Experimental Limits on Solar Reflected Dark Matter with a New Approach on Accelerated-Dark-Matter-Electron Analysis in Semiconductors.

Recently a dark matter-electron (DM-electron) paradigm has drawn much attention. Models beyond the standard halo model describing DM accelerated by high energy celestial bodies are under intense examination as well. In this Letter, a velocity components analysis (VCA) method dedicated to swift analysis of accelerated DM-electron interactions via semiconductor detectors is proposed and the first HPGe detector-based accelerated DM-electron analysis is realized. Utilizing the method, the first germanium based constraint on sub-GeV solar reflected DM-electron interaction is presented with the 205.4 kg·day dataset from the CDEX-10 experiment. In the heavy mediator scenario, our result excels in the mass range of 5-15 keV/c^{2}, achieving a 3 orders of magnitude improvement comparing with previous semiconductor experiments. In the light mediator scenario, the strongest laboratory constraint for DM lighter than 0.1 MeV/c^{2} is presented. The result proves the feasibility and demonstrates the vast potential of the VCA technique in future accelerated DM-electron analyses with semiconductor detectors.

[Epidemiological characteristics of diarrheagenic Escherichia coli infection in infectious diarrhea outpatients aged 15 years and older in Shanghai, 2014-2021].

Objective: To understand the epidemiological characteristics of diarrheagenic Escherichia (E. ) coli infection in infectious diarrhea outpatients aged 15 years and older in Shanghai and provide evidence for the development of disease control strategies. Methods: Based on multistage systematic sampling, diarrhea surveillance was conducted in 22 sentinel hospitals in Shanghai, the information about cases' demographic, clinical, and epidemiological characteristics were collected. Stool samples were collected for the detection and typing of diarrheagenic E. coli by local centers for disease control and prevention. The positive rate of diarrheagenic E. coli in different populations and seasons from 2014 to 2021 were analyzed. Statistical analysis was conducted by using χ2 test. Results: In 15 185 diarrhea cases, 8.05% (1 222/15 185) were positive for diarrheagenic E. coli. The positive rate was higher in men (8.74%, 684/7 824) than in women (7.31%, 538/7 361). The positive rate was highest in age group 15-29 years (9.14%, 335/3 665) and the annual positive rate was highest in 2021 (10.21%, 83/813), the differences were all significant (P<0.05). In the 1 264 strains of diarrheagenic E. coli analyzed through PCR, enterotoxingenic E. coli was the most frequently identified pathogen (50.24%, 635/1 264), followed by enteroadhesive E. coli (27.93%, 353/1 264), and enteropathogenic E. coli (21.36%, 270/1 264). The positive rate of diarrheagenic E. coli showed obvious seasonality with peak in summer (13.92%, 774/5 562) (χ2=495.73, P<0.001). Conclusions: Diarrheagenic E. coli has become a prominent pathogen in infectious diarrhea cases in Shanghai, the disease can occur all the year round with incidence peak during summer and autumn. Predominant subtypes included enterotoxingenic E. coli, enteroadhesive E. coli and enteropathogenic E. coli. Targeted prevention and control strategies are needed for diarrheagenic E. coli-induced infectious diarrhea in different age groups, seasons and for different types of infections.

[System analysis of the ecological distribution of bacteriophages in hospital wastewater].

Phage therapy is one of the most important tools for the treatment of infections with multi-drug resistant bacteria. Such phages are usually isolated from hospital effluents, however, no systematic study on the distribution of phages in hospital effluents has been conducted so far. The aim of this study was to isolate the corresponding phages of common pathogenic bacteria isolated in the clinic as hosts, so as to assess the ecological distribution of phages in hospital wastewater and to provide a reference for the isolation and application of phages of drug-resistant bacteria in the clinic. A cross-sectional study design was used in this study. The 125 pathogenic bacteria (belonging to 16 different strains) isolated from the clinical microbiology laboratory of Qilu Hospital of Shandong University from May to June 2023 were selected as the target strains, and the phages corresponding to these strains were isolated and purified from the hospital wastewater by using the double-layer plate sandwich method. At the same time, the distribution of pathogenic bacteria in the same batch of wastewater was analyzed with the help of mNGS sequencing technology, so as to preliminarily investigate the abundance correspondence between pathogenic bacteria and phages in wastewater. The results showed that a total of 56 phage strains were isolated from 125 clinical pathogens as hosts, corresponding to six pathogens, including Acinetobacter baumannii, Klebsiella pneumoniae, Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, and Stenotrophomonas maltophilia. All six pathogenic bacteria contained strains with different degrees of drug resistance, with a higher percentage of multi-drug resistant strains in A. baumannii, Escherichia coli and P. aeruginosa. The phage acquisition rates of these six pathogens were, in descending order, Escherichia coli (80%), Stenotrophomonas maltophilia (75%), Pseudomonas aeruginosa (70%), Klebsiella pneumoniae (66.67%), Acinetobacter baumannii (36.36%) and Staphylococcus aureus (12.5%). Preliminary mNGS sequencing results showed that the pathogenic bacteria with higher abundance in the batch of effluent were Enterococcus faecalis, Klebsiella pneumoniae, Escherichia coli, Enterococcus faecalis, Acinetobacter baumannii, Klebsiella aerogenes, Klebsiella michiganensis and Pseudomonas aeruginosa. In conclusion, phages of most common clinical Gram-negative pathogens were isolated from hospital wastewater with high isolation rates; however, phages of Gram-positive pathogens were isolated at lower rates, and only phages corresponding to Staphylococcus aureus were isolated in this study. The corresponding mNGS sequencing results showed that the distribution of Gram-negative pathogens in sewage may had a positive correlation with the ecological distribution of phages.

[5 cases of occupational heat illness].

Objective: Through the analysis of five cases of occupational heat illness caused by high temperature, we expounded the pathogenesis and summarized the clinical characteristics of heat cramp and heat exhaustion of the newly revised diagnostic criteria for occupational heat illness (GBZ41-2019), in order to prevent the occurrence of occupational heat illness to put forward controllable countermeasures. Methods: According to the occupational history, clinical diagnosis and treatment and the other relevant data submitted by five patients, the diagnosis process was analyzed and summarized. Results: Five patients developed symptoms from July to August in summer, belonging to high-temperature operation. They improved by timely treatment. The symptoms, signs and laboratory tests of the five patients were different, but they were diagnosed as occupational heat illness. Conclusion: Employers should pay attention to the high temperature protection and cooling work, and strengthen the labor protection. If patients with heat cramp and heat exhaustion were timely treated, they could basically recover. Occupational disease diagnosticians should seriously study the new diagnostic criteria of occupational disease and constantly improve their diagnostic ability.

[Characteristics and clinical analysis of MLH1 c.463dupC gene mutation in a Lynch syndrome family].

In this study, a case of Lynch syndrome (LS) family line with a novel mutation site in the MLH1 c.463dupC gene was reported and the clinical and pathogenic genetic features of this family were analyzed. A 40-year-old female patient with colon cancer diagnosed at the First Affiliated Hospital of Kunming Medical University on October 2, 2020 was retrospectively included. The clinical data of the family were collected and the family lineage was drawn. The family tumor history met the Amsterdam Criteria Ⅱ and the diagnostic criteria of LS in Chinese, which was a typical LS family lineage. A germline code-shift missense mutation c.463dupC in the MLH1 gene located in exon 6, a possible pathogenic variant, was detected by second-generation sequencing (NGS) in the patient. Subsequently, Sanger sequencing was performed on a total of 20 direct lineage members of the family of the MLH1 gene, 7 cases were found to harbor the mutation and included in the LS high-risk control. Follow-up to October 2023 showed that the patient had endometrial and cervical polyps, one case had colorectal cancer, and two cases had intestinal polyps, all were treated with early intervention and therapy; two cases did not show any clinical symptoms. This study is the first to report a new mutation site for the potentially pathogenic MLH1 c.463dupC, providing a rationale for the pathogenicity of the mutation and standardized health management for familial carriers.

[Analysis of parainfluenza virus infection in acute respiratory tract infection adult cases in Shanghai, 2015-2021].

Objective: To study the infection status and epidemiological characteristics of parainfluenza virus (PIV) in acute respiratory tract infection adult cases in Shanghai from 2015 to 2021, and to provide a scientific basis for preventing and controlling PIV. Methods: Acute respiratory tract infections were collected from 13 hospitals in Shanghai from 2015 to 2021. Relevant information was registered, and respiratory specimens were sampled to detect respiratory pathogens by multiplex PCR. Results: A total of 5 104 adult acute respiratory tract infection cases were included; the overall positive rate of the respiratory pathogens was 29.37% (1 499/5 104). The positive rate of PIV was 2.61% (133/5 104), compared with 2.32% (55/2 369) and 2.85% (78/2 735) in influenza-like cases (ILI) and severe acute respiratory infection (SARI) cases, respectively. Among them, PIV3 accounted for the highest proportion (62.41%, 83/133), followed by PIV1 (18.80%, 25/133), PIV2 (9.77%, 13/133), and PIV4 (9.02%, 12/133). The incidence of PIV-positive cases was mainly distributed in the first and second quarters, accounting for 62.41% (83/133). The difference in the incidence in each quarter was significant (χ2=24.78, P<0.001). Mixed infection accounted for 18.80% (25/133) of 133 PIV-positive cases, the mixed infection rates of ILI and SARI were 18.18% (10/55) and 19.23% (15/78), respectively, and the main mixed pathogen of PIV was coronavirus 229E. Conclusions: There are a certain proportion of PIV-positive acute respiratory tract infection cases in Shanghai. It is necessary to strengthen the etiological surveillance in acute respiratory tract infection cases, especially the mixed infection of PIV and other pathogens.

[Epidemic trends and predictive analysis of other infectious diarrhea in Jiangxi Province, 2017-2022].

Objective: To analyze epidemic trends of other infectious diarrhea in Jiangxi Province from 2017 to 2022, and explore the application of autoregressive integrated moving average (ARIMA) model in the prediction of the incidence of other infectious diarrhea in Jiangxi Province, providing reference for the prediction and prevention and control of other infectious diarrhea. Methods: To conduct a descriptive epidemiological analysis of other infectious diarrhea cases in Jiangxi Province from 2017 to 2022, and establish an ARIMA model to predict the number of other infectious diarrhea cases in 2023. Results: From 2017 to 2022, Jiangxi Province reported 204 842 cases of other infectious diarrhea. The annual average reported incidence rate was 74.32/100 000. The cases were reported in each age group with obvious seasonal characteristics of the main peak. There were two peak periods of incidence in winter and spring (from January to March) and in summer and autumn (from July to September) and the peak value was higher in winter and spring. All parameters of the model ARIMA (0,1,2)(2,1,0)12 and ARIMA (1,0,0)(2,1,0)12 were statistically significant (P<0.05), and the minimum values of Bayesian information criterion were 13.83 and 9.12, respectively. The residual series were all white noise (P>0.05); The predicted value of the model is in good agreement with the actual value, and the predicted trend is consistent with the actual trend. The model has a good prediction effect. Conclusions: The other infectious diarrhea occurred in 2017-2022 was still the first case of notifiable disease in Jiangxi Province. The prevention and control situation cannot be ignored. Disease monitoring and health education for families of children under 3 years of age and scattered children among key populations for prevention and control should be strengthened during the epidemic season. The ARIMA model can be used for short-term prediction and trend analysis of other infectious diarrhea outbreaks in Jiangxi Province.

[Changes in epidemic intensity of influenza during 2014-2020 in Shanghai].

Objective: To evaluate the performance of the influenza surveillance network and compare the epidemic intensity of influenza during 2014-2020 in Shanghai. Methods: Based on the weekly reports of influenza-like illness (ILI) and laboratory-confirmed influenza cases from January 1, 2014 to December 31, 2020. This study first evaluated the data reporting and specimen collection of ILI cases for each sentinel hospital, and then calculated the percentage of ILI (ILI%), the proportion of specimens tested positive for influenza, and the incidence of influenza among all ILI outpatient and emergency visits to measure the epidemic intensity of influenza. Finally, seasonal autoregressive integrated moving average (ARIMA) model was applied to quantify the changes in epidemic intensity of influenza in 2020. Results: The proportion of influenza surveillance sentinel hospitals with a score of less than 5 in the evaluation of ILI data reporting and samples collection were 9.68% and 21.05% in 2020 in Shanghai, respectively. ILI% was estimated to be 1.51% (95%CI: 1.50%-1.51%) and 2.31% (95%CI: 2.30%-2.32%), respectively for 2014-2019 and 2020; the proportion of specimens tested positive was 24.27% (95%CI: 24.02%- 24.51%) and 7.15% (95%CI: 6.78%-7.54%), respectively; and the incidence of influenza was 3.66‰ (95%CI: 3.62‰-3.70‰) and 1.65‰ (95%CI: 1.57‰-1.74‰), respectively. ARIMA model showed that ILI% was increased by 45.25% in 2020 in Shanghai, and the proportion of specimens tested positive and the incidence of influenza were reduced by 78.45% and 51.80%, respectively. Conclusions: In 2020, the performance of influenza surveillance system has changed, ILI% has increased, the proportion of specimens tested positive and the incidence of influenza has decreased in Shanghai. The change in the quality of influenza surveillance is also a potential factor affecting the epidemic intensity of influenza. In the future, the quality control of influenza surveillance network still needs to be further strengthened.

[Long term follow-up evaluation of combined surgery for congenital tibial pseudarthrosis in children].

Objective: To explore the long-term effect of combined surgery for the treatment of congenital tibial pseudarthrosis in children. Methods: The clinical data of 44 children with congenital tibial pseudarthrosis who underwent combined surgery (tibial pseudarthrosis tissue resection, intramedullary rod fixation, Ilizarov external fixator fixation, wrapped autologous iliac bone graft) from August 2007 to October 2011 at the Department of Pediatric Orthopedics, Hunan Children's Hospital were collected retrospectively. There were 33 males and 11 females. The age at the time of surgery was (3.7±2.2)years (range:0.6 to 12.4 years), including 25 cases under 3 years old and 19 cases above 3 years old.Among them, 37 cases were complicated with neurofibromatosis type 1.The operation status, postoperative complications and follow-up results were recorded. Results: The follow-up time after surgery was (10.9±0.7)years (range:10 to 11 years).Thirty-nine out of 44 patients (88.6%) achieved initial healing of tibial pseudarthrosis, with an average healing time of (4.3±1.1)months (range:3 to 10months).In the last follow-up, 36 cases (81.8%) had unequal tibial length, 20 cases (45.4%) had refractures, 18 cases (40.9%) had ankle valgus, 9 cases (20.4%) had proximal tibial valgus, and 11 cases (25.0%) had high arched feet.Nine cases (20.4%) developed distal tibial epiphyseal plate bridging.17 cases (38.6%) had abnormal tibial mechanical axis.Seven cases (15.9%) developed needle infection, and one case (2.3%) developed tibial osteomyelitis. 21 patients (47.7%) had excessive growth of the affected femur.Five patients (11.3%) had ankle stiffness, and 34 patients (77.2%) had intramedullary rod displacement that was not in the center of the tibial medullary cavity.Among them, 8 cases (18.1%) protruded the tibial bone cortex and underwent intramedullary rod removal.18 children have reached skeletal maturity, while 26 children have not been followed up until skeletal maturity. Conclusion: Combined surgery for the treatment of congenital pseudarthrosis of the tibia in children has a high initial healing rate, but complications such as unequal tibia length, refracture, and ankle valgus occur during long-term follow-up, requiring multiple surgical treatments.

[Clinical and neuroelectrophysiological characteristics of primary peripheral nerve hyperexcitability syndrome].

Objective: To investigate the clinical and neuroelectrophysiological characteristics of patients with primary peripheral nerve hyperexcitability syndrome (PNHS). Methods: The clinical data of 20 patients who were diagnosed with PNHS in Beijing Tiantan Hospital from April 2016 to January 2023 were retrospectively collected. All patients underwent neuroelectrophysiological examinations. Clinical and electrophysiological characteristics were compared between the antibody positive and antibody negative groups, according to serum and cerebrospinal fluid anti-contactin-associated protein-like 2 (CASPR2) and/or anti-leucine-rich glioma-inactivated protein 1 (LGI-1) antibodies. Results: There were 12 males and 8 females, with a mean age of (44.0±17.2) years and the disease course of [M (Q1, Q3)] 2.3 (1.1, 11.5) months. Motor symptoms included fasciculations, myokymia, muscle pain, cramps, and stiffness. These symptoms were commonly seen in the lower limbs (17 patients), followed by upper limbs (11 patients), face (11 patients) and trunk (9 patients). Nineteen (19/20) patients had sensory abnormalities and/or autonomic dysfunction, 13 patients had central nervous system involvement, and 5 patients had concomitant lung cancer or thymic lesions. The characteristic spontaneous potentials on needle electromyography (EMG) were myokymia potential (19 patients), fasciculation potential (12 patients), spastic potential (3 patients), neuromyotonic potential (1 patients), etc, which were commonly seen in the lower limb muscles, especially the gastrocnemius muscle(12 patients). After-discharge potential was found in 8 patients, and 7 were in the tibial nerve. Seven patients had positive serum anti-CASPR2 antibodies, and 3 of them had concomitant anti-LGI1 antibodies. And 1 patient had positive serum anti-LGI1 antibody alone. Compared with patients in the antibody negative group (n=12), the patients who had anti-VGKC complex antibodies (n=8) had a shorter course of disease [M (Q1, Q3): 1.8 (1, 2) months vs 9.5 (3.3, 20.3) months, P=0.012], higher incidence of after-discharge potential (6/8 vs 2/12, P=0.019). The immunotherapy regimen (multi-dru, single-drug, no immunotherapy: 6, 2, 0 patients) in antibody-positive patients was different from the antibody-negative group (3, 6, 3 patients, U=21.00, P=0.023). Conclusions: The symptoms of motor nerve hyperexcitation, characteristic EMG spontaneous potentials and after-discharge potentials in PNHS patients are most commonly seen in the lower limbs. Attention should be paid to concomitant sensory and autonomic nerve hyperexcitation. PNHS patients with positive serum anti-CASPR2 antibodies may require immunotherapy with multiple drugs.

Salvage camrelizumab for an intractable NK/T cell lymphoma patient with two instances of intestinal perforation: a case report and literature review.

BACKGROUND: The prognosis of natural killer/T cell lymphoma (NKTCL) with multifocal small intestine involvement complicated by intestinal perforation is extremely poor. There is no evidence-based treatment strategy for this intractable condition. CASE PRESENTATION: A 30-year-old male was admitted to our hospital in April 2017 and presented with recurrent fever for three months and multiple painless subcutaneous nodules in the abdominal wall. An excision biopsy of the subcutaneous nodules in the abdominal wall revealed NKTCL. The patient was diagnosed with stage IVB NKTCL with skin and multifocal small intestinal involvement according to the imaging results. The first intestinal perforation occurred due to tumor infiltration before the initial treatment. The second intestinal perforation occurred after receiving two cycles of chemotherapy with a modified SMILE regimen. The histone deacetylase inhibitor (HDACi) chidamide was administered as a single-agent therapy after recovery from the second intestinal perforation. Complete remission was achieved. Unfortunately, five months later, the patient was confirmed to have relapsed and received the salvage chemotherapy. The patient suffered from disease progression again after the fourth cycle of chemotherapy. At this point, from May 29, 2018, the patient started to receive injections of the anti-programmed death 1 (PD-1) antibody camrelizumab as a salvage treatment. Two months after the initial anti-PD-1 antibody camrelizumab injection, the response was partial remission. Disease progression was confirmed in March 2021, with a progression-free survival time of 34 months. CONCLUSIONS: NKTCL patients with multifocal small intestine involvement have a high risk of intestinal perforation. The possible etiologies of bowel perforation include tumor infiltration, tumor necrosis in response to therapy, and acute inflammation. The anti-PD-1 antibody camrelizumab may be a new candidate agent for treating this type of intractable NKTCL. Further observations are necessary to identify the efficacy and safety of new agents in the future.

[Clinical and genetic characteristics of 9 rare cases with coexistence of dual genetic diagnoses].

Objective: To analyze the clinical and genetic characteristics of pediatric patients with dual genetic diagnoses (DGD). Methods: Clinical and genetic data of pediatric patients with DGD from January 2021 to February 2022 in Peking University First Hospital were collected and analyzed retrospectively. Results: Among the 9 children, 6 were boys and 3 were girls. The age of last visit or follow-up was 5.0 (2.7,6.8) years. The main clinical manifestations included motor retardation, mental retardation, multiple malformations, and skeletal deformity. Cases 1-4 were all all boys, showed myopathic gait, poor running and jumping, and significantly increased level of serum creatine kinase. Disease-causing variations in Duchenne muscular dystrophy (DMD) gene were confirmed by genetic testing. The 4 children were diagnosed with DMD or Becker muscular dystrophy combined with a second genetic disease, including hypertrophic osteoarthropathy, spinal muscular atrophy, fragile X syndrome, and cerebral cavernous malformations type 3, respectively. Cases 5-9 were clinically and genetically diagnosed as COL9A1 gene-related multiple epiphyseal dysplasia type 6 combined with NF1 gene-related neurofibromatosis type 1, COL6A3 gene-related Bethlem myopathy with WNT1 gene-related osteogenesis imperfecta type XV, Turner syndrome (45, X0/46, XX chimera) with TH gene-related Segawa syndrome, Chromosome 22q11.2 microduplication syndrome with DYNC1H1 gene-related autosomal dominant lower extremity-predominant spinal muscular atrophy-1, and ANKRD11 gene-related KBG syndrome combined with IRF2BPL gene-related neurodevelopmental disorder with regression, abnormal movement, language loss and epilepsy. DMD was the most common, and there were 6 autosomal dominant diseases caused by de novo heterozygous pathogenic variations. Conclusions: Pediatric patients with coexistence of double genetic diagnoses show complex phenotypes. When the clinical manifestations and progression are not fully consistent with the diagnosed rare genetic disease, a second rare genetic disease should be considered, and autosomal dominant diseases caused by de novo heterozygous pathogenic variation should be paid attention to. Trio-based whole-exome sequencing combining a variety of molecular genetic tests would be helpful for precise diagnosis.

[Analysis of efficacy and safety of a new endoscopic anastomosis clip in the treatment of defects after endoscopic full-thickness resection].

Objective: To investigate the efficacy and safety of a new endoscopic anastomosis clip in the treatment of defects after endoscopic full-thickness resection (EFTR). Methods: Retrospective cohort study. Fourteen patients [4 males and 10 females, aged (55.9±8.2) years (45-69 years)] with gastric submucosal tumors underwent EFTR at the First Affiliated Hospital of Soochow University were included from December 2018 to January 2021. Patients were divided into new anastomotic clamp group (n=6) and nylon ring combined with metal clips group (n=8). Preoperative endoscopic ultrasound examinations were required to all patients to evaluate the wound condition. The size of the defect, operation time required for wound closure, success rate of closure, postoperative gastric tube placement time, postoperative hospital stay, incidence of complications, preoperative and postoperative serological indexes were compared between the two groups. All patients were followed up after the operation, among which the general endoscopy was reviewed in the first month after the operation, and the telephone and questionnaire follow-up were used in the second, third, sixth month and one year after the operation to evaluate the therapeutic effect of the new endoscopic anastomosis clip and nylon rope combined with metal clip after the EFTR operation. Results: Both groups successfully completed EFTR and were successfully closed. There was no significant difference between the age, tumor diameter and defect diameter of the two groups (all P>0.05). Compared with the nylon ring combined with metal clip group, the operation time of the new anastomotic clip group was shortened [(5.0±1.8) minutes vs (35.6±10.2) minutes, P<0.001]. The operation time was shortened [(62.2±12.5) minutes vs (92.5±0.2) minutes, P=0.007]. Postoperative fasting time decreased [(2.8±0.8) days vs (4.9±1.1) days, P=0.002]. The hospital stay after operation was also shortened [(5.2±0.8) days vs (6.9±1.5) days, P=0.023]. The total intraoperative bleeding volume decreased [(20.00±5.48) ml vs (35.63±14.75) ml, P=0.031]. The patients in both groups received endoscopic examination 1 month after operation, and there was no delayed perforation and bleeding after operation. There was no obvious symptoms of discomfort. Conclusion: The new anastomotic clamp is suitable for the treatment of full-thickness gastric wall defects after EFTR, and shows advantages of shorter operation, less bleeding, and fewer postoperative complications.

[Clinical effects of fractional carbon dioxide laser combined with minimally invasive scar release in the treatment of post-acne atrophic scars].

Objective: To explore the clinical effects of fractional carbon dioxide laser combined with minimally invasive scar release in the treatment of post-acne atrophic scars. Methods: A retrospectively observational study was conducted. From January to June 2021, 60 patients with grade 3 and 4 post-acne atrophic scars who met the inclusion criteria were admitted to the First Affiliated Hospital of Henan University of Traditional Chinese Medicine. According to the adopted treatment methods, 30 patients treated with fractional carbon dioxide laser combined with minimally invasive scar release were included in combined treatment group (19 males and 11 females, aged (26±4) years), and 30 patients treated with fractional carbon dioxide laser alone were included in laser alone group (18 males and 12 females, aged (25±6) years). All the patients received the treatment once every two months, totally 3 times. Before the first treatment and 2 months after the last treatment, the scars were assessed by échelle d'évaluation clinique des cicatrices d'acné (ECCA). In 2 months after the last treatment, the curative effect was evaluated and the total effective rate was calculated according to the ECCA score. The adverse reactions of patients during the treatment were recorded. Data were statistically analyzed with independent sample t test, Wilcoxon rank-sum test, Mann-Whitney U test, chi-square test, and Fisher's exact probability test. Results: Before the first treatment, the ECCA scores of patients in the two groups were similar (P>0.05). In 2 months after the last treatment, the ECCA scores of patients in combined treatment group were significantly lower than those of laser alone group (Z=-2.89, P<0.05). The ECCA scores of patients in combined treatment group and laser alone group in 2 months after the last treatment were both significantly lower than those before the first treatment (with Z values of -4.81 and -4.79, respectively, P<0.05). In 2 months after the last treatment, the treatment in laser alone group cured the scars in 2 patients, and were markedly effective in 13 patients, effective in 7 patients, and ineffective in 8 patients; the treatment in combined treatment group cured the scars in 4 patients, and were markedly effective in 22 patients, effective in 3 patients, and ineffective in one patients. The total effective rate of scar treatment in combined treatment group (96.67%, 29/30) was significantly higher than 73.33% (22/30) in laser alone group (P<0.05). During treatment, in combined treatment group, 3 patients had pain, one patient had redness and swelling, and one patient had pigmentation. In laser alone group, one patient had pain, and 2 patients had pigmentation. No infection occurred in the wounds of all the patients in the two groups. Conclusions: Compared with fractional carbon dioxide laser alone, fractional carbon dioxide laser combined with minimally invasive scar release for post-acne atrophic scars can result in a higher total effective rate, with simple operation and good effect, so it is worthy of clinical application.

[The study of mitochondrial disorder pedigree associated with FASTKD2 variants and uniparental disomy].

Objective: To analyse the genetic cause of a proband with mitochondrial disease caused by FASTKD2 gene variation and uniparental disomy. Methods: Detailed medical history of a child suspected "mitochondrial disease" were inquired in Peking University First Hospital on November 23, 2017. c.810_820dup homozygous variation in FASTKD2 gene was found by high-throughput sequencing, and her mother had heterozygous variation, but her father didn't have such variation, which didn't conform to the genetic law of variation. Further clinical examinations and molecular genetic tests were carried out. The venous blood of the child and her parents was drawn, and genomic DNA was extracted. Sanger sequencing, polymerase chain reaction (PCR) testing, short tandem repeat (STR) analysis, chromosome microarray analysis and loss of heterozygosity (LOH) genetic relationship analysis were performed on the proband and the parents to determine the variation. Results: The clinical manifestations, physical examination and laboratory examination of the child supported the diagnosis of mitochondrial disease. c.810_820dup(p.Ser274Phefs*8) homozygous variant in FASTKD2 gene was identified. Sanger sequencing indicated that the mother was a heterozygote of the variant, while the father had no such variation, which did not conform to the genetic law. PCR testing and Sanger sequencing review to eliminate sampling errors, PCR amplification and sequencing errors. Non-biological father was excluded by STR analysis. Three large segmental LOH of FASTKD2 gene were found by chromosome microarray analysis, then the LOH relative analysis verified the child was a mixed maternal uniparental disomy of chromosome 2. The child was diagnosed as mitochondrial disease caused by oxidative phosphorylation coupling defect of type 44. Conclusions: In this study, an autosomal recessive mitochondrial disease which does not conform to the genetic law was found, and it was confirmed that this mitochondrial disease family had both pathogenic variation and uniparental disomy phenomenon. It was diagnosed as mitochondrial disease caused by type 44 oxidative phosphorylation coupling defect.

Shared genetic architecture between type 2 diabetes and COVID-19 severity.

PURPOSE: Patients with type 2 diabetes (T2D) have demonstrated a higher risk for developing more severe cases of COVID-19, but the complex genetic mechanism between them is still unknown. The aim of the present study was to untangle this relationship using genetically based approaches. METHODS: By leveraging large-scale genome-wide association study (GWAS) summary statistics of T2D and COVID-19 severity, linkage disequilibrium score regression and Mendelian randomization (MR) analyses were utilized to quantify the genetic correlations and causal relationships between the two traits. Gene-based association and enrichment analysis were further applied to identify putative functional pathways shared between T2D and COVID-19 severity. RESULTS: Significant, moderate genetic correlations were detected between T2D and COVID-19 hospitalization (rg = 0.156, SE = 0.057, p = 0.005) or severe disease (rg = 0.155, SE = 0.057, p = 0.006). MR analysis did not support evidence for a causal effect of T2D on COVID-19 hospitalization (OR 1.030, 95% CI 0.979, 1.084, p = 0.259) or severe disease (OR 0.999, 95% CI 0.934, 1.069, p = 0.982). Genes having pgene < 0.05 for both T2D and COVID-19 severe were significantly enriched for biological pathways, such as response to type I interferon, glutathione derivative metabolic process and glutathione derivative biosynthetic process. CONCLUSIONS: Our findings further confirm the comorbidity of T2D and COVID-19 severity, but a non-causal impact of T2D on severe COVID-19. Shared genetically modulated molecular mechanisms underlying the co-occurrence of the two disorders are crucial for identifying therapeutic targets.

[Analysis of MRI features of hepatocyte nuclear factor 1α-inactivated hepatocellular adenoma].

Objective: To investigate the MRI imaging features of hepatocyte nuclear factor 1α- inactivated hepatocellular adenoma (H-HCA). Methods: Clinical data and MRI images of 19 H-HCA cases who were pathologically confirmed at Zhongshan Hospital Affiliated to Fudan University between August 2014 and July 2020 were retrospectively analyzed. Among them, there were 15 females and 4 males, aged 16-47 (32± 7) years old. Tumor number, location, shape, size, boundary, MRI plain scan signal intensity, dynamic enhancement features of each phase, presence or absence of intratumoral fat content, pseudocapsule, and others were analyzed. The differences in apparent diffusion coefficient (ADC) values between the lesion and the surrounding normal liver parenchyma were compared for statistical significance. t-test was used for statistical analysis. Results: There were a total of 24 lesions in 19 cases. 14 cases had solitary lesions, and five cases had multiple lesions. 15 and nine lesions were located in the right and left lobes of the liver, respectively. 20 lesions were round or quasi-round, and four were irregular or lobulated. The tumor's maximal diameter was 0.6-8.6 (3.5 ± 2.4) cm. T(1)-weighted image (WI) showed hyperintense to iso-intense signals in 20 lesions and hypointense signals in four. T(2)WI showed iso-to-slightly high signal intensity in 16 lesions, with two hyperintense and six hypointense signals. Diffusion-weighted image (DWI) revealed hyperintense to iso-intense signals. Lesions mean ADC value was (1.289 ± 0.222)×10(-3) mm(2)/s, while the adjacent normal liver parenchyma's mean ADC value was (1.307 ± 0.236)×10(-3) mm(2)/s, with no statistically significant difference between the two (P > 0.05). During the arterial phase, 15 of the 18 lesions that underwent dynamic contrast-enhanced scanning with gadoxetate disodium (Gd-DTPA) were mildly to moderately enhanced and three were strongly enhanced. The portal and hepatic venous phases had no continuous enhancement, while the delayed phase showed a hypointense signal. During the arterial phase, two of the six lesions scanned by gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid ((Gd-EOB-DTPA) dynamic enhancement were mildly to moderately enhanced, while four were strongly enhanced. The portal and hepatic venous phases had no continuous enhancement, while the transition and hepatobiliary-specific phases showed hypointense signals. Intracellular steatosis occurred in 21 lesions, of which 19 were diffuse steatosis and 16 formed pseudocapsules in the delayed phase. Conclusion: H-HCA often occurs in young females as solitary lesions and has certain MRI features. T1WI anti-phase diffuse signal reduction and post-enhanced hypovascular withdrawal enhancement patterns can aid in accurately diagnosing the disease condition.

[Evaluation of the clinical manifestations of COVID-19 in patients with aplastic anemia undergoing immunosuppressive therapy: a prospective cohort study (NICHE)].

Objective: To investigate the clinical features of coronavirus disease 2019 (COVID-19) in patients with aplastic anemia (AA) undergoing immunosuppressive therapy (IST) . Methods: In this prospective cohort study, we collected the demographic and clinical data of patients with AA and COVID-19 from December 1, 2022, to January 31, 2023. We described the clinical features of COVID-19 among patients with AA and evaluated the effects of IST on the signs and severity of COVID-19. Results: A total of 170 patients with AA and COVID-19 were included. The common early symptoms, including fever, dizziness or headache, muscle or body aches, and sore throat, disappeared within 1-2 weeks. Approximately 25% of the patients had persistent fatigue within 2 weeks. Many patients experienced cough after an initial 1-3 days of infection, which lasted for more than 2 weeks. There were no differences in the duration of total fever episodes and maximum body temperature when patients were stratified according to whether or not they underwent IST, by IST duration, or by use of anti-lymphocyte globulin (ALG) (P>0.05). No differences were observed in the occurrence of symptoms in either the early or recovery stages when patients with AA were stratified according to whether or not they underwent IST, or by IST duration (P>0.05). However, patients who received ALG had fewer fever episodes within 1 week after infection (P=0.035) and more sore throat episodes within 2 weeks after infection (P=0.015). There were no other significant differences in clinical symptoms between patients who did and patients who did not receive ALG (P>0.05) . Conclusion: The majority of patients with AA and COVID-19 recovered within 2 weeks of noticing symptoms when treated with IST.

[Potential transmission risk of key parasitic diseases and responses to the risk during the construction of an ecological city in Shanghai Municipality].

A blueprint on Shanghai's ecological space design between 2021 and 2035 was released in 2021, aiming to build an ecological city and improve the development of ecological civilization. The transmission of parasitic diseases is strongly associated with climate and ecological environments. Currently, the prevalence of parasitic diseases has been maintained at extremely low-transmission levels, and there are almost no local cases; however, the alteration of ecological environments may results in a potential transmission risk of parasitic diseases. Hereby, the current status of key parasitic diseases in Shanghai Municipality was described, and the potential transmission risk of parasitic diseases and responses to this risk were analyzed during the construction of an ecological city in Shanghai Municipality. In addition, the suggestions pertaining to surveillance and management of parasitic diseases were proposed during the mid- and long-term construction of an ecological city in Shanghai Municipality.