives of gut microbiota and metabolomics. MethodsAntibiotics were used to induce pseudo-sterile mice. Thirty pseudo-sterile mice were randomized into a normal fecal microbiota transplantation group （n=10） and a T2DM （syndrome of internal accumulation of dampness-heat） fecal microbiota transplantation group （n=20）. The mice were then administrated with suspensions of fecal microbiota from healthy volunteers and a patient with T2DM due to internal accumulation of dampness-heat by gavage， respectively. Each mouse received 200 µL suspension every other day for a total of 15 times to reshape the gut microbiota. The T2DM model mice were then assigned into a model group （n=8） and a BBR-BAI group （n=11）. BBR was administrated at a dose of 200 mg·kg^-1， and BAI was administrated in a ratio of BBR-BAI 10∶1 based on preliminary research findings. The administration lasted for 8 consecutive weeks. Fasting blood glucose （FBG）， glycated hemoglobin （HbA1c）， insulin （INS）， triglycerides （TG）， total cholesterol （CHOL）， low-density lipoprotein cholesterol （LDL-C）， high-density lipoprotein cholesterol （HDL-C）， aspartate aminotransferase （AST）， and alanine aminotransferase （ALT） levels were measured to evaluate the effects of the BBR-BAI combination on glucose and lipid metabolism and liver function in T2DM mice. Hematoxylin-eosin staining was employed to observe pathological changes in the colon tissue. The expression of claudin-1， zonula occludens-1 （ZO-1）， and occludin in the colon tissue was determined by Western blot. Real-time quantitative polymerase chain reaction（Real-time PCR） was employed to assess the levels of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and interleukin-6 （IL-6） in the colon tissue. The fecal microbiota composition and differential metabolites were analyzed by 16S rRNA sequencing and ultra-high performance liquid chromatography-quadrupole-time of flight tandem mass spectrometry （UPLC-Q-TOF-MS）， respectively. ResultsThe BBR-BAI combination lowered the FBG， HbA1c， and INS levels （P<0.05， P<0.01） and alleviated insulin resistance （P<0.01） in T2DM mice. Additionally， BBR-BAI elevated the levels of ZO-1， occludin， and claudin-1 （P<0.05， P<0.01） and down-regulated the expression levels of TNF-α， IL-1β， and IL-6 in the colon （P<0.05， P<0.01）. The results of 16S rRNA sequencing showed that BBR-BAI increased the relative abundance of Ligilactobacillus， Phascolarctobacterium， and Akkermansia （P<0.05）， while significantly decreasing the relative abundance of Alistipes， Odoribacter， and Colidextribacter （P<0.05）. UPLC-Q-TOF-MS identified 28 differential metabolites， which were primarily involved in arachidonic acid metabolism and α-linolenic acid metabolism. ConclusionBBR-BAI can ameliorate T2DM due to internal accumulation of dampness-heat by modulating the relative abundance of various bacterial genera in the gut microbiota and the expression of fecal metabolites.

ObjectiveTo explore the effect of different drying conditions on the appearance and intrinsic quality indicators of Pinelliae Rhizoma for screening suitable drying conditions， so as to provide reference for its standardized production and quality evaluation. MethodsDifferent dried samples of Pinelliae Rhizoma were prepared by lime-assisted sweating method and intermittent drying method. Visual analysis was employed to measure the color brightness values（L^*） of the surface， cross-section and powder of the samples， texture analyzer was used to determine the hardness of the samples under different drying conditions. The total starch content was calculated by measuring the contents of amylose and amylopectin in the samples with ultraviolet-visible spectroscopy. High performance liquid chromatography（HPLC） was used to determine the contents of seven nucleoside components（uracil， hypoxanthine， uridine， inosine， guanosine， β-thymidine and adenosine） in the samples. Pearson correlation analysis was conducted to explore the correlation between the external characteristics and intrinsic indicators of the different dried samples. Principal component analysis（PCA） was used to comprehensively rank the data of various indicators， and partial least squares-discriminant analysis（PLS-DA） was used to screen differential components with variable importance in the projection（VIP） value>1. Furthermore， the difference between the optimal drying condition for Pinelliae Rhizoma and the traditional sun-drying method was explored by independent samples t-test. ResultsWith the increase of temperature， the color of the intermittently dried samples gradually deepened， while their hardness gradually decreased. Concurrently， the contents of extract， total starch， uridine and adenosine exhibited an upward trend， whereas the contents of uracil， hypoxanthine and inosine displayed a downward trajectory. Compared with the intermittent drying group， the content of extract in the samples subjected to lime-assisted sweating increased. With the increase of lime dose， the hardness and the total content of nucleoside components in the samples showed a downward trend， while the total starch content showed an upward trend. Correlation analysis showed that the comprehensive score of L^* was negatively correlated with the contents of uracil， hypoxanthine and inosine， and positively correlated with the contents of uridine， guanosine and adenosine. Hardness was negatively correlated with adenosine content， and positively correlated with the contents of inosine， uracil and hypoxanthine. Through comprehensive consideration and comprehensive score of principal components， the method of 5% lime-mixed sweating for 6 days emerged as the top-ranking approach. Except for the extract， the results of independent samples t-test showed that there was no significant difference between the 5% lime-mixed sweating for 6 days and the traditional sun-drying in terms of other content indicators. ConclusionThe whiteness and firmness of Pinelliae Rhizoma exhibit significant correlations with its chemical composition， while uridine， uracil， guanosine， adenosine and inosine are the key constituents responsible for the quality difference of Pinelliae Rhizoma under different drying conditions. The lime-assisted sweating method optimized in this study can be proposed as a viable alternative to the traditional sun-drying method. This method not only ensures the quality of the medicinal material but also effectively reduces the drying time and prevents mold contamination， which provides a valuable reference for the standardization of drying conditions and the establishment of quality evaluation criteria for Pinelliae Rhizoma.

Objective To explore the correlation between the incidence of foodborne diseases and meteorological factors in Jinan, and to provide targeted measures for the prevention and control of foodborne diseases. Methods Data from the reporting systems of two sentinel hospitals for active surveillance of foodborne diseases from 2013 to 2021 in Jinan were collected. The meteorological data in the same period in Jinan were also collected. The generalized additive model was used to explore the nonlinear relationship between meteorological factors and the incidence of foodborne diseases, and threshold function analysis was use to perform subsection regression. Results The incidence of foodborne diseases was positively correlated with daily average temperature (r_s=0.23), relative humidity (r_s=0.05), and daily average wind speed (r_s=0.01), and negatively correlated with daily average air pressure (r_s=-0.19). Based on the GAM results and segmented regression analysis of meteorological factors, it was found that when the daily average temperature was below or above the threshold of 24.63°C, for every 1°C increase in daily average temperature, the incidence of foodborne diseases correspondingly increased by 0.04% and 0.18%. When the daily average wind speed was above the threshold of 2.26 m/s, the incidence of foodborne diseases decreased by 0.36% for every 1 m/s increase in the daily average wind speed. Conclusion Nine years of observation and data analysis have shown that meteorological factors such as daily average temperature, relative humidity, air pressure, and wind speed are related to the incidence of foodborne diseases. These findings suggest that meteorological factors may be important factors leading to foodborne diseases, which provides an important scientific basis for formulating effective prevention and control measures.

Objective:To analyze the clinical features and diagnostic modalities of adult Meckel′s diverticulum.Methods:The clinical manifestations, diagnostic modalities, treatments and pathology of 40 adult patients with Meckel′s diverticulum admitted in Beijing Friendship Hospital, Capital Medical University from January 2013 to October 2023 were retrospectively analyzed.Results:There were 32 male cases (80.0%) and 8 female cases (20.0%) with male to female ratio of 4∶1 and a median age of 39 years. Patients with gastrointestinal bleeding, abdominal pain and asymptomatic patients accounted for 52.5% (21/40), 12.5%(5/40) and 35.0% (14/40), respectively. The average minimum hemoglobin was(67±14)g/L and 47.6% patients (10/21) received blood transfusion. The preoperative diagnostic rates of CT scan, angiography, Tc-99m pertechnetate scintigraphy and tagged red blood cell (TRBC) scan were 1/39, 0/7, 3/7 and 2/4, respectively. The diagnostic rates of capsule endoscopy and retrograde single balloon enteroscopy were 1/12 and 17/20 (85.0%). The distance between Meckel′s diverticulum and ileocecal valve was 20-170 cm. Histopathological examination revealed ectopic gastric mucosa and ectopic pancreatic tissue in 23.5% (7/34) and 5.9% (2/34) patients.Conclusions:Adult Meckel′s diverticulum is more common in male patients, often presenting with gastrointestinal bleeding as the initial symptom. Diagnosis is most commonly made through retrograde single balloon enteroscopy, and surgery is the recommended treatment method.

Objectives To explore the trend characteristics of foodborne diseases in Jinan City and apply the seasonal autoregressive integrated moving average model (SARIMA) for prediction. Methods The incidence data of foodborne diseases from two active monitoring sentinel hospitals in Jinan City from 2014 to 2020 were collected to establish a time series. The SARIMA model was used to fit the incidence situation. The numbers of cases in 2021 were compared with the predicted values to validate the model and evaluate the predictive effect. Results The SARIMA (2, 0, 1) (0, 1, 1)₁₂ model was established and fitted the time series of food borne diseases in Jinan well, with AIC=687.22. Using Ljung Box function, P=0.499 was obtained, indicating that the residual error belonged to the white noise series. The data in 2021 was used to test the model extrapolation effect, and the actual values fell within the 95% confidence interval of the predicted value. The model prediction effect was relatively ideal. Conclusion SARIMA (2, 0, 1) (0, 1, 1)₁₂ model can better fit the temporal change of foodborne diseases, and therefore can be used to fit and predict the monthly incidence of foodborne diseases.

OBJECTIVE To provide evidence for the safe clinical application of Trastuzumab for injection. METHODS Reports of adverse drug reaction （ADR） related to Trastuzumab for injection submitted in Beijing from June 2018 to May 2023 were collected. Statistical analyses were performed using SPSS 25.0 software. The gender and age of patients with ADRs， outcome， types of cancer， and the time of onset， severity， affected organs/systems of ADRs were included for analyses. The univariate Logistic regression analysis was conducted on patient fever and ADR prognosis. RESULTS A total of 195 patients with 318 instances of ADRs were included in the study. Women （87.69%） and patients aged 60-69 （33.85%） were more likely to experience ADRs. Breast cancer dominated （86.67%） in terms of cancer types； in terms of outcomes， most patients （67.69%） showed improvement， and some patients （27.69%） achieved full recovery. Overall， 68.72% of ADRs mainly occurred on the day of medication， and 95.38% of ADRs were of “moderate” severity. The most affected organs/systems were general diseases and various reactions at the administration site （40.57%）， with chills （18.87%） and fever （18.24%） being the most common. Univariate Logistic regression analysis showed that fever mostly occurred within 1 day of medication （OR＝5.63， 95%CI was 2.26-14.02， P＜ 0.001）. The time of onset of ADR greater than 1 day was a risk factor for poor ADR prognosis （OR＝20.08， 95%CI was 2.45- 164.43， P＝0.005）， mainly manifesting as bone marrow suppression and liver function abnormalities. Neutrophilia， cardiorespiratory arrest， and mixed liver damage were new ADRs not recorded in the drug’s instructions. CONCLUSION Women and patients aged ≥60 are high-risk groups for ADRs of Trastuzumab for injection. Chills and fever remain the most common ADRs of this drug， and these symptoms mostly occur within 1 day of medication， which have better prognoses. Close attention should be paid to the patient’s temperature changes on the day of drug infusion， with timely intervention. Regular monitoring of the patient’s hematological indicators is necessary to detect any bone marrow suppression and liver function abnormalities after medication.

ObjectiveTo investigate the mechanism of neferine（Nef） in promoting vascular regeneration against cerebral ischemia through modulation of mitochondrial calcium uniporter（MCU） ion channel. MethodTaking the area of subintestinal vessels in microvascular deficiency zebrafish as an index， the vascular regenerative efficacy of Nef was evaluated， and the median effective concentration（EC₅₀） was calculated. Rats were randomly divided into a sham operation group， a model group， a positive drug group（butylphthalide， 6 mg·kg^-1）， and Nef low， medium， and high dose groups（0.125， 0.625， 3.125 μg·kg^-1）. Except for the sham operation group， the middle cerebral artery occlusion（MCAO） model was established in other groups. After modeling， the groups were administered the corresponding dose of drugs by gavage， while the sham operation and model groups received equal volumes of saline， once a day for 7 consecutive days. Neurobehavioral scores were assessed for each group of rats， and the infarct rate of ischemic brain tissue was calculated by 2，3，5-triphenyltetrazolium chloride（TTC） staining. The regional cerebral blood flow（rCBF） of each group was measured using a speckle contrast imaging. Immunofluorescence and Western blot were conducted to detect the expression of vascular endothelial growth factor（VEGF）， platelet endothelial cell adhesion molecule-1（CD31）， and hypoxia-inducible factor-1α（HIF-1α） proteins in each group. Human umbilical vein endothelial cells（HUVECs） were divided into the normal group， model group， positive drug group（astragaloside Ⅳ， 10 μmol·L^-1）， and Nef group （32 nmol·L^-1）. In the verification of mitochondrial protection of Nef and its mechanism in promoting vascular regeneration， the spermine（MCU agonist） and Nef+spermine group were added. HUVECs model of oxygen-glucose deprivation（OGD） was established in all groups except the normal group， the cell viability was assessed using 3-（4，5-dimethylthiazol-2-yl）-2，5-diphenyltetrazolium bromide（MTT） assay， and cell migration ability was evaluated through scratch and tube formation assays. Fluorescent probes（Rhod-2 AM， Fluo-3 AM， JC-1， Calcein AM） and a cellular energy metabolism analyzer were used to analyze the mitochondrial protective effects of Nef. Molecular docking was performed to predict the binding ability of Nef with MCU and HIF-1α， and Western blot was used to detect the effects of Nef on the protein expressions of MCU， B-cell lymphoma-2 associated X protein（Bax）， Caspase-3 and HIF-1α in the OGD model HUVECs. ResultThe results of vascular regeneration in microvascular deficiency zebrafish showed that compared to the normal group， the area of subintestinal vessels in the model group significantly decreased（P<0.01）. Compared to the model group， different concentrations of Nef could significantly increase the area of subintestinal vessels（P<0.01）， with the maximum tolerated concentration of 10.24 μmol·L^-1 and the EC₅₀ of 0.23 μmol·L^-1. Anti-cerebral ischemia results on MCAO rats showed that compared to the sham operation group， the model group had a significant decrease in rCBF and a significant increase in infarct rate， while CD31 expression significantly decreased（P<0.01）， and VEGF and HIF-1α protein expressions significantly increased（P<0.05）. Compared to the model group， the treated groups showed significant increases in rCBF， significant reductions in infarct volume， and significant increases in CD31， VEGF， and HIF-1α protein expression（P<0.01）. Cell experiment results showed that compared to the normal group， the model group had decreased cell viability and migration ability， increased intracellular Ca²⁺ and mitochondrial Ca²⁺ levels， reduced mitochondrial permeability transition pore（MPTP） opening， and decreased mitochondrial energy metabolism capability， with increased expressions of MCU， Bax， Caspase-3 and HIF-1α proteins（P<0.05， P<0.01）. Compared to the model group， the Nef group showed increased cell viability and migration ability， decreased intracellular Ca²⁺ and mitochondrial Ca²⁺ levels， increased MPTP opening， enhanced mitochondrial energy metabolism capability， decreased expressions of MCU， Bax and Caspase-3 proteins， and increased HIF-1α protein expression（P<0.05， P<0.01）. ConclusionNef can stabilize mitochondrial membrane potential and inhibit mitochondrial apoptosis. By down-regulating the expression of MCU， it suppresses the activation of intracellular Bax and Caspase-3 while activating the HIF-1α signaling pathway， enhancing the expression of VEGF and CD31， thereby promoting vascular regeneration to treat ischemic brain injury.

OBJECTIVE To prepare meloxicam solid dispersions tablets, and to investigate their dissolution in vitro. METHODS Crystal inhibition experiments were carried out to screen the carrier materials, and the solid dispersion was characterized by X-ray diffraction(XRD) amd differential scanning calorimeter(DCS). The improved bioavailability of solid dispersions was evaluated through in vivo pharmacokinetic studies. The optimum preparation process of meloxicam solid dispersion tablets was investigated, and the in vitro dissolution curve similarity factor f2 was used as the main evaluation index to screen and optimize the dosage of pH regulator, filler, disintegrator, lubricant, flow aid and the mixing time in the prescription. RESULTS The solid dispersion prepared with Kollidon@VA64 as carrier effectively maintained the supersaturated state of the drug in solution. The results of XRD and DSC showed that the crystal state of meloxicam in the solid dispersion was completely transformed into amorphous state. Compared with meloxicam, solid dispersions significantly increased the solubility, and its peak blood concentration(Cmax) and relative bioavailability were increased by 208.09% and 241.78%, respectively. The optimal formulation and process of meloxicam solid dispersion tablets prepared by direct powder pressing method were meloxicam solid dispersion 35.2%, lactose∶microcrystalline cellulose =1∶1.5, sodium citrate 9.8%, crosslinked povidone 8%, magnesium stearate 0.75%, silica 0.8%, and mixing time 5 min. The dissolution similarity factor f2 of the prepared meloxicam solid dispersion tablets and the original reference preparation in different pH medium was above 50. CONCLUSION Meloxicam solid dispersible tablets are prepared by hot melt extrusion and powder pressing method. The dissolution and bioavailability of meloxicam are improved, and the dissolution behavior of meloxicam is similar to that of the original reference preparation.

OBJECTIVE To analyze and evaluate serious adverse drug reaction(SADR) and drug-drug interactions(DDIs) in the real-world, so as to obtain the clinical evidence of DDIs-related SADR, and to provide a reference for rational clinical use. METHODS The SADR reports reported to the National Adverse Drug Reaction Monitoring Center from January 2011 to December 2020 were collected, and Lexi-Interaction® software in UpToDate was used to analyze ≥2 drugs in SADR to evaluate whether there were potential DDIs. And the possible adverse drug reactions caused by DDIs were statistically analyzed. RESULTS Among the 360 cases of SADR, males were slightly more than females(50.83% vs 49.17%), the mean age was (65.27±14.71) years old, and 56.39% were ≥65 years old. Cardiovascular agents were the most common implicated pharmacological group, and the gastrointestinal system was the most frequently affected system, and aspirin was the most frequently reported drug. Among 150 cases of SADR with at least two suspected drugs, 64 cases had potential DDIs, while 42 cases had clinically significant DDIs, of which only 16 and 2 cases of SADR were caused by actual DDIs in category D and X, respectively. The majority of reports(71.43%) were caused by additive pharmacodynamic interactions. Aspirin was the most common drug in both potential DDIs and actual DDIs, while aspirin and clopidogrel was the most commonly involved drug pair in actual DDIs, with gastrointestinal bleeding being the most common SADR. CONCLUSION Attention should be paid to the influence of drug interactions on SADR, and prescription should be optimized, especially in the elderly population. According to the results of potential DDIs, therapeutic drugs should be rationally selected. Meanwhile, monitoring of cardiovascular drugs and key populations should be strengthened to ensure drug safety.

Objective:To analyze the clinical and genetic characteristics of congenital hypogonadotropic hypogonadism (CHH) in boys.Methods:Cross-sectional study.Clinical data, laboratory data and genetic results of boys who were genetically diagnosed with CHH at the Department of Endocrinology of Shenzhen Children′s Hospital from December 2019 to February 2023 were collected in this retrospective study.Their clinical manifestations, hormone levels and gene mutations were analyzed.The non-normal distribution was represented by the median.The rank sum test was used to compare the non-normal distribution data between the two groups.Results:A total of 27 boys were genetically diagnosed with CHH, with the age at first diagnosis ranging from 0.3 to 16.6 years old.All these children presented with micropenis (100%), of whom 16 were complicated with cryptorchidism (59.3%), 9 with microrchidia (33.3%), 7 with simple micropenis (25.9%), and no had simple cryptorchidism.Three children had cardiovascular dysplasia.The median of basal luteinizing hormone(LH) level was 0.09 IU/L, and 92.5%(25/27) of children had the basal LH level below 1.00 IU/L.The median of peak LH level after gonadotropin-releasing hormone(GnRH) stimulation was 1.42 IU/L, and 96.2%(26/27) of children had the peak LH level below 4.00 IU/L.The median of serum inhibin B was 41.15 μg/L, and the median of serum anti-Müllerian hormone(AMH) was 12.62 mg/L.The serum AMH level of children with cryptorchidism was significantly lower than that of children without cryptorchidism (10.02 mg/L vs.50.50 mg/L, P<0.05). A total of 12 gene mutations were detected in the 27 children, of which 1 was biallelic mutation.The most common gene mutations were in CHD7 and ANOS1 genes (7 children each, both accounting for 51.8%), followed by FGFR1 gene (3 children, 11.1%). After short-term treatment by GnRH pump or subcutaneous injection of recombinant human follicle stimulating hormone in 4 children, the levels of serum inhibin B and AMH increased significantly, and the testicular volume also increased. Conclusions:CHH is a congenital disease with different clinical manifestations at different ages.The main manifestations in childhood are micropenis and cryptorchidism, and some children have microrchidia.Its diagnosis in prepuberty is difficult, but genetic testing is of great significance for early diagnosis.