Objective:To discuss the clinical manifestations and laboratory examination results of agranulocytosis and reactive plasmacytosis(RP)in the patient with Graves'disease(GD)after treated with methimazole(MMI),and to provide the basis for the clinicians to differentiate RP from multiple myeloma(MM).Methods:The clinical manifestations,laboratory examinations,diagnosis and treatment processes of one patient with GD agranulocytosis complicated with RP were analyzed,and the related literatures were reviewed.Results:The patient had a history of GD and abdominal infection.Upon admission,a complete blood count revealed a significant decrease in white blood cell count accompanied by neutropenia,and a smear re-examination showed suspicious plasma cells.The bone marrow cytology examination results showed the percentage of bone marrow plasma cells was 33％,and the percentage of plasma cells in peripheral blood was 4％;the serum immunoglobulin results showed polyclonal hyperplasia;the serum immunofixation electrophoresis results were negative;the flow cytometry analysis results indicated the immunophenotype of the plasma cells was normal.Based on the medical history and laboratory results,MM was largely excluded,supporting the diagnosis of RP.Neutropenia was considered to be related to medication,so MMI was discontinued,granulocyte colony-stimulating factor was administered to increase the number of white blood cells,and specialized GD treatment was conducted after controlling the abdominal infection.The patient had a good prognosis,and his blood count was normal upon re-examination 6 months later.Conclusion:Agranulocytosis complicated with RP in the GD patients is clinically rare.Serum immunofixation electrophoresis,blood cell morphology,and cell immunophenotype analysis are helpful for the accurate diagnosis.After actively treating the primary disease causing RP,the patient's prognosis is favorable.

Objective: Total neoadjuvant therapy has been used to improve tumor responses and prevent distant metastases in patients with locally advanced rectal cancer (LARC). Patients with complete clinical responses (cCR) then have the option of choosing a watch and wait (W&W) strategy and organ preservation. It has recently been shown that hypofractionated radiotherapy has better synergistic effects with PD-1/PD-L1 inhibitors than does conventionally fractionated radiotherapy, increasing the sensitivity of microsatellite stable (MSS) colorectal cancer to immunotherapy. Thus, in this trial we aimed to determine whether total neoadjuvant therapy comprising short-course radiotherapy (SCRT) combined with a PD-1 inhibitor improves the degree of tumor regression in patients with LARC. Methods: TORCH is a prospective, multicenter, randomized, phase II trial (TORCH Registration No. NCT04518280). Patients with LARC (T3-4/N+M0, distance from anus ≤10 cm) are eligible and are randomly assigned to consolidation or induction arms. Those in the consolidation arm receive SCRT (25Gy/5 Fx), followed by six cycles of toripalimab plus capecitabine and oxaliplatin (ToriCAPOX). Those in the induction arm receive two cycles of ToriCAPOX, then undergo SCRT, followed by four cycles of ToriCAPOX. Patients in both groups undergo total mesorectal excision (TME) or can choose a W&W strategy if cCR has been achieved. The primary endpoint is the complete response rate (CR, pathological complete response [pCR] plus continuous cCR for more than 1 year). The secondary endpoints include rates of Grade 3-4 acute adverse effects (AEs) etc. Results: Up to 30 September 2022, 62 patients attending our center were enrolled (Consolidation arm: 34, Induction arm:28). Their median age was 53 (27-69) years. Fifty-nine of them had MSS/pMMR type cancer (95.2%), and only three MSI-H/dMMR. Additionally, 55 patients (88.7%) had Stage III disease. The following important characteristics were distributed as follows: lower location (≤5 cm from anus, 48/62, 77.4%), deeper invasion by primary lesion (cT4 7/62, 11.3%; mesorectal fascia involved 17/62, 27.4%), and high risk of distant metastasis (cN2 26/62, 41.9%; EMVI+ 11/62, 17.7%). All 62 patients completed the SCRT and at least five cycles of ToriCAPOX, 52/62 (83.9%) completing six cycles of ToriCAPOX. Finally, 29 patients achieved cCR (46.8%, 29/62), 18 of whom decided to adopt a W&W strategy. TME was performed on 32 patients. Pathological examination showed 18 had achieved pCR, four TRG 1, and 10 TRG 2-3. The three patients with MSI-H disease all achieved cCR. One of these patients was found to have pCR after surgery whereas the other two adopted a W&W strategy. Thus, the pCR and CR rates were 56.2% (18/32) and 58.1% (36/62), respectively. The TRG 0-1 rate was 68.8% (22/32). The most common non-hematologic AEs were poor appetite (49/60, 81.7%), numbness (49/60, 81.7%), nausea (47/60, 78.3%) and asthenia (43/60, 71.7%); two patients did not complete this survey. The most common hematologic AEs were thrombocytopenia (48/62, 77.4%), anemia (47/62, 75.8%), leukopenia/neutropenia (44/62, 71.0%) and high transaminase (39/62, 62.9%). The main Grade III-IV AE was thrombocytopenia (22/62, 35.5%), with three patients (3/62, 4.8%) having Grade IV thrombocytopenia. No Grade V AEs were noted. Conclusions: SCRT-based total neoadjuvant therapy combined with toripalimab can achieve a surprisingly good CR rate in patients with LARC and thus has the potential to offer new treatment options for organ preservation in patients with MSS and lower-location rectal cancer. Meanwhile, the preliminary findings of a single center show good tolerability, the main Grade III-IV AE being thrombocytopenia. The significant efficacy and long-term prognostic benefit need to be determined by further follow-up.
Humans ; Middle Aged ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Chemoradiotherapy ; Immune Checkpoint Inhibitors/therapeutic use* ; Neoadjuvant Therapy ; Prospective Studies ; Rectal Neoplasms/pathology* ; Thrombocytopenia/drug therapy* ; Treatment Outcome ; Adult ; Aged

Humans ; Renal Artery ; Constriction, Pathologic ; Hypertension, Renovascular/therapy* ; Vascular Diseases ; Renal Artery Obstruction/therapy* ; Embolization, Therapeutic

MicroRNA-21(miRNA-21)is highly expressed in various tumors.Small-molecule inhibition of miRNA-21 is considered to be an attractive novel cancer therapeutic strategy.In this study,fluoroquinolone de-rivatives Al-A43 were synthesized and used as miRNA-21 inhibitors.Compound A36 showed the most potent inhibitory activity and specificity for miRNA-21 in a dual-luciferase reporter assay in HeLa cells.Compound A36 significantly reduced the expression of mature miRNA-21 and increased the protein expression of miRNA-21 target genes,including programmed cell death protein 4(PDCD4)and phos-phatase and tensin homology deleted on chromosome ten(PTEN),at 10 uM in HeLa cells.The Cell Counting Kit-8 assay(CCK-8)was used to evaluate the antiproliferative activity of A36;the results showed that the IC50 value range of A36 against six tumor cell lines was between 1.76 and 13.0 μM.Meanwhile,A36 did not display cytotoxicity in BEAS-2B cells(lung epithelial cells from a healthy human donor).Furthermore,A36 significantly induced apoptosis,arrested cells at the G0/G1 phase,and inhibited cell-colony formation in HeLa cells.In addition,mRNA deep sequencing showed that treatment with A36 could generate 171 dysregulated mRNAs in HeLa cells,while the expression of miRNA-21 target gene dual-specificity phosphatase 5(DUSP5)was significantly upregulated at both the mRNA and protein levels.Collectively,these findings demonstrated that A36 is a novel miRNA-21 inhibitor.

OBJECTIVES: To investigate the incidence of extrauterine growth retardation (EUGR) and its risk factors in very preterm infants (VPIs) during hospitalization in China. METHODS: A prospective multicenter study was performed on the medical data of 2 514 VPIs who were hospitalized in the department of neonatology in 28 hospitals from 7 areas of China between September 2019 and December 2020. According to the presence or absence of EUGR based on the evaluation of body weight at the corrected gestational age of 36 weeks or at discharge, the VPIs were classified to two groups: EUGR group (n=1 189) and non-EUGR (n=1 325). The clinical features were compared between the two groups, and the incidence of EUGR and risk factors for EUGR were examined. RESULTS: The incidence of EUGR was 47.30% (1 189/2 514) evaluated by weight. The multivariate logistic regression analysis showed that higher weight growth velocity after regaining birth weight and higher cumulative calorie intake during the first week of hospitalization were protective factors against EUGR (P<0.05), while small-for-gestational-age birth, prolonged time to the initiation of total enteral feeding, prolonged cumulative fasting time, lower breast milk intake before starting human milk fortifiers, prolonged time to the initiation of full fortified feeding, and moderate-to-severe bronchopulmonary dysplasia were risk factors for EUGR (P<0.05). CONCLUSIONS It is crucial to reduce the incidence of EUGR by achieving total enteral feeding as early as possible, strengthening breastfeeding, increasing calorie intake in the first week after birth, improving the velocity of weight gain, and preventing moderate-severe bronchopulmonary dysplasia in VPIs.
Female ; Fetal Growth Retardation ; Gestational Age ; Hospitalization ; Humans ; Incidence ; Infant ; Infant, Newborn ; Infant, Premature ; Infant, Very Low Birth Weight ; Prospective Studies ; Risk Factors

OBJECTIVE: To explore clinical effect of locking plate external fixation combined with membrane induction technology in treating open and comminuted tibial fractures with bone defects. METHODS: Totally 92 patients of open and comminuted tibial fractures with bone defects were chosen form January 2018 to July 2019, and randomly divided into external fixation group and internal fixation group, 46 patients in each group. In external fixation group, there were 29 males and 17 females, aged from 25 to 62 years old, with an average of (37.45±10.92) years old;according to AO classification, 15 patients were type A, 22 patients were type B and 9 patients were type C;according to Gustilo classification, 21 patients were typeⅡ, 10 patients were type ⅢA, 10 patients were type ⅢB, 5 patients were type Ⅲ C;treated by fracture reduction with locking plate external fixation. In internal fixation group, there were 31 males and 15 females, aged from 23 to 60 years old, with an average of(36.88±10.64) years old;according to AO classification, 18 patients were type A, 20 patients were type B and 8 patients were type C; according to Gustilo classification, 22 patients were typeⅡ, 11 patients were type ⅢA, 7 patients were type ⅢB, 6 patients were type Ⅲ C;treated by traditional open reduction with plate internal fixation. Operation time, intraoperative blood loss, incision length, hospital stay, fracture healing time and lower limb full weight-bearing time and postoperative complications between two groups were observed and compared, bone mineral density, osteocalcin, blood calcium and phosphorus before operation and 1 month after operation. RESULTS: All patients were followed up from 12 to 18 months with an average of (14.92±2.46) months. Operation time, intraoperative blood loss, incision length, hospital stay, fracture healing time and lower limb full weight-bearing time of external fixation group were significantly better than that of internal fixation group( CONCLUSION Locking plate external fixation combined with membrane induction technology in treating open and comminuted tibial fractures with severe post-traumatic bone defects has advantages of less trauma, reliable fixation, shorter fracture healing time, and could improve bone metabolic activity with less postoperative complications.
Adult ; Bone Plates ; External Fixators ; Female ; Fracture Fixation ; Fracture Fixation, Internal ; Fractures, Comminuted/surgery* ; Humans ; Male ; Middle Aged ; Technology ; Tibial Fractures/surgery* ; Treatment Outcome ; Young Adult

Phyllanthi Fructus, a unique Chinese and Tibetan medicinal plant with both edible and medical values, has high potential of cultivation and development. The resources of Phyllanthi Fructus in China are rich, mainly distributed in Yunnan, Sichuan, Fujian, Guangdong, Guangxi, etc. Phyllanthi Fructus is widely used in the clinical practice of Chinese medicine and plays an important role in Tibetan medicine, Uyghur medicine, Yi medicine, and Mongolian medicine. Phyllanthi Fructus mainly contains phenolic acids,tannins, terpenes, sterols, fatty acids, flavonoids, amino acids and other compounds. Modern pharmacological studies show that Phyllanthi Fructus has antioxidant, anticancer, blood lipid-lowering, liver protective, antimicrobial, anti-inflammatory, and immune regulatory activities. In this paper, the research status of Phyllanthi Fructus was reviewed from the aspects of herbal textual research,chemical composition, and pharmacological action. The quality markers(Q-markers) of Phyllanthi Fructus were predicted and analyzed from the aspects of biogenic pathway, specificity and measurability of chemical components, efficacy, properties, new clinical uses, drug-food homology, and transformation of polyphenols. The results will provide a scientific basis for the quality control, quality evaluation, and standard formulation of Phyllanthi Fructus.
China ; Drugs, Chinese Herbal ; Fruit ; Medicine, Tibetan Traditional ; Quality Control

Pulmonary hypertension (PH) is a severe pathophysiological condition characterized by pulmonary artery remodeling and continuous increases in pulmonary artery pressure, which may eventually develop to right heart failure and death. Although newly discovered and incredible treatment strategies in recent years have improved the prognosis of PH, limited types of effective and economical drugs for PH still makes it as a life-threatening disease. Some drugs from Chinese materia medica (CMM) have been traditionally applied in the treatment of lung diseases. Accumulating evidence suggests active pharmaceutical ingredients (APIs) derived from those medicines brings promising future for the prevention and treatment of PH. In this review, we summarized the pharmacological effects of APIs derived from CMM which are potent in treating PH, so as to provide new thoughts for initial drug discovery and identification of potential therapeutic strategies in alternative medicine for PH.
China ; Drugs, Chinese Herbal ; Humans ; Hypertension, Pulmonary/drug therapy* ; Materia Medica ; Medicine, Chinese Traditional

Phyllanthus emblica is a kind of traditional medicine and medicinal and edible plant, with rich variety resources and high development value. It is a key poverty alleviation variety in China at present. As P. emblica processing industry is rising gradually in recent years, in order to fully develop and utilize its industrial resources, this paper systematically introduces current comprehensive development and utilization of P. emblica, discusses the problems in P. emblica processing industry, and puts forward comprehensive development and utilization strategies and industrial models in terms of cultivation, breeding, grading, quality evaluation and waste recycling, so as to provide a certain reference for promoting the high-quality development of P. emblica industry in China.
China ; Medicine ; Medicine, Traditional ; Phyllanthus emblica ; Plant Breeding ; Plant Extracts