Objective To summarize the clinical characteristics of children with drug-induced hypersensitivity syndrome(DIHS)complicated with herpesvirus reactivation,and to promote the early and accurate identification,diagnosis,and treatment of DIHS in children.Methods The medication history,clinical manifestations,treatment,and prognosis of 12 children confirmed DIHS complicated with herpesvirus reactivation in Guangzhou Women and Children's Medical Center between January 2018 and March 2023 were retrospectively analyzed.The changes in hematological parameters,inflammatory indexes,and hepatic and renal function within 5 d before the eruption,5 d,and 6-10 d after eruption were compared.Results Of the 12 patients,the male-to-female ratio was 5∶1,with a median age of 27(interquartile range 20.50-34.75)months.Two or more antibiotics were used at least two to six weeks before onset,with a combination of 3 or more antibiotics in 7 children,and a combined or sequential application of 2 antibiotics in 5 children.The antibiotics included cephalosporins(n=12),semisynthetic penicillins(n=5),vancomycin(n=4)and azithromycins(n=7).All 12 patients presented fever,rashes,and multiple organ involvement.The rashes were red maculopapules in the early stage and then gradually developed into massive fusion exceeding 50%of the whole body.Among them,seven children were accompanied by facial edema,and two had purplish-red facial rashes.11 children suffered from exfoliative dermatitis in the later stage.12 children presented obviously enlarged lymph nodes.Liver involvement was the most common(100%,simple increase of transaminase in four children,cholestasis in six children,and hepatic failure in two children),and lung involvement was found in nine children.Laboratory examination showed no significant increase in leukocytes or eosinophils within 5 d before the eruption,but low levels of atypical lymphocytes.After the eruption,leukocytes,eosinophils,and atypical lymphocytes increased progressively.Inflammatory indexes of hypersensitive C-reactive protein(CRP),procalcitonin(PCT)increased dramatically before and after the eruption.All the children received intravenous immunoglobulin(IVIG)and methylprednisolone,two children were given antiviral therapy,and nine children were treated with multiple plasma exchanges.After treatment,nine children were cured,one developed immune reconstitution syndrome,and two died of hepatic failure.Conclusions Antibiotics are common allergenic drugs for DIHS in children.Its clinical manifestations include fever and rashes,accompanied by multiple organ involvement,such as the liver and lung.When leukocytes,eosinophils,and atypical lymphocytes are progressively elevated after the eruption,DIHS should be highly suspected,herpesvirus activation should be monitored,medication history should be traced,and early active immunotherapy and antiviral therapy should be conducted if necessary.

Objective:To investigate the diagnostic value of cervical cell DNA ploidy analysis combined with negative costimulatory molecule B7 homolog 4 (B7-H4) and protein kinase Cδ (PKCδ) for cervical cancer.Methods:A total of 160 cervical cancer patients diagnosed and treated at Shijiazhuang People's Hospital from January 2018 to January 2022 were selected as the cervical cancer group. Meantime, 160 women who were screened for cervical cancer in our hospital during this period were selected as the control group. According to the examination results, they were divided into normal or inflammatory group ( n=52), low-grade cervical intraepithelial neoplasia (CIN) group ( n=68) and high-grade CIN group ( n=40). The automatic cell image analysis system was used to analyze the DNA ploidy of cervical cells. The levels of B7-H4 and PKCδ in serum were determined by enzyme-linked immunosorbent assay. Pearson method was used to analyze the correlation between serum B7-H4 and PKCδ; the diagnostic value of cervical cell DNA ploidy analysis combined with serum B7-H4 and PKCδ in cervical cancer was evaluated by the receiver operator characteristic (ROC) curve; multivariate logistic regression was used to analyze the risk factors of cervical cancer. Results:The numbers of DNA ploidy positive cases of cervical cells in normal or inflammatory group, low-grade CIN group, high-grade CIN group and cervical cancer group were 16 (30.8%), 27 (39.7%), 26 (65.0%) and 127 (79.4%), respectively, with a statistically significant difference ( H=55.86, P<0.001). Further pin-by-pair comparison showed that compared with normal or inflammatory groups, the proportion of DNA ploidy positive in high-grade CIN group and cervical cancer group were higher (both P<0.05). The proportion of DNA ploidy positive in cervical cancer group was higher than that in low-grade CIN group ( P<0.05). Serum B7-H4 levels in normal or inflammatory group, low-grade CIN group, high-grade CIN group and cervical cancer group were (57.21±10.21), (79.17±11.34), (92.73±15.36), (126.56±20.25) ng/ml, respectively, with a statistically significant difference ( F=285.45, P<0.001). Serum PKCδ levels were (89.34±18.29), (71.79±15.82), (53.39±11.84), (40.23±10.21) ng/ml, respectively, with a statistically significant difference ( F=216.28, P<0.001). Further pin-by-pair comparison showed that serum B7-H4 levels in normal or inflammatory groups, low-grade CIN group, high-grade CIN group and cervical cancer group increased in turn (all P<0.05). Serum PKCδ levels in normal or inflammatory groups, high-grade CIN group and cervical cancer group were decreased in turn (all P<0.05). Pearson correlation analysis showed that the serum B7-H4 and PKCδ levels in patients with cervical cancer were negatively correlated ( r=-0.47, P<0.001). ROC curve analysis showed that the area under the curve (AUC) of cervical cell DNA ploidy for cervical cancer diagnosis was 0.82 (95% CI: 0.78-0.86), and the sensitivity and specificity were 83.9% and 79.9%, respectively. The AUC of serum B7-H4 in the diagnosis of cervical cancer was 0.92 (95% CI: 0.89-0.95), the sensitivity and specificity were 95.7% and 76.1%, respectively, and the cutoff value was 111.12 ng/ml. The AUC of serum PKCδ for diagnosis of cervical cancer was 0.92 (95% CI: 0.89-0.95), the sensitivity and specificity were 85.6% and 88.9%, respectively, and the cut-off value was 54.83 ng/ml. The AUC of the combined diagnosis of cervical cancer was 0.99 (95% CI: 0.97-0.99), and the sensitivity and specificity were 98.3% and 75.9%, respectively. The AUC of the combined diagnosis of cervical cancer was higher than that of DNA ploidy ( Z=8.00, P<0.001), serum B7-H4 ( Z=4.34, P<0.001), and serum PKCδ ( Z=4.61, P<0.001) alone. Multivariate logistic regression analysis showed that high level of B7-H4 in serum ( OR=2.94, 95% CI: 1.78-4.84, P<0.001), low level of PKCδ ( OR=4.33, 95% CI: 1.88-10.00, P=0.001) and positive DNA ploidy in cervical cells ( OR=5.77, 95% CI: 2.38-13.99, P<0.001) were independent risk factors for cervical cancer. Conclusion:The positive proportion of DNA ploidy in cervical cells of patients with cervical cancer is increased, the serum B7-H4 level is increased, the PKCδ level is decreased, and cervical cell DNA ploidy analysis combined with serum B7-H4 and PKCδ has a high diagnostic value for cervical cancer.

【Objective】 To investigate the role of LIF/LIFR/STAT3 pathway in endometrial receptivity in rats with polycystic ovary syndrome (PCOS). 【Methods】 Forty 21-day-old SD female rats were divided into normal (control) group, model group, sham-operation group, and LIF group with 10 rats in each. The rat model of PCOS was constructed by subcutaneous injection of prasterone sodium sulfate at the back of the neck. The serum levels of testosterone (T), glucose and insulin in each group were detected. The morphological changes of the uterus in each group were observed by HE staining, and the morphological changes of endometrium were measured. Immunohistochemistry, Western blotting, and Real-time fluorescence quantitative PCR(qRT-PCR) were used to determine the protein expression and mRNA expression of LIF and STAT3 in rat endometrium. 【Results】 Compared with control group, the levels of integrin avb3, serum T, insulin and glucose in PCOS rats were significantly increased (P=0.000, P=0.000, P=0.001). Supplementation of exogenous LIF could significantly reduce the levels of integrin avb3, serum T, glucose and insulin in PCOS rats (P=0.000, P=0.002, P=0.003, P=0.007). HE results showed that exogenous LIF could reduce uterine cavity and glandular morphology in PCOS rats and increase the equivalent diameter (P=0.000, P=0.000) and area (P=0.000, P=0.000) of uterine glands and glandular cavity, the ratio of glandular interstitial area (P=0.000), and the average endometrial thickness (P=0.006), with statistically significant differences. Immunohistochemistry, Western blotting, and qRT-PCR results showed that the expression levels of LIF and p-STAT3 protein and mRNA in model group were significantly decreased compared with control group. Compared with model group, the protein and mRNA expressions of LIF and p-STAT3 in LIF group were significantly increased (P<0.05). 【Conclusion】 Exogenous LIF supplementation can improve endometrial receptivity in PCOS rats, and its mechanism is related to the LIF/LIFR/STAT3 pathway.

Objective To investigate the clinical and gene mutation features of sodium taurocholate cotransporting polypeptide (NTCP) deficiency. Methods A total of 10 children, aged < 18 years, who were diagnosed with NTCP deficiency in Guangzhou Women and Children's Medical Center from June 2020 to June 2021 were enrolled, and related data were analyzed, including general information (sex, age, body height, body weight, family history, and past history), clinical manifestation, disease outcome, laboratory examination (routine blood test, liver function, hepatotropic virus, and autoimmune hepatitis screening), and gene mutation. Results All 10 children had normal growth and development, among whom there were 8 boys and 2 girls, with an age of 3-37 months at the time of diagnosis. The etiology of children attending the hospital for the first time was prolonged jaundice (5/10, 50%), elevation of aminotransferases (2/10, 20%), abnormal physical examination results (2/10, 20%), and pneumonia (1/10, 10%). At the time of diagnosis, all children had a significant increase in serum total bile acid (TBA), 2 children had increases in alanine aminotransferase and aspartate aminotransferase, and 1 child had an increase in total bilirubin (TBil), mainly direct bilirubin (DBil) (DBil/TBil ratio > 50%). Second-generation gene sequencing showed that all 10 children had a homozygous mutation of the SLC10A1 gene, i.e., c.800C > T(p.Ser267Phe, chr14∶70245193). Conclusion Although NTCP deficiency often has no symptoms, some of the children may manifest as infant cholestasis in the early stage. The possibility of NTCP deficiency should be considered when there is persistent hypercholanemia and the changing trend of serum TBA is not consistent with that of other liver function parameters.

Objective To analyze the clinical courses and outcomes of COVID-19 cases and the influencing factors in Guangdong province and provide basis for the formulation or adjustment of medical care and epidemic control strategy for COVID-19. Methods We collected demographic data, medical histories, clinical courses and outcomes of 1 350 COVID-19 patients reported in Guangdong as of 4 March 2020 via epidemiological investigation and process tracking. Disease severity and clinical course characteristics of the patients and influencing factors of severe illness were analyzed in our study. Results Among 1 350 cases of COVID-19 cases in Guangdong, 72 (5.3%) and 1049 (77.7%) were mild and ordinary cases, 164 (12.1%) were severe cases, 58 (4.3%) were critical cases and 7 (0.5%) were fatal. The median duration of illness were 23 days ( P 25 - P 75 : 18-31 days) and the median length of hospitalization were 20 days ( P 25 - P 75 : 15-27 days). For severe cases, the median time of showing severe manifestations was on the 12th day after onset ( P 25 - P 75 : 9th to 15th days), and the median time of severe manifestation lasted for 8 days P 25 - P 75 : 4-14 days). Among 1 066 discharged/fetal cases, 36.4% (36/99) and 1.0% (1/99) of the mild cases developed to ordinary cases and severe cases respectively after admission; and 5.2% (50/968) and 0.6% (6/968) of the ordinary cases developed to severe cases, and critical cases respectively after admission. In severe cases, 11.4% developed to critical cases (10/88). The influencing factors for severe illness or worse included male (a HR =1.87, 95% CI : 1.43-2.46), older age (a HR =1.67, 95% CI : 1.51-1.85), seeking medical care on day 2-3 after onset (a HR =1.73, 95% CI : 1.20-2.50) pre-existing diabetes (a HR =1.75, 95% CI : 1.12-2.73) and hypertension (a HR =1.49, 95% CI : 1.06-2.09). Conclusions The course of illness and length of hospitalization of COVID-19 cases were generally long and associated with severity of disease clinical outcomes. The severe cases were mainly occurred in populations at high risk. In the epidemic period, classified management of COVID-19 cases should be promoted according to needs for control and prevention of isolation and treatment for the purpose of rational allocation of medical resources.

Objective:To analyze the viral nucleic acid and cytokines in 12 children with 2019-nCoV infection.Methods:Clinical and laboratory data of the children diagnosed with 2019-nCoV infection in Guangzhou Women and Children′s Medical Center from January to April 2020 were retrospectively analyzed. Throat and anal swabs were collected on alternate days for the detection of 2019-nCoV nucleic acid by fluorescence quantitative PCR. Flow cytometry was used to detect serum cytokines including IFN-γ, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-17A, IL-17F, IL-22, TNF-α and TNF-β during the early (both throat and anal swab tests were positive), the intermediate (throat swab test was negative, while anal swab test remained positive), and the convalescence (both throat and anal swab tests were negative) stages of infection.Results:A total of 12 children were enrolled in this study. The male-to-female ratio was 5∶1. The average age was (7.0±4.3) years. There were two asymptomatic, five mild and five common cases. No severe or critical cases were involved. Initially, throat and anal swab nucleic acid tests were simultaneously positive in nine children newly diagnosed in our hospital and the median time of viral shedding in throat swab was longer than that in throat swab [32 (4.5, 45.0) d vs 3 (2, 9) d, Z=11.0, P=0.010]. The median difference of viral shedding time between anal swab and pharyngeal swab was 25.5 (1.5, 42.8) d. The overall levels of serum cytokines IL-17A, IL -4 and IL-5 in different stages of the disease (early, intermediate and convalescence stage) were statistically different ( Z or F, P values were 8.33, 0.016; 5.36, 0.010 and 6.56, 0.004, respectively), and a significant increase was observed in the intermediate stage of infection. IL-17F, IL-2 and IL-22 were all increased during the infection, but there was no significant statistical difference among the three stages ( P>0.05). Conclusions:It was noted that intestinal viral shedding needed a longer time. Although the infectivity has not been determined, higher requirements have been put forward for disease prevention and control. Cytokines secreted by Th2 and Th17 cells were involved in the immune response in children with non-severe 2019-nCoV infection. Monitoring viral shedding and cytokine changes in pediatric patients would be conducive to disease assessment.

Objective:Analysis of clustering characteristics of coronavirus disease 2019 (COVID-19) in Guangdong Province.Methods:The COVID-19 cases in Guangdong Province onset from January 1 to February 29, 2020 were collected from Chinese information system for disease control and prevention and Emergency Public Reporting System. Obtain the epidemiological survey data of the cluster epidemic situation, and clarify the scale of cluster epidemic situation, the characteristics of the index cases, family and non-family subsequent cases. Calculate serial interval according to the onset time of the index cases and subsequent cases, secondary attack rate based on the close contacts tracking results, the characteristics of different cases in the clustered epidemic were compared.Results:A total of 283 cluster were collected, including 633 index cases, 239 subsequent cases. Families are mainly clustered, the total number involved in each cluster is in the range of 2-27, M( P25, P75) are 2.0 (2.0, 4.0). During January 15 to February 29, the secondary attack rate is 2.86% (239/8 363) in Guangdong Province, the family secondary attack rate was 4.84% (276/3 697), and the non-family secondary attack rate was 1.32% (61/4 632). According to the reporting trend of the number of cases in Guangdong Province, it can be divided into four stages, the rising stage, the high platform stage, the descending stage and the low level fluctuation period. The secondary attack rate of the four stages were 3.5% (140/3 987), 2.3% (55/2 399), 2.6% (37/1 435), 1.3% (7/542), respectively. The difference was statistically significant ( P=0.003). Conclusion:COVID-19 cluster mainly occurs in families in Guangdong Province. The scale of the clustered epidemic was small; the serial interval was short; and the overall secondary attack rate was low.

Objective:Analysis of clustering characteristics of coronavirus disease 2019 (COVID-19) in Guangdong Province.Methods:The COVID-19 cases in Guangdong Province onset from January 1 to February 29, 2020 were collected from Chinese information system for disease control and prevention and Emergency Public Reporting System. Obtain the epidemiological survey data of the cluster epidemic situation, and clarify the scale of cluster epidemic situation, the characteristics of the index cases, family and non-family subsequent cases. Calculate serial interval according to the onset time of the index cases and subsequent cases, secondary attack rate based on the close contacts tracking results, the characteristics of different cases in the clustered epidemic were compared.Results:A total of 283 cluster were collected, including 633 index cases, 239 subsequent cases. Families are mainly clustered, the total number involved in each cluster is in the range of 2-27, M( P25, P75) are 2.0 (2.0, 4.0). During January 15 to February 29, the secondary attack rate is 2.86% (239/8 363) in Guangdong Province, the family secondary attack rate was 4.84% (276/3 697), and the non-family secondary attack rate was 1.32% (61/4 632). According to the reporting trend of the number of cases in Guangdong Province, it can be divided into four stages, the rising stage, the high platform stage, the descending stage and the low level fluctuation period. The secondary attack rate of the four stages were 3.5% (140/3 987), 2.3% (55/2 399), 2.6% (37/1 435), 1.3% (7/542), respectively. The difference was statistically significant ( P=0.003). Conclusion:COVID-19 cluster mainly occurs in families in Guangdong Province. The scale of the clustered epidemic was small; the serial interval was short; and the overall secondary attack rate was low.

Objective: To investigate the clinical manifestations, diagnosis, and treatment of H1N1 influenza A-associated encephalopathy (IAE) in children. Methods: The clinical manifestations, laboratory tests, cranial magnetic resonance imaging (MRI), electroencephalography (EEG) examinations and treatments of seven children with H1N1 IAE hospitalized in Guangzhou Women and Children′s Medical Center from December 2018 to January 2019 were retrospectively analyzed. Results: Five of the seven children with H1N1 IAE were female. The age at admission was 4 years and 5 months (range 7 months-9 years). Neurological symptoms occurred simultaneously or early (0-3 days) after the flu-like symptom appeared. The main clinical manifestations of neurological symptoms were seizures (repeated seizures in five cases and status convulsion in two cases, including one case of unexpected fever and repeated seizures in a nine-year old girl) accompanied with altered consciousness (drowsiness in five cases and coma in two cases). Cranial MRI in three cases displayed multifocal lesions, mainly in the bilateral thalamus, brainstem and cerebellar hemisphere. MRI also showed reversible splenial lesion in the corpus callusumin in three cases. EEG tracings were characterized by diffuse slow wave activity in four cases, and status epilepticus was monitored in one case. All the 7 cases were treated with oral oseltamivir. Three cases were treated with pulsed methylprednisolone and intravenous immunoglobulin. One case was treated with intravenous immunoglobulin alone and all the patients received oral oseltamivir. All the patients survived, with three patients had minor neurological sequelae at discharge. Conclusions The main clinical manifestations of H1N1 IAE are seizures and altered consciousness. Cranial MRI combined with EEG is helpful for early diagnosis. Intravenous immunoglobulin and (or) methylprednisolone should be considered for severe cases.

OBJECTIVE： To investigate the effects of Lindera aggregate of stir-baking with vinegar-Aucklandia lappa on gastric emptying and gastrointestinal hormones in functional dyspepsia liver depression and qi stagnation （FDLDQS） model rats. METHODS： Totally 60 SD rats were randomly divided into blank group （n＝10） and modeling group （n＝50）； FDLDQS model was induced by chronic stress restraint or food deprivation or excessive fatigue in modeling group. After modeling， model rats were randomly divided into model group （normal saline）， L. aggregate of stir-baking with vinegar group （1.62 g/kg， calculated by crude drug）， A. lappa group （1.62 g/kg， calculated by crude drug）， L. aggregate of stir-baking with vinegar-A. lappa group （1 ∶ 1， m/m，1.62 g/kg， calculated by crude drug） and mosapride group （positive control， 1.35 mg/kg）， with 10 rats in each group. Administration groups were given relevant medicine intragastrically once a day； blank group and model group were given constant volume of normal saline intragastrically， for consecutive 14 d. 2 h after last medication， gastric emptying rate and small intestinal propulsion rate of rats in each group were measured by phenol red content method. After HE staining， the morphological changes of antrum tissue were observed under microscope. The contents of motilin （MTL）， gastrin （GAS） and cholecystokinin （CCK） in serum were determined by ELISA method. RESULTS： Compared with blank group， gastric emptying rate and small intestinal propulsion rate of rats were decreased significantly in model group （P＜0.01）； the serum contents of MTL and GAS were decreased significantly （P＜0.01）， while the content of CCK was increased significantly （P＜0.01）. No organic damage was found in all model groups. Compared with model group， L. aggregate stir-baking with vinegar group and A. lappa group， gastric emptying rate and small intestinal propulsion rate of rats were increased significantly in L. aggregate of stir-baking with vinegar-A. lappa group and mosapride group （P＜0.05 or P＜0.01）； serum contents of MTL and GAS were increased significantly （P＜0.01）， while the content of CCK was decreased significantly （P＜0.01）. CONCLUSIONS： L. aggregate of stir-baking with vinegar-A. lappa can accelerate gastric emptying and small intestinal propulsion rate of FDLDQS rats， increase serum contents of MTL and GAS but decrease the content of CCK； its effects are better than that of them alone.