Abnormal activation of the Janus kinase/signal transducer and activator of transcription （JAK/STAT） signaling pathway is involved in the pathogenesis of diffuse large B-cell lymphoma （DLBCL）. In recent years， inhibitors targeting JAK2 and STAT3 have emerged as promising therapeutic candidates in DLBCL. This review summarizes the efficacy and safety profiles of JAK2 inhibitors （e.g.， ruxolitinib） and STAT3 inhibitors （direct small-molecule inhibitors， the antisense oligonucleotide， and proteolysis targeting chimeras， etc.） in preclinical models and clinical trials. Accumulating evidence indicates that JAK2 and STAT3 inhibitors exhibit antitumor activity and are generally well tolerated in a subset of DLBCL patients. Meanwhile， the development of novel drug delivery systems has significantly enhanced the stability， bioavailability， and targeting ability of the compounds. Furthermore， JAK2 and STAT3 inhibitors may exhibit synergistic effects when combined with other therapy strategies （such as combinations with B-cell receptor signaling pathway inhibitors， immunomodulators， or other targeted drugs）. However， current clinical applications are still in their early stages. Future research should concentrate on precision treatment strategies based on the genetic subtyping of DLBCL， and further refine the delivery systems for inhibitors as well as combination drug regimens to improve clinical outcomes.

Most tumor cells and healthy neurons are at rest during G0 phase.Once the cell cycle is abnormally re-entered under certain conditions,the proliferation of tumor cells and the degenerative necrosis of neurons can be initiated.From the perspective of the cell cycle,cancer and central nervous system diseases,two seemingly different disease types,have a common pathogenesis.This type of diseases is named aberrant cell cycle diseases.As a newly discovered microRNA(miR),miR-1976 is closely related to the regulation of the cell cycle.This review summarizes the progress in the research on miR-1976 in cancer and central nervous system diseases,aiming to provide a reference for the clinical application of miR-1976 in aberrant cell cycle diseases in the future.
MicroRNAs/genetics* ; Humans ; Cell Cycle/genetics* ; Neoplasms/genetics* ; Central Nervous System Diseases/genetics*

Objective:To investigate the expression and clinical significance of microRNA-124(miR-124)and microRNA-1976(miR-1976)in the serum of patients with Parkinson's disease(PD).Methods:A total of 58 patients with PD were selected from September 2020 to June 2022 and categorized as the PD group.The Unified Parkinson's Disease Rating Scale(UPDRS)score was used to divide the PD patients into two groups: those with a UPDRS score≤60(25 patients)and those with a UPDRS score >60(33 patients). The Hoehn-Yahr grading scale was used to grade the PD patients.Additionally, 30 healthy individuals who had undergone a physical examination during the same period were selected as the control group.After collecting the subjects' serum, we performed real-time fluorescent quantitative PCR(qRT-PCR)to detect the expressions of miR-124 and miR-1976 in the serum.Logistic regression analysis was employed to analyze the influencing factors, and the diagnostic significance of serum miR-124 and miR-1976 in PD patients was evaluated using the receiver operating characteristic(ROC)curve.To predict the target genes of miR-1976, we utilized several software including TargetScan and Mirtarbase.Results:Compared to the control group, the PD group showed a significant down-regulation of serum miR-124 expression[(1.49±0.36) vs.(1.02±0.32)]( t=8.85, P<0.001), while miR-1976 expression was sharply up-regulated[(0.98±0.30) vs.(1.33±0.37)]( t=6.92, P<0.001). The low expression of serum miR-124 and the overexpression of miR-1976 were identified as independent risk factors for PD( OR>1, P<0.05). The Hoehn-Yahr rating of PD patients with a UPDRS score above 60 was higher than that of patients with a UPDRS score below 60[(3.42 ± 0.73) vs.(2.16 ± 0.42)]( t=3.05, P<0.05). However, there was no significant difference in serum miR-124 and miR-1976 expression between groups with different UPDRS scores[miR-124: (1.09±0.26) vs.(0.98±0.38)( t=0.89, P>0.05); miR-1976: (1.42±0.43) vs.(1.23±0.68)( t=0.62, P>0.05)]. The ROC analysis results demonstrated that miR-124 and miR-1976 had area under the curve(AUC)values of 0.832 and 0.797, respectively, in diagnosing PD.The corresponding cutoff values were 1.205 and 1.196, respectively.The sensitivity for miR-124 was 74.1%, while for miR-1976 it was 51.8%.The specificity for miR-124 was 77.8%, and for miR-1976 it was 90.1%.When both miR-124 and miR-1976 were combined in the diagnosis of PD, the AUC was 0.912, with a sensitivity of 76.4% and a specificity of 93.2%.Furthermore, it was found that miR-1976 targeted the PINK1 gene, suggesting its potential as a target gene in PD. Conclusions:The expression of miR-124 was found to be decreased in PD patients, while the expression of miR-1976 was increased.Both miR-124 and miR-1976 showed some reference value in PD diagnosis, and their combined diagnostic value was higher.This suggests that further study on their significance is warranted.However, it should be noted that the expressions of miR-124 and miR-1976 were not found to be correlated with the UPDRS score of PD patients.

Tuberous sclerosis complex(TSC)is a rare genetic disease that can lead to benign dysplasia in multiple organs such as the skin, brain, eyes, oral cavity, heart, lungs, kidneys, liver, and bones. Its main symptoms include epilepsy, intellectual disabilities, skin depigmentation, and facial angiofibromas, whilst incidence is approximately 1 in 10 000 to 1 in 6000 newborns. This case presents a middle-aged woman who initially manifested with epilepsy and nodular depigmentation. Later, she developed a lower abdominal mass, elevated creatinine, and severe anemia. Based on clinical features and whole exome sequencing, the primary diagnosis was confirmed as TSC. Laboratory and imaging examinations revealed that the lower abdominal mass originated from the uterus. CT-guided biopsy pathology and surgical pathology suggested a combination of leiomyoma and abscess. With the involvement of multiple organs and various complications beyond the main diagnosis, the diagnostic and therapeutic process for this patient highlights the importance of rigorous clinical thinking and multidisciplinary collaboration in the diagnosis and treatment of rare and challenging diseases.

Objective To evaluate the efficacy and safety of brexpiprazole in treating acute schizophrenia.Methods Patients with schizophrenia were randomly divided into treatment group and control group.The treatment group was given brexpiprozole 2-4 mg·d-1 orally and the control group was given aripiprazole 10-20 mg·d-1orally,both were treated for 6 weeks.Clinical efficacy of the two groups,the response rate at endpoint,the changes from baseline to endpoint of Positive and Negative Syndrome Scale(PANSS),Clinical Global Impression-Improvement(CGI-S),Personal and Social Performance scale(PSP),PANSS Positive syndrome subscale,PANSS negative syndrome subscale were compared.The incidence of treatment-related adverse events in two groups were compared.Results There were 184 patients in treatment group and 186 patients in control group.After treatment,the response rates of treatment group and control group were 79.50％(140 cases/184 cases)and 82.40％(150 cases/186 cases),the scores of CGI-I of treatment group and control group were(2.00±1.20)and(1.90±1.01),with no significant difference(all P＞0.05).From baseline to Week 6,the mean change of PANSS total score wese(-30.70±16.96)points in treatment group and(-32.20±17.00)points in control group,with no significant difference(P＞0.05).The changes of CGI-S scores in treatment group and control group were(-2.00±1.27)and(-1.90±1.22)points,PSP scores were(18.80±14.77)and(19.20±14.55)points,PANSS positive syndrome scores were(-10.30±5.93)and(-10.80±5.81)points,PANSS negative syndrome scores were(-6.80±5.98)and(-7.30±5.15)points,with no significant difference(P＞0.05).There was no significant difference in the incidence of treatment-related adverse events between the two group(69.00％vs.64.50％,P＞0.05).Conclusion The non-inferiority of Brexpiprazole to aripiprazole was established,with comparable efficacy and acceptability.

In salivary gland disease, accessory parotid gland (APG) lesions are relatively low, and tumor is the most common manifestation. Currently, surgery is the primary treatment method for APG tumors. Although numerous surgical procedures are available, there is no standard protocol. Due to the location of the APG in the midcheek area, the complications and aesthetic concerns connected with conventional surgery for treating APG tumors sometimes cause significant distress to patients. With the progress of medical technology as well as improving patients' aesthetic and functional requirements, surgical excision methods and incision design are constantly improving. More beautiful and minimally invasive treatments, such as concealed transoral approach and endoscopically aided extracapsular dissection of APG, have been gradually developed. This review focuses on surgical techniques, benefits, and drawbacks of APG tumor surgery that have been carried out and provides an outlook based on the preliminary application of endoscopically assisted accessory parotid tumor resection.

Malaria is an insect-borne disease transmitted by Anopheles mosquitoes or the importation of Plasmodium-infected blood, posing a serious threat to human health and life safety. This study aims to analyze the incidence of malaria in Qingdao at various stages from 1949 to 2021, to collate the control measures taken at different epidemic stages to assess the effectiveness of malaria control, and to identify a set of malaria control strategies suitable for Qingdao, while providing Chinese experience for other countries or cities in their malaria elimination efforts. A retrospective survey was used to collect information on malaria cases, control measures and prevention and control effects in Qingdao from 1949 to 2021, and to evaluate malaria control strategies and measures in Qingdao. 704 155 cases have been reported from 1949 to 2021, with three epidemic peaks: the incidence rate was 1715.9/100 000 in 1961, 1409.7/100 000 in 1965, and the most severe case occurred in 1972, with an incidence rate of 1635.6/100 000 and a case count exceeding 90 000. Throughout the various stages of malaria epidemics, Qingdao has effectively eliminated indigenous malaria by implementing diverse preventive and control measures. Since the last indigenous case of Plasmodium vivax was reported in 2002, all locally reported cases have been imported, mainly by returning migrant workers from Africa. This study examines a range of malaria prevention and control strategies and interventions that are appropriate for Qingdao. These measures have enabled Qingdao to successfully eliminate malaria and maintain malaria-free status for more than 20 years. These measures can also serve as a reference for similarly situated cities in Africa and Southeast Asia.

Objective To investigate the effects of Rehmanniae Radix before and after processing on the intestinal flora of rats with kidney yin deficiency syndrome.Methods SD rats were randomly divided into blank group,model group,probiotic group(0.35 g·kg-1),high-/medium-/low-dose groups of Rehmanniae Radix Praeparata(3.5,1.75,0.875 g·kg-1),and high-/medium-/low-dose groups of Rehmanniae Radix(3.5,1.75,0.875 g·kg-1),with 9 rats in each group.Except for the blank group,rats in each group were injected intramuscularly with Dexamethasone Sodium Phosphate Injection(0.35 mg·kg-1)once a day for 21 days.The drug was administered by gavage once a day on the seventh day of modelling for 14 days.The adrenal histopathological changes were observed by using HE staining;the levels of serum cyclic adenosine monophosphate(cAMP),cyclic guanosine monophosphate(cGMP),corticotropin-releasing hormone(CRH),adrenocorticotropic hormone(ACTH),and corticosterone(CORT)were detected by ELISA;and the levels of short-chain fatty acids in the feces and changes in the diversity of intestinal flora were detected by a targeted metabolomic approach in conjunction with 16SrRNA sequencing in the rats in each group.Results(1)Compared with the blank group,the body mass of rats in the model group was significantly decreased on days 7,14 and 21(P＜0.05,P＜0.01);serum levels of cAMP,CRH,ACTH,CORT and the cAMP/cGMP ratio were all significantly increased(P＜0.01),and the cGMP content was significantly decreased(P＜0.01);and the adrenal cortex was thinned,with the boundaries of various layers of the cortex unclear.Compared with the model group,the body mass of rats in the Rehmanniae Radix Praeparata administration group on day 21 were all significantly increased(P＜0.05,P＜0.01),and the serum content of cAMP,CRH,ACTH,CORT and the cAMP/cGMP ratio were all significantly decreased(P＜0.05,P＜0.01),and the content of cGMP was significantly increased(P＜0.05,P＜0.01)in the rats;body mass of rats in the Rehmanniae Radix administration group did not change significantly(P＞0.05),CRH and CORT contents in serum of rats in the high-dose group of Rehmanniae Radix were significantly reduced(P＜0.01),and ACTH contents in serum of rats in the medium-dose group of Rehmanniae Radix were significantly reduced(P＜0.05);the adrenal cortex of rats in all the administration groups were improved,in particular,the thickening of the adrenal cortex layers was obvious in the Rehmanniae Radix Praeparata group,and the improvement effect was superior to that in the Rehmanniae Radix group.(2)Compared with the blank group,the difference of Coverage index was not statistically significant(P＞0.05),and the coverage of each group was good;the abundance index(Sobs,Ace,Chao)and diversity index(Shannon)of the model group were significantly increased(P＜0.01),and the Simpson index was significantly decreased(P＜0.01).Compared with the model group,Sobs index was significantly decreased in the medium-and high-dose groups of Rehmanniae Radix Praeparata(P＜0.05),Chao index was significantly decreased in the administered groups of Rehmanniae Radix Praeparata and high-dose group of Rehmanniae Radix(P＜0.05,P＜0.01),and Simpson index was significantly increased in the high-dose group of Rehmanniae Radix Praeparata(P＜0.05).The changes of Rehmanniae Radix on the richness and diversity of intestinal microbial community in kidney yin-deficient rats were small,while Rehmanniae Radix Praeparata could better maintain the stability of the richness and diversity of intestinal microbial community in kidney yin-deficient rats.(3)Compared with the blank group,the abundance of phylum firmicutes in the feces of the model group was significantly decreased,while the abundance of bacteroides and actinomycetes was significantly increased.The abundance of Lactobacillus was significantly decreased(P＜0.01),while the abundance of norank_f__Muribaculaceae and Bifidobacterium was significantly increased(P＜0.01).Compared with the model group,the trend of recovery of bacterial abundance in the probiotic group and the high-dose group of Rehmanniae Radix Praeparata was more similar to that of the blank group,which showed that it had the best regulating effect on the ratio of bacterial flora;the abundance of lactobacillus in all administered groups was increased,with that of the probiotic group was significantly increased(P＜0.01);the abundance of norank__f__Muribaculaceae and Bifidobacterium were all decreased,among which the probiotic group and the medium-and high-dose groups of Rehmanniae Radix Praeparata were significantly decreased(P＜0.01),and the effect was significantly superior to that of Rehmanniae Radix.The COG functions of the samples in each group were mainly focused on amino acid transport and metabolism,carbohydrate transport and metabolism,translation,ribosomal structure and biogenesis,replication,recombination and repair,but the abundance information of each function was different between groups,which may be due to the differences caused by dysbiosis of intestinal flora.(4)Compared with the blank group,the levels of acetic acid,butyric acid and propionic acid in the faeces of rats in the model group were significantly decreased(P＜0.05,P＜0.01),and the level of isobutyric acid was significantly increased(P＜0.01).Compared with the model group,the levels of acetic acid,butyric acid and propionic acid in the faeces of rats in the probiotic group and the low-,medium-and high-dose groups of Rehmanniae Radix Praeparata were significantly increased(P＜0.05,P＜0.01)and the levels of isobutyric acid were significantly decreased(P＜0.05,P＜0.01);although the above indexes in the Rehmanniae Radix group were improved,the difference was not statistically significant(P＞0.05).Conclusion The enhanced therapeutic effect of Rehmanniae Radix after processing on rats with kidney yin deficiency syndrome may be related to its adjusting effect on intestinal flora.

【Objective】 To reduce the incidence of postoperative intestinal obstruction, we tried to improve surgical techniques by closing the cavity formed during radical cystectomy + ileal passage (Bricker) via laparoscopy to prevent the formation of abdominal hernia. 【Methods】 During Oct.2018 and Feb.2022, 41 patients were involved (conventional group). After standard laparoscopic radical cystectomy + pelvic lymphadenectomy, the ileum channel was established. The right medial retroperitoneum was sutured to cover the mesothelium and end of the ileum channel under open operation or endoscope. The space between the ureter and mesothelium of the ileum channel was sealed, and the end of the ileum channel and both ureters were externalized. During Feb.2022 and Dec.2022, 15 patients were involved (modified group). The right inner and outer lateral peritoneums below the ileal conduit were sutured to "bottom out" the gap between the ileal conduit and the right abdominal wall in addition to standard procedures. The recovery of intestinal function and incidence of bowel obstruction were compared between the two groups. 【Results】 In the conventional group, the intestinal function recovered within 2 to 6 days after surgery, with a median ventilation time of 3 days. Intestinal obstruction occurred in 3 patients, 2 of whom improved after conservative treatment while 1 underwent surgical exploration after ineffective conservative therapy. There were no significant differences in the time of discharge and ventilation between the two groups, but no intestinal obstruction occurred in the modified group. 【Conclusion】 Peritoneal externalization at the end of ileal passage can reduce the incidence of intra-abdominal hernia and postoperative intestinal obstruction, which is worthy of clinical application.

OBJECTIVE: To observe the effect of Shugan Tiaoshen acupuncture (acupuncture for soothing the liver and regulating the mentality) combined with western medication on depression and sleep quality in the patients with depression-insomnia comorbidity due to COVID-19 quarantine, and investigate the potential mechanism from the perspective of cortical excitability. METHODS: Sixty patients with depression-insomnia comorbidity due to COVID-19 quarantine were randomly divided into an acupuncture group and a sham-acupuncture group, 30 cases in each one. The patients of both groups were treated with oral administration of sertraline hydrochloride tablets. In the acupuncture group, Shugan Tiaoshen acupuncture was supplemented. Body acupuncture was applied to Yintang (GV 24⁺), Baihui (GV 20), Hegu (LI 4), Zhaohai (KI 6), Qihai (CV 6), etc. The intradermal needling was used at Xin (CO₁₅), Gan (CO₁₂) and Shen (CO₁₀). In the sham-acupuncture group, the sham-acupuncture was given at the same points as the acupuncture group. The compensatory treatment was provided at the end of follow-up for the patients in the sham-acupuncture group. In both groups, the treatment was given once every two days, 3 times a week, for consecutive 8 weeks. The self-rating depression scale (SDS) and insomnia severity index (ISI) scores were compared between the two groups before and after treatment and 1 month after the end of treatment (follow-up) separately. The cortical excitability indexes (resting motor threshold [rMT], motor evoked potential amplitude [MEP-A], cortical resting period [CSP]) and the level of serum 5-hydroxytryptamine (5-HT) were measured before and after treatment in the two groups. RESULTS: After treatment and in follow-up, SDS and ISI scores were decreased in both groups compared with those before treatment (P<0.05), and the scores in the acupuncture group were lower than those in the sham-acupuncture group (P<0.05), and the decrease range in the acupuncture group after treatment was larger than that in the sham-acupuncture group (P<0.05). After treatment, rMT was reduced (P<0.05), while MEP-A and CSP were increased (P<0.05) in the acupuncture group compared with that before treatment. The levels of serum 5-HT in both groups were increased compared with those before treatment (P<0.05). The rMT in the acupuncture group was lower than that in the sham-acupuncture group, while MEP-A and CSP, as well as the level of serum 5-HT were higher in the acupuncture group in comparison with the sham-acupuncture group (P<0.05). CONCLUSION Shugan Tiaoshen acupuncture combined with western medication can relieve depression and improve sleep quality in the patients with depression-insomnia comorbidity due to COVID-19 quarantine, which is probably related to rectifying the imbalanced excitatory and inhibitory neuronal functions.
Humans ; Depression ; Quarantine ; Serotonin ; Sleep Initiation and Maintenance Disorders ; COVID-19 ; Acupuncture Therapy ; Comorbidity