Objective We aim to analyse semaglutide related adverse events in real-world,overall and by gender and age subgroups and compare the differences of different gender and age patients in adverse events,in order to supply references for security usage in the clinic.Methods OpenVigil 2.1 was used to search FDA Adverse Event Reporting System for semaglutide related adverse events from the establishment of the databases to April 2023.According to age and gender,patients were divided into 18-64 years old group and≥65 years old group,male group and female group.We selected ten adverse events which we interested(nausea,diarrhoea,vomiting,pancreatitis,cholecystitis,cholelithiasis,hypoglycaemia,diabetic retinopathy,acute kidney injury and thyroid cancer/medullary thyroid cancer)and analyzed overall and each group of semaglutide adverse events.Results A total of 5 330 cases and 15 558 adverse events were collected.2 935 patients aged 18-64 old group years with 8 553 adverse events;2 395 patients aged≥65 years old group with 7 005 adverse events.2 231 male group patients with 6 195 adverse events;3 059 female group patients with 9 277 adverse events.The sex of 40 patients was unknown.Nausea(1 089 cases/7.00％),vomiting(775 cases/4.98％)and diarrhoea(545 cases/3.50％)remained the most common adverse events.The constituent ratio of pancreatitis was significantly higher in patients aged 18-64 years old group than in patients aged 65 years old group(P＜0.05);the constituent ratio of diarrhoeaand cholelithiasis was significantly lower in patients aged 18-64 years old group than patients aged≥65 years old group(P＜0.05).The constituent ratio of diarrhoea,vomiting,pancreatitis,cholecystitis,cholelithiasis,diabetic retinopathy,and acute kidney injurywas significantly higher in male group patients than in female group(P＜0.05).Conclusion Nausea,diarrhoea and vomiting remined the most common adverse events of semaglutide.Male should be more concerned about gastrointestinal,pancreatitis,gallbladder events,retinopathy and acute kidney injury.Elderly patients should be more alert diarrhoea and cholelithiasis.

Objective:To investigate the effect of CD8+CD28-T cells on acute graft-versus-host disease(aGVHD)after haploidentical hematopoietic stem cell transplantation(haplo-HSCT).Methods:The relationship between absolute count of CD8+CD28-T cells and aGVHD in 60 patients with malignant hematological diseases was retrospectively analyzed after haplo-HSCT,and the differences in the incidence rate of chronic graft-versus host disease(cGVHD),infection and prognosis between different CD8+CD28-T absolute cells count groups were compared.Results:aGVHD occurred in 40 of 60 patients after haplo-HSCT,with an incidence rate of 66.67％.The median occurrence time of aGVHD was 32.5(20-100)days.At 30 days after the transplantation,the absolute count of CD8+CD28-T cells of aGVHD group was significantly lower than that of non-aGVHD group(P=0.03).Thus the absolute count of CD8+CD28-T cells at 30 days after transplantation can be used to predict the occurrence of aGVHD to some extent.At 30 days after transplantation,the incidence rate of aGVHD in the low cell count group(CD8+CD28-T cells absolute count＜0.06/μl)was significantly higher than that in the high cell count group(CD8+CD28-T cells absolute count ≥0.06/μl,P=0.011).Multivariate Cox regression analysis further confirmed that the absolute count of CD8+CD28-T cells at 30 days after transplantation was an independent risk factor for aGVHD,and the risk of aGVHD in the low cell count group was 2.222 times higher than that in the high cell count group(P=0.015).The incidence of cGVHD,fungal infection,EBV infection and CMV infection were not significantly different between the two groups with different CD8+CD28-T cells absolute count.The overall survival,non-recurrent mortality and relapse rates were not significantly different between different CD8+CD28-T cells absolute count groups.Conclusion:Patients with delayed CD8+CD28-T cells reconstitution after haplo-HSCT are more likely to develop aGVHD,and the absolute count of CD8+CD28-T cells can be used to predict the incidence of aGVHD to some extent.The absolute count of CD8+CD28-T cells after haplo-HSCT was not associated with cGVHD,fungal infection,EBV infection,and CMV infection,and was also not significantly associated with the prognosis after transplantation.

OBJECTIVE: This study explored whether thyroglobulin and thyroid disease prevalence rates were higher in pregnant Chinese women with a median urinary iodine concentration of 100-149 µg/L, compared with those with a median urinary iodine concentration of 150-249 μg/L maintained through sustainable universal salt iodization. METHODS: This was a cross-sectional study in which 812 healthy pregnant women were enrolled to collect samples of their household edible salt, urine, and blood during their routine antenatal care in the 18 counties in Fujian Province, China. The levels of salt iodine concentration, urinary iodine concentration (UIC), free triiodothyronine (FT3), free thyroid hormone (FT4), thyroid-stimulating hormone (TSH), thyroglobulin (Tg), thyroid peroxidase antibody and thyroglobulin antibody were assessed during the routine antenatal care visits. RESULTS: The median UIC (mUIC) in pregnant women was 130.8 μg/L (interquartile range = 91.5-198.1 μg/L) in the counties with an mUIC of 100-149 μg/L (Group I), and 172.0 μg/L (interquartile range = 123.5-244.4 μg/L) in the counties with an mUIC of 150-249 μg/L (Group II). Goiter prevalence and thyroid nodule detection rates showed no difference between Group I and Group II ( P > 0.05). Except for FT4 values, the TSH, FT4, FT3, Tg and Tg values > 40 (μg/L) and the thyroid diseases prevalence rate (TDR) showed no significant differences between Group I and Group II ( P > 0.05), whether or not iodine supplementation measures were taken. CONCLUSION Compared with an mUIC of 150-249 μg/L, not only there was no difference in thyroid morphology, but also the Tg value, rate of Tg values > 40 µg/L, and TDR were not higher in pregnant women in the counties with an mUIC of 100-149 μg/L achieved through sustainable universal salt iodization in Fujian Province, China.
Female ; Humans ; Pregnancy ; Cross-Sectional Studies ; Iodine/urine* ; Pregnant Women ; Sodium Chloride, Dietary ; Thyroglobulin ; Thyroid Gland ; Thyrotropin ; East Asian People

Dead heart is an important trait of pith-decayed Scutellariae Radix. The purpose of this study was to clarify the scientific connotation of the dead heart using multi-omics. Metabolomics and transcriptomics combined with multivariate statistical analysis such as principal component analysis(PCA) and partial least squares discriminant analysis(PLS-DA) were used to systematically compare the differences in chemical composition and gene expression among phloem, outer xylem and near-dead xylem of pith-decayed Scutella-riae Radix. The results revealed significant differences in the contents of flavonoid glycosides and aglycones among the three parts. Compared with phloem and outer xylem, near-dead xylem had markedly lowered content of flavonoid glycosides(including baicalin, norwogonin-7-O-β-D-glucuronide, oroxylin A-7-O-β-D-glucuronide, and wogonoside) while markedly increased content of aglycones(including 3,5,7,2',6'-pentahydroxy dihydroflavone, baicalin, wogonin, and oroxylin A). The differentially expressed genes were mainly concentrated in KEGG pathways such as phenylpropanoid metabolism, flavonoid biosynthesis, ABC transporter, and plant MAPK signal transduction pathway. This study systematically elucidated the material basis of the dead heart of pith-decayed Scutellariae Radix with multiple growing years. Specifically, the content of flavonoid aglycones was significantly increased in the near-dead xylem, and the gene expression of metabolic pathways such as flavonoid glycoside hydrolysis, interxylary cork development and programmed apoptosis was significantly up-regulated. This study provided a theoretical basis for guiding the high-quality production of pith-decayed Scutellariae Radix.
Drugs, Chinese Herbal/chemistry* ; Scutellaria baicalensis/chemistry* ; Glucuronides ; Multiomics ; Flavonoids/chemistry*

Objective: To investigate the effects of human umbilical cord mesenchymal stem cells (hUCMSCs) combined with autologous Meek microskin transplantation on patients with extensive burns. Methods: The prospective self-controlled study was conducted. From May 2019 to June 2022, 16 patients with extensive burns admitted to the 990^th Hospital of PLA Joint Logistics Support Force met the inclusion criteria, while 3 patients were excluded according to the exclusion criteria, and 13 patients were finally selected, including 10 males and 3 females, aged 24-61 (42±13) years. A total of 20 trial areas (40 wounds, with area of 10 cm×10 cm in each wound) were selected. Two adjacent wounds in each trial area were divided into hUCMSC+gel group applied with hyaluronic acid gel containing hUCMSCs and gel only group applied with hyaluronic acid gel only according to the random number table, with 20 wounds in each group. Afterwards the wounds in two groups were transplanted with autologous Meek microskin grafts with an extension ratio of 1∶6. In 2, 3, and 4 weeks post operation, the wound healing was observed, the wound healing rate was calculated, and the wound healing time was recorded. The specimen of wound secretion was collected for microorganism culture if there was purulent secretion on the wound post operation. In 3, 6, and 12 months post operation, the scar hyperplasia in wound was assessed using the Vancouver scar scale (VSS). In 3 months post operation, the wound tissue was collected for hematoxylin-eosin (HE) staining to observe the morphological changes and for immunohistochemical staining to observe the positive expressions of Ki67 and vimentin and to count the number of positive cells. Data were statistically analyzed with paired samples t test and Bonferronni correction. Results: In 2, 3, and 4 weeks post operation, the wound healing rates in hUCMSC+gel group were (80±11)%, (84±12)%, and (92±9)%, respectively, which were significantly higher than (67±18)%, (74±21)%, and (84±16)% in gel only group (with t values of 4.01, 3.52, and 3.66, respectively, P<0.05). The wound healing time in hUCMSC+gel group was (31±11) d, which was significantly shorter than (36±13) d in gel only group (t=-3.68, P<0.05). The microbiological culture of the postoperative wound secretion specimens from the adjacent wounds in 2 groups was identical, with negative results in 4 trial areas and positive results in 16 trial areas. In 3, 6, and 12 months post operation, the VSS scores of wounds in gel only group were 7.8±1.9, 6.7±2.1, and 5.4±1.6, which were significantly higher than 6.8±1.8, 5.6±1.6, and 4.0±1.4 in hUCMSC+gel group, respectively (with t values of -4.79, -4.37, and -5.47, respectively, P<0.05). In 3 months post operation, HE staining showed an increase in epidermal layer thickness and epidermal crest in wound in hUCMSC+gel group compared with those in gel only group, and immunohistochemical staining showed a significant increase in the number of Ki67 positive cells in wound in hUCMSC+gel group compared with those in gel only group (t=4.39, P<0.05), with no statistically significant difference in the number of vimentin positive cells in wound between the 2 groups (P>0.05). Conclusions: The application of hyaluronic acid gel containing hUCMSCs to the wound is simple to perform and is therefore a preferable route. Topical application of hUCMSCs can promote healing of the autologous Meek microskin grafted area in patients with extensive burns, shorten wound healing time, and alleviate scar hyperplasia. The above effects may be related to the increased epidermal thickness and epidermal crest, and active cell proliferation.
Female ; Humans ; Male ; Burns/surgery* ; Cicatrix ; Eosine Yellowish-(YS) ; Hyaluronic Acid/therapeutic use* ; Hyperplasia ; Ki-67 Antigen ; Prospective Studies ; Umbilical Cord ; Vimentin ; Young Adult ; Adult ; Middle Aged

OBJECTIVE: To investigate whether Omicron BA.1 breakthrough infection after receiving the SARS-CoV-2 vaccine could create a strong immunity barrier. METHODS: Blood samples were collected at two different time points from 124 Omicron BA.1 breakthrough infected patients and 124 controls matched for age, gender, and vaccination profile. Live virus-neutralizing antibodies against five SARS-CoV-2 variants, including WT, Gamma, Beta, Delta, and Omicron BA.1, and T-lymphocyte lymphocyte counts in both groups were measured and statistically analyzed. RESULTS: The neutralizing antibody titers against five different variants of SARS-CoV-2 were significantly increased in the vaccinated population infected with the Omicron BA.1 variant at 3 months after infection, but mainly increased the antibody level against the WT strain, and the antibody against the Omicron strain was the lowest. The neutralizing antibody level decreased rapidly 6 months after infection. The T-lymphocyte cell counts of patients with mild and moderate disease recovered at 3 months and completely returned to the normal state at 6 months. CONCLUSION Omicron BA.1 breakthrough infection mainly evoked humoral immune memory in the original strain after vaccination and hardly produced neutralizing antibodies specific to Omicron BA.1. Neutralizing antibodies against the different strains declined rapidly and showed features similar to those of influenza. Thus, T-lymphocytes may play an important role in recovery.
Humans ; Antibodies, Neutralizing ; Prospective Studies ; SARS-CoV-2 ; Breakthrough Infections ; COVID-19 Vaccines ; COVID-19 ; T-Lymphocytes ; China/epidemiology* ; Antibodies, Viral

Objective:To analyze the clinical features and the effects of different treatments on 5-year overall survival (OS) rate and 5-year disease free survival (DFS) rate of stage 0-Ⅲ triple-negative breast cancer (TNBC).Methods:The data of 209 patients diagnosed as stage 0-Ⅲ TNBC in Ward 2 of Department of General Surgery of the Fifth Medical Center of PLA General Hospital from January 2004 to December 2013 were selected. The relationships between the clinical features, treatments and 5-year OS rate, 5-year DFS rate were retrospectively analyzed. Kaplan-Meier method was used to draw survival curves, and Cox proportional risk model was used for multivariate analysis.Results:Univariate analysis found that clinical stage and methods of surgery were associated with 5-year OS rate ( χ2=52.615, P<0.001; χ2=17.329, P=0.001) and 5-year DFS rate ( χ2=55.112, P<0.001; χ2=18.816, P<0.001). Multivariate analysis showed that clinical stage was an independent prognostic factor of DFS ( HR=3.637, 95% CI: 2.146-6.164, P<0.001) and OS ( HR=3.545, 95% CI: 2.091-6.009, P<0.001). For the TNBC patients without axillary lymph node metastasis ( n=118), the 5-year OS rates of patients with breast conservation surgery + sentinel lymph node biopsy, total breast resection + sentinel lymph node biopsy, modified radical mastectomy and breast conserving surgery + axillary lymph node dissection were 97.6%, 97.7%, 91.4%, 100% respectively, the 5-year DFS rates were 97.3%, 94.3%, 85.8%, 100% respectively, and there were no significant differences among the four groups ( χ2=3.369, P=0.338; χ2=3.868, P=0.276). The 5-year OS rate (74.5% vs. 91.1%) and 5-year DFS rate (73.6% vs. 86.8%) were significantly different in patients receiving neoadjuvant chemotherapy ( n=106) compared with those receiving adjuvant chemotherapy ( n=80) ( χ2=4.504, P=0.034; χ2=4.683, P=0.030). The patients receiving neoadjuvant chemotherapy had later clinical stages than those receiving adjuvant chemotherapy ( χ2=35.314, P<0.001). There were no significant differences in 5-year OS rate and 5-year DFS rate between the patients receiving neoadjuvant chemotherapy and adjuvant chemotherapy with the same clinical stage (all P>0.05). The 5-year OS rates of patients with pathologic complete response (pCR), partial response (PR) and stable disease (SD) obtained by neoadjuvant chemotherapy were 100%, 75.8% and 57.1% respectively, and the 5-year DFS rates were 100%, 74.5% and 55.7% respectively, with statistically significant differences ( χ2=10.086, P=0.006; χ2=10.399, P=0.006). Between the pCR group and the PR group, the 5-year OS rate ( χ2=4.238, P=0.040) and 5-year DFS rate ( χ2=4.525, P=0.033) were significantly different. Between the pCR group and the SD group, the 5-year OS rate ( χ2=8.163, P=0.004) and 5-year DFS rate ( χ2=8.509, P=0.004) were significantly different. Between the PR group and the SD group, the 5-year OS rate ( χ2=3.931, P=0.047) and 5-year DFS rate ( χ2=3.896, P=0.048) were significantly different. Conclusion:For the patients with stage 0-Ⅲ TNBC, clinical stage is an independent prognostic factor. For the TNBC patients without axillary lymph node metastasis, breast conservation surgery + sentinel lymph node biopsy, total breast resection + sentinel lymph node biopsy, modified radical mastectomy and breast conserving surgery + axillary lymph node dissection have similar outcomes. There is no significant difference between neoadjuvant chemotherapy and adjuvant chemotherapy in the prognosis of patients with the same clinical stage, but patients with pCR or PR obtained by neoadjuvant chemotherapy can achieve better survival.

Nonalcoholic fatty liver disease (NAFLD) is characterized by hepatic steatosis and insulin resistance and there are currently no approved drugs for its treatment. Hyperactivation of mTOR complex 1 (mTORC1) and subsequent impairment of the transcription factor EB (TFEB)-mediated autophagy-lysosomal pathway (ALP) are implicated in the development of NAFLD. Accordingly, agents that augment hepatic TFEB transcriptional activity may have therapeutic potential against NAFLD. The objective of this study was to investigate the effects of nuciferine, a major active component from lotus leaf, on NAFLD and its underlying mechanism of action. Here we show that nuciferine activated ALP and alleviated steatosis, insulin resistance in the livers of NAFLD mice and palmitic acid-challenged hepatocytes in a TFEB-dependent manner. Mechanistic investigation revealed that nuciferine interacts with the Ragulator subunit hepatitis B X-interacting protein and impairs the interaction of the Ragulator complex with Rag GTPases, thereby suppressing lysosomal localization and activity of mTORC1, which activates TFEB-mediated ALP and further ameliorates hepatic steatosis and insulin resistance. Our present results indicate that nuciferine may be a potential agent for treating NAFLD and that regulation of the mTORC1-TFEB-ALP axis could represent a novel pharmacological strategy to combat NAFLD.

Objective To investigate the relationship between changes in protein tyrosine kinase 7 (PTK7) and receptor tyrosine kinase-like orphan receptor 2 ( ROR2) expression in the brainstem and the pathogenesis of amyotrophic lateral sclerosis (ALS). Methods Forty-four human superoxide dismutase 1( hSODl)-G93A mutant ALS transgenic mice were selected, and an equal number of wild-type littermates was used as control. The brainstems were isolated at da)' 70, day 95, day 108 and da)' 122 after birth, and the morphology of frypoglossal nucleus (12N) and nucleus of facial nerve(7N) neurons in the brainstem of the model mice were observed by Nissl staining. The mRNA and protein expression of PTK7 and ROR2 were detected by RT-PCR and Western blotting respectively, and the cellular localization and distribution of PTK7 and ROR2 in 12N and 7N were observed by immunofluorescence double-labeling technique. Results The result of Nissl staining showed that Nissl bodies in the neurons reduced distinctly with vacuolar degeneration of neurons, cell body atrophy and nuclear volume reduction in the 12N and 7N brainstems of ALS transgenic mice. RT-PCR result indicated that ROR2 and PTK7 mRNA level in the brainstem of ALS transgenic mice were up-regulated at da)' 70, da)' 95, day 108 and day 122 compared with wild-type littermates. Western blotting result showed that PTK7 protein was up-regulated at day 70, day 95, day 108 and day 122, ROR2 protein was up-regulated at day 70, day 95, day 108, and down-regulated at day 122 in the brainstem of ALS transgenic mice compared with wild-type littermates. Immunofluorescence result showed that ROR2/neuronal nuclei (NeuN)and PTK7/NeuN double positive cells, ROR2/glial fibrillary acidic protein (GFAP) and PTK7/GFAP double positive cells were observed in the 12N and 7N of the brainstem of ALS transgenic mice and wild-type mice, suggesting that ROR2 and PTK7 were expressed both in neurons and astrocytes. Conclusion PTK7 and ROR2 are abnormally expressed in the brainstem of ALS transgenic mice, which is closely related to the pathogenesis of ALS.

In this paper， through consulting relevant records in materia medica， medical and prescription books， and combining with modern literature， the name， origin， producing area， collection and processing of Gentianae Macrophyllae Radix in famous classical formulas from The Catalogue of Ancient Famous Classical Formulas （The First Batch） was systematically sorted out and textual research was carried out， in order to provide a basis for the development of the famous classical formulas containing Gentianae macrophyllae Radix. After textual research， it was found that Gentianae Macrophyllae Radix was the rectification of name in the past dynasties. In addition， there were other names such as Qinjiao， Qingua and Qinzhua. Gentiana macrophylla， G. straminea， G. dahurica and G. siphonantha were the main origin of this herb in ancient literature. Among them， G. macrophylla is the mainstream. In the Southern and Northern dynasties， G. straminea and G. macrophylla produced in northern Sichuan were recommended as the best. In the early Tang dynasty， G. macrophylla from the Liupan Mountain area at the border of Shanxi and Gansu provinces was the mainstream. During the Northern Song dynasty， G. siphonantha from Linxia and Qilian Mountain of Gansu province and G. macrophylla from eastern Shaanxi province were two new producing areas. In the Ming and Qing dynasties， the abundant base and production areas of Gentianae Macrophyllae Radix were gradually formed. In the past dynasties， harvesting was carried out in spring and autumn， and stored mainly by aeration drying or shade drying treatment. The processing methods are mainly the raw products after the net selection， cutting and drying， in addition to the frying， processing with wine and milk. G. macrophylla is recommended as the first choice for the herbal medicine involved in the famous classical formulas. Among them， wild products produced in Gansu and Shaanxi are the best， and raw products are recommended to be used. At the same time， it is suggested that G. siphonantha should be added to the subsequent edition of Chinese Pharmacopoeia as one of origins of Gentianae Macrophyllae Radix.